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Sample records for preventing allograft rejection

  1. Veto cell suppression mechanisms in the prevention of allograft rejection

    DEFF Research Database (Denmark)

    Jacobsen, I M; Claesson, Mogens Helweg

    1998-01-01

    on the surface of the veto-active cell. Data from a large number of experimental and clinical studies strongly indicate that veto-active cells function in vivo and are capable of preventing allograft rejection. Thus, donor-cell-mediated veto activity is the most likely explanation for the well-known graft...

  2. Corneal allograft rejection: Risk factors, diagnosis, prevention, and treatment

    Directory of Open Access Journals (Sweden)

    Dua Harminder

    1999-01-01

    Full Text Available Recent advances in corneal graft technology, including donor tissue retrieval, storage and surgical techniques, have greatly improved the clinical outcome of corneal grafts. Despite these advances, immune mediated corneal graft rejection remains the single most important cause of corneal graft failure. Several host factors have been identified as conferring a "high risk" status to the host. These include: more than two quadrant vascularisation, with associated lymphatics, which augment the afferent and efferent arc of the immune response; herpes simplex keratitis; uveitis; silicone oil keratopathy; previous failed (rejected grafts; "hot eyes"; young recipient age; and multiple surgical procedures at the time of grafting. Large grafts, by virtue of being closer to the host limbus, with its complement of vessels and antigen-presenting Langerhans cells, also are more susceptible to rejection. The diagnosis of graft rejection is entirely clinical and in its early stages the clinical signs could be subtle. Graft rejection is largely mediated by the major histocompatibility antigens, minor antigens and perhaps blood group ABO antigens and some cornea-specific antigens. Just as rejection is mediated by active immune mediated events, the lack of rejection (tolerance is also sustained by active immune regulatory mechanisms. The anterior chamber associated immune deviation (ACAID and probably, conjunctiva associated lymphoid tissue (CALT induced mucosal tolerance, besides others, play an important role. Although graft rejection can lead to graft failure, most rejections can be readily controlled if appropriate management is commenced at the proper time. Topical steroids are the mainstay of graft rejection management. In the high-risk situations however, systemic steroids, and other immunosuppressive drugs such as cyclosporin and tacrolimus (FK506 are of proven benefit, both for treatment and prevention of rejection.

  3. 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.

  4. Role of tacrolimus prolonged release in the prevention of allograft rejection

    Directory of Open Access Journals (Sweden)

    Peter Abrams

    2010-08-01

    Full Text Available Peter Abrams, Abhinav Humar, Henkie P TanDepartment of Surgery, Thomas E Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pennsylvania, USAAbstract: Successful management of the solid-organ transplant recipient begins with prevention of rejection and achieving a balance between insufficient and excessive immunosuppression. Standard tacrolimus therapy for prevention of solid-organ transplant rejection consists of 2 divided doses per day. In an effort to simplify tacrolimus dosing to once daily, a new formulation (tacrolimus prolonged release [PR] was chosen for its combination of a similar extent of bioavailability and a substantially reduced rate of clearance. Several clinical conversion studies have now been completed using PR to clarify its pharmacokinetics, efficacy at prevention of allograft rejection, and safety profiles in solid-organ transplant patients. A cohort of 67 stable kidney transplant recipients was converted from standard tacrolimus to PR in an open-label, multicenter study in the United States and Canada. A second open-label, multicenter study was performed in liver transplant recipients with stable graft function on standard tacrolimus therapy converted to PR. A third conversion study was performed as an open-label study at 5 centers in the United States in stable pediatric liver transplant recipients. As medication noncompliance can significantly contribute to the incidence of graft rejection and graft loss in transplant recipients, a potentially significant advance in the transplant community’s ongoing mission to optimize prevention of rejection occurred with the development of a once-daily tacrolimus PR. The results of these preliminary studies suggest that select solid-organ transplant recipients converted to PR can be safely maintained using the same monitoring and patient care techniques historically used for standard tacrolimus therapy.Keywords: immunosuppression, tacrolimus allograft

  5. Local Tacrolimus (FK506) Delivery for Prevention of Acute Rejection in the Nonhuman Primate Delayed Mixed Chimerism Vascularized Composite Allograft Tolerance Induction Protocol

    Science.gov (United States)

    2016-10-01

    Chimerism Vascularized Composite Allograft Tolerance Induction Protocol PRINCIPAL INVESTIGATORS: Dr. Curtis L. Cetrulo CONTRACTING ORGANIZATION...Tacrolimus (FK506) Delivery for Prevention of Acute Rejection in the Nonhuman Primate Delayed Mixed Chimerism Vascularized Composite Allograft Tolerance...tacrolimus, FK506, vascularized composite allografts, immune rejection, preclinical, transplant, nonhuman primate model, degradable polymer, tyrosine

  6. 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

  7. Mycophenolate mofetil for prevention of liver allograft rejection: initial results of a controlled clinical trial.

    Science.gov (United States)

    Sterneck, M; Fischer, L; Gahlemann, C; Gundlach, M; Rogiers, X; Broelsch, C

    2000-01-01

    Mycophenolate Mofetil (M MF) is a new immunosuppressive agent with proven efficacy for the prevention of kidney allograft rejection. However, only little experience is available with the use of MMF in liver transplant recipients. In this prospective, controlled trial the efficacy and safety of MMF and Azathioprine (AZA) were compared in a Neoral based quadruple immunosuppressive regimen after orthotopic liver transplantation. Between 12/96 and 12/98 57 adult patients were enrolled in the study at the University of Hamburg. 28 patients were randomised to MMF, 29 patients to AZA in combination with equivalent doses of lymphocyte antibodies, Neoral and methylprednisolone. After a median follow-up of 10+/-3.2 months patient or graft survival did not differ significantly between the MMF and AZA group. However, MMF treated patients experienced less frequently acute rejection episodes (MMF: 6/28; 21.4% versus AZA: 13/29; 44.8%) (p=0.06). Furthermore, thrombocytopenia (MMF: 6/28; 21.4% versus AZA: 14/29; 48.3%) (ppreliminary data suggest that after liver transplantation primary immunosuppression with MMF is advantageous over AZA with regard to safety and efficacy.

  8. Prevention of corneal allograft rejection in a mouse model of high risk recipients

    Czech Academy of Sciences Publication Activity Database

    Vítová, Andrea; Filipec, M.; Zajícová, Alena; Krulová, Magdalena; Holáň, Vladimír

    2004-01-01

    Roč. 88, - (2004), s. 1338-1342 ISSN 0007-1161 R&D Projects: GA MZd NR7816; GA MZd NI7531; GA MŠk LN00A026; GA ČR GP310/02/D162; GA ČR GD310/03/H147 Institutional research plan: CEZ:AV0Z5052915 Keywords : Corneal allograft, rejection Subject RIV: EC - Immunology Impact factor: 2.000, year: 2004

  9. The role of CD8+ T cells during allograft rejection

    Directory of Open Access Journals (Sweden)

    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.

  10. Combined HLA matched limbal stem cells allograft with amniotic membrane transplantation as a prophylactic surgical procedure to prevent corneal graft rejection after penetrating keratoplasty: case report

    Directory of Open Access Journals (Sweden)

    Paolo Capozzi

    2014-09-01

    Full Text Available Purpose. To determine if the use of combined HLA matched limbal stem cells allograft with amniotic membrane transplantation (AMT is a safe and effective prophylactic surgical procedure to prevent corneal graft after penetrating keratoplasty (PK. Methods. We report the case of a 17 years old patient with a history of congenital glaucoma, trabeculectomy and multiple corneal graft rejections, presenting total limbal cell deficiency. To reduce the possibility of graft rejection in the left eye after a new PK, a two step procedure was performed. At first the patient underwent a combined HLA matched limbal stem cells allograft (LAT and AMT and then, 10 months later, a new PK. Results. During 12 months of follow-up, the corneal graft remained stable and smooth, with no sign of graft rejection. Conclusions. In our patient, the prophylactic use of LAT from HLA-matched donors and AMT before PK, may result in a better prognosis of corneal graft survival.

  11. Blockade of T-lymphocyte KCa3.1 and Kv1.3 channels as novel immunosuppression strategy to prevent kidney allograft rejection

    DEFF Research Database (Denmark)

    Grgic, I; Wulff, H; Eichler, I

    2009-01-01

    Currently, there is an unmet clinical need for novel immunosuppressive agents for long-term prevention of kidney transplant rejection as alternatives to the nephrotoxic calcineurin inhibitor cyclosporine (CsA). Recent studies have shown that K(+) channels have a crucial role in T-lymphocyte activ......Currently, there is an unmet clinical need for novel immunosuppressive agents for long-term prevention of kidney transplant rejection as alternatives to the nephrotoxic calcineurin inhibitor cyclosporine (CsA). Recent studies have shown that K(+) channels have a crucial role in T......-lymphocyte activity. We investigated whether combined blockade of the T-cell K(+) channels K(Ca)3.1 and K(v)1.3, both of which regulate calcium signaling during lymphocyte activation, is effective in prevention of rejection of kidney allografts from Fisher rats to Lewis rats. All recipients were initially treated...

  12. Everolimus immunosuppression for renal protection, reduction of allograft vasculopathy and prevention of allograft rejection in de-novo heart transplant recipients: could we have it all?

    Science.gov (United States)

    Gude, Einar; Gullestad, Lars; Andreassen, Arne K

    2017-06-01

    De-novo introduction of everolimus (Eve) in heart transplant recipients opens for early reduction of calcineurin inhibitors (CNI) and potential of preserving renal function, attenuate progression of coronary allograft vasculopathy (CAV) and maintain rejection efficacy. The first trials demonstrated adequate rejection prophylaxis and favorable outcomes on CAV, but observed enhanced nephrotoxicity because of insufficient CNI reduction. The SCHEDULE trial compared de-novo Eve with significantly reduced CNI exposure and conversion to CNI-free treatment week 7-11 postheart transplant, with standard CNI immunosuppression. Improved renal function and attenuation of CAV was found among Eve patients, with higher numbers of treated acute rejections observed. With sustained superior renal and CAV related data also after 36 months with the Eve protocol, cardiac function was equally well preserved in both groups. According to the International Society of Heart and Lunge Transplantation registry, mammalian target of rapamycin inhibitor treatment is uncommon during the first postoperative year, with a prevalence of 20% in patients after 5 years. Current evidence suggests a greater benefit from these immunosuppressives if introduced at an earlier timepoint. Immunosuppressive protocols based on Eve treatment in de-novo patients should be further investigated and developed, enabling CNI avoidance before accelerating side-effects lead to irreversible damage.

  13. T-cell exhaustion in allograft rejection and tolerance.

    Science.gov (United States)

    Thorp, Edward B; Stehlik, Christian; Ansari, M Javeed

    2015-02-01

    The role of T-cell exhaustion in the failure of clearance of viral infections and tumors is well established. There are several ongoing trials to reverse T-cell exhaustion for treatment of chronic viral infections and tumors. The mechanisms leading to T-cell exhaustion and its role in transplantation, however, are only beginning to be appreciated and are the focus of the present review. Exhausted T cells exhibit a distinct molecular profile reflecting combinatorial mechanisms involving the interaction of multiple transcription factors important in control of cell metabolism, acquisition of effector function and memory capacity. Change of microenvironmental cues and limiting leukocyte recruitment can modulate T-cell exhaustion. Impaired leukocyte recruitment induces T-cell exhaustion and prevents allograft rejection. Preventing or reversing T-cell exhaustion may lead to prevention of transplant tolerance or triggering of rejection; therefore, caution should be exercised in the use of agents blocking inhibitory receptors for the treatment of chronic viral infections or tumors in transplant recipients. Further definition of the role of T-cell exhaustion in clinical transplantation and an understanding of the mechanisms of induction of T-cell exhaustion are needed to develop strategies for preventing allograft rejection and induction of tolerance.

  14. Cell-Free DNA and Active Rejection in Kidney Allografts.

    Science.gov (United States)

    Bloom, Roy D; Bromberg, Jonathan S; Poggio, Emilio D; Bunnapradist, Suphamai; Langone, Anthony J; Sood, Puneet; Matas, Arthur J; Mehta, Shikha; Mannon, Roslyn B; Sharfuddin, Asif; Fischbach, Bernard; Narayanan, Mohanram; Jordan, Stanley C; Cohen, David; Weir, Matthew R; Hiller, David; Prasad, Preethi; Woodward, Robert N; Grskovic, Marica; Sninsky, John J; Yee, James P; Brennan, Daniel C

    2017-07-01

    Histologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell-mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), P rejection at a cutoff of 1.0% dd-cfDNA were 61% and 84%, respectively. The AUC for discriminating ABMR from samples without ABMR was 0.87 (95% CI, 0.75 to 0.97). Positive and negative predictive values for ABMR at a cutoff of 1.0% dd-cfDNA were 44% and 96%, respectively. Median dd-cfDNA was 2.9% (ABMR), 1.2% (T cell-mediated types ≥IB), 0.2% (T cell-mediated type IA), and 0.3% in controls ( P =0.05 for T cell-mediated rejection types ≥IB versus controls). Thus, dd-cfDNA may be used to assess allograft rejection and injury; dd-cfDNA levels rejection (T cell-mediated type ≥IB or ABMR) and levels >1% indicate a probability of active rejection. Copyright © 2017 by the American Society of Nephrology.

  15. Rejection Study of Cancelous Allograft in Emergency Orthopaedic Operation

    International Nuclear Information System (INIS)

    Manjas, Menkher; Hilmy Nazly

    2002-01-01

    The fast development of national and international tissue bank, increased the use of bone allografts in orthopaedic surgery including emergency open reduction and internal fixation at fresh bone fractures. The aim of this work is to evaluate rejection and usefulness of cancelous bone allografts which have been used in emergency orthopaedic operation. Dwing February until June 2000 two group of 20 patients each, were studied. after preferring emergency open reduction and internal fixation. The first group was treated with cancelous allograft transplantation at the site of the fracture, but the second group did not get any graft. Radiation sterilized allograft were used at this study. Parameters observed were local reaction of wound operation, local rejection and callus formation. The results show that there is no rejection of cancelous bone allograft detected from local and systemic reaction of wound operation. After three week, operation there was no significant different number of callus formation can be detected by conventional radiology examination but after 6 weeks there was a significant increasing in number of callus formation in the group of cancelous allograft transplantation (P < 0.05)

  16. 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

  17. [Combined rapamycin eye drop in nanometer vector and poly (lactic acid) wafers of cyclosporine A effectively prevents high-risk corneal allograft rejection in rabbits].

    Science.gov (United States)

    Jiang, Wei; Sun, Hui-Min; Li, Xiao-Rong; Yuan, Xu-Bo; Wang, Yu-Qing; Zhang, Shu-Xian; Tian, En-Jiang; Yuan, Jia-Qin

    2009-06-01

    To evaluate the combined effect of topical rapamycin (RAPA) eye drop in nanometer vector and poly (lactic acid) (PLA) wafers of cyclosporine A (CsA) in the prevention of acute allograft rejection after rabbit corneal transplantation. Methods It was an experimental study. RAPA was incorporated into the nanometer particles and CsA was incorporated into PLA wafers. A was syngeneic control whose both donor and recipient are New Zealand rabbit. Gray donor corneas were implanted into the 102 recipients of New Zealand albino rabbits with corneal neovascularization who were randomly divided into B, C, D, E, F, G 6 groups to receive the different types of therapy: B was no therapy control; C was eye drop of nanometer vector but no RAPA twice a day, 28 days; D was PLA wafers in the anterior chamber of rabbit eyes but no drugs; E was 0.5% RAPA eye drop of nanometer vector twice a day, 28 days; F was PLA wafers of CsA in the anterior chamber of rabbit eyes; G was PLA wafers of CsA in the anterior chamber of rabbit eyes and 0.5% RAPA eye drop of nanometer vector eye drop twice a day for 28 days together. Postoperative evaluation included slit-lamp biomicroscopy, histopathology and immunohistology, Cytokines related with neovascularization and immunosuppression in the corneal tissue by RT-PCR. The graft survival was assessed by One-Way ANOVA and q test. Corneal allograft survival time: A (100.00 +/- 0.00), B (8.44 +/- 1.24), C (8.89 +/- 2.57), D (8.56 +/- 2.30), E (43.11 +/- 5.58), F (43.67 +/- 9.54), G (72.00 +/- 15.34) d. Group G led to a statistically significant prolongation of transplant survival and was superior than group E and F which was a statistical prolongation compared with group B, C and D (qGE = 11.42, qGF = 11.24, qEB = 13.64, qEC = 13.38, qED = 13.46, qFB = 13.82, qFC = 13.56, qFD = 13.64; P < 0.01). Immunohistopathologically, the grafts were subjected to an immune response contained a dense infiltrate of neutrophils, CD4+ and CD8+ T lymphocytes in the group B

  18. 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’...

  19. B-cell-mediated strategies to fight chronic allograft rejection

    Directory of Open Access Journals (Sweden)

    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

  20. Apoptotic tubular cell death during acute renal allograft rejection

    NARCIS (Netherlands)

    Wever, P. C.; Aten, J.; Rentenaar, R. J.; Hack, C. E.; Koopman, G.; Weening, J. J.; ten Berge, I. J.

    1998-01-01

    Tubular cells are important targets during acute renal allograft rejection and induction of apoptosis might be a mechanism of tubular cell destruction. Susceptibility to induction of apoptosis is regulated by the homologous Bcl-2 and Bax proteins. Expression of Bcl-2 and Bax is regulated by p53,

  1. Neurotoxin from Naja naja atra venom inhibits skin allograft rejection in rats.

    Science.gov (United States)

    Xu, Yin-Li; Kou, Jian-Qun; Wang, Shu-Zhi; Chen, Cao-Xin; Qin, Zheng-Hong

    2015-09-01

    Recent studies reported that Naja naja atra venom (NNAV) regulated immune function and had a therapeutic effect on adjunctive arthritis and nephropathy. We hypothesized that NNAV and its active component, neurotoxin (NTX), might inhibit skin allograft rejection. Skin allografts were used to induce immune rejection in rats. In addition, mixed lymphocyte culture (MLC) was used to mimic immune rejection reaction in vitro. Both NNAV and NTX were orally given starting from 5days prior to skin allograft surgery. The results showed that oral administration of NNAV or NTX prolonged the survival of skin allografts and inhibited inflammatory response. The production of Th1 cytokines (IFN-γ, IL-2) was also suppressed. NTX inhibited T-cell proliferation and CD4(+) T cell division induced by skin allografts. NTX also showed immunosuppressive activity in mixed lymphocyte culture. Atropine alone inhibited Con A-induced proliferation of T cells and potentiated NTX' s inhibitory effects on T cells, while pilocarpine only slightly enhanced Con A-induced T cell proliferation and partially reversed the inhibitory effect of NTX. On the other hand, neither nicotine nor mecamylamine had an influence on NTX's inhibitory effects on Con A-induced T cell proliferation in vitro. NTX inhibited T cell proliferation by arresting the cell cycle at the G0/G1 phase. The present study revealed that NNAV and NTX suppressed skin allograft rejection by inhibiting T cell-mediated immune responses. These findings suggest both NNAV and NTX as potential immunosuppressants for preventing the immune response to skin allografts. Copyright © 2015. Published by Elsevier B.V.

  2. Autoantibodies to vimentin cause accelerated rejection of cardiac allografts.

    Science.gov (United States)

    Mahesh, Balakrishnan; Leong, Hon-Sing; McCormack, Ann; Sarathchandra, Padmini; Holder, Angela; Rose, Marlene L

    2007-04-01

    Autoimmune responses to vimentin occur after solid organ transplantation, but their pathogenic effects are unclear. The aim of these studies was to investigate the effects of vimentin preimmunization on allogeneic and isografted hearts in a murine transplant model. Immunization of C57BL/6 mice with murine vimentin in complete Freund's adjuvant resulted in anti-vimentin antibodies and vimentin-reactive Th-1 cells. Transplantation of 129/sv hearts into vimentin-immunized C57BL/6 recipients resulted in accelerated rejection (8.4 +/- 1.5 days; n = 18), compared with hen egg lysozyme-immunized C57BL/6 (13.3 +/- 2.2 days; n = 10; P rejection, shown by the fact that vimentin-immunized B-cell-deficient IgH6 mice did not show accelerated rejection of 129/sv allografts, but rejection was restored by adoptive transfer of serum containing anti-vimentin antibodies. Eluates from donor hearts placed in vimentin/complete Freund's adjuvant recipients contained anti-vimentin antibodies, shown by Western blotting. Confocal imaging of rejected hearts de-monstrated presence of vimentin and C3d on apoptosed leukocytes, endothelial cells, and platelet/leukocyte conjugates. These results demonstrate that autoantibodies to vimentin, in conjunction with the alloimmune response, have a pathogenic role in allograft rejection.

  3. Intramyocardial impedance measurements for diagnosis of acute cardiac allograft rejection.

    Science.gov (United States)

    Pfitzmann, R; Müller, J; Grauhan, O; Hetzer, R

    2000-08-01

    Measurements of intramyocardial impedance at high frequencies can indicate alterations in cell membranes and intracellular spaces during acute cardiac allograft rejection. Fifteen beagle dogs underwent heterotopic heart transplantation and were immunosuppressed with cyclosporine and methyl prednisolone (MP). Impedance was determined twice daily by means of four screw-in electrodes in the right and left ventricle. Transmyocardial biopsies and the intramyocardial electrogram (IMEG) were performed as reference methods. A total of 23 rejection episodes were induced. When acute rejection was recognized histologically and through IMEG readings, the animals were treated with a bolus of 125 mg of methyl prednisolone over 5 consecutive days. Treatment of rejection was controlled by biopsy and IMEG. All hearts showed a uniform decrease in impedance of about 28.3%+/-5.5% immediately after transplantation, which subsequently reached a stable plateau after 7 to 8 days. Impedance values then remained unchanged as long as rejection was absent. Biopsy findings of grades 1A to 1B (ISHLT) were accompanied by a statistically significant increase in impedance of 12.2%+/-2.5%; of grades 2 to 3A of 19.2%+/-3.2% and of grades 3B to 4 of 27.0%+/-2.9%. Sensitivity was 96%, specificity 91%. Successful treatment of rejection led to a decrease of impedance to the initial levels. The amount of increase in impedance of high frequencies is a method to stratify acute cardiac allograft rejection into grades like histologically grading. The effectiveness of rejection treatment can also be monitored through impedance measurement. The method is also applicable for telemetric rejection monitoring by means of an implantable device.

  4. Late Acute Rejection Occuring in Liver Allograft Recipients

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. Diagnostic value of plasma and bronchoalveolar lavage samples in acute lung allograft rejection: differential cytology.

    Science.gov (United States)

    Speck, Nicole E; Schuurmans, Macé M; Murer, Christian; Benden, Christian; Huber, Lars C

    2016-06-21

    Diagnosis of acute lung allograft rejection is currently based on transbronchial lung biopsies. Additional methods to detect acute allograft dysfunction derived from plasma and bronchoalveolar lavage samples might facilitate diagnosis and ultimately improve allograft survival. This review article gives an overview of the cell profiles of bronchoalveolar lavage and plasma samples during acute lung allograft rejection. The value of these cells and changes within the pattern of differential cytology to support the diagnosis of acute lung allograft rejection is discussed. Current findings on the topic are highlighted and trends for future research are identified.

  7. Effect of HMG-CoA reductase inhibitors on chronic allograft rejection.

    Science.gov (United States)

    Katznelson, S

    1999-07-01

    Although chronic rejection is the most important cause of late allograft loss, none of the currently available immunosuppressive agents successfully target this problem. Clinical and laboratory studies suggest that 3-hydroxy-3-methyl-glutaryl co-enzyme A (HMG-CoA) reductase inhibitors (HRIs) may decrease the incidence of and pathophysiologic factors leading to chronic rejection. A number of clinical and laboratory investigations have been designed to evaluate the effect of HRIs on chronic rejection. Clinical trials in heart transplant patients suggest that HRIs decrease the incidence of chronic rejection in a manner that may be independent of lipid lowering. Subsequent studies in animal transplant models confirm that HRIs reduce chronic rejection. In further studies to elucidate the possible mechanisms of this effect, it has been observed that HRIs have an inhibitory effect on an number of lymphoid cell lines and vascular smooth muscle cells. HRIs may also prevent chronic rejection by protecting the endothelium from injury and dysfunction, perhaps by up-regulating nitric oxide synthesis. HRIs may be the first agents to be effective in preventing chronic rejection. Although the mechanism behind this protective effect is unclear, it seems likely that HRIs may affect multiple factors that could lead to chronic rejection.

  8. 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

  9. Lung allograft rejection in the rat. I. Accelerated rejection caused by graft lymphocytes

    International Nuclear Information System (INIS)

    Prop, J.; Nieuwenhuis, P.; Wildevuur, C.R.

    1985-01-01

    To find out to what extent rejection of lungs differs from that of other organs, functional rejection of lung allografts was studied in five combinations of inbred rat strains. Rejection could be monitored accurately by perfusion scintigraphy, and equally well by chest roentgenography. The rejection of lung grafts was found to proceed remarkably fast, when compared with heart grafts, in combinations with strong RT1-incompatibilities. This accelerated rejection pattern could be converted into rejection at a normal pace by pretreatment of the donor with 10 Gy roentgen irradiation one day before transplantation. Donor pretreatment depleted the lung graft's bronchus-associated lymphoid tissue (BALT) of lymphocytes. When grafts were depleted of all other passenger cells as well--by retransplantation from a cyclosporine-treated intermediate host--they showed an even more reduced immunogenicity, probably because of the loss of donor-type dendritic cells. These results indicate that lymphocytes from the BALT of lung grafts are capable of accelerating the rejection response

  10. Clinical utility of labeled cells for detection of allograft rejection and myocardial infarction

    International Nuclear Information System (INIS)

    Fawwaz, R.A.

    1984-01-01

    The choice of a specific radiolabeled blood component for use in detection of allograft rejection depends on several factors including the immunosuppressive agents used, the type of organ allografted, and particularly the length of time the allograft resides in the host and the duration of rejection. To date, only the use of 111In-labeled platelets in renal allograft recipients immunosuppressed with azathioprine and corticosteroids has shown clinical promise in the detection of early allograft rejection. Radiolabeled blood components are unlikely to play a significant role in detection of myocardial infarction. The use of these agents for monitoring therapeutic interventions or as indicators of prognosis in patients with myocardial infarction continues to be investigated

  11. Targeted inhibition of renal Rho kinase reduces macrophage infiltration and lymphangiogenesis in acute renal allograft rejection

    NARCIS (Netherlands)

    Poosti, Fariba; Yazdani, Saleh; Dolman, M. Emmy M.; Kok, Robbert Jan; Chen, Cheng; Ding, Guohua; Lacombe, Marie; Prakash, Jai; van den Born, Jacob; Hillebrands, Jan-Luuk; van Goor, Harry; de Borst, Martin H.

    2012-01-01

    The Rho kinase pathway plays an important role in epithelial dedifferentiation and inflammatory cell infiltration. Recent studies suggest that inflammation promotes lymphangiogenesis, which has been associated with renal allograft rejection. We investigated whether targeted inhibition of the Rho

  12. Increased circulating follicular helper T cells with decreased programmed death-1 in chronic renal allograft rejection

    OpenAIRE

    Shi, Jian; Luo, Fengbao; Shi, Qianqian; Xu, Xianlin; He, Xiaozhou; Xia, Ying

    2015-01-01

    Background Chronic antibody-mediated rejection is a major issue that affects long-term renal allograft survival. Since follicular helper T (Tfh) cells promote the development of antigen-specific B cells in alloimmune responses, we investigated the potential roles of Tfh cells, B cells and their alloimmune-regulating molecules in the pathogenesis of chronic renal allograft rejection in this study. Methods The frequency of Tfh, B cells and the levels of their alloimmune-regulating molecules inc...

  13. Increased circulating follicular helper T cells with decreased programmed death-1 in chronic renal allograft rejection.

    Science.gov (United States)

    Shi, Jian; Luo, Fengbao; Shi, Qianqian; Xu, Xianlin; He, Xiaozhou; Xia, Ying

    2015-11-03

    Chronic antibody-mediated rejection is a major issue that affects long-term renal allograft survival. Since follicular helper T (Tfh) cells promote the development of antigen-specific B cells in alloimmune responses, we investigated the potential roles of Tfh cells, B cells and their alloimmune-regulating molecules in the pathogenesis of chronic renal allograft rejection in this study. The frequency of Tfh, B cells and the levels of their alloimmune-regulating molecules including chemokine receptor type 5 (CXCR5), inducible T cell co-stimulator (ICOS), programmed death-1 (PD-1), ICOSL, PDL-1 and interleukin-21 (IL-21), of peripheral blood were comparatively measured in 42 primary renal allograft recipients within 1-3 years after transplantation. Among them, 24 patients had definite chronic rejection, while other 18 patients had normal renal function. Tfh-cell ratio was significantly increased with PD-1 down-regulation in the patients with chronic renal allograft rejection, while B cells and the alloimmune-regulating molecules studied did not show any appreciable change in parallel. The patients with chronic renal allograft rejection have a characteristic increase in circulating Tfh cells with a decrease in PD-1 expression. These pathological changes may be a therapeutic target for the treatment of chronic renal allograft rejection and can be useful as a clinical index for monitoring conditions of renal transplant.

  14. Antibody-mediated rejection of single class I MHC-disparate cardiac allografts.

    Science.gov (United States)

    Hattori, Y; Bucy, R P; Kubota, Y; Baldwin, W M; Fairchild, R L

    2012-08-01

    Murine CCR5(-/-) recipients produce high titers of antibody to complete MHC-mismatched heart and renal allografts. To study mechanisms of class I MHC antibody-mediated allograft injury, we tested the rejection of heart allografts transgenically expressing a single class I MHC disparity in wild-type C57BL/6 (H-2(b)) and B6.CCR5(-/-) recipients. Donor-specific antibody titers in CCR5(-/-) recipients were 30-fold higher than in wild-type recipients. B6.K(d) allografts survived longer than 60 days in wild-type recipients whereas CCR5(-/-) recipients rejected all allografts within 14 days. Rejection was accompanied by infiltration of CD8 T cells, neutrophils and macrophages, and C4d deposition in the graft capillaries. B6.K(d) allografts were rejected by CD8(-/-)/CCR5(-/-), but not μMT(-/-)/CCR5(-/-), recipients indicating the need for antibody but not CD8 T cells. Grafts recovered at day 10 from CCR5(-/-) and CD8(-/-)/CCR5(-/-) recipients and from RAG-1(-/-) allograft recipients injected with anti-K(d) antibodies expressed high levels of perforin, myeloperoxidase and CCL5 mRNA. These studies indicate that the continual production of antidonor class I MHC antibody can mediate allograft rejection, that donor-reactive CD8 T cells synergize with the antibody to contribute to rejection, and that expression of three biomarkers during rejection can occur in the absence of this CD8 T cell activity. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

  15. Sensitivity of scintigraphy with 111In-lymphocytes for detection of cardiac allograft rejection

    International Nuclear Information System (INIS)

    Eisenberg, S.B.; Eisen, H.J.; Sobel, B.E.; Bergmann, S.R.; Bolman, R.M. III

    1988-01-01

    We recently demonstrated the feasibility of noninvasive detection of cardiac allograft rejection after administration of indium-111-labeled lymphocytes. To determine the sensitivity and specificity of the technique, as well as its value for delineating the severity of rejection, we studied 16 dogs with heterotopic thoracic cardiac allografts. Five animals were evaluated while exposed to immunosuppressive agents. Animals were scanned sequentially after administration of 100-400 microCi of indium-111-labeled autologous lymphocytes. Myocardial lymphocyte infiltration was expressed as the indium excess (IE), defined as the ratio of indium activity of the transplant or native heart compared with that in blood. Scintigraphic results were compared with characteristics of simultaneously obtained endomyocardial biopsies. Among 17 biopsy documented episodes of rejection, 16 were detected scintigraphically. Among 18 biopsies with no evidence of rejection, scintigraphy was uniformly negative. Thus, the sensitivity and specificity of scintigraphy were 94 and 100%, respectively. Biopsies graded as showing no rejection were associated with an IE of 0.3 +/- 0.5 (+/- SD); those graded as mild, 2.8 +/- 1.7; those as moderate, 10.7 +/- 7.2; and those graded as indicative of severe rejection, 14.2 +/- 4.5. Thus, scintigraphy with indium-111-labeled lymphocytes sensitively and specifically detects cardiac allograft rejection and delineates the intensity of the rejection process. It should be useful clinically for assessing potential allograft rejection noninvasively

  16. Detection and measurement of tubulitis in renal allograft rejection

    Science.gov (United States)

    Hiller, John B.; Chen, Qi; Jin, Jesse S.; Wang, Yung; Yong, James L. C.

    1997-04-01

    Tubulitis is one of the most reliable signs of acute renal allograft rejection. It occurs when mononuclear cells are localized between the lining tubular epithelial cells with or without disruption of the tubular basement membrane. It has been found that tubulitis takes place predominantly in the regions of the distal convoluted tubules and the cortical collecting system. The image processing tasks are to find the tubule boundaries and to find the relative location of the lymphocytes and epithelial cells and tubule boundaries. The requirement for accuracy applies to determining the relative locations of the lymphocytes and the tubule boundaries. This paper will show how the different sizes and grey values of the lymphocytes and epithelial cells simplify their identification and location. Difficulties in finding the tubule boundaries image processing will be illustrated. It will be shown how proximate location of epithelial cells and the tubule boundary leads to distortion in determination of the calculated boundary. However, in tubulitis the lymphocytes and the tubule boundaries are proximate.In these cases the tubule boundary is adequately resolved and the image processing is satisfactory to determining relativity in location. An adaptive non-linear anisotropic diffusion process is presented for image filtering and segmentation. Multi-layer analysis is used to extract lymphocytes and tubulitis from images. This paper will discuss grading of tissue using the Banff system. The ability to use computer to use computer processing will be argued as obviating problems of reproducability of values for this classification. This paper will also feature discussion of alternative approaches to image processing and provide an assessment of their capability for improving the identification of the tubule boundaries.

  17. Correlation between nuclear perfusion parameters and duplex US indices in the diagnosis of renal allograft rejection

    International Nuclear Information System (INIS)

    Kim, E.E.; Maklad, N.F.; Pjura, G.A.; Lowry, P.A.

    1986-01-01

    Fifty nuclear perfusion and duplex US studies in 30 patients who had received renal allografts were prospectively analyzed to evaluate their respective measures of blood flow as indicators of rejection. The nuclear study (Tc-99m DTPA) generated three parameters, and a real-time, pulsed Doppler sector scanner generated resistance and pulsatility indices. In nine cases with a greater than 70% resistance index and 1.4 pulsatility index on US, the US findings correlated well with changes in nuclear perfusion parameters, indication rejection. The authors conclude that the combination of decreasing nuclear perfusion parameters and positive US indices may obviate the need for biopsy in the diagnosis of allograft rejection

  18. Scabies in a bilateral hand allograft recipient: An additional mimicker of acute skin rejection in vascularized composite allotransplantation.

    Science.gov (United States)

    Kanitakis, Jean; Morelon, Emmanuel

    2017-06-01

    Vascularized composite tissue allografts include skin, which frequently undergoes, in the early post-graft period, acute rejections. The diagnosis of acute rejection may be difficult as it can be mimicked by several dermatoses. We present a bilateral hand allograft recipient who developed, 16.5 years post-graft, cutaneous lesions raising suspicion about rejection. Physical examination and skin biopsy were diagnostic of scabies. This ectoparasitosis should be added in the list of dermatoses that can mimic allograft rejection in vascular composite allografts. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Injury to Allografts: innate immune pathways to acute and chronic rejection

    International Nuclear Information System (INIS)

    Land, W. G.

    2005-01-01

    An emerging body of evidence suggests that innate immunity, as the first line of host defense against invading pathogens or their components [pathogen-associated molecular patterns, (PAMPs)], plays also a critical role in acute and chronic allograft rejection. Injury to the donor organ induces an inflammatory milieu in the allograft, which appears to be the initial key event for activation of the innate immune system. Injury-induced generation of putative endogenous molecular ligand, in terms of damaged/danger-associated molecular patterns (DAMPs) such as heat shock proteins, are recognized by Toll-like receptors (TLRs), a family of pattern recognition receptors on cells of innate immunity. Acute allograft injury (e.g. oxidative stress during donor brain-death condition, post-ischemic reperfusion injury in the recipient) includes DAMPs which may interact with, and activate, innate TLR-bearing dendritic cells (DCs) which, in turn, via direct allo-recognition through donor-derived DCs and indirect allo-recogntion through recipient-derived DCs, initiate the recipient's adaptive alloimmune response leading to acute allograft rejection. Chronic injurious events in the allograft (e.g. hypertension, hyperlipidemia, CMV infection, administration of cell-toxic drugs [calcineurin-inhibitors]) induce the generation of D AMPs , which may interact with and activate innate TLR-bearing vascular cells (endothelial cells, smooth muscle cells) which, in turn, contribute to the development of atherosclerosis of donor organ vessels (alloatherosclerosis), thus promoting chronic allograft rejection. (author)

  20. Expression of Mitochondrial-Encoded Genes in Blood Differentiate Acute Renal Allograft Rejection

    Directory of Open Access Journals (Sweden)

    Silke Roedder

    2017-11-01

    Full Text Available Despite potent immunosuppression, clinical and biopsy confirmed acute renal allograft rejection (AR still occurs in 10–15% of recipients, ~30% of patients demonstrate subclinical rejection on biopsy, and ~50% of them can show molecular inflammation, all which increase the risk of chronic dysfunction and worsened allograft outcomes. Mitochondria represent intracellular endogenous triggers of inflammation, which can regulate immune cell differentiation, and expansion and cause antigen-independent graft injury, potentially enhancing the development of acute rejection. In the present study, we investigated the role of mitochondrial DNA encoded gene expression in biopsy matched peripheral blood (PB samples from kidney transplant recipients. Quantitative PCR was performed in 155 PB samples from 115 unique pediatric (<21 years and adult (>21 years renal allograft recipients at the point of AR (n = 61 and absence of rejection (n = 94 for the expression of 11 mitochondrial DNA encoded genes. We observed increased expression of all genes in adult recipients compared to pediatric recipients; separate analyses in both cohorts demonstrated increased expression during rejection, which also differentiated borderline rejection and showed an increasing pattern in serially collected samples (0–3 months prior to and post rejection. Our results provide new insights on the role of mitochondria during rejection and potentially indicate mitochondria as targets for novel immunosuppression.

  1. Blockade of Vascular Adhesion Protein-1 Inhibits Lymphocyte Infiltration in Rat Liver Allograft Rejection

    OpenAIRE

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

    2004-01-01

    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/gro...

  2. Comparative immunohistologic studies in an adoptive transfer model of acute rat cardiac allograft rejection

    International Nuclear Information System (INIS)

    Forbes, R.D.; Lowry, R.P.; Gomersall, M.; Blackburn, J.

    1985-01-01

    It has been shown that fulminant acute rejection of rat cardiac allografts across a full haplotype disparity may occur as a direct result of adoptive transfer of sensitized W3/25+ MRC OX8- SIg- T helper/DTH syngeneic spleen cells to sublethally irradiated recipients. In order to establish the immunohistologic parameters of this form of rejection, allografts and recipient lymphoid tissue were analyzed using a panel of monoclonal antibodies of known cellular distribution. These data were compared with those obtained following reconstitution of irradiated allograft recipients with unseparated sensitized spleen cells, with unreconstituted irradiated donor recipient pairs, with unmodified first-set rejection, and with induced myocardial infarction of syngeneic heart grafts transplanted to normal and to sublethally irradiated recipients. Rejecting cardiac allografts transplanted to all reconstituted irradiated recipients were characterized by extensive infiltration with MRC OX8+ (T cytotoxic-suppressor, natural killer) cells even when this subset was virtually excluded from the reconstituting inocula. A similar proportional accumulation of MRC OX8+ cells observed at the infarct margins of syngeneic heart grafts transplanted to irradiated unreconstituted recipients greatly exceeded that present in normal nonirradiated controls. These data provide evidence that under conditions of heavy recipient irradiation, MRC OX8+ cells may be sequestered within heart grafts in response to nonspecific injury unrelated to the rejection process

  3. Long term results of total lymphoid irradiation in the treatment of cardiac allograft rejection

    International Nuclear Information System (INIS)

    Wolden, Suzanne L.; Tate, David J.; Hunt, Sharon A.; Strober, Samuel; Hoppe, Richard T.

    1996-01-01

    Purpose: To evaluate the short and long term effects of total lymphoid irradiation (TLI) in the treatment of allograft rejection in cardiac transplant patients. Materials and Methods: From 1986 to 1995, 48 courses of TLI were delivered to 47 patients who had received cardiac transplants at Stanford University. In 38 cases, TLI was administered for chronic, intractable allograft rejection despite conventional anti-rejection therapy, including corticosteroids, azathioprine, cyclosporine, OKT3, DHPG, RATG, and methotrexate. Ten patients received TLI prophylactically, beginning radiation between 5 and 16 days after heart transplantation. The prescribed radiation dose was 800 cGy given in 80 cGy fractions twice weekly to all major lymph node regions using mantle and inverted Y fields. Patients continued to receive all medications except azathioprine which was held during TLI to prevent severe marrow suppression. All patients were closely monitored for episodes of rejection, infection, prednisone requirements, blood counts, and complications of treatment. Post-irradiation follow up ranged from 6 months to 9.1 years with a mean of 3.1 years. Results: The actual mean dose of radiation was 730 cGy delivered over a mean of 39 calendar days. Fifty six percent of patients required treatment delay or abbreviation because of thrombocytopenia, leukopenia, infection, or unrelated problems. In patients treated for intractable rejection, the frequency of rejection dropped from 0.46 episodes/patient/month before radiation to 0.14 episodes/patient/month during TLI (p 3 during TLI (p = 0.01) and remained low at 167.6 cells/mm 3 2-4 months after treatment (p = 0.05). CD8+ lymphocytes also decreased during treatment from 233.2 to 65.8 cells/mm 3 (p = 0.003) but rose significantly above normal to 381.3 cells/mm 3 2-4 months after TLI (p 0.05). Thus, the ratio of helper/suppresser T-cells was chronically decreased. Infection rates were not significantly different before, during or after

  4. Identification of common blood gene signatures for the diagnosis of renal and cardiac acute allograft rejection.

    Directory of Open Access Journals (Sweden)

    Li Li

    Full Text Available To test, whether 10 genes, diagnostic of renal allograft rejection in blood, are able to diagnose and predict cardiac allograft rejection, we analyzed 250 blood samples from heart transplant recipients with and without acute rejection (AR and with cytomegalovirus (CMV infection by QPCR. A QPCR-based logistic regression model was built on 5 of these 10 genes (AR threshold composite score >37%  = AR and tested for AR prediction in an independent set of 109 samples, where it correctly diagnosed AR with 89% accuracy, with no misclassifications for AR ISHLT grade 1b. CMV infection did not confound the AR score. The genes correctly diagnosed AR in a blood sample within 6 months prior to biopsy diagnosis with 80% sensitivity and untreated grade 1b AR episodes had persistently elevated scores until 6 months after biopsy diagnosis. The gene score was also correlated with presence or absence of cardiac allograft vasculopathy (CAV irrespective of rejection grade. In conclusion, there is a common transcriptional axis of immunological trafficking in peripheral blood in both renal and cardiac organ transplant rejection, across a diverse recipient age range. A common gene signature, initially identified in the setting of renal transplant rejection, can be utilized serially after cardiac transplantation, to diagnose and predict biopsy confirmed acute heart transplant rejection.

  5. Intramyocardial electrogram recordings for diagnosis and therapy monitoring of cardiac allograft rejection.

    Science.gov (United States)

    Grauhan, O; Warnecke, H; Müller, J; Knosalla, C; Cohnert, T; Voss, A; Hetzer, R

    1993-01-01

    The registration of intramyocardial ECG amplitudes (IMEG) is a non-invasive diagnostic method of monitoring cardiac allograft rejection. In order to detect possible sources of error IMEG signals were recorded in heterotopic neck hearts in ten beagle dogs. Immunosuppression was based on cyclosporin A. The rejection process was followed by IMEG registrations as well as by serial myocardial biopsies. Intramyocardial electrogram recordings were made via three unipolar and three bipolar leads obtained from screw-in electrodes in both ventricles and the apex of the allograft. A 10% voltage drop was used as an indicator of rejection. In four dogs, the first rejection episode was treated with methyl-prednisolone and the therapy's success was monitored by IMEG and repeat biopsy. At autopsy the histology of each electrode circumference was correlated with the corresponding IMEG. The average sensitivity of a single lead was not acceptable (unipolar: 28%, bipolar: 47%). When the voltages of different leads were summed up the sensitivity rose to 43% (3 x unipolar), 85% (3 x bipolar) and 100% (all leads). During rejection therapy the IMEG recovered within 24-48 h. We conclude that in moderate allograft rejection (grade 2/3a ISHT classification), the rejection-related changes of intramyocardial ECG voltage amplitude (IMEG) seem to follow a "focal pattern" similar to the histology. Therefore the recording of several, preferably bipolar, electrode configurations appears to enhance adequate diagnostic reliability.

  6. Somatostatin receptor scintigraphy predicts impending cardiac allograft rejection before endomyocardial biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Aparici, C.M.; Martin, J.C.; Tembl, A.; Flotats, A.; Estorch, M.; Catafau, A.M.; Berna, L.; Carrio, I. [Nuclear Medicine Department, Hospital Sant Pau, Barcelona (Spain); Narula, J.; Puig, M.; Camprecios, M.; Ballester, M. [Cardiology Department, Sant Pau Hospital, Barcelona (Spain)

    2000-12-01

    The invasive nature of endomyocardial biopsy has led to a search for alternative diagnostic modalities for the detection of cardiac allograft rejection. To date, no non-invasive test meets all the requirements for the detection of acute and chronic rejection. The rejection process usually presents with lymphocyte infiltration with or without myocyte necrosis, which indicates the severity of cardiac allograft rejection and the necessity of treatment. Activated lymphocytes express somatostatin receptors; thus somatostatin receptor imaging could be used to target them. The aim of this study was to assess the feasibility of using somatostatin receptor imaging to target activated lymphocytes in the process of cardiac allograft rejection. Thirteen somatostatin receptor imaging studies were performed on ten cardiac allograft recipients 12-4745 days after transplantation, simultaneously with endomyocardial biopsy, to assess the imaging of activated lymphocytes in comparison with histological findings. Somatostatin receptor imaging was performed 4 h after the injection of 110 MBq of the somatostatin analogue indium-111 pentetreotide. {sup 111}In-pentetreotide uptake was visually scored and semi-quantitatively estimated by the calculation of a heart-to-lung ratio (HLR). The visual score correlated with the HLR. Intense/moderate uptake on visual assessment and an HLR >1.6 was observed in eight studies. In three of these studies there was significant rejection in the simultaneous endomyocardial biopsy [International Society of Heart and Lung Transplantation (ISHLT) rejection grade 3A/4]. Intense/moderate uptake was associated with mild or no rejection in the remaining five patients, and in four of them the next endomyocardial biopsy performed 1 week later demonstrated significant rejection requiring treatment. Two patients with low uptake and an HLR <1.6 had no evidence of rejection either in the simultaneous endomyocardial biopsy or in the endomyocardial biopsy performed the

  7. 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

  8. 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

  9. 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

  10. Diagnosis of cardiac allograft rejection with MR imaging

    International Nuclear Information System (INIS)

    Soulen, R.L.; Fraser, C.D.; Hutchins, G.M.; Baumgartner, W.A.; Reitz, B.A.

    1987-01-01

    Serial MR images and endomyocardial biopsy specimens of heterotopic cervical cardiac allotransplants were obtained in six dogs during 2 weeks of immunosuppression followed by 1 week without such therapy. A surface coil and gated spin-echo technique were used. Myocardial intensity (MI) measurements and histopathologic interpretations were performed independently. All six dogs showed a decrease in MI between their first and second MR studies, while showing no rejection. One dog had no rejection and died; in five dogs studies gated to every other beat showed progressive increase in MI that correlated significantly with increasing rejection, though absolute MI values did not correlated with a specific biopsy score. Severe rejection also caused overt increase in myocardial mass. The MI in the early postoperative period may reflect reperfusion injury. Absolute intensity values cannot predict rejection. Serial studies in transplant patients may prove clinically useful

  11. Rejection of stable cultured allografts by active or passive (adoptive) immunization.

    OpenAIRE

    Vesole, D H; Dart, G A; Talmage, D W

    1982-01-01

    Injection of live lymphoid cells of donor strain or immune cells of recipient strain resulted in rejection of previously stable cultured mouse thyroid allografts. The results are interpreted to indicate that a cultured graft is relatively ineffective in activating recipient lymphocytes but is capable of maintaining them in an activated state and serving as a target for them once they are activated.

  12. Diagnosis of cardiac allograft rejection with indium-111 labeled platelets in cyclosporin treated rats

    International Nuclear Information System (INIS)

    Fawwaz, R.A.; Iga, C.; Hardy, M.A.; Alderson, P.O.

    1984-01-01

    Rejection of heart transplants remains difficult to diagnose. Indium-111 (In-111) labeled lymphocytes accumulate in rat cardiac allografts when recipients are treated with Cyclosporin (Cy), even in the absence of clinical rejection. This presumably occurs because of the non-specific 'interstitial infiltration' caused by Cy. This study examines the usefulness of In-111 labeled platelets in differentiating experimental cardiac allograft rejection from Cy-induced tissue changes. The authors initially examined the migration patterns of syngeneic In-111 labeled platelets in groups of Lewis recipients of ACI cardiac allografts treated with IM Cy (10mg/kg) for 6-14 days. In addition, 10 control animals were not immunosuppressed, and 10 were treated with Cy but received Lewis cardiac isografts. Syngeneic In-111 platelets were injected IV into each animal 24 hours prior to sacrifice. Three to five rats from each group were killed at 3 ,7, 14, 21 and 28 days after transplantation and the % ID/gm in the transplanted hearts and native hearts were determined and correlated with histopathology. Untreated Lewis recipients rejected ACI hearts in 6.5 +- 0.4 days while Cy prolonged allograft survival in a variable fashion. In-111 platelet accumulation correlated well with the degree of rejection determined independently by histopathology. No significant In-111 platelet accumulation was detected in non-rejecting cardiac transplants or in native hearts in Cy treated or control animals. The results suggest that In-111 labeled platelets will be an effective agent for diagnosis of cardiac rejection, even in the presence of Cy treatment

  13. Noninvasive monitoring of cardiac allograft rejection by intramyocardial electrogram recordings.

    Science.gov (United States)

    Warnecke, H; Schüler, S; Goetze, H J; Matheis, G; Süthoff, U; Müller, J; Tietze, U; Hetzer, R

    1986-11-01

    Rejection after cardiac transplantation was monitored in nine patients by control of intramyocardial electrogram (IMEG) recordings transmitted by an implanted telemetric pacemaker. Under immunosuppression with cyclosporin A and prednisolone, 33 out of a total of 119 endomyocardial biopsy specimens showed moderate rejection (infiltrate with myocytolysis). Twenty-nine of these rejection episodes could be correctly predicted from IMEG recordings with a voltage drop above 15% used as a criterion (sensitivity 87.9%). Eighty-three of 86 negative biopsy results corresponded to negative IMEG results (specificity 96.5%). In this group of patients, amplitude of body surface electrocardiograms was not useful for the diagnosis of rejection because of the broad range of spontaneous variation. Control of IMEG voltage amplitude appears to be more accurate than body surface electrocardiogram amplitude in the detection of rejection episodes. Thus the onset of rejection during biopsy intervals is more readily detected and treatment is instituted earlier. The method is suitable for ambulatory patient monitoring by the patient's local physician.

  14. Pharmacologic strategies in the prevention and treatment of corneal transplant rejection.

    Science.gov (United States)

    Tabbara, Khalid F

    2008-06-01

    Corneal transplantation remains one of the most successful organ transplantation procedures in humans. The unique structure of the cornea, with its absence of blood vessels and corneal lymphatic, allows the survival of corneal allograft. Recent advances in sutures, storage media, microsurgical instrumentation, and new pharmacological strategies have greatly improved the success of corneal transplantation and the prevention of corneal allograft rejection. Our strategies in the management and prevention of corneal graft rejection can modify and improve the survival of corneal allografts. Preoperative evaluation, understanding the risk factors, and management of ocular surface disorders may greatly improve the survival of the corneal transplant. Early recognition of corneal allograft rejection and aggressive treatment may improve the survival of the corneal graft. Furthermore, patients who undergo corneal transplantation should be maintained under close ophthalmic surveillance and patients should be informed to report immediately whenever symptoms of corneal graft rejection occur. The mainstay of therapy is topical corticosteroids. In severe cases, periocular, intravenous, and oral corticosteroids therapy can be rendered. New therapeutic modalities such as cyclosporine, tacrolimus, daclizumab, mycophenolate mofetil, leflunomide, rapamycin, and others may prove to be of help in the prevention and treatment of corneal graft rejection. Early recognition of corneal graft rejection and prompt treatment are mandatory for the successful survival of the corneal allograft.

  15. Time-dependent changes in B-type natriuretic peptide after heart transplantation: correlation with allograft rejection and function.

    Science.gov (United States)

    Bader, Feras M; Rogers, R Kevin; Kfoury, Abdallah G; Gilbert, Edward M; Horne, Ben D; Stehlik, Josef; Renlund, Dale G

    2009-01-01

    Endomyocardial biopsy is the gold standard to diagnose cardiac allograft rejection, although a noninvasive modality such as brain natriuretic peptide (BNP) is attractive. The authors examined the correlation of BNP levels with rejection patterns and allograft function in cardiac allograft recipients followed up to 8 years. One hundred forty-four consecutive patients underwent endomyocardial biopsy, right heart catheterization, and blood sampling. BNP levels decreased during the first 6 months after transplant but then reached a plateau. Time-dependent correlations were made between BNP levels and allograft rejection, left ventricular ejection fraction, pulmonary capillary wedge pressure, right atrial pressure, and serum creatinine. BNP levels were not different between patients with any rejection pattern and no rejection prior to or after 6 months following transplant. BNP levels did not correlate with ejection fraction, pulmonary capillary wedge pressure, right atrial pressure, or creatinine in the first 6 months after transplant. Statistically significant correlations existed between BNP and these parameters after 6 months following transplant. In cardiac transplant recipients, BNP levels decrease in the first 6 months following transplant and then reach a plateau regardless of the presence, type, or severity of allograft rejection. BNP levels do predict allograft rejection but correlate with allograft function after 6 months following transplant.

  16. 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

  17. 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

  18. A model of acute renal allograft rejection in outbred Yorkshire piglets.

    Science.gov (United States)

    Lassiter, Randi; Wang, Youli; Fang, Xuexiu; Winn, Matt; Ghaffari, Arina; Ho, Chak-Sum; Helman, Sandra; Jajosky, Ryan; Kleven, Daniel; Stanley Nahman, N; Merchen, Todd D

    2017-06-01

    Pigs represent a desirable animal model for the study of rejection in kidney transplantation with inbred Yucatan miniature swine (YMS) the most commonly studied strain due to well defined swine leukocyte antigen (SLA) genotypes. However, limitations to YMS may include cost and availability. Outbred Yorkshire pigs are widely available and significantly cheaper than YMS. Recent advances in SLA genotyping have allowed its application to outbred strains. On this basis, we theorized that Yorkshire pigs would be a viable alternative to YMS for the study of rejection in kidney transplantation. To address this question, we performed auto (Auto) and allotransplants (Allo) in 24 Yorkshire pigs, and assessed SLA genotypes and acute rejection after 72h. At sacrifice, and when compared to autotransplants, allotransplants had significant elevations in serum creatinine (8.4±1.3 vs 2.8±2.0mg/dL for Allo vs autotransplants, respectively) and BUN (61±9 vs 19.2±15mg/dL for Allo vs autotransplants, respectively). Warm ischemia times between the two groups did not differ (24±2.3 vs 26.4±1.4min for Auto vs Allo, respectively). There were 16 distinct SLA haplotypes identified from pigs undergoing allotransplantion, no matched donor-recipient pairs, and all allografts demonstrated rejection. Type IIA cellular rejection (Banff) was the most common. One allograft demonstrated hyperacute rejection due a blood group incompatibility. Histologically, the expression of regulatory Tcells and dendritic cells was increased in allografts. These data suggest that Yorkshire pigs may be a useful model for the study of acute rejection in experimental kidney transplantation. Copyright © 2017. Published by Elsevier B.V.

  19. Antimyosin monoclonal antibodies for early detection of cardiac allograft rejection

    International Nuclear Information System (INIS)

    Schuetz, A.; Fritsch, S.; Kemkes, B.M.; Kugler, C.; Angermann, C.; Spes, C.; Anthuber, M.; Weiler, A.; Wenke, K.; Gokel, J.M.

    1990-01-01

    Sixty-eight indium 111-labeled antimyosin Fab-DTPA imaging studies (0.5 mg intravenously with a radioactivity of 65 to 75 MBq) were executed on 37 of 116 patients undergoing heart transplantation to assess diagnostic accuracy and clinical utility. As controls, 21 patients with cardiomyopathy (n = 8), unstable angina (n = 9), and myocardial infarction (n = 4) were selected. After 48 hours, single photon emission computed tomographic images were evaluated visually, and heart/lung ratios were measured, using the region of interest technique. They were compared with echocardiographic and endomyocardial biopsy results. In 40 studies a heart/lung ratio less than or equal to 1.6 corresponded to a negative biopsy result in 98% (40/41). Echocardiography enabled correct identification of 95% of the patients with normal biopsy findings. In 91% (22/24) a positive biopsy finding correlated with a heart/lung ratio greater than 1.6 including 20 mild rejections, but in only 64%, with an increase in wall thickness and/or decrease of fractional diameter shortening seen on echocardiogram. In addition, the various stages of rejection episodes determined the amount of the heart-lung ratio. There was a significant relationship between the histologic findings and the antimyosin uptake. In 13 patients a second investigation was performed after rejection therapy. All patients had a negative biopsy result, and the heart/lung ratio decreased to normal ranges (less than or equal to 1.6). Five antimyosin antibody studies were excluded, as in these cases, negative uptake results were found during rejection therapy with high-dose steroids. The overall sensitivity was calculated at 93% and the specificity at 98%

  20. Inhibition of chemokine-glycosaminoglycan interactions in donor tissue reduces mouse allograft vasculopathy and transplant rejection.

    Directory of Open Access Journals (Sweden)

    Erbin Dai

    2010-05-01

    allograft rejection, reducing vascular inflammation and prolonging allograft survival. Although chemokines direct both local and systemic cell migration, interruption of inherent chemokine responses in the donor tissue unexpectedly had a greater therapeutic impact on allograft vasculopathy.

  1. Use of [18F]FDG PET to Monitor The Development of Cardiac Allograft Rejection

    Science.gov (United States)

    Daly, Kevin P.; Dearling, Jason L. J.; Seto, Tatsuichiro; Dunning, Patricia; Fahey, Frederic; Packard, Alan B.; Briscoe, David M.

    2014-01-01

    Background Positron Emission Tomography (PET) has the potential to be a specific, sensitive and quantitative diagnostic test for transplant rejection. To test this hypothesis, we evaluated 18F-labeled fluorodeoxyglucose ([18F]FDG) and 13N-labeled ammonia ([13N]NH3) small animal PET imaging in a well-established murine cardiac rejection model. Methods Heterotopic transplants were performed using minor MHC mismatched B6.C-H2bm12 donor hearts in C57BL/6(H-2b) recipients. C57BL/6 donor hearts into C57BL/6 recipients served as isograft controls. [18F]FDG PET imaging was performed weekly between post-transplant days 7 and 42 and the percent injected dose was computed for each graft. [13N]NH3 imaging was performed to evaluate myocardial perfusion. Results There was a significant increase in [18F]FDG uptake in allografts from day 14 to day 21 (1.6% to 5.2%; Ptransplant days 21 (5.2% vs. 0.9%; P=0.005) and 28 (4.8% vs. 0.9%; P=0.006) compared to isograft controls. Furthermore, [18F]FDG uptake correlated with an increase in rejection within allografts between days 14 and 28 post-transplant. Finally, the uptake of [13N]NH3 was significantly lower relative to the native heart in allografts with chronic vasculopathy compared to isograft controls on day 28 (P=0.01). Conclusions PET imaging with [18F]FDG can be used following transplantation to monitor the evolution of rejection. In addition, decreased uptake of [13N]NH3 in rejecting allografts may be reflective of decreased myocardial blood flow. These data suggest that combined [18F]FDG and [13N]NH3 PET imaging could be used as a non-invasive, quantitative technique for serial monitoring of allograft rejection and has potential application in human transplant recipients. PMID:25675207

  2. 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.

  3. Nitration and Inactivation of Manganese Superoxide Dismutase in Chronic Rejection of Human Renal Allografts

    Science.gov (United States)

    MacMillan-Crow, L. A.; Crow, John P.; Kerby, Jeffrey D.; Beckman, Joseph S.; Thompson, John A.

    1996-10-01

    Inflammatory processes in chronic rejection remain a serious clinical problem in organ transplantation. Activated cellular infiltrate produces high levels of both superoxide and nitric oxide. These reactive oxygen species interact to form peroxynitrite, a potent oxidant that can modify proteins to form 3-nitrotyrosine. We identified enhanced immunostaining for nitrotyrosine localized to tubular epithelium of chronically rejected human renal allografts. Western blot analysis of rejected tissue demonstrated that tyrosine nitration was restricted to a few specific polypeptides. Immunoprecipitation and amino acid sequencing techniques identified manganese superoxide dismutase, the major antioxidant enzyme in mitochondria, as one of the targets of tyrosine nitration. Total manganese superoxide dismutase protein was increased in rejected kidney, particularly in the tubular epithelium; however, enzymatic activity was significantly decreased. Exposure of recombinant human manganese superoxide dismutase to peroxynitrite resulted in a dose-dependent (IC50 = 10 μ M) decrease in enzymatic activity and concomitant increase in tyrosine nitration. Collectively, these observations suggest a role for peroxynitrite during development and progression of chronic rejection in human renal allografts. In addition, inactivation of manganese superoxide dismutase by peroxynitrite may represent a general mechanism that progressively increases the production of peroxynitrite, leading to irreversible oxidative injury to mitochondria.

  4. Intramyocardial electrogram recordings (IMEG) for diagnosis of cellular and humoral mediated cardiac allograft rejection.

    Science.gov (United States)

    Knosalla, C; Grauhan, O; Muller, J; Pfitzmann, R; Fietze, E; Cohnert, T; Volk, H D; Hetzer, R

    2000-04-01

    The purpose of this study was to prove the reliability of intramyocardial electrogram (IMEG) recordings for diagnosis and treatment monitoring of (1) cellular and (2) humoral mediated allograft rejection after heart transplantation. Fifteen beagle dogs underwent heterotopic neck-heart transplantation. Eight of them were previously sensitized through several skin transplantations. IMEG recordings were performed daily. Donor-specific antibodies (IgG, IgM) were determinated in serum daily. Transmyocardial biopsies were performed every two days. In the sensitized group (group I) accelerated rejection occurred under triple drug immunosuppression with cyclosporine A, azathioprine, and cortisone on the fifth postoperative day (range: 4th-5th). All episodes were detected through IMEG diagnosis. In each case rejection could be treated successfully. In the cellular mediated group (group II), the average sensitivity for rejection diagnosis of a single lead was 24% for the unipolar and 42% for the bipolar leads. When the voltages of different leads were summed up the sensitivity rose to 36% (3 unipolar), 81% (3 bipolar) and 100% (all leads). During rejection therapy the IMEG recovered within 24-48 hours. The IMEG detects cellular and humoral mediated rejection early and with high reliability. The rejection-related changes of grade 2/3a rejection in IMEG seem to follow a Ofocal patternO similar to the histology. Therefore the recording of several, preferably bipolar, electrode configurations appears to enhance diagnostic reliability.

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

    International Nuclear Information System (INIS)

    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

  6. MicroRNA-10b downregulation mediates acute rejection of renal allografts by derepressing BCL2L11

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xiaoyou [Department of Organ Transplantation, Zhujiang Hospital, Guangzhou 510282 (China); Dong, Changgui [Institute of Molecular Ecology and Evolution, East China Normal University, Shanghai 200062 (China); Jiang, Zhengyao [Department of Organ Transplantation, Zhujiang Hospital, Guangzhou 510282 (China); Wu, William K.K. [Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China); State Key Laboratory of Digestive Diseases, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China); Chan, Matthew T.V. [Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China); Zhang, Jie [Department of Organ Transplantation, Zhujiang Hospital, Guangzhou 510282 (China); Li, Haibin; Qin, Ke [Guangxi Key Laboratory for Transplantation Medicine Department of Organ Transplantation in Guangzhou Military Region, Institute of Transplant Medicine, 303 Hospital of People' s Liberation Army, Nanning, Guangxi 530021 (China); Sun, Xuyong, E-mail: sunxuyong0528@163.com [Guangxi Key Laboratory for Transplantation Medicine Department of Organ Transplantation in Guangzhou Military Region, Institute of Transplant Medicine, 303 Hospital of People' s Liberation Army, Nanning, Guangxi 530021 (China)

    2015-04-10

    Kidney transplantation is the major therapeutic option for end-stage kidney diseases. However, acute rejection could cause allograft loss in some of these patients. Emerging evidence supports that microRNA (miRNA) dysregulation is implicated in acute allograft rejection. In this study, we used next-generation sequencing to profile miRNA expression in normal and acutely rejected kidney allografts. Among 75 identified dysregulated miRNAs, miR-10b was the most significantly downregulated miRNAs in rejected allografts. Transfecting miR-10b inhibitor into human renal glomerular endothelial cells recapitulated key features of acute allograft rejection, including endothelial cell apoptosis, release of pro-inflammatory cytokines (interleukin-6, tumor necrosis factor α, interferon-γ, and chemokine (C–C motif) ligand 2) and chemotaxis of macrophages whereas transfection of miR-10b mimics had opposite effects. Downregulation of miR-10b directly derepressed the expression of BCL2L11 (an apoptosis inducer) as revealed by luciferase reporter assay. Taken together, miR-10b downregulation mediates many aspects of disease pathogenicity of acute kidney allograft rejection. Restoring miR-10b expression in glomerular endothelial cells could be a novel therapeutic approach to reduce acute renal allograft loss. - Highlights: • miR-10b was the most downregulated microRNAs in acutely rejected renal allografts. • miR-10b downregulation triggered glomerular endothelial cell apoptosis. • miR-10b downregulation induced release of pro-inflammatory cytokines. • miR-10b downregulation derepressed its pro-apoptotic target BCL2L11.

  7. Serum level of soluble fibrinogen-like protein 2 in renal allograft recipients with acute rejection: a preliminary study.

    Science.gov (United States)

    Zhao, Z; Yang, C; Tang, Q; Zhao, T; Jia, Y; Ma, Z; Rong, R; Xu, M; Zhu, T

    2012-12-01

    Soluble fibrinogen-like protein 2 (sfgl2), which is mainly secreted by T cells, is a novel effector of regulatory T cells with immunosuppressive functions. The aim of this study was to investigate serum levels of sfgl2 among renal allograft recipients. From November 2010 to August 2011 we retrospectively divided 47 renal allograft recipients into an acute rejection (n = 19) versus a stable group (n = 28) according to allograft biopsy results, using the Banff 2007 classification. The acute rejection group was subdivided into grade I (n = 8) versus grade II T-cell-mediated (n = 6) or antibody-mediated rejection episodes (n = 5). Peripheral blood samples were collected at the time of biopsy. Fourteen healthy volunteers were included as normal group controls. Serum levels of sfgl2 were analyzed by enzyme-linked immunosorbent assay. Serum levels of sfgl2 were increased among renal allograft recipients suffering from biopsy-proven acute rejection episodes (61.91 ± 45.68 ng/mL), versus those with stable allografts (38.59 ± 19.92 ng/mL, P rejection episodes (41.71 ± 16.44 ng/mL, P rejection (34.10 ± 9.26 ng/mL, P rejection episodes to an extent dependent upon the pathological type and severity of the response. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  8. 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.

  9. Sleep influences the immune response and the rejection process alters sleep pattern: Evidence from a skin allograft model in mice.

    Science.gov (United States)

    Ruiz, Francieli Silva; Andersen, Monica Levy; Guindalini, Camila; Araujo, Leandro Pires; Lopes, José Daniel; Tufik, Sergio

    2017-03-01

    Sleep generally regulates immune functions in a supportive manner and can affect parameters that are directly involved in the rejection process. The first objective was to assess whether sleep deprivation (SD) or sleep restriction (SR) affects the allograft rejection process in mice. The second objective was to investigate whether the rejection process itself modulates the sleep pattern of allografted mice. Adult BALB/c and C57BL/6J male mice were used as the donors and recipients, respectively, except for the syngeneic group (ISOTX), which received skin from mice of the same strain (C57BL/6J). The recipients were randomly assigned to either one of two control groups - TX (allogenic) or ISOTX (syngeneic) - which underwent stereotaxic surgery to enable sleep recording prior to the allograft but were not sleep deprived; one of two paradoxical sleep deprived groups - SDTX and TXSD - which underwent 72h of continuous SD either before or after the allograft respectively, and one of two sleep restricted groups - SRTX and TXSR - which underwent 21h of SD and 3h of sleep for 15days either before or after the allograft respectively. The skin allograft was inspected daily to determine the survival time, expected as 8.0±0.4days in this transplant model under no treatment. The sleep pattern was controlled throughout the rejection process in the SD and SR groups. Draining lymph nodes, spleen, blood and skin grafts were harvested on the 5th day after transplantation for evaluation of the immune parameters related to allograft rejection. In the control groups, we observed a reduction in paradoxical sleep throughout the entire allograft rejection process. Acute and chronic experimental sleep loss in the SD and SR groups produced marked alterations in the immune response. Both SD and SR prolonged allograft survival compared to the non-sleep-deprived group. There were reductions in the following parameters involved in the allograft rejection under sleep loss: CD4 + and CD8 + T cell

  10. MORPHOLOGICAL AND IMMUNOHISTOCHEMICAL MANIFESTATIONS OF DIFFERENT VARIANTS OF ACUTE KIDNEY ALLOGRAFT REJECTION

    Directory of Open Access Journals (Sweden)

    A.V Trailin

    2009-01-01

    Full Text Available The aim of this study was morphological characteristics of peculiar properties of acute T-cells- (ATMR and antibody-mediated kidney allograft rejection (AAMR. Histological slices of kidney allograft biopsies were examined after coloration by routine methods and immunohistochemical proceeding for C4d, CD45R0 T-lymphocytes antigen and CD68 macrophages antigen. We’ve determined that the key features of ATMR are: increasing of T-lymphocytes interstitial infi ltration with the same level of macrophages infi ltration comparing with implantation biopsies, mild mononuclear glomerulitis and capillaritis; tubulitis. Morphological traits of AAMR are neutrophilic and T-lymphocytes glomerulitis, diffuse capillaritis, capillaries dilatation and margination of mononuclear cells with admixture of neutrophils, macrophagal interstitial infi ltration under semiquantitative evaluation, as well as, more pronounced, than in ATMR, T-lymphoctes and macrophages interstitial infi ltration under quantitative evaluation.

  11. A Model of Acute Antibody-Mediated Renal Allograft Rejection in the Sensitized Rata.

    Science.gov (United States)

    Chandran, Sharmila Ramessur; Mulley, William R; Kanellis, John; Nikolic-Paterson, David J; Ma, Frank Y

    2017-07-31

    Antibody-mediated rejection in transplant recipients with preexisting donor-specific antibodies is a challenging clinical situation. However, we lack suitable animal models to study this scenario. The aim of this study was to develop an animal model of acute antibody-mediated rejection of renal allografts in sensitized recipients. We used major histocompatibility complex class I and II incompatible rat strains (Dark Agouti RT1av1 and Lewis RT1l), which develop aggressive rejection. Recipient Lewis rats were immunized with donor strain spleen cells 5 days before surgery to induce donor-specific antibodies. Rats underwent bilateral nephrectomy and orthotopic transplant of the donor kidney. To minimize T-cell-mediated rejection while allowing the development of donor-specific antibodies, recipient animals were given tacrolimus starting the day before surgery. Hyperacute rejection was not seen, but acute graft dysfunction was evident on day 1 with a rapid deterioration of graft function by day 3. Histologic damage featured glomerulopathy, capillaritis, capillary thrombosis, and acute tubular injury. Recipients exhibited high serum levels of donor-specific antibodies and deposition of immunoglobulin G and C4d on graft endothelium. Immunostaining showed substantial endothelial damage, fibrin deposition in glomerular and peritubular capillaries, and infiltrates of macrophages, neutrophils, and natural killer cells. T-cell activation was efficiently suppressed by tacrolimus. We have developed a clinically relevant model of acute antibody-mediated rejection in recipients with preexisting donor-specific antibodies, which is suitable for testing novel therapies.

  12. Critical appraisal on the use of everolimus in renal transplantation as an immunosuppressant to prevent organ transplant rejection

    Directory of Open Access Journals (Sweden)

    Fernando Giron

    2010-01-01

    Full Text Available Fernando Giron, Yenny BaezKidney Transplant Service, Colombiana de Trasplantes, Bogota, ColombiaAbstract: Everolimus is a proliferation inhibitor designed to target chronic allograft nephropathy including prevention of acute rejection. Acute renal allograft rejection incidence varies with the therapy used for immunosuppression. Registry data show that 15% to 35% of kidney recipients will undergo treatment for at least one episode of acute rejection within the first post-transplant year. Everolimus has been used as therapy with full- or reduced-dose cyclosporine A without evidence of increasing the acute rejection incidence. This review will summarize the available clinical trial data on the use of everolimus and its role in preventing acute rejection incidence in renal transplantation.Keywords: calcineurin inhibitors, cyclosporine, everolimus, biopsy-proven acute rejection, renal transplantation, acute rejection

  13. T-Cell Cytokines as Predictive Markers of the Risk of Allograft Rejection.

    Science.gov (United States)

    Brunet, Mercè; Millán López, Olga; López-Hoyos, Marcos

    2016-04-01

    Over the last decade, several biomarkers and surrogate markers have surfaced as promising predictive markers of risk of rejection in solid organ transplantation. The monitoring of these markers can help to improve graft and recipient care by personalizing immunomodulatory therapies. The complex immune system response against an implanted graft can change during long-term follow-up, and the dynamic balance between effector and regulatory T-cell populations is a crucial factor in antidonor response, risk of rejection, and immunosuppression requirements. Therefore, at any time before and after transplantation, T-effector activity, which is associated with increased production and release of proinflammatory cytokines, can be a surrogate marker of the risk of rejection and need for immunosuppression. In addition, immunosuppressive drugs may have a different effect in each individual patient. The pharmacokinetics and pharmacodynamics of these drugs show high interpatient variability, and pharmacodynamic markers, strongly associated with the specific mechanism of action, can potentially be used to measure individual susceptibility to a specific immunosuppressive agent. The monitoring of a panel of valid biomarkers can improve patient stratification and the selection of immunosuppressive drugs. After transplantation, therapy can be adjusted based on the prediction of rejection episodes (maintained alloreactivity), the prognosis of allograft damage, and the individual's response to the drugs. This review will focus on current data indicating that changes in the T-cell production of the intracellular cytokines interferon-γ and interleukin-2 could be used to predict the risk of rejection and to guide immunosuppressive therapy in transplant recipients.

  14. Immune Responses to Tissue-Restricted Nonmajor Histocompatibility Complex Antigens in Allograft Rejection

    Directory of Open Access Journals (Sweden)

    Ankit Bharat

    2017-01-01

    Full Text Available Chronic diseases that result in end-stage organ damage cause inflammation, which can reveal sequestered self-antigens (SAgs in that organ and trigger autoimmunity. The thymus gland deletes self-reactive T-cells against ubiquitously expressed SAgs, while regulatory mechanisms in the periphery control immune responses to tissue-restricted SAgs. It is now established that T-cells reactive to SAgs present in certain organs (e.g., lungs, pancreas, and intestine are incompletely eliminated, and the dysregulation of peripheral immuneregulation can generate immune responses to SAgs. Therefore, chronic diseases can activate self-reactive lymphocytes, inducing tissue-restricted autoimmunity. During organ transplantation, donor lymphocytes are tested against recipient serum (i.e., cross-matching to detect antibodies (Abs against donor human leukocyte antigens, which has been shown to reduce Ab-mediated hyperacute rejection. However, primary allograft dysfunction and rejection still occur frequently. Because donor lymphocytes do not express tissue-restricted SAgs, preexisting Abs against SAgs are undetectable during conventional cross-matching. Preexisting and de novo immune responses to tissue-restricted SAgs (i.e., autoimmunity play a major role in rejection. In this review, we discuss the evidence that supports autoimmunity as a contributor to rejection. Testing for preexisting and de novo immune responses to tissue-restricted SAgs and treatment based on immune responses after organ transplantation may improve short- and long-term outcomes after transplantation.

  15. Long-term results of total lymphoid irradiation in the treatment of cardiac allograft rejection

    International Nuclear Information System (INIS)

    Wolden, Suzanne L.; Tate, David J.; Hunt, Sharon A.; Strober, Samuel; Hoppe, Richard T.

    1997-01-01

    Purpose: To evaluate the short and long-term effects of total lymphoid irradiation (TLI) in the treatment of cardiac transplant rejection. Methods and Materials: Between 1986 and 1995, 48 courses of TLI were delivered to 47 cardiac transplant patients. In 37 patients, TLI was administered for intractable allograft rejection despite conventional therapy while 10 patients received TLI prophylactically. The prescribed radiation dose was 8 Gy in 0.8 Gy fractions twice weekly to mantle and inverted-Y plus spleen fields. Postirradiation follow-up ranged from 6 months to 9.1 years, with a mean of 3.1 years. Results: The actual mean dose was 7.3 Gy delivered over a mean of 39 days. Fifty-six percent of patients required treatment delay or abbreviation because of thrombocytopenia, leukopenia, infection, or unrelated problems. In patients treated for intractable rejection, rejection rates dropped from 0.46 to 0.14 and to 0.06 episodes/patient/month before, during, and after TLI (p < 0.0001). Rejection rates continued to drop throughout follow-up. Prednisone requirements decreased from 0.41 mg/kg before treatment to 0.21 mg/kg afterward (p < 0.0001). The ratio of helper to cytotoxic-suppressor T-cells decreased during TLI from 1.33 to 0.89, and remained low at 0.44, 2-4 months after treatment. Infection rates were not increased and two patients developed malignancy. Rejection rates were high during prophylactic treatment and this protocol was abandoned. Three-year actuarial survival after irradiation was 60% for patients with intractable rejection and 70% for the prophylactic cohort. Conclusion: TLI is an effective treatment for control of intractable cardiac rejection. Episodes of rejection and steroid dosage requirements are decreased for up to 9.1 years. A possible mechanism of action is long term alteration in T-lymphocyte subsets. Patients experience transient bone marrow suppression but no increase in infection or bleeding. Long-term complications of TLI are not

  16. Relationship between natriuretic peptides and inflammation: proteomic evidence obtained during acute cellular cardiac allograft rejection in humans.

    Science.gov (United States)

    Meirovich, Yael F; Veinot, John P; de Bold, Mercedes L Kuroski; Haddad, Haissam; Davies, Ross A; Masters, Roy G; Hendry, Paul J; de Bold, Adolfo J

    2008-01-01

    Cardiac natriuretic peptides (NPs) atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) are polypeptide hormones secreted by the heart. Previously, we found that BNP, but not ANF, plasma levels may increase during an acute cellular cardiac allograft rejection episode. In vitro, the pro-inflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) produced a selective increase of BNP gene expression and secretion. Other pro-inflammatory cytokines had no such effects. We identified cytokines associated with the selective upregulation of BNP during cardiac allograft rejection using a proteomics approach to measure 120 cytokines and related substances in the plasma of 16 transplant patients before, during and after an acute rejection episode. The values obtained were correlated with BNP plasma levels. Cytokines identified as being significantly related to BNP plasma levels were tested in neonatal rat ventricular cardiocytes in culture for their ability to selectively promote BNP secretion. The signaling pathway related to this phenomenon was pharmacologically characterized. Regulated-on-activation, normal T-expressed and secreted (RANTES), neutrophil-activating protein-2 (NAP-2) and insulin growth factor binding protein-1 (IGFBP-1) had significant correlations with BNP plasma levels during Grade 3A (Grade 2 revised [2R]) or above rejection as diagnosed by endomyocardial biopsy score according to the International Society for Heart and Lung Transplantation (ISHLT) grading system. In rat neonatal ventricular cardiocyte cultures, IGFBP-1 and RANTES were capable of promoting BNP, but not ANF secretion, as observed in rejecting patients. The BNP-promoting secretion activity of the identified cytokines was abolished by SB203580, a specific p38 MAP kinase inhibitor. This work shows that cytokines other than pro-inflammatory cytokines correlate with BNP plasma levels observed during acute cardiac allograft rejection, and that

  17. A Two-Step Model of Acute CD4 T-Cell Mediated Cardiac Allograft Rejection1

    OpenAIRE

    Grazia, Todd J.; Pietra, Biagio A.; Johnson, Zachary A.; Kelly, Brian P.; Plenter, Robert J.; Gill, Ronald G.

    2004-01-01

    CD4 T cells are both necessary and sufficient to mediate acute cardiac allograft rejection in mice. This process requires “direct” engagement of donor MHC class II molecules. That is, acute rejection by CD4+ T cells requires target MHC class II expression by the donor and not by the host. However, it is unclear whether CD4+ T cell rejection requires MHC class II expression on donor hemopoietic cells, nonhemopoietic cells, or both. To address this issue, bone marrow transplantation in mice was...

  18. Reliability of intramyocardial electrogram for the noninvasive diagnosis of acute allograft rejection after heart transplantation in rats.

    Science.gov (United States)

    Shi, Jiahai; Qian, Shiguo; Meng, Xu; Han, Jie; Chen, Yangtian; Wang, Jiangang; Zhang, Haibo; Jia, Yixin

    2014-02-01

    To examine the reliability of the QRS amplitude of the autonomous intramyocardial electrogram (IMEG) and the maximum slope of the descending T wave (Tslew) of the ventricular evoked response (VER) for surveillance of acute allograft rejection (AR) after heart transplantation in rats. Forty rats underwent heterotopic heart transplantation, including ten isograft (isograft group) and 30 allograft (allograft group) recipients. Autonomous IMEG and VER were recorded with epicardiac pacing leads. Isograft recipients were sacrificed on postoperative day 7 and allograft recipients on postoperative days 3, 5 and 7. Graft heart histopathological examinations were performed at the corresponding time points. Postoperative QRS amplitude and Tslew gradually decreased in the allograft group, but were unaltered in the isograft group. Decreases in the allograft group QRS amplitudes and Tslew values correlated with the histopathological results. At the optimal cutoff point of 90%, Tslew had 94.74% sensitivity, 81.82% specificity, 82.61% positive and 90% negative predictive values. QRS had 68.42% sensitivity, 90.91% specificity, 92.86% positive and 62.50% negative predictive values at its optimal cutoff point of 72.3%. The QRS amplitude of the autonomous IMEG and Tslew of VER are reliable markers for monitoring AR after heart transplantation in rats.

  19. An objective measure to identify pediatric liver transplant recipients at risk for late allograft rejection related to non-adherence.

    Science.gov (United States)

    Venkat, Veena L; Nick, Todd G; Wang, Yu; Bucuvalas, John C

    2008-02-01

    Non-adherence to a prescribed immunosuppressive regimen increases risk for late allograft rejection (LAR). We implemented a protocol for immunosuppression management which decreased variation in calcineurin inhibitor blood levels in pediatric liver transplant recipients by controlling for confounders such as physician practice variability. We hypothesized that patients with increased variation in tacrolimus blood levels despite implementation of the immunosuppression management protocol were at increased risk for LAR. We conducted a single center retrospective cohort study of 101 pediatric liver transplant recipients who were at least one year post liver transplantation and receiving tacrolimus for immunosuppression. The primary outcome variable was biopsy proven allograft rejection. Primary candidate predictor variables were the standard deviation (SD) of tacrolimus blood levels (a marker of drug level variability), mean tacrolimus blood level, age, and insurance type. SD of tacrolimus blood levels was determined for each patient from a minimum of four outpatient levels during the study period. Unadjusted and adjusted logistic regression models were used to determine the prognostic value of candidate predictors. The median and interquartile range of the SD of tacrolimus blood levels was 1.6 (1.1, 2.1). Eleven episodes of LAR occurred during the study period. Ten of the 11 episodes occurred in patients with tacrolimus blood level SD > 2. Insurance type, mean tacrolimus blood level and SD of tacrolimus blood levels were significantly related to LAR in the unadjusted analyses (ptype, mean and SD of tacrolimus blood levels was significantly associated with LAR (validated C-statistic = 0.88, p = 0.012). The adjusted odds of rejection for a one unit increase in the SD of tacrolimus blood level was 3.49 (95% CI 1.31 to 9.29). Effects of age and insurance status on LAR did not provide independent prognostic value after controlling for SD. Variation in tacrolimus blood

  20. Bowman Capsulitis Predicts Poor Kidney Allograft Outcome in T Cell-Mediated Rejection.

    Science.gov (United States)

    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.

  1. 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)

  2. Mouse NK cell-mediated rejection of bone marrow allografts exhibits patterns consistent with Ly49 subset licensing.

    Science.gov (United States)

    Sun, Kai; Alvarez, Maite; Ames, Erik; Barao, Isabel; Chen, Mingyi; Longo, Dan L; Redelman, Doug; Murphy, William J

    2012-02-09

    Natural killer (NK) cells can mediate the rejection of bone marrow allografts and exist as subsets based on expression of inhibitory/activating receptors that can bind MHC. In vitro data have shown that NK subsets bearing Ly49 receptors for self-MHC class I have intrinsically higher effector function, supporting the hypothesis that NK cells undergo a host MHC-dependent functional education. These subsets also play a role in bone marrow cell (BMC) allograft rejection. Thus far, little in vivo evidence for this preferential licensing across mouse strains with different MHC haplotypes has been shown. We assessed the intrinsic response potential of the different Ly49(+) subsets in BMC rejection by using β2-microglobulin deficient (β2m(-/-)) mice as donors. Using congenic and allogeneic mice as recipients and depleting the different Ly49 subsets, we found that NK subsets bearing Ly49s, which bind "self-MHC" were found to be the dominant subset responsible for β2m(-/-) BMC rejection. This provides in vivo evidence for host MHC class I-dependent functional education. Interestingly, all H2(d) strain mice regardless of background were able to resist significantly greater amounts of β2m(-/-), but not wild-type BMC than H2(b) mice, providing evidence that the rheostat hypothesis regarding Ly49 affinities for MHC and NK-cell function impacts BMC rejection capability.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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

  5. The ratio of circulating regulatory T cells (Tregs/Th17 cells is associated with acute allograft rejection in liver transplantation.

    Directory of Open Access Journals (Sweden)

    Ying Wang

    Full Text Available CD4(+CD25(+FoxP3(+ regulatory T cells (Tregs and Th17 cells are known to be involved in the alloreactive responses in organ transplantation, but little is known about the relationship between Tregs and Th17 cells in the context of liver alloresponse. Here, we investigated whether the circulating Tregs/Th17 ratio is associated with acute allograft rejection in liver transplantation. In present study, thirty-eight patients who received liver transplant were enrolled. The patients were divided into two groups: acute allograft rejection group (Gr-AR (n = 16 and stable allograft liver function group (Gr-SF (n = 22. The frequencies of circulating Tregs and circulating Th17 cells, as well as Tregs/Th17 ratio were determined using flow cytometry. The association between Tregs/Th17 ratio and acute allograft rejection was then analyzed. Our results showed that the frequency of circulating Tregs was significantly decreased, whereas the frequency of circulating Th17 cells was significantly increased in liver allograft recipients who developed acute rejection. Tregs/Th17 ratio had a negative correlation with liver damage indices and the score of rejection activity index (RAI after liver transplantation. In addition, the percentages of CTLA-4(+, HLA-DR(+, Ki67(+, and IL-10(+ Tregs were higher in Gr-SF group than in Gr-AR group. Our results suggested that the ratio of circulating Tregs/Th17 cells is associated with acute allograft rejection, thus the ratio may serve as an alternative marker for the diagnosis of acute rejection.

  6. Increased Expression of Peripheral Blood Leukocyte Genes Implicate CD14+ Tissue Macrophages in Cellular Intestine Allograft Rejection

    Science.gov (United States)

    Ashokkumar, Chethan; Ningappa, Mylarappa; Ranganathan, Sarangarajan; Higgs, Brandon W.; Sun, Qing; Schmitt, Lori; Snyder, Sara; Dobberstein, Jennifer; Branca, Maria; Jaffe, Ronald; Zeevi, Adriana; Squires, Robert; Alissa, Feras; Shneider, Benjamin; Soltys, Kyle; Bond, Geoffrey; Abu-Elmagd, Kareem; Humar, Abhinav; Mazariegos, George; Hakonarson, Hakon; Sindhi, Rakesh

    2011-01-01

    Recurrent rejection shortens graft survival after intestinal transplantation (ITx) in children, most of whom also experience early acute cellular rejection (rejectors). To elucidate mechanisms common to early and recurrent rejection, we used a test cohort of 20 recipients to test the hypothesis that candidate peripheral blood leukocyte genes that trigger rejection episodes would be evident late after ITx during quiescent periods in genome-wide gene expression analysis and would achieve quantitative real-time PCR replication pre-ITx (another quiescent period) and in the early post-ITx period during first rejection episodes. Eight genes were significantly up-regulated among rejectors in the late post-ITx and pre-ITx periods, compared with nonrejectors: TBX21, CCL5, GNLY, SLAMF7, TGFBR3, NKG7, SYNE1, and GK5. Only CCL5 was also up-regulated in the early post-ITx period. Among resting peripheral blood leukocyte subsets in randomly sampled nonrejectors, CD14+ monocytes expressed the CCL5 protein maximally. Compared with nonrejectors, rejectors demonstrated higher counts of both circulating CCL5+CD14+ monocytes and intragraft CD14+ monocyte-derived macrophages in immunohistochemistry of postperfusion and early post-ITx biopsies from the test and an independent replication cohort. Donor-specific alloreactivity measured with CD154+ T-cytotoxic memory cells correlated with the CCL5 gene and intragraft CD14+ monocyte-derived macrophages at graft reperfusion and early post-ITx. CCL5 gene up-regulation and CD14+ macrophages likely prime cellular ITx rejection. Infiltration of reperfused intestine allografts with CD14+ macrophages may predict rejection events. PMID:21854741

  7. Splenic microenvironment and self recognition as factors in allograft rejection in rats. A study using indium-111-labeled cells

    International Nuclear Information System (INIS)

    Pollak, R.; Blanchard, J.M.; Lazda, V.A.

    1986-01-01

    Splenectomy facilitates organ allograft survival in some rat strains, and in weak donor-recipient histoincompatible pairs. We have found using a heart spleen twin graft model, using ACI rats as recipients and Lewis rats as donors, that the transplanted heart will survive in most recipients after delayed host splenectomy. The presence of a viable mass of splenic tissue will allow rejection to proceed only when the transplanted spleen is of host origin, and not when it comes from the donor (i.e., when it is allogeneic). The use of 111In-labeled cells has allowed us to show that lymphocyte traffic and trapping is markedly altered in the transplanted allogeneic spleens, when compared with control transplanted syngeneic spleens. Thus, despite the presence of the splenic ''microenvironment,'' cardiac allograft rejection does not occur in the absence of syngeneic splenic tissue. We conclude that the role of the spleen in the immune response is to facilitate the recognition of self and the acquisition of alloreactivity in weak responder rat strains and donor-recipient pairs

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

    Directory of Open Access Journals (Sweden)

    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

  9. Soluble BAFF Cytokine Levels and Antibody-Mediated Rejection of the Kidney Allograft.

    Science.gov (United States)

    Slavcev, Antonij; Brozova, Jitka; Slatinska, Janka; Sekerkova, Zuzana; Honsova, Eva; Skibova, Jelena; Striz, Ilja; Viklicky, Ondrej

    2016-12-01

    The B-cell activating factor (BAFF) cytokine has important functions for the survival and maturation of B lymphocytes, which implies that this cytokine might play a role in the development of antibody-mediated rejection (AMR) after kidney transplantation. In our study, we compared the concentrations of the soluble BAFF cytokine in kidney graft recipients with AMR and patients without rejection with the goal of testing the hypothesis whether BAFF level measurement might be useful as a diagnostic marker of AMR. The study included a cohort of 19 high-risk patients with diagnosed AMR and 17 control patients free of rejection. BAFF was measured in all patients before transplantation, during the rejection episodes, and three months after transplantation in patients free of rejection using the Luminex technique. Before transplantation, the serum concentrations of BAFF in patients with AMR and kidney recipients without rejection did not significantly differ. After transplantation, however, BAFF levels were significantly lower in patients with AMR and also in patients with concurrent humoral and cellular rejection compared with patients without rejection (p BAFF and the production of donor-specific antibodies (DSA) before and after transplantation. Patients experiencing AMR and simultaneous cellular and AMR had significantly lower concentrations of BAFF in comparison with patients free of rejection.

  10. Intragraft FOXP3 Protein or mRNA During Acute Renal Allograft Rejection Correlates With Inflammation, Fibrosis, and Poor Renal Outcome

    NARCIS (Netherlands)

    Yapici, Unsal; Bemelman, Fréderike J.; Scheepstra, Cornelis G.; Roelofs, Joris J. T. H.; Claessen, Nike; van der Loos, Chris; van Donselaar-van der Pant, Karlijn; Bouts, Antonia H. M.; Idu, Mirza M.; Rowshani, Ajda T.; ten Berge, Ineke J. M.; Florquin, Sandrine

    2009-01-01

    Background: Forkhead box (FOXP3) is considered to be a specific marker for regulatory T cells. The aim of this study was to correlate intragraft FOXP3 at mRNA and cellular levels during renal allograft rejection to response to therapy and late clinical outcome. Methods: Immunostainings and

  11. Association of Local Intrapulmonary Production of Antibodies Specific to Donor Major Histocompatibility Complex Class I With the Progression of Chronic Rejection of Lung Allografts.

    Science.gov (United States)

    Miyamoto, Ei; Motoyama, Hideki; Sato, Masaaki; Aoyama, Akihiro; Menju, Toshi; Shikuma, Kei; Sowa, Terumasa; Yoshizawa, Akihiko; Saito, Masao; Takahagi, Akihiro; Tanaka, Satona; Takahashi, Mamoru; Ohata, Keiji; Kondo, Takeshi; Hijiya, Kyoko; Chen-Yoshikawa, Toyofumi F; Date, Hiroshi

    2017-05-01

    Antibody-mediated rejection may lead to chronic lung allograft dysfunction, but antibody-mediated rejection may develop in the absence of detectable donor-specific antibody (DSA) in recipient serum. This study investigated whether humoral immune responses develop not only systemically but locally within rejected lung allografts, resulting in local production of DSA. Lewis rats received orthotopic left lung transplantation from Lewis (syngeneic control) or Brown-Norway (major histocompatibility complex-mismatched allogeneic) donor rats. Rats that underwent allogeneic lung transplantation were subsequently administered cyclosporine until day 14 (short immunosuppression) or day 35 (long immunosuppression). The lung grafts and spleens of recipient animals were tissue cultured for 4 days, and the titer of antibody against donor major histocompatibility complex molecules was assayed by flow cytometry. Explanted lung grafts were also evaluated pathologically. By day 98, DSA titers in supernatants of lung graft (P = 0.0074) and spleen (P = 0.0167) cultures, but not serum, from the short immunosuppression group were significantly higher than titers in syngeneic controls. Cultures and sera from the long immunosuppression group showed no production of DSA. Microscopically, the lung grafts from the short immunosuppression group showed severe bronchiole obliteration and parenchymal fibrosis, along with lymphoid aggregates containing T and B cells, accompanying plasma cells. These findings suggestive of local humoral immune response were not observed by days 28 and 63. DSA can be locally produced in chronically rejected lung allografts, along with intragraft immunocompetent cells. Clinical testing of DSA in serum samples alone may underestimate lung allograft dysfunction.

  12. Significance and suppression of redundant IL17 responses in acute allograft rejection by bioinformatics based drug repositioning of fenofibrate.

    Directory of Open Access Journals (Sweden)

    Silke Roedder

    Full Text Available Despite advanced immunosuppression, redundancy in the molecular diversity of acute rejection (AR often results in incomplete resolution of the injury response. We present a bioinformatics based approach for identification of these redundant molecular pathways in AR and a drug repositioning approach to suppress these using FDA approved drugs currently available for non-transplant indications. Two independent microarray data-sets from human renal allograft biopsies (n = 101 from patients on majorly Th1/IFN-y immune response targeted immunosuppression, with and without AR, were profiled. Using gene-set analysis across 3305 biological pathways, significant enrichment was found for the IL17 pathway in AR in both data-sets. Recent evidence suggests IL17 pathway as an important escape mechanism when Th1/IFN-y mediated responses are suppressed. As current immunosuppressions do not specifically target the IL17 axis, 7200 molecular compounds were interrogated for FDA approved drugs with specific inhibition of this axis. A combined IL17/IFN-y suppressive role was predicted for the antilipidemic drug Fenofibrate. To assess the immunregulatory action of Fenofibrate, we conducted in-vitro treatment of anti-CD3/CD28 stimulated human peripheral blood cells (PBMC, and, as predicted, Fenofibrate reduced IL17 and IFN-γ gene expression in stimulated PMBC. In-vivo Fenofibrate treatment of an experimental rodent model of cardiac AR reduced infiltration of total leukocytes, reduced expression of IL17/IFN-y and their pathway related genes in allografts and recipients' spleens, and extended graft survival by 21 days (p<0.007. In conclusion, this study provides important proof of concept that meta-analyses of genomic data and drug databases can provide new insights into the redundancy of the rejection response and presents an economic methodology to reposition FDA approved drugs in organ transplantation.

  13. Interleukin 18 (IL-18) upregulation in acute rejection of kidney allograft

    Czech Academy of Sciences Publication Activity Database

    Stříž, I.; Krásná, E.; Honsová, E.; Lácha, J.; Petříčková, Kateřina; Jarešová, M.; Lodererová, A.; Böhmová, R.; Valhová, Š.; Slavcev, A.; Vitko, S.

    2005-01-01

    Roč. 99, - (2005), s. 30-35 ISSN 0165-2478 R&D Projects: GA MZd NI6843 Institutional research plan: CEZ:AV0Z50200510 Keywords : kidney transplantation * IL-18 * acute rejection Subject RIV: EE - Microbiology, Virology Impact factor: 2.301, year: 2005

  14. A New Immunosuppressive Molecule Emodin Induces both CD4+FoxP3+ and CD8+CD122+ Regulatory T Cells and Suppresses Murine Allograft Rejection

    Directory of Open Access Journals (Sweden)

    Feifei Qiu

    2017-11-01

    Full Text Available Due to vigorous alloimmunity, an allograft is usually rejected without any conventional immunosuppressive treatment. However, continuous global immunosuppression may cause severe side effects, including tumors and infections. Mounting evidence has shown that cyclosporine (CsA, a common immunosuppressant used in clinic, impedes allograft tolerance by dampening regulatory T cells (Tregs, although it inhibits allograft rejection at the same time. Therefore, it is necessary to seek an alternative immunosuppressive drug that spares Tregs with high efficiency in suppression but low toxicity. In this study, we investigated the capacity of emodin, an anthraquinone molecule originally extracted from certain natural plants, to prolong transplant survival in a mouse model and explored the cellular and molecular mechanisms underlying its action. We found that emodin significantly extended skin allograft survival and hindered CD3+ T cell infiltration in the allograft, accompanied by an increase in CD4+Foxp3+ and CD8+CD122+ Treg frequencies and numbers but a reduction in effector CD8+CD44highCD62Llow T cells in recipient mice. Emodin also inhibited effector CD8+ T cells proliferation in vivo. However, CD4+CD25+, but not CD8+CD122+, Tregs derived from emodin-treated recipients were more potent in suppression of allograft rejection than those isolated from control recipients, suggesting that emodin also enhances the suppressive function of CD4+CD25+ Tregs. Interestingly, depleting CD25+ Tregs largely reversed skin allograft survival prolonged by emodin while depleting CD122+ Tregs only partially abrogated the same allograft survival. Furthermore, we found that emodin hindered dendritic cell (DC maturation and reduced alloantibody production posttransplantation. Finally, we demonstrated that emodin inhibited in vitro proliferation of T cells and blocked their mTOR signaling as well. Therefore, emodin may be a novel mTOR inhibitor that suppresses alloimmunity by

  15. 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)

  16. Cardiac allograft immune activation: current perspectives

    Directory of Open Access Journals (Sweden)

    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

  17. A standardized fold change method for microarray differential expression analysis used to reveal genes involved in acute rejection in murine allograft models.

    Science.gov (United States)

    Zhou, Weichen; Wang, Yi; Fujino, Masayuki; Shi, Leming; Jin, Li; Li, Xiao-Kang; Wang, Jiucun

    2018-03-01

    Murine transplantation models are used extensively to research immunological rejection and tolerance. Here we studied both murine heart and liver allograft models using microarray technology. We had difficulty in identifying genes related to acute rejections expressed in both heart and liver transplantation models using two standard methodologies: Student's t test and linear models for microarray data (Limma). Here we describe a new method, standardized fold change (SFC), for differential analysis of microarray data. We estimated the performance of SFC, the t test and Limma by generating simulated microarray data 100 times. SFC performed better than the t test and showed a higher sensitivity than Limma where there is a larger value for fold change of expression. SFC gave better reproducibility than Limma and the t test with real experimental data from the MicroArray Quality Control platform and expression data from a mouse cardiac allograft. Eventually, a group of significant overlapping genes was detected by SFC in the expression data of mouse cardiac and hepatic allografts and further validated with the quantitative RT-PCR assay. The group included genes for important reactions of transplantation rejection and revealed functional changes of the immune system in both heart and liver of the mouse model. We suggest that SFC can be utilized to stably and effectively detect differential gene expression and to explore microarray data in further studies.

  18. The impact of HLA class I-specific killer cell immunoglobulin-like receptors on antibody-dependent natural killer cell-mediated cytotoxicity and organ allograft rejection

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    Raja Rajalingam

    2016-12-01

    Full Text Available Natural killer (NK cells of the innate immune system are cytotoxic lymphocytes that play important roles following transplantation of solid organs and hematopoietic stem cells. Recognition of self HLA class I molecules by inhibitory killer cell immunoglobulin-like receptors (KIR is involved in the calibration of NK cell effector capacities during a developmental stage, allowing the subsequent recognition and elimination of target cells with decreased expression of self HLA class I (due to virus infection or tumor transformation or HLA class I disparities (in the setting of allogeneic transplantation. NK cells expressing an inhibitory KIR binding self HLA can be activated when confronted with allografts lacking a ligand for the inhibitory receptor. Following the response of the adaptive immune system, NK cells can further destroy allograft endothelium by antibody-dependent cell-mediated cytotoxicity (ADCC, triggered through cross-linking of the CD16 Fc receptor by donor-specific antibodies bound to allograft. Upon recognizing allogeneic target cells, NK cells also secrete cytokines and chemokines that drive maturation of dendritic cells to promote cellular and humoral adaptive immune responses against the allograft. The cumulative activating and inhibitory signals generated by ligation of the receptors regulates mature NK cell killing of target cells and their production of cytokines and chemokines. This review summarizes the role of NK cells in allograft rejection and proposes mechanistic concepts that indicate a prominent role for KIR-HLA interactions in facilitating NK cells for Fc receptor-mediated ADCC effector function involved in antibody-mediated rejection of solid organ transplants.

  19. 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

  20. 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.

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

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    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.

  2. 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.

  3. 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.

  4. A single administration of LFA-1 antibody confers prolonged allograft survival.

    Science.gov (United States)

    Talento, A; Nguyen, M; Blake, T; Sirotina, A; Fioravanti, C; Burkholder, D; Gibson, R; Sigal, N H; Springer, M S; Koo, G C

    1993-02-01

    C57BL/6 (B6) thyroid gland transplanted to the left kidney capsule of an allogeneic (BALB/c) host was typically rejected in 14 days. A single administration of 500 micrograms of an antibody to the adhesion molecule, leucocyte function-associated antigen (LFA-1, CD11a), prevented all thyroid allograft rejection for at least 70 days. Fifty percent of the treated recipients retained intact allografts for 470 days. However, the same treatment with anti-CD11a could not protect a sensitized BALB/c mouse from rejecting a second B6 thyroid allograft. Production of donor-specific alloantibodies elicited by allograft rejection was also inhibited in this system. In this transplant model, the Ab therapy is more efficacious than that of FK506, administered daily for 14 days at 15 mg/kg. These results demonstrate the remarkable effect of an anti-LFA-1 antibody in promotion of allograft survival.

  5. Corneal Allograft Rejection: Topical Treatment Vs. Pulsed Intravenous Methylprednisolone - Ten Years' Result [rejeição De Transplantes De Córnea: Tratamento Tópico Vs. Pulsoterapia - Resultados De 10 Anos

    OpenAIRE

    Costa D.C.; de Castro R.S.; Ferraz de Camargo M.S.; Kara-Jose N.

    2008-01-01

    Purpose: To evaluate the efficacy of intravenous 500 mg methylprednisolone in addition to topical treatment with 1% prednisolone in the treatment of the first episode of corneal endothelial rejection in patients that were submitted to corneal allograft transplantation. Methods: Retrospective casecontrol study with 81 patients that presented the first episode of corneal endothelial rejection and were treated within the first 15 days of the onset of symptoms. Results: 67 patients were treated w...

  6. The synergistic immunoregulatory effects of culture-expanded mesenchymal stromal cells and CD4(+25(+Foxp3+ regulatory T cells on skin allograft rejection.

    Directory of Open Access Journals (Sweden)

    Jung Ho Lee

    Full Text Available Mesenchymal stromal cells (MSCs are seen as an ideal source of cells to induce graft acceptance; however, some reports have shown that MSCs can be immunogenic rather than immunosuppressive. We speculate that the immunomodulatory effects of regulatory T cells (Tregs can aid the maintenance of immunoregulatory functions of MSCs, and that a combinatorial approach to cell therapy can have synergistic immunomodulatory effects on allograft rejection. After preconditioning with Fludarabine, followed by total body irradiation and anti-asialo-GM-1(ASGM-1, tail skin grafts from C57BL/6 (H-2k(b mice were grafted onto the lateral thoracic wall of BALB/c (H-2k(d mice. Group A mice (control group, n = 9 did not receive any further treatment after preconditioning, whereas groups B and C (n = 9 received cell therapy with MSCs or Tregs, respectively, on days -1, +6 and +13 relative to the skin transplantation. Group D (n = 10 received cell therapy with MSCs and Tregs on days -1, +6 and +13. Cell suspensions were obtained from the spleens of five randomly chosen mice from each group on day +7, and the immunomodulatory effects of the cell therapy were evaluated by flow cytometry and real-time PCR. Our results show that allograft survival was significantly longer in group D compared to the control group (group A. Flow cytometric analysis and real-time PCR for splenocytes revealed that the Th2 subpopulation in group D increased significantly compared to the group B. Also, the expression of Foxp3 and STAT 5 increased significantly in group D compared to the conventional cell therapy groups (B and C. Taken together, these data suggest that a combined cell therapy approach with MSCs and Tregs has a synergistic effect on immunoregulatory function in vivo, and might provide a novel strategy for improving survival in allograft transplantation.

  7. 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...

  8. IFN-γ-producing Th1-like regulatory T cells may limit acute cellular renal allograft rejection: Paradoxical post-transplantation effects of IFN-γ.

    Science.gov (United States)

    Xu, Xiaoguang; Huang, Haiyan; Wang, Qiang; Cai, Ming; Qian, Yeyong; Han, Yong; Wang, Xinying; Gao, Yu; Yuan, Ming; Xu, Liang; Yao, Chen; Xiao, Li; Shi, Bingyi

    2017-02-01

    IFN-γ is a protypical proinflammatory cytokine that plays a central role in inflammation and acute graft rejection. Accumulating evidence indicates that IFN-γ can exert previously unexpected immunoregulatory activities. However, little is known about the role of IFN-γ secreted by Th1-like regulatory T cells in human kidney transplantation. To determine the function of IFN-γ in acute T cell-mediated renal allograft rejection (ACR), we examined serum cytokine expression profiles in ACR patients by human cytokine multiplex immunoassay and analyzed the cellular origins of IFN-γ in peripheral blood and renal allograft biopsies from ACR cases and controls by flow cytometry and immunohistochemistry, respectively. The results showed significant reduction in serum concentrations of Th1-inducing cytokines IL-12p70 and IFN-γ as well as Th2-related cytokine IL-4 in ACR patients compared with stable controls. However, levels of several Th1-, Th2- and Th17-related cytokines, such as IL-2, TNF-α, TNF-β, IL-12 (p40), IL-10, IL-15, IL-17, IL-21, and IL-23, as well as the frequencies of Th1 and Th17 cell, did not differ between ACR cases and stable controls. Moreover, we found the levels of IFN-γ were correlated with those of the anti-inflammatory factor, IL-1 receptor antagonist (IL-1Ra) in ACR. Notably, the Th1-like Treg cell-to-Foxp3 - Th1 cell ratio was significantly lower in ACR patients compared with that in stable controls. In graft biopsies from ACR patients, Treg cells and Th1-like Treg cells were less abundant than those without ACR. Our study indicates that IFN-γ secreted from Th1-like Treg cells negatively modulates ACR. Copyright © 2016 Elsevier GmbH. All rights reserved.

  9. 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.

  10. Combination of monoclonal antibodies with DST inhibits accelerated rejection mediated by memory T cells to induce long-lived heart allograft acceptance in mice.

    Science.gov (United States)

    Shao, Wei; Chen, Jibing; Dai, Helong; Peng, Yuanzheng; Wang, Feng; Xia, Junjie; Thorlacius, Henrik; Zhu, Qi; Qi, Zhongquan

    2011-08-30

    Donor-reactive memory T cells mediated accelerated rejection is known as a barrier to the survival of transplanted organs. We investigated the combination of different monoclonal antibodies (mAbs) and donor-specific transfusion (DST) in memory T cells-based adoptive mice model. In the presence of donor-reactive memory T cells, the mean survival time (MST) of grafts in the anti-CD40L/LFA-1/DST group was 49.8d. Adding anti-CD44/CD70 mAbs to anti-CD40L/LFA-1/DST treatment. The MST was more than 100 d (MST>100 d). Compared with anti-CD40L/LFA-1/DST group, anti-CD40L/LFA-1/CD44/CD70/DST group notably reduced the expansion of memory T cells, enhanced the proportion of CD4+Foxp3+ regulatory T cells (Tregs) and suppressed donor-specific responses. Our data suggest that anti-CD40L/LFA-1/CD44/CD70mAbs and DST can synergistically inhibit accelerated rejection mediated by memory T cells to induce long-lived heart allograft acceptance in mice. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Chronic Antibody-Mediated Rejection in Nonhuman Primate Renal Allografts: Validation of Human Histological and Molecular Phenotypes.

    Science.gov (United States)

    Adam, B A; Smith, R N; Rosales, I A; Matsunami, M; Afzali, B; Oura, T; Cosimi, A B; Kawai, T; Colvin, R B; Mengel, M

    2017-11-01

    Molecular testing represents a promising adjunct for the diagnosis of antibody-mediated rejection (AMR). Here, we apply a novel gene expression platform in sequential formalin-fixed paraffin-embedded samples from nonhuman primate (NHP) renal transplants. We analyzed 34 previously described gene transcripts related to AMR in humans in 197 archival NHP samples, including 102 from recipients that developed chronic AMR, 80 from recipients without AMR, and 15 normal native nephrectomies. Three endothelial genes (VWF, DARC, and CAV1), derived from 10-fold cross-validation receiver operating characteristic curve analysis, demonstrated excellent discrimination between AMR and non-AMR samples (area under the curve = 0.92). This three-gene set correlated with classic features of AMR, including glomerulitis, capillaritis, glomerulopathy, C4d deposition, and DSAs (r = 0.39-0.63, p < 0.001). Principal component analysis confirmed the association between three-gene set expression and AMR and highlighted the ambiguity of v lesions and ptc lesions between AMR and T cell-mediated rejection (TCMR). Elevated three-gene set expression corresponded with the development of immunopathological evidence of rejection and often preceded it. Many recipients demonstrated mixed AMR and TCMR, suggesting that this represents the natural pattern of rejection. These data provide NHP animal model validation of recent updates to the Banff classification including the assessment of molecular markers for diagnosing AMR. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  12. Investigation of Killer Immunoglobulin-like Receptor (KIR) and HLA Genotypes to Predict the Occurrence of Acute Allograft Rejection after Kidney Transplantation.

    Science.gov (United States)

    Jafari, Davood; Nafar, Mohsen; Yekaninejad, Mir Saeed; Abdolvahabi, Razieh; Lesan Pezeshki, Mahboob; Razaghi, Efat; Amirzargar, Ali Akbar

    2017-06-01

    After kidney transplantation, natural killer (NK) cells play a pivotal role in triggering the immune response to the allogeneic grafts primarily by their killer-cell immunoglobulin-like receptors (KIR). This process may be one mechanism that contributes to graft rejection. In this study, we have evaluated whether acute rejection after kidney transplantation was associated with predicted NK cell alloreactivity based on KIR gene and ligand along with KIR/HLA compound genotype analysis. After kidney transplantation, natural killer (NK) cells play a pivotal role in triggering the immune response to the allogeneic grafts primarily by their killer-cell immunoglobulin-like receptors (KIR). This process may be one mechanism that contributes to graft rejection. In this study, we have evaluated whether acute rejection after kidney transplantation was associated with predicted NK cell alloreactivity based on KIR gene and ligand along with KIR/HLA compound genotype analysis. DNA from 65 patients with biopsy-proven acute kidney allograft rejection (AKAR), 61 clinically stable graft function (SGF) recipients and 176 healthy subjects were identified for the presence or absence of 10 variable KIR genes (both activating and inhibitory receptors) and their HLA ligands using polymerase chain reaction-sequence specific primers (PCR-SSP) assay. Although no significant difference in the frequency of individual KIR genes, was found the gene content, and the haplotypic distribution between the three categories were detected, the frequency of the KIR3DL1+HLA-Bw4*A allele combination was significantly lower in AKAR patients compared to SGF recipients (p=0.004, OR=0.34, CI=0.16-0.72) and healthy subjects (p=0.019, OR=0.47, CI=0.25-0.89). Kaplan-Meier survival test showed that the KIR3DL1+HLA-Bw4*A allele combination could be considered protective for AKAR (p=0.04 by log-rank). The results of this study suggest that KIR/HLA polymorphism may be a genetic susceptibility factor to alloreactivity

  13. Monitoring pharmacologically induced immunosuppression by immune repertoire sequencing to detect acute allograft rejection in heart transplant patients: a proof-of-concept diagnostic accuracy study.

    Directory of Open Access Journals (Sweden)

    Christopher Vollmers

    2015-10-01

    Full Text Available It remains difficult to predict and to measure the efficacy of pharmacological immunosuppression. We hypothesized that measuring the B-cell repertoire would enable assessment of the overall level of immunosuppression after heart transplantation.In this proof-of-concept study, we implemented a molecular-barcode-based immune repertoire sequencing assay that sensitively and accurately measures the isotype and clonal composition of the circulating B cell repertoire. We used this assay to measure the temporal response of the B cell repertoire to immunosuppression after heart transplantation. We selected a subset of 12 participants from a larger prospective cohort study (ClinicalTrials.gov NCT01985412 that is ongoing at Stanford Medical Center and for which enrollment started in March 2010. This subset of 12 participants was selected to represent post-heart-transplant events, with and without acute rejection (six participants with moderate-to-severe rejection and six without. We analyzed 130 samples from these patients, with an average follow-up period of 15 mo. Immune repertoire sequencing enables the measurement of a patient's net state of immunosuppression (correlation with tacrolimus level, r = -0.867, 95% CI -0.968 to -0.523, p = 0.0014, as well as the diagnosis of acute allograft rejection, which is preceded by increased immune activity with a sensitivity of 71.4% (95% CI 30.3% to 94.9% and a specificity of 82.0% (95% CI 72.1% to 89.1% (cell-free donor-derived DNA as noninvasive gold standard. To illustrate the potential of immune repertoire sequencing to monitor atypical post-transplant trajectories, we analyzed two more patients, one with chronic infections and one with amyloidosis. A larger, prospective study will be needed to validate the power of immune repertoire sequencing to predict rejection events, as this proof-of-concept study is limited to a small number of patients who were selected based on several criteria including the

  14. 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

    necrosis are used. These terms create some difficulties in understanding or interpreting the various grades. The main problem is to distinguish between grade 1A and grade 3A. Despite the difficulties, the grading system is easy to use, but a revision is needed.......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...... systems have evolved. Most recently, the International Grading System was introduced in The Journal of Heart and Lung Transplantation. In this study the interobserver reproducibility of both the Stanford Classification and the International Grading System is evaluated using Kappa statistics. Three...

  15. Repeated measurements of NT-pro-B-type natriuretic peptide, troponin T or C-reactive protein do not predict future allograft rejection in heart transplant recipients.

    Science.gov (United States)

    Battes, Linda C; Caliskan, Kadir; Rizopoulos, Dimitris; Constantinescu, Alina A; Robertus, Jan L; Akkerhuis, Martijn; Manintveld, Olivier C; Boersma, Eric; Kardys, Isabella

    2015-03-01

    Studies on the prognostic value of serial biomarker assays for future occurrence of allograft rejection (AR) are scarce. We examined whether repeated measurements of NT-pro-B-type natriuretic peptide (NT-proBNP), troponin T (TropT) and C-reactive protein (CRP) predict AR. From 2005 to 2010, 77 consecutive heart transplantation (HTx) recipients were included. The NT-proBNP, TropT, and CRP were measured at 16 ± 4 (mean ± standard deviation) consecutive routine endomyocardial biopsy surveillance visits during the first year of follow-up. Allograft rejection was defined as International Society for Heart and Lung Transplantation (ISHLT) grade 2R or higher at endomyocardial biopsy. Joint modeling was used to assess the association between repeated biomarker measurements and occurrence of future AR. Joint modeling accounts for dependence among repeated observations in individual patients. The mean age of the patients at HTx was 49 ± 9.2 years, and 68% were men. During the first year of follow-up, 1,136 biopsies and concurrent blood samples were obtained, and 56 patients (73%) experienced at least one episode of AR. All biomarkers were elevated directly after HTx and achieved steady-state after ∼ 12 weeks, both in patients with or without AR. No associations were present between the repeated measurements of NT-proBNP, TropT, or CRP and AR both early (weeks 0-12) and late (weeks 13-52) in the course after HTx (hazard ratios for weeks 13-52: 0.96 (95% confidence interval, 0.55-1.68), 0.67 (0.27-1.69), and 1.44 (0.90-2.30), respectively, per ln[unit]). Combining the three biomarkers in one model also rendered null results. The temporal evolution of NT-proBNP, TropT, and CRP before AR did not predict occurrence of acute AR both in the early and late course of the first year after HTx.

  16. Portal versus systemic drainage of small bowel allografts: comparative assessment of survival, function, rejection, and bacterial translocation.

    Science.gov (United States)

    Berney, Thierry; Kato, Tomoaki; Nishida, Seigo; Tector, A Joseph; Mittal, Naveen K; Madariaga, Juan; Nery, Jose R; Cantwell, G Patricia; Ruiz, Philip; Tzakis, Andreas G

    2002-12-01

    Portal venous drainage of small bowel grafts is theoretically more physiologic than systemic drainage, but is technically more demanding. Comparisons in animal models have not demonstrated a clear advantage of one technique over the other, but clinical data are lacking. Clinical records of 36 patients who underwent 37 small bowel transplantation procedures from January 1995 to August 2001 were reviewed. Portal drainage was performed in 19 patients (PD group). Systemic drainage was performed in 18 patients (SD group). Median followup was 531 days. PD and SD patients had similar ICU stays (median 7 versus 9 days) and endotracheal intubation durations (median 3 versus 5 days). All current survivors, with the exception of one patient in each group, are independent from parenteral nutrition. Liver function tests were similar in both groups. There was a twofold increase in tacrolimus dosage in the PD group to achieve similar trough levels indicating a "first-pass" hepatic clearance effect. Cumulative incidence of acute rejection episodes and OKT3-requiring rejection episodes were similar in both groups. To the contrary, a lower incidence of gram-negative rods of Enterococcus sp. in blood or bronchoalveolar lavage suggested that the clearance of translocated intestinal bacteria was more efficient in the PD group. Graft and patient survival rates were similar in both groups. Systemic venous drainage of small bowel transplants is a dependable technique, associated with similar results as portal venous drainage, in terms of overall mortality, morbidity, rejection, function, and patient and graft survival. But attention should be paid to an impaired clearance of intestinal bacterial translocation after systemic drainage.

  17. SUCCESSFUL APPLICATION OF PERIPHERAL VENO-ARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION FOR CARDIAC ALLOGRAFT ANTIBODY-MEDIATED REJECTION WITH SEVERE HEMODYNAMIC COMPROMISE

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    V. N. Poptsov

    2015-01-01

    Full Text Available Introduction. Acute antibody-mediated rejection (AMR is one of the severe complications of early and late period after heart transplantation (HT. Only few case reports and studies presented of mechanical circulatory support (MCS application for refractory acute rejection causing hemodynamic compromise. Aim. We report the case of a woman with cardiogenic shock caused by severe AMR that was successfully treatment by peripheral venoarterial extracorporeal membrane oxygenation (VA ECMO. Material and methods. In december 2014, a 60-year-old woman with dilated cardiomyopathy was operated for HT. The patient had a good initial cardiac allograft function and no and was discharged from ICU on the 4th day after HT. 1st endomyocardial biopsy (EMB (the 7th day after HT showed absence of acute cellular and antibody-mediated rejection. On the 11th day after HT patient aggravated and presented clinical signs of life-threatening acute cardiac allograft dysfunction: arterial blood pressure 78/49/38 mm Hg, HR 111 in min, CVP 20 mm Hg, PAP 47/34/25 mm Hg, PCWP 25 mm Hg, CI 1.5 l/min/m2, adrenalin 110 ng/kg/min, dopamine 15 mcg/kg/min. ECG showed impairment of systolic left (LVEF 25% and right (RVEF 15% ventricle function, left and right ventricle diffuse hypokinesis, thickness of IVS, LV and RV wall 1.7, 1.4 and 0.8 cm, tricuspid and mitral valve regurgitation 2–3 degrees. EMB presented AMR. In conscience peripheral VA ECMO was installed. We used peripheral transcutaneous cannulation technique via femoral vessels – arterial cannula 15 F, venous cannula – 23 F, vascular catheter 14 G for anterograde leg’s perfusion. ACT 130–150 sec. AMR therapy included: methylprednisolon pulse-therapy (10 mg/kg for 5 day, IgG, plasmapheresis (No 7, rituximab. Results. Under MCS by VA ECMO we noted quick improvement of hemodynamic, metabolic homeostasis and organ functions. On the 6th day of VA ECMO (blood flow 1.8 l/min: arterial blood pressure 133/81/54 mm Hg, CVP 5 mm

  18. Antagonism of antiviral and allogeneic activity of a human public CTL clonotype by a single altered peptide ligand: implications for allograft rejection

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    Ely, Lauren K.; Green, Katherine J.; Beddoe, Travis; Clements, Craig S.; Miles, John J.; Bottomley, Stephen P.; Zernich, Danielle; Kjer-Nielsen, Lars; Purcell, Anthony W.; McCluskey, James; Rossjohn, Jamie; Burrows, Scott R. (Monash)

    2010-06-30

    Alloreactive T lymphocytes are central mediators of graft-versus-host disease and allograft rejection. A public CTL clonotype with specificity for the alloantigens HLA-B*4402 and B*4405 is often expanded to large numbers in healthy HLA-B*0801{sup +} individuals, driven by cross-reactive stimulation with the common, persistent herpesvirus EBV. Since such alloreactive memory CTL expansions have the potential to influence transplantation outcome, altered peptide ligands (APLs) of the target HLA-B*0801-binding EBV peptide, FLRGRAYGL, were screened as specific antagonists for this immunodominant clonotype. One APL, FLRGRFYGL, exerted powerful antagonism of a prototypic T cell clone expressing this immunodominant TCR when costimulated with target cells presenting HLA-B*0801{sup FLRGRAYGL}. Significantly, this APL also reduced the lysis of allogeneic target cells expressing HLA-B*4402 by up to 99%. The affinities of the agonist and antagonist complexes for the public TCR, measured using solution and solid-phase assays, were 8 and 138 {micro}M, respectively. Surprisingly, the half-life of the agonist and antagonist complexes was similar, yet the association rate for the antagonist complex was significantly slower. These observations were further supported by structural studies that suggested a large conformational hurdle was required to ligate the immunodominant TCR to the HLA-B*0801 antagonist complex. By defining an antagonist APL against an immunodominant alloreactive TCR, these findings raise the prospect of exploiting such peptides to inhibit clinical alloreactivity, particularly against clonal T cell expansions that react with alloantigens.

  19. 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

  20. Alloantigen-specific CD4(+) regulatory T cells induced in vivo by ultraviolet irradiation after alloantigen immunization require interleukin-10 for their induction and activation, and flexibly mediate bystander immunosuppression of allograft rejection.

    Science.gov (United States)

    Hori, Tomohide; Kuribayashi, Kagemasa; Saito, Kanako; Wang, Linan; Torii, Mie; Uemoto, Shinji; Kato, Takuma

    2015-06-01

    Ultraviolet (UV) irradiation prior to antigen immunization is employed to induce antigen-specific regulatory T cells (Tregs). UV-induced Tregs demonstrate unique bystander suppression, although antigen-specific activation is required initially. We previously reported the phenotype of alloantigen-specific transferable Tregs induced by UV-B irradiation after immunization was the same as T regulatory type 1-like CD4(+) T cells, with antigen-specific interleukin (IL)-10 production. Here, by using semi-allogeneic transplantation models in vivo, we investigated the role of IL-10 in the induction and activation of these Tregs, and the possibility of bystander suppression of third-party allograft rejection. Naïve mice (H-2(b)) were immunized with alloantigen (H-2(b/d)), and received UV-B irradiation (40 kJ/m(2)) 1 week later. Four weeks afterwards, splenic CD4(+) T cells were purified from the UV-irradiated immunized mice, and were transferred into naïve mice (H-2(b)). Allografts expressing the same alloantigen as T-cell donors were immunized against (H-2(b/d)) or an irrelevant alloantigen (H-2(b/k)) were transplanted to CD4(+) T-cell-transferred mice, and an alloantigen-specific prolongation of allograft survival observed. Experiments where IL-10 was neutralized by monoclonal antibody in the induction or effector phase revealed that IL-10 is critical, not only for induction but also for immunosuppressive function of CD4(+) Tregs induced by UV irradiation after alloantigen immunization. Third-party allografts (H-2(d/k)) were transplanted to CD4(+) T-cell-transferred mice, and graft survival was also prolonged. Even a graft only partially compatible with immunized alloantigen worked well in vivo to activate CD4(+) Tregs induced by UV irradiation after alloantigen immunization, which resulted in the bystander suppression of third-party allograft rejection. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Pembrolizumab for metastatic melanoma in a renal allograft recipient with subsequent graft rejection and treatment response failure: a case report.

    Science.gov (United States)

    Kwatra, Vineet; Karanth, Narayan V; Priyadarshana, Kelum; Charakidis, Michail

    2017-03-19

    Transplant patients were excluded from the pivotal phase III trials of checkpoint inhibitors in metastatic melanoma. The efficacy and toxicity profiles of checkpoint inhibitors in this cohort of patients are not well described. To the best of our knowledge, this is the first case report of a renal transplant patient with stage IV melanoma treated with a programmed cell death protein 1 checkpoint inhibitor that led to both treatment failure and renal graft rejection. We present a case of a 58-year-old white man with a long-standing cadaveric renal transplant who was diagnosed with a B-Raf Proto-Oncogene, Serine/Threonine Kinase wild-type metastatic melanoma. He was treated with first-line pembrolizumab but experienced subsequent graft failure and rapid disease progression. This case highlights the risks associated with the administration of checkpoint inhibitors in patients with a renal transplant and on immunosuppressive therapy. More specifically, it adds to the literature indicating that, compared with the cytotoxic T-lymphocyte-associated protein 4 inhibitor ipilimumab, anti-programmed cell death protein 1 agents are more likely to lead to renal graft failure. Additionally, these novel immunotherapeutics may be ineffective in transplant patients; therefore, clinicians should be very aware of those risks and carefully consider selection of agents and full disclosure of the risks to their patients.

  2. Acute lung allograft rejection: diagnostic role of probe-based confocal laser endomicroscopy of the respiratory tract.

    Science.gov (United States)

    Yserbyt, Jonas; Dooms, Christophe; Decramer, Marc; Verleden, Geert M

    2014-05-01

    Acute cellular rejection (AR) after lung transplantation may result in significant morbidity and mortality both on the short and long term. Transbronchial biopsy through flexible bronchoscopy is highly sensitive for the diagnosis of AR, but reproducibility of histopathologic interpretation is less convincing. Probe-based confocal laser endomicroscopy (pCLE), a novel imaging tool in the field of respiratory medicine, enables real-time imaging of the pulmonary acini. We performed 105 bronchoscopies in lung transplant recipients, combining both transbronchial biopsies and pCLE. We conducted an observational survey for pCLE findings in AR. Calculations for cellularity showed a median cell count (ACA) of 50 (IQR 18 to 120) cells per microscopic field for AR and 10 (IQR 0 to 15) cells per microscopic field for matched controls (p = 0.0004). Cellular autofluorescence in the AR group was 1,163 (± 157) units and 489 (± 101) units for the matched controls (p = 0.0009). Autofluorescent cells were present in 73% (± 10) of the recorded frames in the AR group and in only 42% (± 9) of the recorded frames in the control group (p = 0.03). Contingency analysis for the presence/absence of ACA in the AR group versus the control group showed a sensitivity of 0.93 and a specificity of 0.46 (relative risk = 6.5 [95% CI 0.94 to 44.8], p = 0.01). The consecutive application of 3 pCLE criteria resulted in a sensitivity of 0.93 and a specificity of 0.83 for detection of AR. Our observational survey suggests the existence of specific pCLE characteristics in patients with AR. Further efforts are necessary to validate these findings prospectively. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  3. Meniscal Allograft Transplantation Does Not Prevent or Delay Progression of Knee Osteoarthritis.

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    Catherine Van Der Straeten

    Full Text Available Meniscal tears are common knee injuries. Meniscal allograft transplantation (MAT has been advocated to alleviate symptoms and delay osteoarthritis (OA after meniscectomy. We investigated (1 the long-term outcome of MAT as a treatment of symptomatic meniscectomy, (2 most important factors affecting survivorship and (3 OA progression.From 1989 till 2013, 329 MAT were performed in 313 patients. Clinical and radiographic results and MAT survival were evaluated retrospectively. Failure was defined as conversion to knee arthroplasty (KA or total removal of the MAT.Mean age at surgery was 33 years (15-57; 60% were males. No-to-mild cartilage damage was found in 156 cases, moderate-to-severe damage in 130. Simultaneous procedures in 118 patients included cartilage procedures, osteotomy or ACL-reconstruction. At a mean follow-up of 6.8 years (0.2-24.3years, 5 patients were deceased and 48 lost (14.6%, 186 MAT were in situ (56.5% whilst 90 (27.4% had been removed, including 63 converted to a KA (19.2%. Cumulative allograft survivorship was 15.1% (95% CI:13.9-16.3 at 24.0 years. In patients <35 years at surgery, survival was significantly better (24.1% compared to ≥35 years (8.0% (p = 0.017. In knees with no-to-mild cartilage damage more allografts survived (43.0% compared to moderate-to-severe damage (6.6% (p = 0.003. Simultaneous osteotomy significantly deteriorated survival (0% at 24.0 years (p = 0.010. 61% of patients underwent at least one additional surgery (1-11 for clinical symptoms after MAT. Consecutive radiographs showed significant OA progression at a mean of 3.8 years (p<0.0001. Incremental Kellgren-Lawrence grade was +1,1 grade per 1000 days (2,7yrs.MAT did not delay or prevent tibiofemoral OA progression. 19.2% were converted to a knee prosthesis at a mean of 10.3 years. Patients younger than 35 with no-to-mild cartilage damage may benefit from MAT for relief of symptoms (survivorship 51.9% at 20.2 years, but patients and healthcare payers

  4. Both absolute and relative quantification of urinary mRNA are useful for non-invasive diagnosis of acute kidney allograft rejection.

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    Jung-Woo Seo

    Full Text Available Urinary mRNA analysis with three-gene set (18S rRNA, CD3ε, and IP-10 has been suggested as a non-invasive biomarker of acute rejection (AR in kidney transplant recipients using quantitative real-time PCR (qPCR. Application of droplet digital PCR (ddPCR, which has been suggested to provide higher sensitivity, accuracy, and absolute quantification without standard curves, could be a useful method for the quantifying low concentration of urinary mRNA. We investigated the urinary expression of these three genes in Korean patients with kidney transplantation and also evaluated the usefulness of ddPCR. 90 urine samples were collected at time of allograft biopsy in kidney recipients (n = 67 and from patients with stable renal function more than 10 years (n = 23. Absolute quantification with both PCR system showed significant higher mRNA levels of CD3ε and IP-10 in AR patients compared with stable transplants (STA, but there was no difference in 18S rRNA expression across the patient groups. To evaluate discrimination between AR and STA, ROC curve analyses of CTOT-4 formula yielded area under the curve values of 0.72 (95% CI 0.60-0.83 and 0.77 (95% CI 0.66-0.88 for qPCR and ddPCR, respectively. However, 18S normalization of absolute quantification and relative quantification with 18S showed better discrimination of AR from STA than those of the absolute method. Our data indicate that ddPCR system without standard curve would be useful to determine the absolute quantification of urinary mRNA from kidney transplant recipients. However, comparative method also could be useful and convenient in both qPCR and ddPCR analysis.

  5. A shift in the collagen V antigenic epitope leads to T helper phenotype switch and immune response to self-antigen leading to chronic lung allograft rejection.

    Science.gov (United States)

    Tiriveedhi, V; Angaswamy, N; Brand, D; Weber, J; Gelman, A G; Hachem, R; Trulock, E P; Meyers, B; Patterson, G; Mohanakumar, T

    2012-01-01

    Immune responses to human leucocyte antigen (HLA) and self-antigen collagen V (Col-V) have been proposed in the pathogenesis of chronic rejection (bronchiolitis obliterans syndrome, BOS) following human lung transplantation (LTx). In this study, we defined the role for the shift in immunodominant epitopes of Col-V in inducing T helper phenotype switch leading to immunity to Col-V and BOS. Sera and lavage from BOS(+) LTx recipients with antibodies to Col-V were analysed. Two years prior to BOS, patients developed antibodies to both Col-V,α1(V) and α2(V) chains. However, at clinical diagnosis of BOS, antibodies became restricted to α1(V). Further, lung biopsy from BOS(+) patients bound to antibodies to α1(V), indicating that these epitopes are exposed. Fourteen Col-V peptides [pep1-14, pep1-4 specific to α1(V), pep5-8 to α1,2(V) and pep9-14 to α2(V)] which bind to HLA-DR4 and -DR7, demonstrated that prior to BOS, pep 6, 7, 9, 11 and 14 were immunodominant and induced interleukin (IL)-10. However, at BOS, the response switched to pep1, 4 and 5 and induced interferon (IFN)-γ and IL-17 responses, but not IL-10. The T helper (Th) phenotype switch is accompanied by decreased frequency of regulatory T cells (T(regs) ) in the lavage. LTx recipients with antibodies to α1(V) also demonstrated increased matrix metalloproteinase (MMP) activation with decreased MMP inhibitor, tissue inhibitor of metalloproteinase (TIMP), suggesting that MMP activation may play a role in the exposure of new Col-V antigenic epitopes. We conclude that a shift in immunodominance of self-antigenic determinants of Col-V results in induction of IFN-γ and IL-17 with loss of tolerance leading to autoimmunity to Col-V, which leads to chronic lung allograft rejection. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

  6. Recombinant human C1-inhibitor prevents acute antibody-mediated rejection in alloimmunized baboons.

    Science.gov (United States)

    Tillou, Xavier; Poirier, Nicolas; Le Bas-Bernardet, Stéphanie; Hervouet, Jeremy; Minault, David; Renaudin, Karine; Vistoli, Fabio; Karam, Georges; Daha, Mohamed; Soulillou, Jean Paul; Blancho, Gilles

    2010-07-01

    Acute antibody-mediated rejection is an unsolved issue in transplantation, especially in the context of pretransplant immunization. The deleterious effect of preformed cytotoxic anti-HLA antibodies through complement activation is well proven, but very little is known concerning complement blockade to prevent/cure this rejection. Here, we used a baboon model of preimmunization to explore the prevention of acute antibody-mediated rejection by an early inhibition of the classical complement pathway using human recombinant C1-inhibitor. Baboons were immunized against peripheral blood mononuclear cells from allogeneic donors and, once a specific and stable immunization had been established, they received a kidney from the same donor. Rejection occurred at day 2 posttransplant in untreated presensitized recipients, with characteristic histological lesions and complement deposition. As recombinant human C1-inhibitor blocks in vitro cytotoxicity induced by donor-specific antibodies, other alloimmunized baboons received the drug thrice daily intravenously during the first 5 days after transplant. Rejection was prevented during this treatment but occurred after discontinuation of treatment. We show here that early blockade of complement activation by recombinant human C1-inhibitor can prevent acute antibody-mediated rejection in presensitized recipients. This treatment could also be useful in other forms of acute antibody-mediated rejection caused by induced antibodies.

  7. Rejeição de transplantes de córnea: tratamento tópico vs. pulsoterapia - resultados de 10 anos Corneal allograft rejection: topical treatment vs. pulsed intravenous methylprednisolone - ten years' result

    Directory of Open Access Journals (Sweden)

    Dácio Carvalho Costa

    2008-02-01

    Full Text Available OBJETIVOS: Avaliar a eficácia da associação de pulsoterapia com 500 mg de metilprednisolona intravenosa ao acetato de prednisolona 1% tópico no tratamento do primeiro episódio de rejeição endotelial de transplantes de córnea. MÉTODOS: Estudo caso-controle retrospectivo com 81 sujeitos que apresentaram o primeiro episódio de rejeição endotelial e submetidos à terapia nos primeiros quinze dias dos sintomas. RESULTADOS: 67 sujeitos foram tratados com acetato de prednisolona 1% tópico de 1 em 1 hora e pulsoterapia com 500 mg de metilprednisolona intravenosa no dia do diagnóstico e 14 sujeitos foram submetidos apenas ao tratamento com acetato de prednisolona 1% tópico formando o grupo controle. Dos 67 sujeitos submetidos a corticoterapia venosa e tópica, 41 (61,19% evoluíram satisfatoriamente e 26 (38,8% apresentaram falência endotelial. Dos 14 sujeitos submetidos apenas à corticoterapia tópica, 4 (28,57% evoluíram com enxerto transparente e os 10 restantes (71,43% com falência endotelial. O teste do qui-quadrado apontou maior taxa de sucesso (pPURPOSE: To evaluate the efficacy of intravenous 500 mg methylprednisolone in addition to topical treatment with 1% prednisolone in the treatment of the first episode of corneal endothelial rejection in patients that were submitted to corneal allograft transplantation. METHODS: Retrospective case-control study with 81 patients that presented the first episode of corneal endothelial rejection and were treated within the first 15 days of the onset of symptoms. RESULTS: 67 patients were treated with 1% topical prednisolone acetate and pulsed intravenous methylprednisolone 500 mg at the diagnosis of corneal allograft rejection. Fourteen patients were submitted to topical treatment only, thus forming the control group. Forty-one of 67 patients (61.2% that were submitted to pulsed steroid had good outcome and 26 (38.8% presented corneal graft failure while only 4 of 14 patients (28.57% that

  8. 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.

  9. Use of donor serum to prevent passive transfer of hyperacute rejection

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    Wang, Jue; Geissler, Edward K.; Fechner, John H.; Burlingham, William J.; Knechtle, Stuart J.

    1994-01-01

    Organ transplantation in presensitized recipients continues to be contraindicated for heart and kidney recipients due to the risk of hyperacute rejection, which has no known treatment at this time. We tested whether donor serum, which contains soluble MHC class I antigen, is able to neutralize the effect of anti-donor antibody in the recipient and prevent hyperacute or accelerated rejection. A rat model of passive immunization was used to test the role of anti-donor antibody in hyperacute rej...

  10. J. Maxwell Chamberlain Memorial Paper. Early fundoplication prevents chronic allograft dysfunction in patients with gastroesophageal reflux disease.

    Science.gov (United States)

    Cantu, Edward; Appel, James Z; Hartwig, Matthew G; Woreta, Hiwot; Green, Cindy; Messier, Robert; Palmer, Scott M; Davis, R Duane

    2004-10-01

    Chronic allograft dysfunction limits the long-term success of lung transplantation. Increasing evidence suggests nonimmune mediated injury such as due to reflux contributes to the development of bronchiolitis obliterans syndrome. We have previously demonstrated that fundoplication can reverse bronchiolitis obliterans syndrome in some lung transplant recipients with reflux. We hypothesized that treatment of reflux with early fundoplication would prevent bronchiolitis obliterans syndrome and improve survival. A retrospective analysis of 457 patients who underwent lung transplantation from April 1992 through July 2003 was conducted. Patients were stratified into four groups: no history of reflux, history of reflux, history of reflux and early (syndrome at 1 and 3 years (100%, 100%) when compared with no fundoplication in patients with reflux (96% +/- 2.5, 60% +/- 7.5; p syndrome and survival. Further research into the mechanisms and treatment of nonalloimmune mediated lung allograft injury is needed to reduce rates of chronic lung failure.

  11. Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T cells and down-regulates cardiac allograft rejection

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, De-Hua [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China); Dou, Li-Ping [Department of Hematology, Chinese PLA General Hospital, No. 28 Fu-Xing Road, Beijing 100853 (China); Wei, Yu-Xiang; Du, Guo-Sheng; Zou, Yi-Ping; Song, Ji-Yong; Zhu, Zhi-Dong; Cai, Ming; Qian, Ye-Yong [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China); Shi, Bing-Yi, E-mail: shibingyi@medmail.com.cn [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China)

    2010-05-14

    Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation of recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-{gamma} by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naive T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4{sup +}CD25{sup high}Foxp3{sup +} regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.

  12. Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4+CD25+Foxp3+ regulatory T cells and down-regulates cardiac allograft rejection

    International Nuclear Information System (INIS)

    Zheng, De-Hua; Dou, Li-Ping; Wei, Yu-Xiang; Du, Guo-Sheng; Zou, Yi-Ping; Song, Ji-Yong; Zhu, Zhi-Dong; Cai, Ming; Qian, Ye-Yong; Shi, Bing-Yi

    2010-01-01

    Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation of recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-γ by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naive T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4 + CD25 high Foxp3 + regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.

  13. Preventing Rejection

    Science.gov (United States)

    ... to know FAQ Living donation What is living donation? Organs Types Being a living donor First steps Being ... brochures What Every Patient Needs to Know Living Donation Multiple Listing Visit UNOS Store Learn more How organs are matched How to become a living donor ...

  14. Efficacy of prophylactic irradiation in altering renal allograft survival

    International Nuclear Information System (INIS)

    Faber, R.; Johnson, H.K.; Braren, H.V.; Richie, R.E.

    1974-01-01

    Renal allograft rejection is a complex phenomenon involving both cell-mediated and humoral antibody responses. Most transplant programs have used a combination of therapeutic modalites to combat the immune system in an attempt to prolong both allograft and patient survival. Corticosteroids (methylprednisolone (Solu-Medrol) and prednisone and azathioprine (Imuran) are widely accepted as immunosuppressive drugs; however, both are non-specific and have the disadvantage of compromising the recipients' defense mechanisms. Nevertheless, these drugs have proved to be essential to the success of renal transplantation and they are routinely used while the efficacy of other modalities continues to be evaluated. We could find no reports of a prospective study to evaluate the efficacy of prophylactic irradiation in the complex therapeutic situation of renal transplantation with the only variable being the administration of local graft irradiation. The purpose of this study was to evaluate prophylactic graft irradiation for its effectiveness in preventing graft rejection in conjunction with Imuran and corticosteroids

  15. 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.

  16. A web-based pilot study of inter-pathologist reproducibility using the ISHLT 2004 working formulation for biopsy diagnosis of cardiac allograft rejection: the European experience

    DEFF Research Database (Denmark)

    Angelini, Annalisa; Andersen, Claus Boegelund; Bartoloni, Giovanni

    2011-01-01

    The aim of this study was to assess, at the European level and using digital technology, the inter-pathologist reproducibility of the ISHLT 2004 system and to compare it with the 1990 system We also assessed the reproducibility of the morphologic criteria for diagnosis of antibody-mediated reject...

  17. Elevated mRNA levels of CTLA-4, FoxP3, and granzyme B in BAL, but not in blood, during acute rejection of lung allografts

    DEFF Research Database (Denmark)

    Madsen, Caroline B; Nørgaard, Astrid; Iversen, Martin

    2010-01-01

    expression and acute rejection is still being debated. Some studies have been performed on blood samples from lung-transplanted patients, while others have investigated the local immune response in the lungs by analysing broncho-alveolar-lavage (BAL) fluids or biopsies. Biopsies are considered the gold...

  18. Comparison of renal allograft (AG) biopsy diagnosis and temporal quantitation of Tc-99m sulfur colloid (SC) in clinically suspected AG rejection

    International Nuclear Information System (INIS)

    George, E.A.; Brown, W.N.; Carney, K.; Naidu, R.G.; Palmer, D.C.

    1984-01-01

    The purpose of this study was to evaluate the diagnostic efficacy of temporal quantitation of SC compared to tissue diagnosis of AG needle biopsy (Bx). The principal clinical criteria for patient selection were sequential or persistent reduction (at least 40-50%) of AG function as determined by serial serum creatinine levels. Thirty-four AG recipients were examined with SC and subsequent AG Bx in 37 instances. %SC AG accumulation and bone marrow extraction were interpreted in view of the significant sequential of persistent reduction of Ag function. Each AG Bx was collected from multiple needle aspirates and processed for light microscopy and immunoflorescent staining. Bx and SC exam were evaluated for acute rejection (AR), chronic rejection (CR) or other, non-rejection pathology. Acute tissue changes superimposed on chronic were regarded as AR. Acute tissue changes and % SC AG accumulation in the rejection range were graded as mild, moderate and marked. In AR there was 28/28 agreement of Bx and SC diagnosis; of which 7/28 were superimposed on CR. In Cr Bx and SC agreed in 3/7 instances, in 3/7 SC Dx was AR and in 1/7 SC exam was normal. Sensitivity and specificity of the SC diagnosis in this series was 100% and 63% for AR, 43% and 100% for CR and 97% and 100% in all instances of rejection. Bx and SC grading of AR agreed in 64%. In conclusion, temporal quantitation of SC demonstrated overall good correlation with AG Bx diagnosis in this series. The poor sensitivity of 43% of SC in Cr and only 64% correlation in grading AR may be due to inherent Bx sampling and SC data analysis error

  19. Clinical Value of Left Ventricular Wall Motion Assessment with Pulsed-Wave Tissue Doppler Echocardiography for Rejection Monitoring and Allograft Coronary Artery Disease Surveillance After Heart Transplantation

    OpenAIRE

    Dandel, Michael

    2010-01-01

    The usefulness of pulsed-wave tissue Doppler imaging (PW-TDI) for detection of ventricular dysfunction linked to acute rejection (AR) and transplant coronary disease (TxCAD) in order to optimize invasive examination timing was assessed over several years in a large number of heart transplant recipients. The results validate wall motion assessment by PW-TDI as being particularly suited for the early detection of LV functional alterations linked to AR and TxCAD and commend this simple echocardi...

  20. The role of mTOR inhibitors in the prevention of organ rejection in adult liver transplant patients: a focus on everolimus

    Directory of Open Access Journals (Sweden)

    Casanovas T

    2014-06-01

    Full Text Available Teresa Casanovas Liver Transplant Unit, Bellvitge University Hospital, Barcelona, Spain Abstract: Liver transplantation remains the therapy of choice for patients with end-stage liver disease and in selected cases of hepatocellular carcinoma. While short-term allograft survival has improved significantly in recent years, there has been little improvement in long-term survival after liver transplantation. A growing body of evidence on factors influencing the long-term outcomes and the safety profiles of existing immunosuppressive agents after liver transplant points to a need to continue searching for alternative strategies. The calcineurin inhibitors (CNIs (cyclosporine and tacrolimus currently represent the backbone of most immunosuppressor regimens. They have had a revolutionary effect on the overall success of transplantation, as is reflected in greatly reduced rates of acute rejection. However, the CNIs have significant toxicities that produce renal dysfunction, cardiovascular disease, and other unwanted effects, such as malignancies. The recognition of these risk factors has sparked interest in regimens that limit exposure to CNIs. Nowadays, the use of immunosuppressive drugs with different mechanisms of action, which allow for a reduction or avoidance of CNIs, is common. Everolimus, which belongs to the mammalian target-of-rapamycin inhibitor family and is best known for its use in kidney and heart transplantation, has recently been approved for liver transplantation. This overview discusses the emerging evidence on the role of everolimus in the prevention of rejection after liver transplantation, in de novo transplants, conversion regimens, or as a rescue therapy. In addition, some of the most relevant and current clinical problems related to everolimus in this field are discussed. Keywords: everolimus, mTOR inhibitors, tacrolimus, liver transplant, cyclosporine, renal impairment

  1. 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

  2. Bioengineering Thymus Organoids to Restore Thymic Function and Induce Donor-Specific Immune Tolerance to Allografts

    Science.gov (United States)

    Fan, Yong; Tajima, Asako; Goh, Saik Kia; Geng, Xuehui; Gualtierotti, Giulio; Grupillo, Maria; Coppola, Antonina; Bertera, Suzanne; Rudert, William A; Banerjee, Ipsita; Bottino, Rita; Trucco, Massimo

    2015-01-01

    One of the major obstacles in organ transplantation is to establish immune tolerance of allografts. Although immunosuppressive drugs can prevent graft rejection to a certain degree, their efficacies are limited, transient, and associated with severe side effects. Induction of thymic central tolerance to allografts remains challenging, largely because of the difficulty of maintaining donor thymic epithelial cells in vitro to allow successful bioengineering. Here, the authors show that three-dimensional scaffolds generated from decellularized mouse thymus can support thymic epithelial cell survival in culture and maintain their unique molecular properties. When transplanted into athymic nude mice, the bioengineered thymus organoids effectively promoted homing of lymphocyte progenitors and supported thymopoiesis. Nude mice transplanted with thymus organoids promptly rejected skin allografts and were able to mount antigen-specific humoral responses against ovalbumin on immunization. Notably, tolerance to skin allografts was achieved by transplanting thymus organoids constructed with either thymic epithelial cells coexpressing both syngeneic and allogenic major histocompatibility complexes, or mixtures of donor and recipient thymic epithelial cells. Our results demonstrate the technical feasibility of restoring thymic function with bioengineered thymus organoids and highlight the clinical implications of this thymus reconstruction technique in organ transplantation and regenerative medicine. PMID:25903472

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

    Science.gov (United States)

    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.

  4. Pretransplant interferon prevents hepatitis C virus-associated glomerulonephritis in renal allografts by HCV-RNA clearance.

    Science.gov (United States)

    Cruzado, Josep M; Casanovas-Taltavull, Teresa; Torras, Joan; Baliellas, Carme; Gil-Vernet, Salvador; Grinyó, Josep M

    2003-03-01

    The purpose of this study was to examine the effect of pretransplant interferon administration on the occurrence of post-transplant de novo glomerulonephritis in hepatitis C virus (HCV)-positive renal allografts. From December 1992 to December 2000, 78 HCV-positive patients received a renal allograft in our unit. Fifteen out of 78 received pretransplant interferon for 1 year. Hepatitis C virus was investigated by serology and qualitative polymerase chain reaction (PCR). Hepatitis C virus-related de novo glomerulonephritis (membranoproliferative or membranous) was suggested by proteinuria (>1.5 g/24 h) and/or microhematuria and always diagnosed by renal biopsy. Of 15 HCV-positive recipients who received pretransplant interferon, 10 (67%) became HCV-RNA negative at the time of transplantation and only one out of the 15 (6.7%) developed de novo glomerulonephritis (this patient was HCV-RNA positive at transplantation). Among non-interferon-treated allograft recipients, 28.7% had negative HCV-RNA and 12 out of 63 (19%) developed de novo glomerulonephritis (9, membranoproliferative; 3 membranous), all 12 having positive HCV-RNA at transplantation (p < 0.0001). In conclusion, pretransplant interferon may reduce the occurrence of post-transplant HCV-related de novo glomerulonephritis. Our results suggest that the indication for pretransplant interferon should be extended to treat all HCV-RNA positive candidates for renal transplantation.

  5. Recombinant human C1-inhibitor prevents acute antibody-mediated rejection in alloimmunized baboons

    NARCIS (Netherlands)

    Tillou, Xavier; Poirier, Nicolas; Le Bas-Bernardet, Stephanie; Hervouet, Jeremy; Minault, David; Renaudin, Karine; Vistoli, Fabio; Karam, Georges; Daha, Mohamed; Soulillou, Jean Paul; Blancho, Gilles

    Acute antibody-mediated rejection is an unsolved issue in transplantation, especially in the context of pretransplant immunization. The deleterious effect of preformed cytotoxic anti-HLA antibodies through complement activation is well proven, but very little is known concerning complement blockade

  6. The number of regulatory T cells in transbronchial lung allograft biopsies is related to FoxP3 mRNA levels in bronchoalveolar lavage fluid and to the degree of acute cellular rejection

    DEFF Research Database (Denmark)

    Krustrup, Dorrit; Madsen, Caroline B; Iversen, Martin

    2013-01-01

    The transcription factor Forkhead Box P3 (FoxP3) is a marker of regulatory T cells (Tregs) - a subset of T cells known to suppress a wide range of immune responses. These cells are considered to be pivotal for the induction of tolerance to donor antigens in human allografts. We aimed to correlate...

  7. Mechanisms and Mediators of Inflammation: Potential Models for Skin Rejection and Targeted Therapy in Vascularized Composite Allotransplantation

    Directory of Open Access Journals (Sweden)

    Theresa Hautz

    2012-01-01

    Full Text Available Vascularized composite allotransplantation (VCA is an effective treatment option for patients suffering from limb loss or severe disfigurement. However, postoperative courses of VCA recipients have been complicated by skin rejection, and long-term immunosuppression remains a necessity for allograft survival. To widen the scope of this quality-of-life improving procedure minimization of immunosuppression in order to limit risks and side effects is needed. In some aspects, the molecular mechanisms and dynamics of skin allograft rejection seem similar to inflammatory skin conditions. T cells are key players in skin rejection and are recruited to the skin via activation of adhesion molecules, cytokines, and chemokines. Blocking these molecules has not only shown success in the treatment of inflammatory dermatoses, but also prolonged graft survival in various models of solid organ transplantation. In addition to T cell recruitment, ectopic lymphoid structures within the allograft associated with chronic rejection in solid organ transplantation might contribute to the strong alloimmune response towards the skin. Selectively targeting the molecules involved offers exciting novel therapeutic options in the prevention and treatment of skin rejection after VCA.

  8. Next-generation calcineurin inhibitors in development for the prevention of organ rejection

    Directory of Open Access Journals (Sweden)

    Gheith O

    2014-03-01

    Full Text Available Osama Gheith, Torki Al-Otaibi, Hany MansourDepartment of Nephrology, Hamed Al-Essa Organ Transplant Center, Ibn Sina Hospital, Shuwaikh, KuwaitAbstract: Calcineurin inhibitors (CNIs remain the cornerstone of immunosuppression after renal transplantation despite their adverse effects. Some CNIs have well known negative impacts on the cardiovascular system, including hypertension, hyperlipidemia, new onset diabetes after transplantation (NODAT, neurotoxicity, hypertrichosis, and nephrotoxicity. Many clinical trials dealing with CNI avoidance or elimination were associated with higher risk of rejection of the transplanted organ. New generation CNIs are concerned with modifying CNI molecules so that they become more potent and are suitable for patients with suboptimal adherence with less adverse effects. In this review, we address these issues.Keywords: calcineurin inhibitors, organ transplant, rejection

  9. Mesenchymal stem cells avoid allogeneic rejection

    Directory of Open Access Journals (Sweden)

    Murphy J Mary

    2005-07-01

    Full Text Available Abstract Adult bone marrow derived mesenchymal stem cells offer the potential to open a new frontier in medicine. Regenerative medicine aims to replace effete cells in a broad range of conditions associated with damaged cartilage, bone, muscle, tendon and ligament. However the normal process of immune rejection of mismatched allogeneic tissue would appear to prevent the realisation of such ambitions. In fact mesenchymal stem cells avoid allogeneic rejection in humans and in animal models. These finding are supported by in vitro co-culture studies. Three broad mechanisms contribute to this effect. Firstly, mesenchymal stem cells are hypoimmunogenic, often lacking MHC-II and costimulatory molecule expression. Secondly, these stem cells prevent T cell responses indirectly through modulation of dendritic cells and directly by disrupting NK as well as CD8+ and CD4+ T cell function. Thirdly, mesenchymal stem cells induce a suppressive local microenvironment through the production of prostaglandins and interleukin-10 as well as by the expression of indoleamine 2,3,-dioxygenase, which depletes the local milieu of tryptophan. Comparison is made to maternal tolerance of the fetal allograft, and contrasted with the immune evasion mechanisms of tumor cells. Mesenchymal stem cells are a highly regulated self-renewing population of cells with potent mechanisms to avoid allogeneic rejection.

  10. The significance of parenchymal changes of acute cellular rejection in predicting chronic liver graft rejection

    NARCIS (Netherlands)

    Gouw, ASH; van den Heuvel, MC; van den Berg, AP; Slooff, NJH; de Jong, KP; Poppema, S

    2002-01-01

    Background. Chronic rejection (CR) in liver allografts shows a rapid onset and progressive course, leading to graft failure within the first year after transplantation. Most cases are preceded by episodes of acute cellular rejection (AR), but histological features predictive for the transition

  11. 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. 

  12. Quantifying the decisional satisfaction to accept or reject the Human Papillomavirus (HPV vaccine: a preference for cervical cancer prevention.

    Directory of Open Access Journals (Sweden)

    Diane M Harper

    Full Text Available OBJECTIVE: Only a portion of the US population is willing to consider HPV vaccination to date. The primary aim of this study is to determine the decisional satisfaction associated with HPV vaccination. STUDY DESIGN: This is a prospective survey conducted at an urban college where women 18-26 years old completed a decisional satisfaction survey about their HPV vaccine experience. RESULTS: Regardless of the decision to accept or reject HPV vaccination, the decisional satisfaction was very high (mean 5-item score = 21.2 (SD 3.8. Women without HPV vaccination were decisionally neutral significantly more often than those already vaccinated; 22% were decisionally neutral for the option to accept HPV vaccination at that visit. Cervical cancer prevention was preferred significantly more often than genital wart prevention in all analyses. CONCLUSIONS: Targeting those who are decisionally neutral about HPV vaccination may result in a higher uptake of HPV vaccination.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  15. LATE RENAL GRAFT REJECTION: PATHOLOGY AND PROGNOSIS

    Directory of Open Access Journals (Sweden)

    E.S. Stolyarevich

    2014-01-01

    Full Text Available Rejection has always been one of the most important cause of late renal graft dysfunction. Aim of the study was to analyze the prevalence of different clinico-pathological variants of rejection that cause late graft dysfunction, and evaluate their impact on long-term outcome. Materials and methods. This is a retrospective study that analyzed 294 needle core biopsy specimens from 265 renal transplant recipients with late (48,8 ± 46,1 months after transplantation allograft dysfunction caused by late acute rejection (LAR, n = 193 or chronic rejection (CR, n = 78 or both (n = 23. C4d staining was performed by immunofl uorescence (IF on frozen sections using a standard protocol. Results. Peritubular capillary C4d deposition was identifi ed in 36% samples with acute rejection and in 62% cases of chronic rejection (including 67% cases of transplant glomerulopathy, and 50% – of isolated chronic vasculopathy. 5-year graft survival for LAR vs CR vs their combination was 47, 13 and 25%, respectively. The outcome of C4d– LAR was (p < 0,01 better than of C4d+ acute rejection: at 60 months graft survival for diffuse C4d+ vs C4d− was 33% vs 53%, respectively. In cases of chronic rejection C4d+ vs C4d– it was not statistically signifi cant (34% vs 36%. Conclusion. In long-term allograft biopsy C4d positivity is more haracteristic for chronic rejection than for acute rejection. Only diffuse C4d staining affects the outcome. C4d– positivity is associated with worse allograft survival in cases of late acute rejection, but not in cases of chronic rejection

  16. HLA-DR overexpression in tubules of renal allografts during early and late renal allograft injuries.

    Science.gov (United States)

    Wen, Jiqiu; Zhang, Mingchao; Chen, Jinsong; Zeng, Caihong; Cheng, Dongrui; Liu, Zhi-Hong

    2013-12-01

    We sought to discover which types of injuries were related to human leukocyte antigen DR expression in acute rejection and late chronic injury in renal allografts. Ninety-two recipients were separated into the early acute rejection group, the late monocyte infiltration group, and the late chronic injury group. Ten subjects with acute cellular rejection received a repeat biopsy. All samples were stained with CD4, CD8, CD20, CD68, and human leukocyte antigen DR by immunochemical staining. Levels of these markers were compared among the subgroups of each group. Human leukocyte antigen DR expression was greater in the early C4d-negative acute rejection group than it was in the early C4d-positive acute rejection group. Human leukocyte antigen DR expression was greater during acute rejection than that was on a repeat biopsy. Human leukocyte antigen DR expression was accord with the infiltration of monocyte infiltration in the acute cellular rejection group. Human leukocyte antigen DR expression was greater during late acute rejection than it was in BK virus nephropathy, which was not in accord with monocyte infiltration. Human leukocyte antigen DR expression was greater during chronic rejection than it was in IgAN, BK virus nephropathy, and TA/IF groups, and even in tubular atrophy. Human leukocyte antigen DR expression in renal tubular cells was associated with early acute cellular rejection and was in accord with monocyte infiltration. Human leukocyte antigen DR expression in renal tubular cells during the late phase (especially in tubular atrophy) was a marker of chronic rejection, but was not in accord with monocyte infiltration in renal allografts.

  17. Glutathione depletion in epithelial lining fluid of lung allograft patients.

    Science.gov (United States)

    Baz, M A; Tapson, V F; Roggli, V L; Van Trigt, P; Piantadosi, C A

    1996-02-01

    The lower respiratory tract is protected against reactive oxygen species (ROS) by a complex antioxidant system. In the epithelial lining fluid (ELF), glutathione (L-alpha-glutamyl-L-cysteinylglycine, GSH) is essential for adequate protection of pneumocytes from potential toxicity mediated by extracellular hydrogen peroxide (H2O2). We assessed the concentration of total GSH in bronchoalveolar lavage fluid (BALF) in lung allograft patients in the absence and presence of acute rejection. Bronchoalveolar lavage (BAL) and biopsies were performed concurrently on 36 occasions in 17 patients who had undergone lung transplantation. BALF samples were divided into two groups on the basis of presence or absence of acute lung rejection on transbronchial biopsy. Seven BALF samples were obtained from control subjects for comparison. The BALF data demonstrated significantly lymphocyte recruitment and evidence of lung injury during acute rejection episodes. Transplant allografts without rejection showed significant depletion of total GSH in the ELF as compared with that of normal volunteers (94.0 +/- 9.7 microM versus 302.6 +/- 40.8 microM, p < 0.01). Transplant allografts with acute rejection had a slightly higher GSH concentration in their ELF (179.8 +/- 34.7), but this was still lower than control values. The deficiency of total GSH in the alveolar fluid may predispose lung allografts to extracellular H2O2-mediated toxicity.

  18. Development crisis of rejection transplant on a background of leucopenia

    Directory of Open Access Journals (Sweden)

    A. A. Korzenewsky

    2014-01-01

    Full Text Available The patient in the remote period after cadaveric kidney allotransplantation developed leukopenia, which required a dose reduction of immunosuppressive drugs. The transplant rejection crisis developed against this background. Thus, the presence of leukopenia in a patient after cadaveric kidney allograft transplantation requires detecting early signs ofnot only infectious complications, but also a crisis of rejection.

  19. Prolongation of segmental and pancreaticoduodenal allografts in the primate with total-lymphoid irradiation and cyclosporine

    Energy Technology Data Exchange (ETDEWEB)

    Du Toit, D.F.; Heydenrych, J.J.; Smit, B.; Louw, G.; Zuurmond, T.; Els, D.; Du Toit, L.B.; Weideman, A.; Davids, H.; van der Merwe, E.

    1987-09-01

    The prolongation of segmental and pancreaticoduodenal allografts (PDA) by total lymphoid irradiation (TLI) and in combination with cyclosporine (CsA) was assessed in a well established total pancreatectomy, diabetic, primate transplantation model. Pancreatic transplantation was performed in 119 pancreatectomized baboons (Papio ursinus). Of a total of 109 allografts performed, 71 were segmental allografts (open duct drainage) and 38 PDA. Of 119 graft recipients, 10 received segmental pancreatic autografts. TLI and CsA administered separately to segmental allograft recipients resulted in modest allograft survival and indefinite graft survival was not observed. 8 of 17 (47%) segmental allograft recipients that received TLI and CsA had graft survival beyond 100 days, indicating highly significant pancreatic allograft survival. All long-term segmental allograft recipients were rendered normoglycemic (plasma glucose less than 8 mmol/L) by this immunosuppressive regimen. In contrast, poor results were observed in PDA recipients treated with TLI and CsA. Mean survival in 18 treated PDA recipients was 23.8 days, 8 survived longer than 20 days (44.4%), and 1 greater than 100 days (5.5%). Despite treatment, early rejection of the duodenum in PDA recipients frequently resulted in necrosis and perforation and contributed to a high morbidity and mortality. This study indicates that, in contrast to the significant prolongation of segmental allografts by TLI and CsA, poor immunosuppression was achieved by this regimen in PDA recipients and was associated with a high morbidity and mortality caused by early rejection of the duodenum.

  20. Prolongation of segmental and pancreaticoduodenal allografts in the primate with total-lymphoid irradiation and cyclosporine

    International Nuclear Information System (INIS)

    Du Toit, D.F.; Heydenrych, J.J.; Smit, B.

    1987-01-01

    The prolongation of segmental and pancreaticoduodenal allografts (PDA) by total lymphoid irradiation (TLI) and in combination with cyclosporine (CsA) was assessed in a well established total pancreatectomy, diabetic, primate transplantation model. Pancreatic transplantation was performed in 119 pancreatectomized baboons (Papio ursinus). Of a total of 109 allografts performed, 71 were segmental allografts (open duct drainage) and 38 PDA. Of 119 graft recipients, 10 received segmental pancreatic autografts. TLI and CsA administered separately to segmental allograft recipients resulted in modest allograft survival and indefinite graft survival was not observed. 8 of 17 (47%) segmental allograft recipients that received TLI and CsA had graft survival beyond 100 days, indicating highly significant pancreatic allograft survival. All long-term segmental allograft recipients were rendered normoglycemic (plasma glucose less than 8 mmol/L) by this immunosuppressive regimen. In contrast, poor results were observed in PDA recipients treated with TLI and CsA. Mean survival in 18 treated PDA recipients was 23.8 days, 8 survived longer than 20 days (44.4%), and 1 greater than 100 days (5.5%). Despite treatment, early rejection of the duodenum in PDA recipients frequently resulted in necrosis and perforation and contributed to a high morbidity and mortality. This study indicates that, in contrast to the significant prolongation of segmental allografts by TLI and CsA, poor immunosuppression was achieved by this regimen in PDA recipients and was associated with a high morbidity and mortality caused by early rejection of the duodenum

  1. 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.

  2. Cell therapy to induce allograft tolerance: Time to switch to plan B?

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    Antoine eSicard

    2015-04-01

    Full Text Available Organ transplantation is widely acknowledged as the best option for end stage failure of vital organs. Long-term graft survival is however limited by graft rejection, a destructive process resulting from the response of recipient’s immune system against donor-specific alloantigens. Prevention of rejection currently relies exclusively on immunosuppressive drugs that lack antigen specificity and therefore increase the risk for infections and cancers. Induction of donor-specific tolerance would provide indefinite graft survival without morbidity and therefore represents the Grail of transplant immunologists.Progresses in the comprehension of immunoregulatory mechanisms over the last decades have paved the way for cell therapies to induce allograft tolerance. The first part of the present article reviews the promising results obtained in experimental models with adoptive transfer of ex vivo-expanded regulatory CD4+ T cells (CD4+ Tregs and discuss which source and specificity should be preferred for transferred CD4+ Tregs. Interestingly, B cells have recently emerged as potent regulatory cells, able to establish a privileged crosstalk with CD4+ T cells. The second part of the present article reviews the evidences demonstrating the crucial role of regulatory B cells in transplantation tolerance. We propose the possibility to harness B cell regulatory functions to improve cell-based therapies aiming at inducing allograft tolerance.

  3. 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.)

  4. Immunomodulatory Strategies Directed Towards Tolerance of Vascularized Composite Allografts

    Science.gov (United States)

    Michel, Sebastian G.; Villani, Vincenzo; Muraglia, Glenn M. La; Torabi, Radbeh; Leonard, David A.; Randolph, Mark A.; Colvin, Robert B.; Yamada, Kazuhiko; Madsen, Joren C.; Cetrulo, Curtis L.; Sachs, David H.

    2015-01-01

    Background Achieving tolerance of vascularized composite allografts (VCAs) would improve the risk-to-benefit ratio in patients who undergo this life-enhancing, though not life-saving, transplant. Kidney co-transplantation along with a short course of high-dose immunosuppression enables tolerance of heart allografts across a full MHC mismatch. In this study, we investigated whether tolerance of VCA across full MHC disparities could be achieved in animals already tolerant of heart and kidney allografts. Methods Miniature swine that were tolerant of heart and/or kidney allografts long-term underwent transplantation of myocutaneous VCA across the same MHC barrier. Prior to VCA transplant, Group 1 (n=3) underwent Class I-mismatched kidney transplantation; Group 2 (n=3) underwent two sequential Class I-mismatched kidney transplantations; Group 3 (n=2) underwent haploidentical MHC-mismatched heart/kidney transplantation; and Group 4 (n=2) underwent full MHC-mismatched heart/kidney transplantation. Results All three animals in Group 1 and two of three animals in Group 2 showed skin rejection ≤85 days; one animal in Group 2 showed prolonged skin survival >200 days. Animals in Groups 3 and 4 showed skin rejection ≤30 days and regained in vitro evidence of donor responsiveness. Conclusion This is the first pre-clinical study in which hearts, kidneys, and VCAs have been transplanted into the same recipient. Despite VCA rejection, tolerance of heart and kidney allografts was maintained. These results suggest that regulatory tolerance of skin is possible but not generally achieved by the same level of immunomodulation that is capable of inducing tolerance of heart and kidney allografts. Achieving tolerance of skin may require additional immunomodulatory therapies. PMID:25757218

  5. Urine Proteomics to Detect Biomarkers for Chronic Allograft Dysfunction

    Science.gov (United States)

    Quintana, Luís F.; Solé-Gonzalez, Amanda; Kalko, Susana G.; Bañon-Maneus, Elisenda; Solé, Manel; Diekmann, Fritz; Gutierrez-Dalmau, Alex; Abian, Joaquin; Campistol, Josep M.

    2009-01-01

    Despite optimal immunosuppressive therapy, more than 50% of kidney transplants fail because of chronic allograft dysfunction. A noninvasive means to diagnose chronic allograft dysfunction may allow earlier interventions that could improve graft half-life. In this proof-of-concept study, we used mass spectrometry to analyze differences in the urinary polypeptide patterns of 32 patients with chronic allograft dysfunction (14 with pure interstitial fibrosis and tubular atrophy and 18 with chronic active antibody-mediated rejection) and 18 control subjects (eight stable recipients and 10 healthy control subjects). Unsupervised hierarchical clustering showed good segregation of samples in groups corresponding mainly to the four biomedical conditions. Moreover, the composition of the proteome of the pure interstitial fibrosis and tubular atrophy group differed from that of the chronic active antibody-mediated rejection group, and an independent validation set confirmed these results. The 14 protein ions that best discriminated between these two groups correctly identified 100% of the patients with pure interstitial fibrosis and tubular atrophy and 100% of the patients with chronic active antibody-mediated rejection. In summary, this study establishes a pattern for two histologic lesions associated with distinct graft outcomes and constitutes a first step to designing a specific, noninvasive diagnostic tool for chronic allograft dysfunction. PMID:19056874

  6. 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

  7. Modeling rejection immunity.

    Science.gov (United States)

    De Gaetano, Andrea; Matone, Alice; Agnes, Annamaria; Palumbo, Pasquale; Ria, Francesco; Magalini, Sabina

    2012-05-20

    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. 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. 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 therapy protocols in the transplanted patient.

  8. Concentration of In-111-oxine-labeled autologous leukocytes in noninfected and nonrejecting renal allografts: concise communication

    International Nuclear Information System (INIS)

    Collier, B.D.; Isitman, A.T.; Kaufman, H.M.; Rao, S.A.; Knobel, J.; Hellman, R.S.; Zielonka, J.S.; Pelc, L.

    1984-01-01

    Autologous leukocytes labeled with In-111 oxine (ILL) concentrated in the renal allografts of eight patients for whom transplant rejection, infection, or acute tubular necrosis (ATN) could be excluded. All patients had good-to-adequate renal function at the time of ILL scintigraphy, and none developed rejection or renal transplant failure during a 1-mo follow-up period. It is concluded that normally functioning renal allografts without evidence of rejection, infection, or ATN often will concentrate ILL. When a baseline study is not available for comparison, this phenomenon limits the value of ILL scintigraphy as a diagnostic test for transplant rejection or infection

  9. 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

  10. Radiation sterilization of skin allograft

    Science.gov (United States)

    Kairiyama, E.; Horak, C.; Spinosa, M.; Pachado, J.; Schwint, O.

    2009-07-01

    In the treatment of burns or accidental loss of skin, cadaveric skin allografts provide an alternative to temporarily cover a wounded area. The skin bank facility is indispensable for burn care. The first human skin bank was established in Argentina in 1989; later, 3 more banks were established. A careful donor selection is carried out according to the national regulation in order to prevent transmissible diseases. As cadaveric human skin is naturally highly contaminated, a final sterilization is necessary to reach a sterility assurance level (SAL) of 10 -6. The sterilization dose for 106 batches of processed human skin was determined on the basis of the Code of Practice for the Radiation Sterilization of Tissue Allografts: Requirements for Validation and Routine Control (2004) and ISO 11137-2 (2006). They ranged from 17.6 to 33.4 kGy for bioburdens of >10-162.700 CFU/100 cm 2. The presence of Gram negative bacteria was checked for each produced batch. From the analysis of the experimental results, it was observed that the bioburden range was very wide and consequently the estimated sterilization doses too. If this is the case, the determination of a tissue-specific dose per production batch is necessary to achieve a specified requirement of SAL. Otherwise if the dose of 25 kGy is preselected, a standardized method for substantiation of this dose should be done to confirm the radiation sterilization process.

  11. Radiation sterilization of skin allograft

    International Nuclear Information System (INIS)

    Kairiyama, E.; Horak, C.; Spinosa, M.; Pachado, J.; Schwint, O.

    2009-01-01

    In the treatment of burns or accidental loss of skin, cadaveric skin allografts provide an alternative to temporarily cover a wounded area. The skin bank facility is indispensable for burn care. The first human skin bank was established in Argentina in 1989; later, 3 more banks were established. A careful donor selection is carried out according to the national regulation in order to prevent transmissible diseases. As cadaveric human skin is naturally highly contaminated, a final sterilization is necessary to reach a sterility assurance level (SAL) of 10 -6 . The sterilization dose for 106 batches of processed human skin was determined on the basis of the Code of Practice for the Radiation Sterilization of Tissue Allografts: Requirements for Validation and Routine Control (2004) and ISO 11137-2 (2006). They ranged from 17.6 to 33.4 kGy for bioburdens of >10-162.700 CFU/100 cm 2 . The presence of Gram negative bacteria was checked for each produced batch. From the analysis of the experimental results, it was observed that the bioburden range was very wide and consequently the estimated sterilization doses too. If this is the case, the determination of a tissue-specific dose per production batch is necessary to achieve a specified requirement of SAL. Otherwise if the dose of 25 kGy is preselected, a standardized method for substantiation of this dose should be done to confirm the radiation sterilization process.

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

    Directory of Open Access Journals (Sweden)

    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

  13. Kidney allograft survival in dogs treated with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Howard, R.J.; Sutherland, D.E.R.; Lum, C.T.; Lewis, W.I.; Kim, T.H.; Slavin, S.; Najarian, J.S.

    1981-01-01

    Total lymphoid irradiation (TLI) is immunosuppressive and, in rodents, can induce a state where transplantation of allogenic bone marrow results in chimerism and permanent acceptance of organ allografts from the donor strain. Twelve splenectomized dogs were treated with TLI (150 rads per fraction, total dose 1950 to 3000 rads) before bilateral nephrectomy and renal allotransplantation. Eight dogs received bone marrow from the kidney donor. In 13 untreated control dogs renal allografts functioned for a mean +- (SE) of 4.7 +- 0.3 days. In the four TLI treated dogs who did not receive bone marrow the renal allografts functioned for 15 to 76 days (two dogs died with functioning grafts). In the eight TLI treated dogs who received donor bone marrow, two died immediately after transplantation, two rejected at 3 and 13 days, one died at 13 days with a functioning graft, and two have had the grafts function for longer than 500 days. Chimerism was not detected in the one dog tested. The response of peripheral blood lymphocytes to stimulation with phytohemaglutinin and in mixed lymphocyte culture was suppressed for at least one month after TLI. The results confirm the immunosuppressive effect of TLI. The absence of kidney rejection in two recipients of donor bone marrow show the potential of this approach to induce long-term immunologic unresponsiveness as to an organ allograft, but the outcome is unpredictable and further experiments are needed to define the optimal conditions for administration of TLI and bone marrow to the recipients

  14. Selective lymphoid irradiation: III. Prolongation of cardiac xenografts and allografts in presensitized rats

    International Nuclear Information System (INIS)

    Hardy, M.A.; Oluwole, S.; Fawwaz, R.; Satake, K.; Nowygrod, R.; Reemtsma, K.

    1982-01-01

    Selective lymphoid irradiation (SLI) with palladium-109-hematoporphyrin (Pd-H) combined with antilymphocyte globulin (ALG) induces either donor-specific permanent rat heart allograft acceptance or significant allograft prolongation depending on the degree of donor-recipient matching. The purpose of this study was to determine if SLI combined with ALG can affect ACI heart allograft survival in Lewis recipients presensitized to ACI, and of hamster heart xenografts of Lewis rats. SLI combined with ALG delays allograft and xenograft rejection in the presence of induced or preformed antidonor antibodies, and converts primarily a humoral rejection into a cellular rejection by mechanisms as yet uncertain. Such peritransplant treatment had significant effect on the levels of antidonor complement-dependent cytotoxic antibody titers but did not correlate directly with graft survival. Histological analysis of rejected hearts in all groups demonstrated primarily a humoral hyperacute rejection in control animals and in recipients treated with ALG alone, while peritransplant treatment with Pd-H and ALG resulted not only in prolonged graft survival but histologically, primarily a cellular rejection of the graft

  15. Significant prolongation of segmental pancreatic allograft survival in two species

    Energy Technology Data Exchange (ETDEWEB)

    Du Toit, D.F.; Heydenrych, J.J.

    1988-06-01

    A study was conducted to assess the suppression of segmental pancreatic allograft rejection by cyclosporine (CSA) alone in baboons and dogs, and subtotal marrow irradiation (TL1) alone and TL 1 in combination with CSA in baboons. Total pancreatectomy in the dog and primate provided a reliable diabetic model, induced an absolute deficiency of insulin and was uniformly lethal if not treated. Continuous administration of CSA in baboons resulted in modest allograft survival. As in baboons, dogs receiving CSA 25 mg/kg/d rendered moderate graft prolongation but a dose of 40 mg/kg/d resulted in significant graft survival (greater than 100 days) in 5 of 8 allograft recipients. Irradiation alone resulted in minimal baboon pancreatic allograft survival of 20 baboons receiving TL1 1,000 rad and CSA, 3 had graft survival greater than of 100 days. Of 15 baboons receiving TL1 800 rad and CSA, 6 had graft survival of greater than 100 days. In conclusion, CSA administration in dogs and TL1 in combination with CSA in baboons resulted in highly significant segmental pancreatic allograft survival.

  16. Significant prolongation of segmental pancreatic allograft survival in two species

    International Nuclear Information System (INIS)

    Du Toit, D.F.; Heydenrych, J.J.

    1988-01-01

    A study was conducted to assess the suppression of segmental pancreatic allograft rejection by cyclosporine (CSA) alone in baboons and dogs, and subtotal marrow irradiation (TL1) alone and TL 1 in combination with CSA in baboons. Total pancreatectomy in the dog and primate provided a reliable diabetic model, induced an absolute deficiency of insulin and was uniformly lethal if not treated. Continuous administration of CSA in baboons resulted in modest allograft survival. As in baboons, dogs receiving CSA 25 mg/kg/d rendered moderate graft prolongation but a dose of 40 mg/kg/d resulted in significant graft survival (greater than 100 days) in 5 of 8 allograft recipients. Irradiation alone resulted in minimal baboon pancreatic allograft survival of 20 baboons receiving TL1 1,000 rad and CSA, 3 had graft survival greater than of 100 days. Of 15 baboons receiving TL1 800 rad and CSA, 6 had graft survival of greater than 100 days. In conclusion, CSA administration in dogs and TL1 in combination with CSA in baboons resulted in highly significant segmental pancreatic allograft survival

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

    NARCIS (Netherlands)

    H.A. de Groot-Kruseman; C.C. Baan (Carla); E.M. Hagman; W.M. Mol (Wendy); H.G.M. Niesters (Bert); P.E. Zondervan (Pieter); W. Weimar (Willem); A.H.M.M. Balk (Aggie); A.W.P.M. Maat (Alex)

    2002-01-01

    textabstractOBJECTIVE: 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

  18. 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

  19. Rejeição de transplante de córnea Corneal Transplant Rejection

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    Dácio Carvalho Costa

    2008-10-01

    Full Text Available A rejeição do transplante de córnea é um processo imunológico celular de ataque a córnea transplantada que pode resultar em sua descompensação. É a causa mais comum de falência de transplantes. Os fatores de risco mais comuns para rejeição são a vascularização corneana, falência prévia por rejeição, sinéquias anteriores, botão doador grande ou descentrado, inflamação intra-ocular e cirurgias no segmento anterior. O quadro clínico é caracterizado por hiperemia, dor ocular, edema corneano e inflamação na câmara anterior. As rejeições podem ser classificadas em epitelial, subepitelial, estromal, endotelial, mista e em retransplantes. A prevenção de rejeições pode ser realizada através de técnica cirúrgica meticulosa, utilização de transplantes lamelares, histocompatibilidade receptor-doador e estratégias farmacológicas. Os corticosteróides são a terapia de escolha para o tratamento da rejeição de transplante de córnea e podem ser utilizados em diversas vias e dosagens. Os autores propõem protocolo de tratamento para rejeições.Corneal transplant rejection is an immunological cellular process that attacks the donor cornea and may cause its failure. It is the most common cause of corneal transplant failure.The most common factors for rejection are corneal neovascularization, previous graft failure, anterior synechiae, large or descentered graft, intraocular inflammation and previous anterior segment surgeries. It commonly presents with hyperemia, ocular pain, corneal edema, and anterior chamber inflammation. Corneal graft rejection can be classified as epithelial rejection, subepithelial rejection, stromal rejection, endothelial rejection, combined stromal and endothelial rejection, and rejection in a repeat graft. Prevention of immune-mediated graft rejection can be achieved through meticulous surgical technique, lamellar surgery, enhanced compatibility between donor tissue and receptor cornea, and

  20. Bone allografting in children

    Science.gov (United States)

    Sadovoy, M. A.; Kirilova, I. A.; Podorognaya, V. T.; Matsuk, S. A.; Novoselov, V. P.; Moskalev, A. V.; Bondarenko, A. V.; Afanasev, L. M.; Gubina, E. V.

    2017-09-01

    A total of 522 patients with benign and intermediate bone tumors of various locations, aged 1 to 15 years, were operated in the period from 1996 to 2016. To diagnose skeleton tumors, we used clinical observation, X-ray, and, if indicated, tomography and tumor site biopsy. In the extensive bone resection, we performed bone reconstruction with the replacement of a defect with an allograft (bone strips, deproteinized and spongy grafts), sometimes in the combination with bone autografting. After segmental resection, the defects were filled with bone strips in the form of matchstick grafts; the allografts were received from the Laboratory for Tissue Preparation and Preservation of the Novosibirsk Research Institute of Traumatology and Orthopedics. According to the X-ray data, a complete reorganization of bone grafts occurred within 1.5 to 3 years. The long-term result was assessed as good.

  1. Safety and Effectiveness of Cadaveric Allograft Sternochondral Replacement After Sternectomy: A New Tool for the Reconstruction of Anterior Chest Wall.

    Science.gov (United States)

    Marulli, Giuseppe; Dell'amore, Andrea; Calabrese, Francesca; Schiavon, Marco; Daddi, Niccolò; Dolci, Giampiero; Stella, Franco; Rea, Federico

    2017-03-01

    Surgical excision with wide margins, prevention of respiratory impairment, and protection of surrounding organs are primary goals in resection and reconstruction of the chest wall. We describe our experience of the use of cadaveric cryopreserved sternal allograft. Eighteen patients underwent surgery. Indications for sternectomy were sternal metastases (n = 9), primary chondrosarcoma (n = 4), sternal dehiscence (n = 2), soft tissue sarcoma (n = 1), malignant solitary fibrous tumor (n = 1), and direct involvement of thymic carcinoma (n = 1). The defect was reconstructed using a cadaveric sternal allograft harvested aseptically, treated with antibiotic solution, and cryopreserved (-80°C). The graft was tailored to fit the defect and fixed in place with titanium plates and screws. Four patients underwent a total sternectomy, 8 a partial lower sternectomy, and 6 a partial upper sternectomy. In 14 patients, muscle flaps were positioned to cover the graft. During the postoperative course, 1 patient died of pulmonary embolism, 1 had systemic Candida infection, and 1 had surgical revision for bleeding at the site of muscle flap. One patient required removal of a screw on the clavicle 4 months after operation because of partial dislocation. At a median follow-up of 36 months, neither infection nor rejection of the graft occurred; 13 patients are alive without disease, and 4 patients had died. None had local tumor relapse. Sternal replacement with cadaveric allograft is safe and effective, providing optimal stability of the chest wall and protection of the surrounding organs, even after extensive chest wall resections. The allograft was biologically well tolerated, allowing a perfect integration into the host. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  2. Allograft Pancreatectomy: Indications and Outcomes.

    Science.gov (United States)

    Nagai, S; Powelson, J A; Taber, T E; Goble, M L; Mangus, R S; Fridell, J A

    2015-09-01

    This study evaluated the indications, surgical techniques, and outcomes of allograft pancreatectomy based on a single center experience. Between 2003 and 2013, 47 patients developed pancreas allograft failure, excluding mortality with a functioning pancreas allograft. Early graft loss (within 14 days) occurred in 16, and late graft loss in 31. All patients with early graft loss eventually required allograft pancreatectomy. Nineteen of 31 patients (61%) with late graft loss underwent allograft pancreatectomy. The main indication for early allograft pancreatectomy included vascular thrombosis with or without severe pancreatitis, whereas one recipient required urgent allograft pancreatectomy for gastrointestinal hemorrhage secondary to an arterioenteric fistula. In cases of late allograft pancreatectomy, graft failure with clinical symptoms such as abdominal discomfort, pain, and nausea were the main indications (13/19 [68%]), simultaneous retransplantation without clinical symptoms in 3 (16%), and vascular catastrophes including pseudoaneurysm and enteric arterial fistula in 3 (16%). Postoperative morbidity included one case each of pulmonary embolism leading to mortality, formation of pseudoaneurysm requiring placement of covered stent, and postoperative bleeding requiring relaparotomy eventually leading to femoro-femoral bypass surgery 2 years after allograftectomy. Allograft pancreatectomy can be performed safely, does not preclude subsequent retransplantation, and may be lifesaving in certain instances. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  3. Kidney Transplant Recipients With Primary Membranous Glomerulonephritis Have a Higher Risk of Acute Rejection Compared With Other Primary Glomerulonephritides

    Directory of Open Access Journals (Sweden)

    Tripti Singh, MD

    2017-11-01

    Conclusions. Patients with MN have higher incidence of acute rejection after kidney transplant but have similar 10-year allograft survival in comparison to the other glomerular diseases like IgAN, FSGS, and LN.

  4. The clinical utility of indium-111 labelled platelet scintigraphy in the diagnoses of renal transplant rejection

    International Nuclear Information System (INIS)

    Desir, G.V.; Bia, M.; Lange, R.C.; Smith, E.O.; Flye, W.; Kashgarian, M.; Schiff, M.; Ezekowitz, M.D.

    1990-01-01

    It is demonstrated that indium-111 labelled platelet scintigraphy is a highly accurate test for detecting acute untreated renal allograft rejection and it is shown that changes in platelet uptake can precede signs and symptoms of rejection by at least 48 hours. (author). 34 refs.; 2 figs.; 1 tab

  5. [Reconstruction of periprosthetic fractures of hip with cortical bone plates allografts].

    Science.gov (United States)

    Zhou, Zong-ke; Pei, Fu-xing; Tu, Chong-qi; Yang, Jing; Shen, Bin; Liu, Lei; Fatou, Camara-yagouba

    2004-12-22

    To observe clinical results for reconstruction of periprosthetic fractures of hip with cortical bone plates allografts by deep-freezing and ethylene oxide treatment. Seven patients with periprosthetic fractures of hip underwent cortical bone plates allografts by deep-freezing at -70 degrees C after being treatment of 48 degrees C ethylene oxide. And evaluate clinical outcome by examining T lymphocytes, Harris scores, X-rays photograph, and bone scintigraphy. There were not activity of immune rejection and infection in all patients. Harris scores of patients increased 21, 32, 40, 40 scores at 3, 6, 12, 24 months after surgery. T-lymphocytes, antibody and immunocomplex in blood was normal postoperation. X-ray film indicated that fracture was healed at 3 months and there was partially bone conjunction between allograft strut and host bone. There was incorporation of 85% allograft strut to host bone, and 15% allograft strut was partially absorbed at 12 months after surgery. The size of femur of host was added 3 mm to 5 mm, averaged 4.3 mm at 12 months postoperation. Density of 80% allograft plates was as same as host bone after remodeling and the absorbtion of 10% allograft plates stopped at 24 months after surgery. There was thick of nuclein in the area of allograft cortical bone plates by bone scintigraphy examination at 3 months postoperation, and the thick of nuclein was stronger at 6, and 12 months after surgery. Allograft cortical bone plates by deep frozen at -70 degrees C after being treatment of 48 degrees C ethylene oxide is suitable for mechanical fixation and biological bone transplantation, and it can increase bone reservation, augment strength of femur once the allograft strut incorporates to host bone, and avoid removing metal implant in second operation when being applied into reconstruction femoral fracture in joint replacement.

  6. Expression of cytotoxic mediators (perforin, granzyme B, FAS, and FAS-l in renal allograft biopsies

    Directory of Open Access Journals (Sweden)

    Therezinha Gauri Leitão

    2006-12-01

    Full Text Available Objectives: To analyze the in situ expression of perforin, granzymeB, FAS-L and FAS in renal allograft biopsies by means ofimmunohistochemistry and correlate these findings with the degreeof histologic rejection and allograft outcome. Methods: Ninety-sixallograft biopsies were divided into three groups: acute rejection (n= 56, chronic rejection (n = 31, and cases with stable renal function(no rejection; n = 9. The expression of perforin, granzyme B, FAS-L,and FAS was evaluated by immunohistochemistry. Results: Asignificantly higher expression of perforin and granzyme B wasobserved in acute rejection biopsies (4.83 ± 0.65 and 30.05 ± 7.93cells/mm2 compared to chronic rejection biopsies (0.71 ± 0.13 and11.4 ± 3.84 cells/mm2; p < 0.001, and p <0.05, respectively, but thiswas not the case for FAS-L (24.44 ± 5.56 in acute rejection versus 18.87± 6.83 in chronic rejection. Perforin, granzyme B, and FAS-L expressionwas significantly higher in the acute rejection group compared to the norejection and control groups. FAS expression was similar in all groups. Amodest correlation between perforin expression and the severity of ARwas observed (r = 0.28, p = 0.05. Perforin was the most reliable markerfor acute rejection diagnosis, with 80% sensitivity and 84.3% specificity.Conclusion: The in situ expression of perforin, granzyme B, and FAS-Lin AR reflects the presence of an active cytotoxic process. Additionalallograft biopsies are necessary in order to evaluate the usefulness ofthese markers for allograft rejection monitoring.

  7. Graft rejection by cytolytic T cells. Specificity of the effector mechanism in the rejection of allogeneic marrow

    International Nuclear Information System (INIS)

    Nakamura, H.; Gress, R.E.

    1990-01-01

    Cellular effector mechanisms of allograft rejection remain incompletely described. Characterizing the rejection of foreign-marrow allografts rather than solid-organ grafts has the advantage that the cellular composition of the marrow graft, as a single cell suspension, can be altered to include cellular components with differing antigen expression. Rejection of marrow grafts is sensitive to lethal doses of radiation in the mouse but resistant to sublethal levels of radiation. In an effort to identify cells mediating host resistance, lymphocytes were isolated and cloned from spleens of mice 7 days after sublethal TBI (650 cGy) and inoculation with allogeneic marrow. All clones isolated were cytolytic with specificity for MHC encoded gene products of the allogeneic marrow donor. When cloned cells were transferred in vivo into lethally irradiated (1025 cGy) recipients unable to reject allogeneic marrow, results utilizing splenic 125IUdR uptake indicated that these MHC-specific cytotoxic clones could suppress marrow proliferation. In order to characterize the effector mechanism and the ability of the clones to affect final engraftment, double donor chimeras were constructed so that 2 target cell populations differing at the MHC from each other and from the host were present in the same marrow allograft. Results directly demonstrated an ability of CTL of host MHC type to mediate graft rejection and characterized the effector mechanism as one with specificity for MHC gene products

  8. Renal allograft loss in the first post-operative month: causes and consequences.

    LENUS (Irish Health Repository)

    Phelan, Paul J

    2013-01-15

    Early transplant failure is a devastating outcome after kidney transplantation. We report the causes and consequences of deceased donor renal transplant failure in the first 30 d at our center between January 1990 and December 2009. Controls were adult deceased donor transplant patients in the same period with an allograft that functioned >30 d. The incidence of early graft failure in our series of 2381 consecutive deceased donor transplants was 4.6% (n = 109). The causes of failure were allograft thrombosis (n = 48; 44%), acute rejection (n = 19; 17.4%), death with a functioning allograft (n = 17; 15.6%), primary non-function (n = 14;12.8%), and other causes (n = 11; 10.1%). Mean time to allograft failure was 7.3 d. There has been a decreased incidence of all-cause early failure from 7% in 1990 to <1% in 2009. Patients who developed early failure had longer cold ischemia times when compared with patients with allografts lasting >30 d (p < 0.001). Early allograft failure was strongly associated with reduced patient survival (p < 0.001). In conclusion, early renal allograft failure is associated with a survival disadvantage, but has thankfully become less common in recent years.

  9. Role of Soluble ST2 as a Marker for Rejection after Heart Transplant

    OpenAIRE

    Lee, Ga Yeon; Choi, Jin-Oh; Ju, Eun-Seon; Lee, Yoo-Jung; Jeon, Eun-Seok

    2016-01-01

    Background and Objectives Endomyocardial biopsy is obligatory during the first year after heart transplant (HTx) for the surveillance of acute rejection. Previous attempts using cardiac biomarkers for the detection of rejection failed to show enough evidence to substitute endomyocardial biopsy. Therefore, this study sought the possibility of using soluble ST2 (sST2), a novel cardiovascular marker, as a surrogate marker for acute allograft rejection after HTx. Subjects and Methods A total of 4...

  10. Left versus right deceased donor renal allograft outcome.

    LENUS (Irish Health Repository)

    Phelan, Paul J

    2009-12-01

    It has been suggested that the left kidney is easier to transplant than the right kidney because of the longer length of the left renal vein, facilitating the formation of the venous anastomosis. There are conflicting reports of differing renal allograft outcomes based on the side of donor kidney transplanted (left or right).We sought to determine the effect of side of donor kidney on early and late allograft outcome in our renal transplant population. We performed a retrospective analysis of transplanted left-right deceased donor kidney pairs in Ireland between January 1, 1998 and December 31, 2008. We used a time to death-censored graft failure approach for long-term allograft survival and also examined serum creatinine at different time points post-transplantation. All outcomes were included from day of transplant onwards. A total of 646 transplants were performed from 323 donors. The incidence of delayed graft function was 16.1% in both groups and there was no significant difference in acute rejection episodes or serum creatinine from 1 month to 8 years post-transplantation.There were 47 death-censored allograft failures in the left-sided group compared to 57 in the right-sided group (P = 0.24). These observations show no difference in renal transplant outcome between the recipients of left- and right-sided deceased donor kidneys.

  11. Primary Nonfunction of Renal Allograft Secondary to Acute Oxalate Nephropathy

    Directory of Open Access Journals (Sweden)

    Ravi Parasuraman

    2011-01-01

    Full Text Available Primary nonfunction (PNF accounts for 0.6 to 8% of renal allograft failure, and the focus on causes of PNF has changed from rejection to other causes. Calcium oxalate (CaOx deposition is common in early allograft biopsies, and it contributes in moderate intensity to higher incidence of acute tubular necrosis and poor graft survival. A-49-year old male with ESRD secondary to polycystic kidney disease underwent extended criteria donor kidney transplantation. Posttransplant, patient developed delayed graft function (DGF, and the biopsy showed moderately intense CaOx deposition that persisted on subsequent biopsies for 16 weeks, eventually resulting in PNF. The serum oxalate level was 3 times more than normal at 85 μmol/L (normal <27 μmol/L. Allograft nephrectomy showed massive aggregates of CaOx crystal deposition in renal collecting system. In conclusion, acute oxalate nephropathy should be considered in the differential diagnosis of DGF since optimal management could change the outcome of the allograft.

  12. PD-L1 Deficiency within Islets Reduces Allograft Survival in Mice.

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    Dongxia Ma

    Full Text Available Islet transplantation may potentially cure type 1 diabetes mellitus (T1DM. However, immune rejection, especially that induced by the alloreactive T-cell response, remains a restraining factor for the long-term survival of grafted islets. Programmed death ligand-1 (PD-L1 is a negative costimulatory molecule. PD-L1 deficiency within the donor heart accelerates allograft rejection. Here, we investigate whether PD-L1 deficiency in donor islets reduces allograft survival time.Glucose Stimulation Assays were performed to evaluate whether PD-L1 deficiency has detrimental effects on islet function. Islets isolated from PDL1-deficient mice or wild- type (WT mice (C57BL/6j were implanted beneath the renal capsule of streptozotocin (STZ-induced diabetic BALB/c mice. Blood glucose levels and graft survival time after transplantation were monitored. Moreover, we analyzed the residual islets, infiltrating immune cells and alloreactive cells from the recipients.PD-L1 deficiency within islets does not affect islet function. However, islet PD-L1 deficiency increased allograft rejection and was associated with enhanced inflammatory cell infiltration and recipient T-cell alloreactivity.This is the first report to demonstrate that PD-L1 deficiency accelerated islet allograft rejection and regulated recipient alloimmune responses.

  13. Cardiac retransplantation is an efficacious therapy for primary cardiac allograft failure

    Directory of Open Access Journals (Sweden)

    Acker Michael A

    2008-05-01

    Full Text Available Abstract Background Although orthotopic heart transplantation has been an effective treatment for end-stage heart failure, the incidence of allograft failure has increased, necessitating treatment options. Cardiac retransplantation remains the only viable long-term solution for end-stage cardiac allograft failure. Given the limited number of available donor hearts, the long term results of this treatment option need to be evaluated. Methods 709 heart transplants were performed over a 20 year period at our institution. Repeat cardiac transplantation was performed in 15 patients (2.1%. A retrospective analysis was performed to determine the efficacy of cardiac retransplantation. Variables investigated included: 1 yr and 5 yr survival, length of hospitalization, post-operative complications, allograft failure, recipient and donor demographics, renal function, allograft ischemic time, UNOS listing status, blood group, allograft rejection, and hemodynamic function. Results Etiology of primary graft failure included transplant arteriopathy (n = 10, acute rejection (n = 3, hyperacute rejection (n = 1, and a post-transplant diagnosis of metastatic melanoma in the donor (n = 1. Mean age at retransplantation was 45.5 ± 9.7 years. 1 and 5 year survival for retransplantation were 86.6% and 71.4% respectively, as compared to 90.9% and 79.1% for primary transplantation. Mean ejection fraction was 67.3 ± 12.2% at a mean follow-up of 32.6 ± 18.5 mos post-retransplant; follow-up biopsy demonstrated either ISHLT grade 1A or 0 rejection (77.5 ± 95.7 mos post-transplant. Conclusion Cardiac retransplantation is an efficacious treatment strategy for cardiac allograft failure.

  14. Evaluation of renal allograft with 99mTc-mononuclear leukocytes

    International Nuclear Information System (INIS)

    Souza, S.A.L.; Oliveira, H.S.; Goncalves, R.T.; Pontes, D.S.; Fonseca, L.B.M.; Gutfilen, B.

    2002-01-01

    Aim: Because kidney biopsy is an invasive procedure that carries a small but significant risk of major complications, a noninvasive test that detects rejection before it is clinically apparent is very much needed. The reversibility of acute rejection is related to the promptness with which treatment is begun. Here we show the evaluation of rejection in the first week post-transplant with 99m Tc-mononuclear leukocyte scintigraphy (99mTc-MLS). Materials and Methods: 70 patients submitted to renal transplant at the Hospital Universitario Clementino Fraga Filho (HUCFF/UFRJ) underwent 99m Tc-MLS at the 1st and 5th post-transplant days. The labeled cells were administered (444MBq) and scans were carried out 3 and 24h post injection. A region of interest (ROI) was drawn at the allograft image and statistics compared between the 3 and 24h images. Percentages above 15% in the 24h image relating to the 3h image were considered abnormal and suspect of rejection. 25 of the 70 patients rejected the renal allograft in the 1st week post-transplant. Results: 99m Tc-MLS has detected rejection in 20 of the 25 patients. Color Doppler was also carried out in all the patients and has detected 16 rejections. Sensitivity and specificity were 80% and 100% for scintigraphy and 64% and 100% for Ultrasound. 99m Tc-MLS is more sensitive in humoral rejection than color Doppler. The latter is better to identify the vascular rejection. Conclusion: In order to evaluate renal allograft and improve the rejection diagnosis the combination of both techniques should be applied. More studies are now in progress

  15. Immediate autogenous cartilage grafts in rhinoplasty after alloplastic implant rejection.

    Science.gov (United States)

    Raghavan, Ullas; Jones, Nick S; Romo, Thomas

    2004-01-01

    It is accepted in rhinoplasty that complications are more common with alloplastic implants than with autografts. There is little guidance in the literature on how to deal with the cosmetic and/or functional problems that follow alloplastic implant rejection. The conventional advice has been to remove the allograft and not place any graft at the same time. The present article presents our experience treating allograft rejection and immediately repairing any structural defect with autografts. To demonstrate that immediate nasal reconstruction using autogenous cartilage is a good technique when an alloplastic material has to be removed because of rejection, inflammation, or infection. A retrospective analysis of outcome for a case series. A retrospective review of the management of 8 patients who presented to 2 tertiary referral centers with alloplastic implant rejection following rhinoplasty. In 7 cases, the alloplastic implant had to be removed because it had migrated and caused a foreign body reaction; in 1 case, the implant had caused a bacterial infection. In all 8 cases, the nasal deformity that followed the removal of the allograft was so marked that the nose was immediately reconstructed with autogenous cartilage. The patients all made a good recovery after immediate reconstruction, although skin changes associated with the alloplastic implant remained after a mean follow-up of 3 years 3 months. The use of autogenous cartilage is a good option for nasal augmentation immediately after the removal of an alloplastic implant.

  16. Thioredoxin priming prolongs lung allograft survival by promoting immune tolerance.

    Science.gov (United States)

    Hu, Hanbo; Zhu, Xiaoyan; Joshi, Sunil; Lu, Li; Xia, Chang-Qing; Patel, Jawaharlal M

    2015-01-01

    Tolerance to allograft antigen is the major challenge and final goal of transplant medicine. Our previous study demonstrated that thioredoxin-1 (Trx) priming of donor lung significantly protected allogeneic lung graft. To determine whether Trx priming of donor lung inhibits allograft rejection, extends allograft survival and induces immune tolerance, orthotopic left lung transplantation was performed from Lewis to Sprague-Dawley rats without immunosuppression. Donor lungs were primed with Trx at 4°C for 4 hr prior to transplantation. After up to 37 days post-transplantation, allograft lung morphology, recipient T cell and humoral alloantigen-specific immune responses were examined. We found that Trx-primed lungs exhibited much reduced acute rejection and associated lung injuries resulting in loss of graft functional area at 5-37 days post-transplant in contrast to the control groups. CD4+ T cells from the recipients with Trx-primed grafts responded to the stimulation of dendritic cells (DCs) of donor origin, in contrast to DCs from the third party, with significantly reduced proliferation. Consistent with above findings, we observed that CD4+Foxp3+ regulatory T cells in spleen cells from the recipients with Trx-primed grafts were significantly increased compared to controls, and CD4+ T cells from the recipients with Trx-primed grafts produced much higher levels of immunosuppressive cytokine, IL-10 when stimulated with allogeneic donor DCs. In addition, humoral immune tolerance was also induced as there was no significant increase levels of serum antibodies against donor antigens in Trx-lung recipients when re-challenged with allogeneic donor antigens. Our results demonstrate that one-time Trx-priming of donor lung grafts prior to transplantation significantly prolongs the survival of the grafts through inducing or promoting cellular and humoral alloantigen-specific immune tolerance, which might be associated with the induction of immunosuppressive regulatory T

  17. Thioredoxin priming prolongs lung allograft survival by promoting immune tolerance.

    Directory of Open Access Journals (Sweden)

    Hanbo Hu

    Full Text Available Tolerance to allograft antigen is the major challenge and final goal of transplant medicine. Our previous study demonstrated that thioredoxin-1 (Trx priming of donor lung significantly protected allogeneic lung graft. To determine whether Trx priming of donor lung inhibits allograft rejection, extends allograft survival and induces immune tolerance, orthotopic left lung transplantation was performed from Lewis to Sprague-Dawley rats without immunosuppression. Donor lungs were primed with Trx at 4°C for 4 hr prior to transplantation. After up to 37 days post-transplantation, allograft lung morphology, recipient T cell and humoral alloantigen-specific immune responses were examined. We found that Trx-primed lungs exhibited much reduced acute rejection and associated lung injuries resulting in loss of graft functional area at 5-37 days post-transplant in contrast to the control groups. CD4+ T cells from the recipients with Trx-primed grafts responded to the stimulation of dendritic cells (DCs of donor origin, in contrast to DCs from the third party, with significantly reduced proliferation. Consistent with above findings, we observed that CD4+Foxp3+ regulatory T cells in spleen cells from the recipients with Trx-primed grafts were significantly increased compared to controls, and CD4+ T cells from the recipients with Trx-primed grafts produced much higher levels of immunosuppressive cytokine, IL-10 when stimulated with allogeneic donor DCs. In addition, humoral immune tolerance was also induced as there was no significant increase levels of serum antibodies against donor antigens in Trx-lung recipients when re-challenged with allogeneic donor antigens. Our results demonstrate that one-time Trx-priming of donor lung grafts prior to transplantation significantly prolongs the survival of the grafts through inducing or promoting cellular and humoral alloantigen-specific immune tolerance, which might be associated with the induction of

  18. Allograft in bone tumour surgery

    International Nuclear Information System (INIS)

    Sengupta, S.

    1999-01-01

    In the last twenty years, there has been a vast improvement in the prognosis of primary malignant tumours of bone. This is due to many factors including early detection, staging and classification of tumours as a result of better staining and imaging techniques, better surgical technology, e.g. endoprosthesis and most importantly adjuvant treatment with cytotoxic drugs. As a result of long term survival, amputation of limb has more or less been replaced by limb salvage surgery. This procedure consists of two parts. Primary objective is of course complete removal of the tumour by adequate soft tissue cover and secondarily by reconstruction of the locomotor system, If possible with retention of the function of the limb. These procedures include endo-prosthetic replacement or arthroplasty and arthrodesis using autologus grafts, allograft or combination. With the development of bone banks and assured safety of preserved bones, reconstructive limb salvage surgery using massive allograft is gradually replacing prosthetic implants. The advantages include replacement of articular surfaces, incorporation of the graft to the host bone, attachment of bone tissue and increased probably permanent survival. Allograft can be used for intercalary replacement, osteo-articular arthroplasty arthrodesis or filling large cavities. Inherent complication of massive allograft are disease transmission, infection, delayed and non-union, pathological fractures, mechanical failure and joint destruction. Several limb salvage procedures using allografts have been carried out in our institution with one failure due to infection. Paucity of available allograft has restricted more such procedures to be carried out

  19. Glomerular damage as a predictor of renal allograft loss

    Directory of Open Access Journals (Sweden)

    G. Moscoso-Solorzano

    2010-06-01

    Full Text Available Interstitial fibrosis and tubular atrophy (IF/TA are the most common cause of renal graft failure. Chronic transplant glomerulopathy (CTG is present in approximately 1.5-3.0% of all renal grafts. We retrospectively studied the contribution of CTG and recurrent post-transplant glomerulopathies (RGN to graft loss. We analyzed 123 patients with chronic renal allograft dysfunction and divided them into three groups: CTG (N = 37, RGN (N = 21, and IF/TA (N = 65. Demographic data were analyzed and the variables related to graft function identified by statistical methods. CTG had a significantly lower allograft survival than IF/TA. In a multivariate analysis, protective factors for allograft outcomes were: use of angiotensin-converting enzyme inhibitor (ACEI; hazard ratio (HR = 0.12, P = 0.001, mycophenolate mofetil (MMF; HR = 0.17, P = 0.026, hepatitis C virus (HR = 7.29, P = 0.003, delayed graft function (HR = 5.32, P = 0.016, serum creatinine ≥1.5 mg/dL at the 1st year post-transplant (HR = 0.20, P = 0.011, and proteinuria ≥0.5 g/24 h at the 1st year post-transplant (HR = 0.14, P = 0.004. The presence of glomerular damage is a risk factor for allograft loss (HR = 4.55, P = 0.015. The presence of some degree of chronic glomerular damage in addition to the diagnosis of IF/TA was the most important risk factor associated with allograft loss since it could indicate chronic active antibody-mediated rejection. ACEI and MMF were associated with better outcomes, indicating that they might improve graft survival.

  20. Live Skin Allograft in the Management of Severe Burns

    African Journals Online (AJOL)

    skin substitutes to promote wound healing, reduce pain, and prevent ... into the healing wound as happens with allografts and xenografts (2). ... burns included open flames in two and hot water, hot tea and petrol in one patient each. Both children and one adult had the mothers as skin donors (Figure 1), while two adults had ...

  1. Assessment of early renal allograft dysfunction with blood oxygenation level-dependent MRI and diffusion-weighted imaging

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung Yoon [Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Chan Kyo, E-mail: chankyokim@skku.edu [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Park, Byung Kwan [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Sung Ju; Lee, Sanghoon [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Huh, Wooseong [Department of Nephrology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2014-12-15

    Highlights: • R2* and ADC in renal allografts are moderately correlated with eGFR. • R2* and ADC are lower in early allograft dysfunction than normal allograft function. • No significant difference between AR and ATN was found in both R2* and ADC. - Abstract: Purpose: To investigate blood oxygenation level-dependent (BOLD) MRI and diffusion-weighted imaging (DWI) at 3 T for assessment of early renal allograft dysfunction. Materials and methods: 34 patients with a renal allograft (early dysfunction, 24; normal, 10) were prospectively enrolled. BOLD MRI and DWI were performed at 3 T. R2* and apparent diffusion coefficient (ADC) values were measured in cortex and medulla of the allografts. Correlation between R2* or ADC values and estimated glomerular filtration rate (eGFR) was investigated. R2* or ADC values were compared among acute rejection (AR), acute tubular necrosis (ATN) and normal function. Results: In all renal allografts, cortical or medullary R2* and ADC values were moderately correlated with eGFR (P < 0.05). Early dysfunction group showed lower R2* and ADC values than normal function group (P < 0.05). AR or ATN had lower R2* values than normal allografts (P < 0.05), and ARs had lower cortical ADC values than normal allografts (P < 0.05). No significant difference of R2* or ADC values was found between AR and ATN (P > 0.05). Conclusion: BOLD MRI and DWI at 3 T may demonstrate early functional state of renal allografts, but may be limited in characterizing a cause of early renal allograft dysfunction. Further studies are needed.

  2. Prolongation of allograft survival by 1,25-dihydroxyvitamin D3.

    Science.gov (United States)

    Hullett, D A; Cantorna, M T; Redaelli, C; Humpal-Winter, J; Hayes, C E; Sollinger, H W; Deluca, H F

    1998-10-15

    1,25-Dihydroxyvitamin D3, the hormonal form of vitamin D, is now believed to play a significant role in the immune responses, both in vitro and in vivo, preventing the development of several autoimmune diseases. These studies suggest that 1,25-dihydroxyvitamin D3 may be effective in prolonging allograph survival. To test the hypothesis that 1,25-dihydroxyvitamin D3 would prolong allograft survival, neonatal heart grafts were transplanted to allogeneic recipients receiving either 19-nor-1,25-dihydroxyvitamin D2 (200 ng/day) or 1,25-dihydroxyvitamin D3 (50 ng/mouse/day) orally through the diet. The efficacy of 1,25-dihydroxyvitamin D3 in prolonging graft survival in a vascularized model was determined by heterotopic ACI to Lewis heart transplants. The provision of exogenous 1,25-dihydroxyvitamin D3 or an analog, 19-nor-1,25-dihydroxyvitamin D2, to mice markedly prolonged the survival of neonatal mouse heart allografts. Similar results were obtained with a vascularized heterotopic heart transplant model in rats. Cyclosporine at a maximum 25 mg/kg dose for mice proved less effective than 1,25-dihydroxyvitamin D3. Graft survival in mice differing at class I and class II loci (B10.A(4R) --> C57BL/10) increased from 13.0+/-1.1 days to 51.0+/-5.6 days and was significantly better than cyclosporine monotherapy (33.2+/-3.6). Rat heart survival in a high responder strain combination (ACI --> Lewis) increased from 6.2+/-0.3 to 25.2+/-2.8 days. The increased survival of the transplants brought about with 1,25-dihydroxyvitamin D3 was not accompanied by hypercalcemia in rats. These results suggest that 1,25-dihydroxyvitamin D3 can be used as an effective agent in preventing graft rejection.

  3. Changing Paradigms in the Management of Rejection in Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    Mirela Maier

    2017-01-01

    Full Text Available Purpose of review: P4 medicine denotes an evolving field of medicine encompassing predictive, preventive, personalized, and participatory medicine. Using the example of kidney allograft rejection because of donor-recipient incompatibility in human leukocyte antigens, this review outlines P4 medicine’s relevance to the various stages of the kidney transplant cycle. Sources of information: A search for English articles was conducted in Medline via OvidSP (up to August 18, 2016 using a combination of subject headings (MeSH and free text in titles, abstracts, and author keywords for the concepts kidney transplantation and P4 medicine. The electronic database search was expanded further on particular subject headings. Findings: Available histocompatibility methods exemplify current applications of the predictive and preventive domains of P4 medicine in kidney transplant recipients’ care. Pharmacogenomics are discussed as means to facilitate personalized immunosuppression regimens and promotion of active patient participation as a means to improve adherence. Limitations: For simplicity, this review focuses on rejection. P4 medicine, however, should more broadly address health concerns in kidney transplant recipients, including competing outcomes such as infections, malignancies, and cardiovascular disease. This review highlights how biomarkers to evaluate these competing outcomes warrant validation and standardization prior to their incorporation into clinical practice. Implications: Consideration of all 4 domains of the P4 medicine framework when caring for and/or studying kidney transplant recipients has the potential of increasing therapeutic efficiency, minimizing adverse effects, decreasing health care costs, and maximizing wellness. Technologies to gauge immune competency, immunosuppression requirements, and early/reversible immune-mediated injuries are required to optimize kidney transplant care.

  4. Changing Paradigms in the Management of Rejection in Kidney Transplantation

    Science.gov (United States)

    Maier, Mirela; Takano, Tomoko; Sapir-Pichhadze, Ruth

    2017-01-01

    Purpose of review: P4 medicine denotes an evolving field of medicine encompassing predictive, preventive, personalized, and participatory medicine. Using the example of kidney allograft rejection because of donor-recipient incompatibility in human leukocyte antigens, this review outlines P4 medicine’s relevance to the various stages of the kidney transplant cycle. Sources of information: A search for English articles was conducted in Medline via OvidSP (up to August 18, 2016) using a combination of subject headings (MeSH) and free text in titles, abstracts, and author keywords for the concepts kidney transplantation and P4 medicine. The electronic database search was expanded further on particular subject headings. Findings: Available histocompatibility methods exemplify current applications of the predictive and preventive domains of P4 medicine in kidney transplant recipients’ care. Pharmacogenomics are discussed as means to facilitate personalized immunosuppression regimens and promotion of active patient participation as a means to improve adherence. Limitations: For simplicity, this review focuses on rejection. P4 medicine, however, should more broadly address health concerns in kidney transplant recipients, including competing outcomes such as infections, malignancies, and cardiovascular disease. This review highlights how biomarkers to evaluate these competing outcomes warrant validation and standardization prior to their incorporation into clinical practice. Implications: Consideration of all 4 domains of the P4 medicine framework when caring for and/or studying kidney transplant recipients has the potential of increasing therapeutic efficiency, minimizing adverse effects, decreasing health care costs, and maximizing wellness. Technologies to gauge immune competency, immunosuppression requirements, and early/reversible immune-mediated injuries are required to optimize kidney transplant care. PMID:28270929

  5. Effects of Lung Cotransplantation on Cardiac Allograft Tolerance Across a Full Major Histocompatibility Complex Barrier in Miniature Swine.

    Science.gov (United States)

    Madariaga, M L L; Spencer, P J; Michel, S G; La Muraglia, G M; O'Neil, M J; Mannon, E C; Leblang, C; Rosales, I A; Colvin, R B; Sachs, D H; Allan, J S; Madsen, J C

    2016-03-01

    A 12-day course of high-dose tacrolimus induces tolerance of major histocompatibility complex-mismatched lung allografts in miniature swine but does not induce tolerance of heart allografts unless a kidney is cotransplanted. To determine whether lungs share with kidneys the ability to induce cardiac allograft tolerance, we investigated heart-lung cotransplantation using the same induction protocol. Hearts (n = 3), heart-kidneys (n = 3), lungs (n = 6), and hearts-lungs (n = 3) were transplanted into fully major histocompatibility complex-mismatched recipients treated with high-dose tacrolimus for 12 days. Serial biopsy samples were used to evaluate rejection, and in vitro assays were used to detect donor responsiveness. All heart-kidney recipients and five of six lung recipients demonstrated long-term graft survival for longer than 272 days, while all heart recipients rejected their allografts within 35 days. Tolerant recipients remained free of alloantibody and showed persistent donor-specific unresponsiveness by cell-mediated lympholysis/mixed-lymphocyte reaction. In contrast, heart-lung recipients demonstrated rejection of both allografts (days 47, 55, and 202) and antidonor responsiveness in vitro. In contrast to kidneys, lung cotransplantation leads to rejection of both heart and lung allografts, indicating that lungs do not have the same tolerogenic capacity as kidneys. We conclude that cells or cell products present in kidney, but not heart or lung allografts, have a unique capacity to confer unresponsiveness on cotransplanted organs, most likely by amplifying host regulatory mechanisms. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  6. Hyperacute Rejection of a Living Unrelated Kidney Graft

    Directory of Open Access Journals (Sweden)

    Dietlind Tittelbach-Helmrich

    2014-01-01

    Full Text Available We present a case report of a 59-year-old man, who received a blood group identical living unrelated kidney graft. This was his second kidney transplantation. Pretransplant T-cell crossmatch resulted negative. B-cell crossmatch, which is not considered a strict contraindication for transplantation, resulted positive. During surgery no abnormalities occurred. Four hours after the transplantation diuresis suddenly decreased. In an immediately performed relaparotomy the transplanted kidney showed signs of hyperacute rejection and had to be removed. Pathological examination was consistent with hyperacute rejection. Depositions of IgM or IgG antibodies were not present in pathologic evaluation of the rejected kidney, suggesting that no irregular endothelial specific antibodies had been involved in the rejection. We recommend examining more closely recipients of second allografts, considering not only a positive T-cell crossmatch but also a positive B-cell crossmatch as exclusion criteria for transplantation.

  7. Proteinuria after kidney transplantation, relationship to allograft histology and survival.

    Science.gov (United States)

    Amer, H; Fidler, M E; Myslak, M; Morales, P; Kremers, W K; Larson, T S; Stegall, M D; Cosio, F G

    2007-12-01

    Proteinuria is associated with reduced kidney allograft survival. Herein we assessed the association between proteinuria, graft histology and survival. The cohort included 613 kidney allograft recipients who had proteinuria (measured) and surveillance biopsies at 1-year posttransplant. Proteinuria >150 mg/day was detected in 276 patients (45%) and in 182 of these, proteinuria was below 500. In >84% of patients even low levels of proteinuria were associated with albuminuria. Proteinuria was associated with the presence of graft glomerular pathology and the use of sirolimus. Eighty percent of patients with proteinuria >1500 mg/day had glomerular pathology on biopsy. However, lower levels of proteinuria were not associated with specific pathologies at 1 year. Compared to no sirolimus, sirolimus use was associated with higher prevalence of proteinuria (40% vs. 76%, p Proteinuria was associated with reduced graft survival (HR = 1.40, p = 0.001) independent of other risk factors including, glomerular pathology, graft function, recipient age and acute rejection. The predominant pathology in lost allografts (n = 57) was glomerular, particularly in patients with 1-year proteinuria >500. Thus, proteinuria, usually at low levels (proteinuria relate to poor graft survival. Proteinuria and glomerular pathology relate independently to survival.

  8. Multidetector computed tomography findings of spontaneous renal allograft ruptures

    Energy Technology Data Exchange (ETDEWEB)

    Basaran, C. [Department of Radiology, Baskent University Faculty of Medicine, Ankara (Turkey)], E-mail: ceylab@baskent-ank.edu.tr; Donmez, F.Y.; Tarhan, N.C.; Coskun, M. [Department of Radiology, Baskent University Faculty of Medicine, Ankara (Turkey); Haberal, M. [Department of General Surgery, Baskent University Faculty of Medicine, Ankara (Turkey)

    2009-05-15

    Aim: To describe the characteristics of spontaneous renal allograft rupture using multidetector computed tomography (MDCT). Method: Five patients with spontaneous renal allograft rupture, as confirmed by pathologic examination, were referred to our institution between 1985 and 2008. The clinical records and preoperative MDCT findings of the patients were studied retrospectively. Results: Clinical and/or histological findings were consistent with acute rejection in all cases. Using MDCT, disruption of the capsular integrity and parenchymal rupture was seen in four patients. Four of the five patients showed decreased enhancement and swollen grafts. Perirenal (n = 4), subcapsular (n = 1), and intraparenchymal (n = 1) haematomas were also seen. In the patient with an intraparenchymal haematoma there was no disruption of capsular integrity, but capsular irregularities were seen near the haematoma. Conclusion: MDCT is a useful investigative tool for the evaluation of suspected spontaneous renal allograft rupture. As well as a swollen graft, disruption of the capsule, parenchyma, and/or haematoma should prompt the radiologist to consider this diagnosis.

  9. Biomechanical properties of bone allografts

    International Nuclear Information System (INIS)

    Pelker, R.R.; Friedlaender, G.E.; Markham, T.C.

    1983-01-01

    The biomechanical properties of allograft bone can be altered by the methods chosen for its preservation and storage. These effects are minimal with deep-freezing or low-level radiation. Freeze-drying, however, markedly diminishes the torsional and bending strength of bone allografts but does not deleteriously affect the compressive or tensile strength. Irradiation of bone with more than 3.0 megarad or irradiation combined with freeze-drying appears to cause a significant reduction in breaking strength. These factors should be considered when choosing freeze-dried or irradiated allogeneic bone that will be subjected to significant loads following implantation

  10. 100 second renal allografts from a single transplantation institution.

    Science.gov (United States)

    Ascher, N L; Ahrenholz, D H; Simmons, R L; Najarian, J S

    1979-01-01

    Between January 1, 1968 and March 1977, 100 of 131 patients who lost their first transplant at the University of Minnesota received a second renal allograft. Overall patient survival in the retransplanted group was 10% less than that in the dialysis group. The best results (graft function and patient survival were seen in young patients, nondiabetics, patients who received two sequential living related groups, and in those whose first graft was lost secondary to chronic rejection. The poorest results were seen in older patients (greater than 40 years), diabetics, and patients with acute rejection during the initial graft. Shared donor antigens do not affect graft outcome. These findings, although not the product of a randomized prospective study, may be useful in advising patients of the relative risks of retransplantation or hemodialysis.

  11. The treatment of peripheral nerve injuries using irradiated allografts and temporary host immunosuppression (in a rat model)

    International Nuclear Information System (INIS)

    Easterling, K.J.; Trumble, T.E.

    1990-01-01

    Irradiation of allografts prior to transplantation and host immunosuppression with cyclosporin-A were studied separately and in combination as means of lessening the rejection of transplanted peripheral nerve tissue. Lewis and Brown Norway rats were used in the animal model, as they differ at both major and minor histocompatibility loci. Sciatic nerve grafts (2.5 cm) were used and the animals were followed for 16 weeks after nerve grafting. The outcome was studied by functional measurements (sensory testing, gait analysis, joint flexion contracture, and muscle weight), as well as by measurements of biochemical and histologic parameters (hydroxyproline concentration and axon counts, respectively). Sensory testing was not reliable because of crossover innervation by the saphenous nerve. Evaluation by standard gait-testing techniques was found to be unsatisfactory. However, the allografted animals receiving cyclosporin-A had significantly smaller flexion contractures, compared to the allografted animals without immunosuppression (17 degrees +/- 12 degrees vs. 44 degrees +/- 13 degrees and 51 degrees +/- 13 degrees, p less than 0.005). Allografted animals receiving short-term cyclosporin-A had contractures that were not significantly different from those seen in isografted control animals (17 degrees +/- 12 degrees vs. 22 degrees +/- 15 degrees, NS). Muscle hydroxyproline concentration analysis revealed a lower hydroxyproline concentration among the allografted groups that received irradiated allografts, compared to groups receiving nonirradiated allogeneic grafts. The studies of muscle hydroxyproline concentration and muscle weight both showed substantial reinnervation, even in allografted animals without pretreatment of the grafts or immunosuppression of the recipient animal

  12. The treatment of peripheral nerve injuries using irradiated allografts and temporary host immunosuppression (in a rat model)

    Energy Technology Data Exchange (ETDEWEB)

    Easterling, K.J.; Trumble, T.E. (Yale Univ. School of Medicine, New Haven, CT (USA))

    1990-10-01

    Irradiation of allografts prior to transplantation and host immunosuppression with cyclosporin-A were studied separately and in combination as means of lessening the rejection of transplanted peripheral nerve tissue. Lewis and Brown Norway rats were used in the animal model, as they differ at both major and minor histocompatibility loci. Sciatic nerve grafts (2.5 cm) were used and the animals were followed for 16 weeks after nerve grafting. The outcome was studied by functional measurements (sensory testing, gait analysis, joint flexion contracture, and muscle weight), as well as by measurements of biochemical and histologic parameters (hydroxyproline concentration and axon counts, respectively). Sensory testing was not reliable because of crossover innervation by the saphenous nerve. Evaluation by standard gait-testing techniques was found to be unsatisfactory. However, the allografted animals receiving cyclosporin-A had significantly smaller flexion contractures, compared to the allografted animals without immunosuppression (17 degrees +/- 12 degrees vs. 44 degrees +/- 13 degrees and 51 degrees +/- 13 degrees, p less than 0.005). Allografted animals receiving short-term cyclosporin-A had contractures that were not significantly different from those seen in isografted control animals (17 degrees +/- 12 degrees vs. 22 degrees +/- 15 degrees, NS). Muscle hydroxyproline concentration analysis revealed a lower hydroxyproline concentration among the allografted groups that received irradiated allografts, compared to groups receiving nonirradiated allogeneic grafts. The studies of muscle hydroxyproline concentration and muscle weight both showed substantial reinnervation, even in allografted animals without pretreatment of the grafts or immunosuppression of the recipient animal.

  13. 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

  14. Heart Allograft Tolerance Induced and Maintained by Vascularized Hind-Limb Transplant in Rats

    Directory of Open Access Journals (Sweden)

    Quan Liu

    2013-01-01

    Full Text Available Organ/tissue transplantation has become an effective therapy for end-stage diseases. However, immunosuppression after transplantation may cause severe side effects. Donor-specific transplant tolerance was proposed to solve this problem. In this study, we report a novel method for inducing and maintaining heart allograft tolerance rats. First, we induced indefinite vascularized hind-limb allograft survival with a short-term antilymphocyte serum + Cyclosporine A treatment. Peripheral blood chimerism disappeared 6-7 weeks after immunosuppression was withdrawn. Then the recipients accepted secondary donor-strain skin and heart transplantation 200 days following vascularized hind-limb transplantation without any immunosuppression, but rejected third party skin allografts, a status of donor-specific tolerance. The ELISPOT results suggested a mechanism of clone deletion. These findings open new perspectives for the role of vascularized hind-limb transplant in the induction and maintenance of organ transplantation tolerance.

  15. Current perspectives on antibody-mediated rejection after lung transplantation

    Directory of Open Access Journals (Sweden)

    Witt CA

    2014-10-01

    Full Text Available Chad A Witt, Ramsey R Hachem Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, Saint Louis, MO, USA Abstract: The role of donor-specific antibodies (DSA to human leukocyte antigens and the burden of antibody-mediated rejection (AMR in lung transplantation remain enigmatic. Over the past several years, evidence has been emerging that humoral immunity plays an important role in the development of both acute and chronic lung allograft dysfunction (CLAD. Multiple case reports and case series have identified lung allograft recipients with clinical findings consistent with acute AMR. However, there is currently no widely accepted definition for AMR in lung transplantation, and this has been a significant barrier to furthering our understanding of this form of rejection. Nonetheless, the development of DSA after transplantation has consistently been identified as an independent risk factor for persistent and high-grade acute cellular rejection and CLAD. This has raised the possibility that chronic AMR may be a distinct phenotype of CLAD although evidence supporting this paradigm is still lacking. Additionally, antibodies to lung-restricted self-antigens (collagen V and K-α 1 tubulin have been associated with primary graft dysfunction early and the development of CLAD late after transplantation, and emerging evidence underscores significant interactions between autoimmunity and alloimmunity after transplantation. There is currently an active International Society for Heart and Lung Transplantation working group that is developing an operational definition for AMR in lung transplantation. This will be critical to improve our understanding of this form of rejection and conduct clinical trials to identify optimal treatment strategies. This review will summarize the literature on DSA and AMR in lung transplantation and discuss the impact of antibodies to self-antigens on lung

  16. Emphysema in the renal allograft

    Energy Technology Data Exchange (ETDEWEB)

    Potter, J.L.; Sullivan, B.M.; Fluornoy, J.G.; Gerza, C.

    1985-04-01

    Two diabetic patients in whom emphysematous pyelonephritis developed after renal transplantation are described. Clinical recognition of this unusual and serious infection is masked by the effects of immunosuppression. Abdominal radiographic, ultrasound, and computed tomography findings are discussed. The clinical presentation includes urinary tract infection, sepsis, and acute tubular malfunction of the allograft in insulin-dependent diabetics.

  17. Combining autologous dendritic cell therapy with CD3 antibodies promotes regulatory T cells and permanent islet allograft acceptance

    NARCIS (Netherlands)

    Baas, M.C.; Kuhn, C.; Valette, F.; Mangez, C.; Duarte, M.S.; Hill, M.; Besancon, A.; Chatenoud, L.; Cuturi, M.C.; You, S.

    2014-01-01

    Cell therapy and the use of mAbs that interfere with T cell effector functions constitute promising approaches for the control of allograft rejection. In the current study, we investigated a novel approach combining administration of autologous tolerogenic dendritic cells with short-term treatment

  18. Pretransplant serum BAFF levels are associated with pretransplant HLA immunization and renal allograft survival.

    Science.gov (United States)

    Friebus-Kardash, Justa; Wilde, Benjamin; Keles, Deniz; Heinold, Andreas; Kribben, Andreas; Witzke, Oliver; Heinemann, Falko Markus; Eisenberger, Ute

    2018-04-01

    The essential function of B cell-activating factor (BAFF) is regulating the survival and differentiation of B cells. The link between pretransplant BAFF levels and pretransplant alloimmunization and its value to predict subsequent acute antibody-mediated rejection (AMR) and outcome after renal transplantation is not fully understood. Objective of our retrospective single-center study was to determine, by ELISA analysis of pretransplant serum BAFF levels in 249 patients undergoing renal transplantation, association between preformed anti-human leukocyte antigen (HLA) antibodies, occurrence of acute antibody mediated rejection (AMR) and renal allograft survival. Pretransplant serum BAFF levels were significantly higher in presensitized recipients with anti-HLA antibodies (3262±2796pg/ml) than in recipients without occurrence of anti-HLA antibodies (2252±1425pg/ml; pBAFF levels correlated with cumulative MFI values of anti-HLA antibodies (r=0.2966, p=0.0025). Patients with high pretransplant BAFF levels (≥2137pg/ml) experienced significantly lower allograft survival rates compared to low pretransplant BAFF levels (80% vs. 91%; p=0.01). Coexistence of high pretransplant BAFF levels and posttransplant AMR was associated with the worst allograft survival rates (56%). Relative risk (RR) for allograft loss was associated with high serum BAFF levels (RR 2.3; p=0.02), presence of anti-HLA antibodies (RR 2.5; p=0.007) or anti-HLA -donor-specific antibodies (DSAs) (RR 2.6; p=0.003) before transplant and AMR post transplant (RR 2.5; p=0.007). AMR was the strongest independent risk factor for allograft failure (RR 2.6; p=0.03). Elevated pretransplant serum BAFF levels negatively affect renal allograft survival and represent a risk factor for allosensitization and subsequent AMR. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Early detection of femoral head avascular necrosis by bone SPECT compared to MRI in renal allograft recipients

    International Nuclear Information System (INIS)

    Kang, Do Young; Yang, Seoung Oh; Lee, Hee Kyung; Han, Duck Jong; Shin, Myung Jin

    1997-01-01

    The prevalence of avascular necrosis (AVN) of femoral head in patients who receive immunosuppresive agents after renal transplantation is reported to be 4-29%. Among patients who develop AVN after renal transplantation, 80% become symptomatic within 2 years after transplantation. As the number of renal transplantation has been increased recently, early detection of femoral head AVN is very important because early surgical core decompression of femoral head can prevent collapse of the head. MRI is known to be very sensitive to diagnose femoral head AVN. However in three cases we report here, bone SPECT showed early changes of femoral head AVN, whereas MRI showed no specific abnormality. Case 1. A 53-year-old female received an allograft kidney transplantation in 1994. Preoperative bone scan was normal. She complained of both hip pain on Mar. 18 1997. Bone SPECT showed cold defect in both femoral heads but MRI showed no abnormality. After 3 months, bone SPECT and MRI showed AVN of both femoral heads. She underwent bilateral total hip replacement arthroplasty. AVN of femoral heads was confirmed by microscopic examination. Case 2. A 38-year-old female received an allograft kidney transplantation in Feb. 27 1997. Preoperative bone scan was normal. She ran a fever and creatinine was elevated from 1.2 to 2.8 mg/dL. She took high dose methylprednisolone therapy for acute reanl rejection. After two days, she complained pain in both hip joints and knee joints. Bone SPECT showed cold defects in both femoral heads but MRI showed no abnormality. A follow-up bone SPECT and MRI 20 days later revealed AVN of both femoral heads. Case 3. A 50-year-old male received an allograft kidney transplantation on Jul. 12 1995. Preoperative bone scan was normal. He complained of right hip pain on Jul, 26 1995. His bone SPECT showed cold defects in both femoral heads while MRI showed only minimal hip joint effusion. He also complained of left hip pain on Oct. 2 1995. He was admitted on Mar 17

  20. Early detection of femoral head avascular necrosis by bone SPECT compared to MRI in renal allograft recipients

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Do Young; Yang, Seoung Oh; Lee, Hee Kyung; Han, Duck Jong; Shin, Myung Jin [Asan Mecical Center, Seoul (Korea, Republic of)

    1997-07-01

    The prevalence of avascular necrosis (AVN) of femoral head in patients who receive immunosuppresive agents after renal transplantation is reported to be 4-29%. Among patients who develop AVN after renal transplantation, 80% become symptomatic within 2 years after transplantation. As the number of renal transplantation has been increased recently, early detection of femoral head AVN is very important because early surgical core decompression of femoral head can prevent collapse of the head. MRI is known to be very sensitive to diagnose femoral head AVN. However in three cases we report here, bone SPECT showed early changes of femoral head AVN, whereas MRI showed no specific abnormality. Case 1. A 53-year-old female received an allograft kidney transplantation in 1994. Preoperative bone scan was normal. She complained of both hip pain on Mar. 18 1997. Bone SPECT showed cold defect in both femoral heads but MRI showed no abnormality. After 3 months, bone SPECT and MRI showed AVN of both femoral heads. She underwent bilateral total hip replacement arthroplasty. AVN of femoral heads was confirmed by microscopic examination. Case 2. A 38-year-old female received an allograft kidney transplantation in Feb. 27 1997. Preoperative bone scan was normal. She ran a fever and creatinine was elevated from 1.2 to 2.8 mg/dL. She took high dose methylprednisolone therapy for acute reanl rejection. After two days, she complained pain in both hip joints and knee joints. Bone SPECT showed cold defects in both femoral heads but MRI showed no abnormality. A follow-up bone SPECT and MRI 20 days later revealed AVN of both femoral heads. Case 3. A 50-year-old male received an allograft kidney transplantation on Jul. 12 1995. Preoperative bone scan was normal. He complained of right hip pain on Jul, 26 1995. His bone SPECT showed cold defects in both femoral heads while MRI showed only minimal hip joint effusion. He also complained of left hip pain on Oct. 2 1995. He was admitted on Mar 17

  1. Infections and solid organ transplant rejection: a cause-and-effect relationship?

    Science.gov (United States)

    Cainelli, Francesca; Vento, Sandro

    2002-09-01

    Although evidence is far from being conclusive, several studies have suggested that infections could trigger rejection in different transplant settings. In this review we examine the evidence linking cytomegalovirus (CMV), adenovirus, enterovirus, parvovirus, and herpes simplex virus infections to the vasculopathy leading to cardiac allograft rejection, the association between CMV and chronic kidney, lung, and liver graft rejection, and the association of human herpesvirus 6 reactivation with CMV-related disease in kidney and liver transplant recipients. We also review the numerous antiviral prophylactic or pre-emptive treatments in use to control CMV infection, and suggest that they do not limit immune reactions leading to graft rejection or lower the risk of developing post-transplantation atherosclerosis in allograft recipients. Finally, we emphasise the need for prospective, international studies to clarify the role of infections in transplant rejection, to look at virus-to-virus interactions, and to establish specific therapeutic strategies. Such strategies must not rely exclusively on expensive antiviral agents but also on vaccination or other, innovative approaches, such as the use of agents able to inhibit the activity of natural killer cells, which might have an important role in acute allograft rejection.

  2. Diagnostic significance of semiquantitative and quantitative parameters of Tc99m-Ethylenedicystine renal allograft scintigraphy.

    Science.gov (United States)

    Barai, Sukanta; Kumar, Rakesh; Mehta, Sada Nand; Dinda, Amit Kumar; Yadav, Rajiv; Bandopadhayaya, Guru Pada; Tarun, Singhal; Malhotra, Arun

    2003-01-01

    No objective parameters for renal allograft evaluation have yet been described for Tc99m-Ethylenedicystine. This study evaluates the diagnostic significance of different quantitative and semi-quantitative parameters of renal allograft scintigraphy using Tc99m-Ethylenedicystine. A total of 72 renal dynamic scintigraphic studies were performed within 2-weeks of renal transplantation in 42 patients. The graft perfusion, kidney/aorta ratio, washout index and retention index were derived from all studies. All these parameters were evaluated for their ability to distinguish between a normal graft, a graft with acute rejection (AR), and a graft with acute tubular necrosis (ATN). Histopathological verification of diagnosis was obtained in all cases. Studies were subdivided into 3 groups according to histopathological findings: acute rejection (n = 42), normal (n = 18) and acute tubular necrosis (n = 12). Normal allografts were visualized with in 2.66 +/- 0.59 seconds of visualization of abdominal aorta. The K/A ratio, wash out index and retention index was 15.22 +/- 6.86, 1.67 +/- 0.45, and 5.48 +/- 0.98 respectively. Allografts with ATN were visualized with in 3.36 +/- 0.80 seconds of visualization of abdominal aorta. The K/A ratio, wash out index and retention index was 12.73 +/- 6.74, 0.60 +/- 0.14, and 9.18 +/- 1.48 respectively. In AR, allografts were visualized 15.18 +/- 9.48 seconds after visualization of abdominal aorta. The K/A ratio, wash out index and retention index was 7.07 +/- 2.15, 0.63 +/- 0.11, and 2.26 +/- 1.28 respectively. Retention index can separate all the three condition of normal, acute rejection and acute tubular necrosis from each other. Retention index of or = 7 is suggestive of acute tubular necrosis. However, perfusion, K/A ratio and washout index can not segregate all the three groups.

  3. Pulsed-wave transmitral Doppler do not diagnose moderate acute rejection after heart transplantation

    NARCIS (Netherlands)

    Mannaerts, H. F.; Simoons, M. L.; Balk, A. H.; Tijssen, J.; van der Borden, S. G.; Zondervan, P. E.; Mochtar, B.; Weimar, W.; Roelandt, J. R.

    1993-01-01

    The value of pulsed-wave transmitral Doppler for the diagnosis of moderate acute rejection was examined in a total of 347 Doppler recordings obtained in 32 consecutive cardiac allograft recipients. Serial Doppler examinations (median, 11 per patient; range, 1 to 23) were performed simultaneously

  4. PULSED-WAVE TRANSMITRAL DOPPLER DO NOT DIAGNOSE MODERATE ACUTE REJECTION AFTER HEART-TRANSPLANTATION

    NARCIS (Netherlands)

    MANNAERTS, HF; SIMOONS, ML; BALK, AH; TIJSSEN, J; VANDERBORDEN, SG; ZONDERVAN, PE; MOCHTAR, B; WEIMAR, W; ROELANDT, [No Value

    1993-01-01

    The value of pulsed-wave transmitral Doppler for the diagnosis of moderate acute rejection was examined in a total of 347 Doppler recordings obtained in 32 consecutive cardiac allograft recipients. Serial Doppler examinations (median, 11 per patient; range, 1 to 23) were performed simultaneously

  5. Role of allografts in spinal surgery

    International Nuclear Information System (INIS)

    Aziz Nather

    1999-01-01

    With development of more tissue banks in the region and internationally, allografts are increasingly being used in orthopaedic surgery including spinal surgery. Two groups of patients will particularly benefit from the use of allografts. The first group is young children in whom iliac crest is cartilaginous and cannot provide sufficient quantity of autografts. The second is the elderly where bones from iliac crest are porotic and fatty. Allografts are used to fulfill two distinct functions in Spinal Surgery. One is to act as a buttress for anterior spinal surgery using cortical allografts. The other is to enhance fusion for posterior spinal surgery. Up to December 1997, 71 transplantations have been performed using allografts from NUH Tissue Bank. Anterior Spinal Surgery has been performed in 15 cases. The indications are mainly Trauma-Burst Fractures and Spinal Secondaries to the Spine. All cases are in thoracic and thoracolumbar region. Allografts used are deep frozen and freeze-dried cortical allografts. Femur is used for thoraco-lumbar region and humerus for upper thoracic region. Instrumentation used ranged from anterior devices (Canada, DCP, Synergy etc) to posterior devices (ISOLA). Deep frozen allografts and more recently freeze-dried allografts are preferred especially for osteoporotic spines. Cortical allografts are packed with autografts from ribs in the medullary canal. Allograft-autograft composites are always used to ensure better incorporation. Postero-lateral fusion has been performed for 56 cases. The indications include congenital and idiopathic scoliosis, degenerative stenosis, degenerative spondylolisthesis, spondylolytic spondylolisthesis, fracture-dislocation, osteoporotic burst fracture, spinal secondaries with cord compression and traumatic spondylolisthesis. Deep frozen bone allografts are used in combination with patient's own autografts from spinous processes to provide a 50% mix. Instrumentation used include Hartshill, Steffee, Isola

  6. CT perfusion technique for assessment of early kidney allograft dysfunction: preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Helck, A.; Notohamiprodjo, M.; Schoen, F.; Nikolaou, K.; Clevert, D.A.; Reiser, M.; Becker, C. [Ludwig-Maximilians-University of Munich, Department of Clinical Radiology, University Hospitals Grosshadern, Munich (Germany); Wessely, M.; Schoenermarck, U.; Fischereder, M. [Ludwig-Maximilians-University of Munich, Department of Internal Medicine IV, Nephrology, University Hospitals Grosshadern, Munich (Germany); Klotz, E. [Siemens Healthcare, Computed Tomography, Forchheim (Germany)

    2013-09-15

    To assess the benefit of quantitative computed tomography (CT) perfusion for differentiating acute tubular necrosis (ATN) and acute rejection (AR) in kidney allografts. Twenty-two patients with acute kidney allograft dysfunction caused by either AR (n = 6) or ATN (n = 16) were retrospectively included in the study. All patients initially underwent a multiphase CT angiography (CTA) protocol (12 phases, one phase every 3.5 s) covering the whole graft to exclude acute postoperative complications. Multiphase CT dataset and dedicated software were used to calculate renal blood flow. Renal biopsy or clinical course of disease served as the standard of reference. Mean effective radiation dose and mean amount of contrast media were calculated. Renal blood flow values were significantly lower (P = 0.001) in allografts undergoing AR (48.3 {+-} 21 ml/100 ml/min) compared with those with ATN (77.5 {+-} 21 ml/100 ml/min). No significant difference (P = 0.71) was observed regarding creatinine level with 5.65 {+-} 3.1 mg/dl in AR and 5.3 {+-} 1.9 mg/dl in ATN. The mean effective radiation dose of the CT perfusion protocol was 13.6 {+-} 5.2 mSv; the mean amount of contrast media applied was 34.5 {+-} 5.1 ml. All examinations were performed without complications. CT perfusion of kidney allografts may help to differentiate between ATN and rejection. (orig.)

  7. Effects of gamma-irradiation on the rejection of transplanted scale melanophores in the teleost, Oryzias latipes

    International Nuclear Information System (INIS)

    Kikuchi, S.; Egami, N.

    1983-01-01

    The effects of gamma-irradiation on allograft rejection in the teleost, Oryzias latipes, were examined at 25 degrees C. The survival of melanophores in the transplanted scale was observed as an index of rejection. Allografts were rejected in non-irradiated fish within 7 days. In the gamma-irradiated recipients (2kR), the grafts were rejected more slowly, but still within 20 days. The gamma-ray effects, however, disappeared almost completely within 25 days after the irradiation. If the same recipient again received transplants, the secondary response occurred clearly and the melanophores were rejected very rapidly. The secondary response was suppressed by gamma-rays if the fish was irradiated just before the second transplantation. Immunologic memory against the first transplants disappeared within 30 days, a period shorter than that of mammals

  8. Organ transplant tissue rejection: detection and staging by fluorescence spectroscopy

    Science.gov (United States)

    MacAulay, Calum E.; Whitehead, Peter D.; McManus, Bruce; Zeng, Haishan; Wilson-McManus, Janet; MacKinnon, Nick; Morgan, David C.; Dong, Chunming; Gerla, Paul; Kenyon, Jennifer

    1998-07-01

    Patients receiving heart or other organ transplants usually require some level of anti-rejection drug therapy, most commonly cyclosporine. The rejection status of the organ must be monitored to determine the optimal anti-rejection drug therapy. The current method for monitoring post-transplant rejection status of heart transplant patients consists of taking biopsies from the right ventricle. In this work we have developed a system employing optical and signal-processing techniques that will allow a cardiologist to measure spectral changes associated with tissue rejection using an optical catheter probe. The system employs time gated illumination and detection systems to deal with the dynamic signal acquisition problems associated with in vivo measurements of a beating heart. Spectral data processing software evaluates and processes the data to produce a simple numerical score. Results of measurements made on 100 excised transplanted isograft and allograft rat hearts have demonstrated the ability of the system to detect the presence of rejection and to accurately correlate the spectroscopic results with the ISHLT (International Society for Heart and Lung Transplantation) stage of rejection determined by histopathology. In vivo measurements using a pig transplant model are now in process.

  9. 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.

  10. Role of Soluble ST2 as a Marker for Rejection after Heart Transplant.

    Science.gov (United States)

    Lee, Ga Yeon; Choi, Jin-Oh; Ju, Eun-Seon; Lee, Yoo-Jung; Jeon, Eun-Seok

    2016-11-01

    Endomyocardial biopsy is obligatory during the first year after heart transplant (HTx) for the surveillance of acute rejection. Previous attempts using cardiac biomarkers for the detection of rejection failed to show enough evidence to substitute endomyocardial biopsy. Therefore, this study sought the possibility of using soluble ST2 (sST2), a novel cardiovascular marker, as a surrogate marker for acute allograft rejection after HTx. A total of 494 blood samples acquired at the time of endomyocardial biopsy were analyzed in 67 HTx cases from September 2006 to August 2014. Significant rejection was defined as International Society of Heart and Lung Transplant (ISHLT) score ≥2R and humoral rejection accompanied by hemodynamic instability. Twenty cases of HTx with 22 blood samples showed significant rejection in endomyocardial biopsy at 4.0 (2.0-9.0) months after HTx. The level of sST2 showed positive correlation with cardiac troponin I, and N-terminal pro-B-type natriuretic peptide (all prejection) (p=0.003). However, when we studied within-subject effects of sST2 using a mixed model, the sST2 level according to the predefined time point was not different according to the presence of significant rejection (p for interaction=0.94). Although sST2 is known as a promising predictor for cardiovascular events, its role in HTx patients to predict acute allograft rejection seems to be limited.

  11. Tubular and endothelial chimerism in renal allografts using fluorescence and chromogenic in situ hybridization (FISH, CISH) technology.

    Science.gov (United States)

    Varga, Zsuzsanna; Gaspert, Ariana; Behnke, Silvia; von Teichman, Adriana; Fritzsche, Florian; Fehr, Thomas

    2012-04-01

    The role of endothelial and tubular chimerism in renal allograft adaptation and rejection varies in different studies. We addressed the correlation between different clinico-pathological settings and sex-chromosomal endothelial and/or tubular chimerism in renal allografts. We examined the presence or absence of the X and Y chromosomes by fluorescence and chromogenic in situ hybridization (FISH, CISH) methodology on paraffin embedded kidney biopsies in 16 gender mismatched renal transplants (1 to 12 years post-transplantation). Twelve patients were male, four female. Four groups were selected: (i) Vascular calcineurin inhibitor toxicity without rejection; (ii) T-cell mediated vascular rejection; (iii) antibody mediated rejection; and (iv) C4d-positivity in AB0-incompatible transplants with or without rejection. Twelve non-transplant kidney biopsies (8 female, 4 male) were used as controls. Tubular chimerism was detected more frequently (69%) than endothelial chimerism (12%) in renal transplants. One of 12 control patients had tubular and endothelial chimeric cells (8%). The Y chromosome occurred in 8/12 male recipients (67%) in tubular epithelial cells and in 5/12 male recipients (42%) in endothelial cells. Double X chromosomes were detected in 3/4 female recipients in tubular epithelium. Tubular chimerism occurred more often with endothelial chimerism and capillaritis without correlation with other parameters, such as rejection. Combined Y chromosomal tubular and lymphatic endothelial chimerism correlated with T-cell mediated vascular rejection in two out of three patients (66%). Combined Y chromosomal tubular and peritubular capillary chimerism correlated with antibody mediated C4d+ rejection in one out of two patients (50%). Tubular and/or endothelial chimerism occur frequently in gender mismatched renal allografts and, when combined, this is associated with T-cell mediated rejection. © 2012 The Authors. Pathology International © 2012 Japanese Society of

  12. Renal allograft rupture: US diagnosis

    International Nuclear Information System (INIS)

    Maklad, N.F.

    1987-01-01

    The US appearances in seven pathologically and/or surgically proved cases of renal allograft rupture are presented. These include a triangular or amorphous echogenic area in the cortex and medulla in a polar location, an echogenic band or wavy, branching anechoic lines in the hyperechoic region, a subcapsular hematoma, and an extrarenal hematoma in direct continuity with the echogenic area. Duplex Doppler examination in renal allograft rupture shows marked reduction of absence of the diastolic component of the velocity waveform in the arcuate and interlobar arteries, with reduction in amplitude of the systolic wave form. Correlation of the US appearances with gross and microscopic pathologic findings indicates that the echogenic area is due to an intrarenal hematoma, while the echogenic band represents the cortical laceration with adherent blood clots. The US-duplex Doppler examination should be the primary diagnostic modality in this life-threatening condition

  13. Vitamin C Fosters the In Vivo Differentiation of Peripheral CD4+ Foxp3- T Cells into CD4+ Foxp3+ Regulatory T Cells but Impairs Their Ability to Prolong Skin Allograft Survival.

    Science.gov (United States)

    Oyarce, Karina; Campos-Mora, Mauricio; Gajardo-Carrasco, Tania; Pino-Lagos, Karina

    2018-01-01

    Regulatory T cells (Tregs) are critical players of immunological tolerance due to their ability to suppress effector T cell function thereby preventing transplant rejection and autoimmune diseases. During allograft transplantation, increases of both Treg expansion and generation, as well as their stable function, are needed to ensure allograft acceptance; thus, efforts have been made to discover new molecules that enhance Treg-mediated tolerance and to uncover their mechanisms. Recently, vitamin C (VitC), known to regulate T cell maturation and dendritic cell-mediated T cell polarization, has gained attention as a relevant epigenetic remodeler able to enhance and stabilize the expression of the Treg master regulator gene Foxp3, positively affecting the generation of induced Tregs (iTregs). In this study, we measured VitC transporter (SVCT2) expression in different immune cell populations, finding Tregs as one of the cell subset with the highest levels of SVCT2 expression. Unexpectedly, we found that VitC treatment reduces the ability of natural Tregs to suppress effector T cell proliferation in vitro , while having an enhancer effect on TGFβ-induced Foxp3 + Tregs. On the other hand, VitC increases iTregs generation in vitro and in vivo , however, no allograft tolerance was achieved in animals orally treated with VitC. Lastly, Tregs isolated from the draining lymph nodes of VitC-treated and transplanted mice also showed impaired suppression capacity ex vivo . Our results indicate that VitC promotes the generation and expansion of Tregs, without exhibiting CD4 + T cell-mediated allograft tolerance. These observations highlight the relevance of the nutritional status of patients when immune regulation is needed.

  14. In situ-targeting of dendritic cells with donor-derived apoptotic cells restrains indirect allorecognition and ameliorates allograft vasculopathy.

    Directory of Open Access Journals (Sweden)

    Zhiliang Wang

    Full Text Available Chronic allograft vasculopathy (CAV is an atheromatous-like lesion that affects vessels of transplanted organs. It is a component of chronic rejection that conventional immuno-suppression fails to prevent, and is a major cause of graft loss. Indirect allo-recognition through T cells and allo-Abs are critical during CAV pathogenesis. We tested whether the indirect allo-response and its impact on CAV is down-regulated by in situ-delivery of donor Ags to recipient's dendritic cells (DCs in lymphoid organs in a pro-tolerogenic fashion, through administration of donor splenocytes undergoing early apoptosis. Following systemic injection, donor apoptotic cells were internalized by splenic CD11c(hi CD8alpha(+ and CD8(- DCs, but not by CD11c(int plasmacytoid DCs. Those DCs that phagocytosed apoptotic cells in vivo remained quiescent, resisted ex vivo-maturation, and presented allo-Ag for up to 3 days. Administration of donor apoptotic splenocytes, unlike cells alive, (i promoted deletion, FoxP3 expression and IL-10 secretion, and decreased IFN-gamma-release in indirect pathway CD4 T cells; and (ii reduced cross-priming of anti-donor CD8 T cells in vivo. Targeting recipient's DCs with donor apoptotic cells reduced significantly CAV in a fully-mismatched aortic allograft model. The effect was donor specific, dependent on the physical characteristics of the apoptotic cells, and was associated to down-regulation of the indirect type-1 T cell allo-response and secretion of allo-Abs, when compared to recipients treated with donor cells alive or necrotic. Down-regulation of indirect allo-recognition through in situ-delivery of donor-Ag to recipient's quiescent DCs constitutes a promising strategy to prevent/ameliorate indirect allorecognition and CAV.

  15. Leiomyoma in a Renal Allograft

    Directory of Open Access Journals (Sweden)

    Yan Jun Li

    2016-01-01

    Full Text Available Leiomyomas are smooth muscle tumours that are rarely found in the kidney. There is one report of a leiomyoma in a kidney transplant in a paediatric recipient. Here, we report an adult renal transplant recipient who developed an Epstein-Barr virus-positive leiomyoma in his allograft 15 years after transplantation. The patient was converted to everolimus for posttransplant immunosuppression management and there was no sign of progression over a year.

  16. Peripheral blood transcriptome sequencing reveals rejection-relevant genes in long-term heart transplantation.

    Science.gov (United States)

    Chen, Yan; Zhang, Haibo; Xiao, Xue; Jia, Yixin; Wu, Weili; Liu, Licheng; Jiang, Jun; Zhu, Baoli; Meng, Xu; Chen, Weijun

    2013-10-03

    Peripheral blood-based gene expression patterns have been investigated as biomarkers to monitor the immune system and rule out rejection after heart transplantation. Recent advances in the high-throughput deep sequencing (HTS) technologies provide new leads in transcriptome analysis. By performing Solexa/Illumina's digital gene expression (DGE) profiling, we analyzed gene expression profiles of PBMCs from 6 quiescent (grade 0) and 6 rejection (grade 2R&3R) heart transplant recipients at more than 6 months after transplantation. Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR) was carried out in an independent validation cohort of 47 individuals from three rejection groups (ISHLT, grade 0,1R, 2R&3R). Through DGE sequencing and qPCR validation, 10 genes were identified as informative genes for detection of cardiac transplant rejection. A further clustering analysis showed that the 10 genes were not only effective for distinguishing patients with acute cardiac allograft rejection, but also informative for discriminating patients with renal allograft rejection based on both blood and biopsy samples. Moreover, PPI network analysis revealed that the 10 genes were connected to each other within a short interaction distance. We proposed a 10-gene signature for heart transplant patients at high-risk of developing severe rejection, which was found to be effective as well in other organ transplant. Moreover, we supposed that these genes function systematically as biomarkers in long-time allograft rejection. Further validation in broad transplant population would be required before the non-invasive biomarkers can be generally utilized to predict the risk of transplant rejection. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. Prolonging survival in vascularized bone allograft transplantation: developing specific immune unresponsiveness

    International Nuclear Information System (INIS)

    Paskert, J.P.; Yaremchuk, M.J.; Randolph, M.A.; Weiland, A.J.

    1987-01-01

    Vascularized bone allografts (VBAs) could be useful adjuncts to the clinical reconstructive surgeon's arsenal. These grafts are known experimentally to be subject to host rejection. One way to control the rejection problem would be to develop specific immune unresponsiveness via host conditioning. Using a proven reliable model in inbred rats for studying heterotopic VBA transplantation, recipient animals were conditioned preoperatively with third-party unrelated blood, donor-specific blood (DSB) alone and with cyclosporine, and ultraviolet irradiated donor-specific blood. The combination of DSB plus cyclosporine delayed rejection of grafts across a strong histocompatibility barrier for three to four weeks. However, rejection was delayed across a weak histocompatibility barrier for five to six weeks using this same host pretreatment. The implications are that specific immunosuppression, although possible, is difficult to achieve in VBA transplantation, and that such techniques will rely on tissue-matching to minimize the genetic disparity between graft and host

  18. Eosinophil count, allergies, and rejection in pediatric heart transplant recipients.

    Science.gov (United States)

    Arbon, Kate S; Albers, Erin; Kemna, Mariska; Law, Sabrina; Law, Yuk

    2015-08-01

    Allograft rejection and long-term immunosuppression remain significant challenges in pediatric heart transplantation. Pediatric recipients are known to have fewer rejection episodes and to develop more allergic conditions than adults. A T-helper 2 cell dominant phenotype, manifested clinically by allergies and an elevated eosinophil count, may be associated with immunologic quiescence in transplant recipients. This study assessed whether the longitudinal eosinophil count and an allergic phenotype were associated with freedom from rejection. This single-center, longitudinal, observational study included 86 heart transplant patients monitored from 1994 to 2011. Post-transplant biannual complete blood counts, allergic conditions, and clinical characteristics related to rejection risk were examined. At least 1 episode of acute cellular rejection (ACR) occurred in 38 patients (44%), antibody-mediated rejection (AMR) occurred in 11 (13%), and 49 patients (57%) were diagnosed with an allergic condition. Patients with ACR or AMR had a lower eosinophil count compared with non-rejectors (p = 0.011 and p = 0.022, respectively). In the multivariable regression analysis, the presence of panel reactive antibodies to human leukocyte antigen I (p = 0.014) and the median eosinophil count (p = 0.011) were the only independent covariates associated with AMR. Eosinophil count (p = 0.010) and female sex (p = 0.009) were independent risk factors for ACR. Allergic conditions or young age at transplant were not protective from rejection. This study demonstrates a novel association between a high eosinophil count and freedom from rejection. Identifying a biomarker for low rejection risk may allow a reduction in immunosuppression. Further investigation into the role of the T-helper 2 cell phenotype and eosinophils in rejection quiescence is warranted. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  19. [Prevention of infections due to musculoskeletal allografts].

    Science.gov (United States)

    Pruß, A

    2017-11-01

    Transplantation of musculoskeletal tissues is widely used in the treatment of extensive defects of the musculoskeletal system, especially in orthopedics for exchange of prostheses, surgical interventions on the spine and in traumatology for reconstruction after extensive tumor resections. A danger after transplantation is the potential transmission of clinically relevant pathogens. Tissue banks have therefore established a safety level approach for musculoskeletal tissue transplants, which includes donor selection, laboratory testing, tissue procurement, tissue processing, tissue storage and quality assurance. In addition, inactivation procedures were also developed to protect the biological properties of the tissue and to guarantee a high microbiological safety against infections. Quality assurance in accordance with the Ordinance for the Production of Medicinal Products and Active Pharmaceutical Ingredients (AMWHV) and the Transplantation Act Tissue Regulations (TPG-GewV), ensures that the work of tissue banks conforms to the legal requirements. A new aspect is that the introduction of the single European code in April 2017, with which all transplants in Germany must be labelled, ensures the traceability of the tissue transplants after potential infections.

  20. 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

  1. Preventing acute rejection, Epstein-Barr virus infection, and posttransplant lymphoproliferative disorders after kidney transplantation: Use of aciclovir and mycophenolate mofetil in a steroid-free immunosuppressive protocol

    DEFF Research Database (Denmark)

    Birkeland, S.A.; Andersen, H.K.; Hamilton-Dutoit, Stephen Jacques

    1999-01-01

    Background: A widely held view is that any increase in the potency of an immunosuppressive agent will lead to an increase in infection and malignancy, such as life-threatening Epstein-Barr virus (EBV) induced posttransplant lymphoproliferative disorders (PTLD), We tested this paradigm by studying......; the effect of adding mofetil to a steroid-free protocol under cover of high-dose aciclovir prophylaxis on the number of acute rejections, EBV infections and PTLDs after kidney transplantation. Methods: EBV serology was performed in 267 consecutive renal transplantations (1990-1997), All were treated...

  2. Processing of gamma irradiated bone allografts for treatment of injuries in a nuclear scenario

    International Nuclear Information System (INIS)

    Singh, Durgeshwer; Singh, Antaryami; Singh, Rita; Shah, Om

    2014-01-01

    Bone allografts fill an important void in the surgical practice of orthopaedic surgery, and their use to replace and reconstruct musculoskeletal structures following injury or disease has gained increasing acceptance by orthopaedic surgeons. Serious mechanical injuries in a nuclear scenario involving compression, displacement and missile hit will lead to high incidence of various kinds of bone fractures, spinal injuries and joint injuries apart from lethality, lung damage and eardrum rupture. Bone allografts can be employed for repairing fracture defects, filling in destroyed regions of bone, management of open fractures and joint injuries. Autologous bone grafts, though ideal, have the drawback of secondary surgery for autograft retrieval, complications of infection and donor site morbidity. Bone allografts eliminate additional incision necessary for acquiring an autograft and consequently reduce operating time, blood loss as well as hospital and medical costs. However, disease transmission and bacterial infection in bone allograft transplantation is of significant concern. Sterilization by gamma irradiation is a definitive method for eliminating microorganisms and can prevent life-threatening allograft associated infections. The present study was carried out with the aim of bioburden assessment, radiation sterilization and clinical evaluation of bone allografts processed from femoral heads obtained from living donors. Femoral heads were obtained during surgery at Department of Orthopaedic Surgery, SN Medical College, Jodhpur and processed as freeze-dried bone allografts. Bioburden of bone allografts was found to be in the range of 2.26 to 3.59 log CFU/g. Verification dose for different batches of processing was 7.24±1.27 kGy. Radiological data of processed gamma irradiated bone grafts used in clinical cases of trauma surgery was recorded and has shown successful graft incorporation in allogenic recipients. (author)

  3. T2' imaging of native kidneys and renal allografts. A feasibility study

    International Nuclear Information System (INIS)

    Mathys, C.; Blondin, D.; Wittsack, H.J.; Miese, F.R.; Rybacki, K.; Walther, C.; Holstein, A.; Lanzman, R.S.

    2011-01-01

    Purpose: To evaluate the feasibility of T2' mapping in native kidneys and renal allografts. Materials and Methods: Following approval of the local ethics committee, 24 renal allograft recipients and 10 control subjects (healthy volunteers) were included in this study. Multi-echo T2 and T2 * imaging was performed on a 1.5 Tesla scanner. Allograft recipients were assigned to two groups: group (a), 8 patients with good (glomerular filtration rate of more than 40 ml/min) allograft function and no evidence of transplant rejection, transplant renal artery stenosis or ureteral obstruction; group (b), 16 patients with deterioration of renal graft function (glomerular filtration rate (GFR) of 40 ml/min or less). Two different imaging protocols were tested. Results: The mean T2' relaxation parameters were 108.33 msec ± 13.34, 100.00 msec ± 18.89 and 124.57 msec ± 6.51 for groups (a), (b) and for control subjects, respectively. The reduction of T2' values in patient group (b) was not statistically significant. However, significant correlations could be demonstrated between T2' values and the glomerular filtration rate (GFR) of renal allograft function. The reproducibility was tested and the coefficients of variation of T2' values in the cortex of transplanted kidneys were 11.1 % within subjects and 11.3 % between subjects. Conclusion: Our results indicate that T2' imaging is a promising non-enhanced technique, which seems to reveal information on transplant function. Further studies are required to determine the clinical value of T2' mapping for monitoring renal allograft recipients. (orig.)

  4. T2' imaging of native kidneys and renal allografts. A feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Mathys, C.; Blondin, D.; Wittsack, H.J.; Miese, F.R.; Rybacki, K.; Walther, C.; Holstein, A.; Lanzman, R.S. [Universitaetsklinikum Duesseldorf (Germany). Inst. fuer Radiologie

    2011-02-15

    Purpose: To evaluate the feasibility of T2' mapping in native kidneys and renal allografts. Materials and Methods: Following approval of the local ethics committee, 24 renal allograft recipients and 10 control subjects (healthy volunteers) were included in this study. Multi-echo T2 and T2{sup *} imaging was performed on a 1.5 Tesla scanner. Allograft recipients were assigned to two groups: group (a), 8 patients with good (glomerular filtration rate of more than 40 ml/min) allograft function and no evidence of transplant rejection, transplant renal artery stenosis or ureteral obstruction; group (b), 16 patients with deterioration of renal graft function (glomerular filtration rate (GFR) of 40 ml/min or less). Two different imaging protocols were tested. Results: The mean T2' relaxation parameters were 108.33 msec {+-} 13.34, 100.00 msec {+-} 18.89 and 124.57 msec {+-} 6.51 for groups (a), (b) and for control subjects, respectively. The reduction of T2' values in patient group (b) was not statistically significant. However, significant correlations could be demonstrated between T2' values and the glomerular filtration rate (GFR) of renal allograft function. The reproducibility was tested and the coefficients of variation of T2' values in the cortex of transplanted kidneys were 11.1 % within subjects and 11.3 % between subjects. Conclusion: Our results indicate that T2' imaging is a promising non-enhanced technique, which seems to reveal information on transplant function. Further studies are required to determine the clinical value of T2' mapping for monitoring renal allograft recipients. (orig.)

  5. Freeze dried bone allografts in dental and maxillofacial reconstructive surgery - experience in Malaysia

    International Nuclear Information System (INIS)

    Abd Rani Samsudin; Meor Zaidi Meor Kamal

    1999-01-01

    The utilisation of vascularised and free bone autografts remain the goal standard in maxillofacial reconstructive surgery in Malaysia, but the use of freeze dried bone allograft is still widely practiced in many centres with variable results. This study evaluate the effectiveness and clinical efficacy of using radiation sterilised freeze dried bone allografts in oral and maxillofacial reconstructive surgery. The bone grafts were prepared at the Malaysian National Tissue Bank. Seventy eight patients who had undergone oral and Maxillofacial surgical procedures with reconstruction using bone allografts were included in this study. 50 patients were male and 28 patients were female and their age ranged from 14 to 75 years. Forty two patients underwent enucleation of benign cystic lesions in the jaws, 15 patients underwent repair of orbital floor fractures, 6 patients of jaw fractures with partial loss of bone while 8 patients underwent augmentation of depressed cheek bone. Another 4 patients had partial resection of the mandible because of cancer and 3 patients had facial osteotomies. A follow up period of 12 months up to 4 years was carried out. The patients were assessed both clinically and radiologically throughout their follow up visits. Clinical assessment showed no evidence of rejection of the implanted freeze dried allografts. Bone allografts implanted as inlay grafts demonstrated a better clinical performance than onlay grafts and the poorest results were obtained following bridging bony defects in the jaws. Radiation sterilised freeze dried bone allografts produced at the Malaysian National Tissue Bank are bio-compatible, functional, and provide predictable results when applied to selected areas of the facial skeleton

  6. Mandibular reconstruction using bone allografts

    International Nuclear Information System (INIS)

    Chang Joon Yim

    1999-01-01

    Further understanding of bone healing mechanisms, bone physiology and bone biology, transplantation immunology, and development of Tissue Banking procedures has enabled oral and maxillofacial surgeons to reconstruct even the most difficult bony defects successfully with the preserved allogeneic bone implant. Although it had been known that bone allografts were clinically effective, its application has not been widespread until the reports of Inclan (I 942), Hyatt and Butler (I 950), and Wilson (I 95 1). Tissue Banking provides the surgeon with a readily available, relatively inexpensive, and relatively safe selection of allogeneic bone for clinical use. Now autogenous bone and allogeneic bone implants present a wide variety of surgical options to surgeons, whether used separately or in combination. The surgeons are able to make judicious and fruitful choices, only with a thorough knowledge of the above-mentioned biological principles and skillful techniques. Many kinds of bone grafting techniques have been tried for reconstructing defective osseous tissues of the oral and maxillofacial region, though they have varying degrees of success. The osseous defects which require grafting include those of various size, shape, position, or amount. Unlike autogenous grafts, whose function is to provide osteogenic cells, allografts are purely passive, offering only a matrix for the inductive phase of bone healing. The condition of the recipient bed is of primary importance, because the host must produce all of the essential elements for the bone allograft to become incorporated. Depending on the processing methods of the allogeneic bone, the bone graft materials have different qualities, different healing potentials and different indications. Proper selection of grafts and surgical techniques requires an understanding of graft immunology and the mechanisms of graft healing. The surgeons should know about the biological principles to raise the clinical success rate

  7. ラット心移植における hyperacute rejection モデルの作製

    OpenAIRE

    Dohi, Kiyohiko; Tabe, Yasuji; Ezaki, Haruo

    1984-01-01

    Using genetically homogeneous inbred ACI and Fischer rats, the author has conducted active immunization with the skin and lymphoid cells from ACI rat to Fischer rat and succeeded in making an experimental model that unfailingly causes hyperacute rejection, which has heretofore been considered to be extremely difficult. Semipermanent survival was gained with syngenetic graft. With allograft, acute rejection of the cardiac graft took place in 8.1±1.4 days. On heart transplantation from ACI ...

  8. Induction of Foxp3-expressing regulatory T-cells by donor blood transfusion is required for tolerance to rat liver allografts.

    Directory of Open Access Journals (Sweden)

    Yuta Abe

    Full Text Available BACKGROUND: Donor-specific blood transfusion (DST prior to solid organ transplantation has been shown to induce long-term allograft survival in the absence of immunosuppressive therapy. Although the mechanisms underlying DST-induced allograft tolerance are not well defined, there is evidence to suggest DST induces one or more populations of antigen-specific regulatory cells that suppress allograft rejection. However, neither the identity nor the regulatory properties of these tolerogenic lymphocytes have been reported. Therefore, the objective of this study was to define the kinetics, phenotype and suppressive function of the regulatory cells induced by DST alone or in combination with liver allograft transplantation (LTx. METHODOLOGY/PRINCIPAL FINDINGS: Tolerance to Dark Agouti (DA; RT1(a rat liver allografts was induced by injection (iv of 1 ml of heparinized DA blood to naïve Lewis (LEW; RT1(l rats once per week for 4 weeks prior to LTx. We found that preoperative DST alone generates CD4(+ T-cells that when transferred into naïve LEW recipients are capable of suppressing DA liver allograft rejection and promoting long-term survival of the graft and recipient. However, these DST-generated T-cells did not express the regulatory T-cell (Treg transcription factor Foxp3 nor did they suppress alloantigen (DA-induced activation of LEW T-cells in vitro suggesting that these lymphocytes are not fully functional regulatory Tregs. We did observe that DST+LTx (but not DST alone induced the time-dependent formation of CD4(+Foxp3(+ Tregs that potently suppressed alloantigen-induced activation of naïve LEW T-cells in vitro and liver allograft rejection in vivo. Finally, we present data demonstrating that virtually all of the Foxp3-expressing Tregs reside within the CD4(+CD45RC(- population whereas in which approximately 50% of these Tregs express CD25. CONCLUSIONS/SIGNIFICANCE: We conclude that preoperative DST, in the absence of liver allograft

  9. Variable Heat Rejection (VHR)

    Data.gov (United States)

    National Aeronautics and Space Administration — Develop advanced technologies to enable a variable heat rejection Thermal Control System (TCS) capable of operating through a wide range of thermal environments...

  10. A new in vitro approach to determine acquired tolerance in long-term kidney allograft recipients

    International Nuclear Information System (INIS)

    Reinsmoen, N.L.; Kaufman, D.; Matas, A.; Sutherland, D.E.; Najarian, J.S.; Bach, F.H.

    1990-01-01

    Previous studies indicate some kidney allograft recipients treated with total lymphoid irradiation, cyclosporine, or conventional immunosuppressive therapy demonstrate specific proliferative unresponsiveness in mixed lymphocyte culture (MLC) to donor cells at various times posttransplant. To investigate possible donor-specific hyporeactivity, we have studied 3 patients treated with TLI whose grafts have survived longer than 10 years; 2 patients given the same immunosuppressive protocol but without TLI whose grafts have survived longer than 10 years; and 27 CsA-treated living-related donor and cadaver-allograft recipients 1 year posttransplant. We confirmed previous observations of hyporeactivity of some patients' cells to stimulation by donor cells. In addition, we identified hyporeactivity to stimulation by homozygous typing cells (HTCs) defining the HLA-Dw specificities of the donor cells for all 3 of the 3 TLI patients, 1 of the 2 non-TLI patients, and 9 of the 27 patients 1 year posttransplant. The LRD recipients with donor-specific hyporeactivity as defined by the HTC analysis demonstrated fewer rejection episodes (25% vs. 57%) and lower mean creatinine levels (1.18 vs 1.78 mg/dL) than patients without donor-specific hyporeactivity. These studies demonstrate the feasibility of monitoring the immune status of allograft recipients posttransplant by means of HTC analysis, eliminating the need for pretransplant specimens. This approach provides a possible means to assess which patients may have acquired donor-specific hyporeactivity to their kidney allograft and thus may require less immunosuppression

  11. [In vivo and in vitro study of the effect of pregnant female serum graft rejection in Salamandra salamandra Lin].

    Science.gov (United States)

    Badet, M T; Chateaureynaud-Duprat, P; Izoard, F; Voisin, G A

    1979-05-14

    Serum from pregnant female Salamandra salamandra inhibits the cytotoxic reaction from the mother towards its larvae. Such a serum accelerates the allograft rejection reaction. In vitro studies show that a serum from pregnant female inhibits the cytotoxic reaction of host spleen cells towards epithelial cells of the donor of the graft.

  12. Recipient-matching of Passenger Leukocytes Prolongs Survival of Donor Lung Allografts in Miniature Swine.

    Science.gov (United States)

    Madariaga, Maria Lucia L; Michel, Sebastian G; La Muraglia, Glenn M; Sihag, Smita; Leonard, David A; Farkash, Evan A; Colvin, Robert B; Cetrulo, Curtis L; Huang, Christene A; Sachs, David H; Madsen, Joren C; Allan, James S

    2015-07-01

    Allograft rejection continues to be a vexing problem in clinical lung transplantation, and the role played by passenger leukocytes in the rejection or acceptance of an organ is unclear. We tested whether recipient-matching of donor graft passenger leukocytes would impact graft survival in a preclinical model of orthotopic left lung transplantation. In the experimental group (group 1), donor lungs were obtained from chimeric swine, in which the passenger leukocytes (but not the parenchyma) were major histocompatibility complex-matched to the recipients (n = 3). In the control group (group 2), both the donor parenchyma and the passenger leukocytes were major histocompatibility complex-mismatched to the recipients (n = 3). Lungs harvested from swine previously rendered chimeric by hematopoietic stem cell transplantation using recipient-type cells showed a high degree of passenger leukocyte chimerism by immunohistochemistry and flow cytometry. The chimeric lungs containing passenger leukocytes matched to the lung recipient (group 1) survived on average 107 days (range, 80-156). Control lung allografts (group 2) survived on average 45 days (range, 29-64; P lung allograft survival.

  13. Technique of endoscopic biopsy of islet allografts transplanted into the gastric submucosal space in pigs.

    Science.gov (United States)

    Fujita, Minoru; McGrath, Kevin M; Bottino, Rita; Dons, Eefje M; Long, Cassandra; Kumar, Goutham; Ekser, Burcin; Echeverri, Gabriel J; Hata, Jiro; Haruma, Ken; Cooper, David K C; Hara, Hidetaka

    2013-01-01

    Currently, islet cells are transplanted into the liver via portal vein infusion. One disadvantage of this approach is that it is not possible to adequately biopsy the islets in the liver to assess for rejection. Islet transplantation (Tx) into the gastric submucosal space (GSMS) can be performed endoscopically and has the potential advantage of histological evaluation by endoscopic biopsy. The aim of this study was to determine whether a representative allograft sample could be obtained endoscopically. We performed islet Tx into the GSMS in nonimmunosuppressed pigs using simple endoscopic submucosal injection. Islets were transplanted at four sites. Endoscopic ultrasonography and biopsy of the transplanted islets at two sites by modified endoscopic submucosal dissection were carried out successfully in all pigs 5 days after islet Tx. Tissue obtained at both biopsy and necropsy (including full-thickness sections of the gastric wall around the sites of the remaining islets and biopsies) were examined by histology and immunohistochemistry to confirm the presence of the islet grafts and any features of rejection. Representative allograft sampling was successfully obtained from all biopsy sites. All biopsies included islets with insulin-positive staining. There was significant CD3(+) and CD68(+) cell infiltration in the islet masses obtained at biopsy and from sections taken at necropsy, with similar histopathological features. Endoscopic biopsy of islet allografts in the GSMS is feasible, provides accurate histopathological data, and would provide a significant advance if translated into clinical practice.

  14. [Measuring bioelectric myocardial impedance as a noninvasive method for diagnosis of graft rejection after heart transplantation].

    Science.gov (United States)

    Pfitzmann, R; Müller, J; Grauhan, O; Cohnert, T; Hetzer, R

    1998-04-01

    12 beagle dogs underwent neck-heart transplantation and were immunosuppressed with cyclosporine and methylprednisolone. Intramyocardial impedance was determined twice daily with four screw-in electrodes in the right and left ventricle. Transmyocardial biopsies and the intra-myocardial electrogram (IMEG) were performed as reference methods. 19 rejection episodes were induced. When acute rejection was seen in histology the animals were treated with pulsed 125 mg methylprednisolone over 5 consecutive days and immunosuppression was raised to sufficient levels. Successful treatment of rejection was controlled by biopsy. All hearts showed a uniform decrease of impedance of about 28.3% +/- 5.5% immediately after implantation, then reaching a stable plateau after 7 to 8 days. Impedance values then remained unchanged as long as rejection was absent. Biopsy findings of grade 1A to 1B (ISHLT) were accompanied by a statistically significant increase of impedance of 12.2% +/- 2.5%, of grade 2 to 3A of 19.2% +/- 3.2%, and of grade 3B to 4 of 27.0% +/- 2.9%. Sensitivity was 95%, specificity 91%. Successful treatment of rejection led to a uniform decrease of impedance to intramyocardial impedance for high frequencies can reliably indicate alterations of the cell membrane and the intracellular space during acute cardiac allograft rejection. The amount of increase of impedance is a reliable noninvasive parameter to graduate acute cardiac allograft rejection. The success of treatment of rejection can also be monitored by impedance. This noninvasive method is applicable for telemetric rejection monitoring via an implantable device, which would allow continuous rejection surveillance of a patient at home without hospital admission.

  15. MORPHOLOGY OF ISCHEMIC INJURY OF LIVER ALLOGRAFT

    Directory of Open Access Journals (Sweden)

    L. V. Shkalova

    2010-01-01

    Full Text Available The literature data in modern transplantology concerning morphology of ischemic injury of liver allograft are analyzed in the article. Questions of pathogenesis of liver allograft ischemic injury, histological features that indicate the possibility of donor liver transplantation are discussed in detail, as well as the role of steatosis and its reverse is highlighted. We tried to systematize the morphological changes depending on severity of ischemic injury; also we focused on the questions of persistency of the ischemic injury in the liver allograft

  16. T10B9 monoclonal antibody: A short-acting nonstimulating monoclonal antibody that spares γδ T-cells and treats and prevents cellular rejection

    Directory of Open Access Journals (Sweden)

    Thomas H Waid

    2009-06-01

    Full Text Available Thomas H Waid1, John S Thompson1, Maria Siemionow2, Stephen A Brown1 1Department of Internal Medicine, University of Kentucky, Lexington, Kentucky, USA; 2Cleveland Clinic, Cleveland, Ohio, USAAbstract: T10B9.1A-31/MEDI-500 is a nonmitogenic immunoglobulin M kappa murine monoclonal antibody (mAb directed against the alpha-beta (αβ heterodimer of the T-lymphocyte receptor complex. The hybridoma was first produced by fusing spleen cells from BALB/C mice immunized with human peripheral blood T-lymphocytes with SP2/O-Ag14 mutant myeloma cells. The mAb is produced and purified using multistep ion exchange and molecular sieve chromatography protocols. T10B9 has been used successfully to treat acute cellular rejection in renal transplantation and as an immunosuppression induction agent in heart and simultaneous kidney-pancreas transplantation. Because T10B9 is nonmitogenic and causes minimal cytokine release, both treatment of rejection and induction of immunosuppression were accomplished with significantly fewer and milder untoward effects (cytokine release syndrome than its comparator OKT3. Since T10B9 is directed against the αβ heterodimer of the CD3 epitope, it spares the gamma delta (γδ region. These gamma delta (γδ T cells have a unique role in the immune response controlling many serious human diseases and perhaps facilitating the development of immunologic tolerance. T10B9 has a relatively short duration of action, depleting T cells for only 10 to 14 days, unlike the protracted depletion seen with thymoglobulin and Campath-1H. There is no B-lymphocyte depletion with T10B9 as there is with both of the aforementioned reagents. The lack of prolonged lymphocyte depletion may account for less infection observed with T10B9 treatment.Keywords: T10B9.1A-31, γδ T-cell, monoclonal antibody, Campath-1H, thymoglobulin, OKT3

  17. Acute rejection episodes after kidney transplantation

    Directory of Open Access Journals (Sweden)

    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.

  18. CT perfusion technique for assessment of early kidney allograft dysfunction: preliminary results.

    Science.gov (United States)

    Helck, A; Wessely, M; Notohamiprodjo, M; Schönermarck, U; Klotz, E; Fischereder, M; Schön, F; Nikolaou, K; Clevert, D A; Reiser, M; Becker, C

    2013-09-01

    To assess the benefit of quantitative computed tomography (CT) perfusion for differentiating acute tubular necrosis (ATN) and acute rejection (AR) in kidney allografts. Twenty-two patients with acute kidney allograft dysfunction caused by either AR (n = 6) or ATN (n = 16) were retrospectively included in the study. All patients initially underwent a multiphase CT angiography (CTA) protocol (12 phases, one phase every 3.5 s) covering the whole graft to exclude acute postoperative complications. Multiphase CT dataset and dedicated software were used to calculate renal blood flow. Renal biopsy or clinical course of disease served as the standard of reference. Mean effective radiation dose and mean amount of contrast media were calculated. Renal blood flow values were significantly lower (P = 0.001) in allografts undergoing AR (48.3 ± 21 ml/100 ml/min) compared with those with ATN (77.5 ± 21 ml/100 ml/min). No significant difference (P = 0.71) was observed regarding creatinine level with 5.65 ± 3.1 mg/dl in AR and 5.3 ± 1.9 mg/dl in ATN. The mean effective radiation dose of the CT perfusion protocol was 13.6 ± 5.2 mSv; the mean amount of contrast media applied was 34.5 ± 5.1 ml. All examinations were performed without complications. CT perfusion of kidney allografts may help to differentiate between ATN and rejection. • Quantitative CT perfusion of renal transplants is feasible. • CT perfusion could help to non-invasively differentiate AR from ATN. • CT perfusion might make some renal biopsies unnecessary.

  19. Structural bone allograft fractures in oncological procedures.

    Science.gov (United States)

    Garcia-Coiradas, Javier; Garcia-Maroto, Roberto; Cebrian, Juan Luis; Lopez-Duran, Luis

    2015-11-01

    We report our experience analysing the risk of fracture amongst allografts in limb-preserving surgery for bone tumours. We retrospectively reviewed our experience with bone allograft and its major complications when used for limb -preserving operations for bone tumours. Forty-one structural allografts were performed in 39 patients between 1992 and 2012. Minimum follow-up was 20 months. Massive allografts have a high complication rate. Excluding infection and nonunion, five acute fractures were found. All fractures occurred after the graft-host junction was united. Local factors-such as graft preservation, weight bearing, fixation to the host or systemic factors such as adjuvant treatments (chemotherapy or radiotherapy)-influence fracture rate. In our study, four patients achieved consolidation with internal fixation and autologous iliac-crest graft, whilst only one required graft exchange. There is no general consensus as to when to treat fractures using open reduction and internal fixation or by exchanging the allograft. Higher fracture rate in relation to systemic treatment was found. Massive structural allograft reconstruction still has a place in limb-preserving surgery, with an acceptable fracture rate and a durable solution.

  20. Alloantigen-induced, T-cell-dependent production of nitic oxide by macrophagesinfiltrating skin allografts in mice

    Czech Academy of Sciences Publication Activity Database

    Krulová, Magdalena; Zajícová, Alena; Frič, Jan; Holáň, Vladimír

    2002-01-01

    Roč. 15, 2-3 (2002), s. 108-116 ISSN 0934-0874 R&D Projects: GA ČR GA310/99/D044; GA ČR GA310/99/0360; GA MZd NI6659; GA MŠk LN00A026 Institutional research plan: CEZ:AV0Z5052915 Keywords : allograft rejection * macrophages * nitric oxide Subject RIV: EC - Immunology Impact factor: 2.520, year: 2002

  1. Alloantigen-induced, T-cell dependent production of nitric oxide by macrophages infiltrating skin allografts in mice

    Czech Academy of Sciences Publication Activity Database

    Krulová, Magdalena; Zajícová, Alena; Frič, Jan; Holáň, Vladimír

    15, 2002, 2-3 (2002), s. 108-116 ISSN 0934-0874 R&D Projects: GA ČR GA310/99/D044; GA ČR GA310/99/0360; GA MZd NI6659; GA MŠk LN00A026 Institutional research plan: CEZ:AV0Z5052915 Keywords : mouse * allograft rejection * nitric oxide Subject RIV: EC - Immunology Impact factor: 2.520, year: 2002

  2. Effect of 34 kinds of traditional Japanese herbal medicines on prolongation of cardiac allograft survival.

    Science.gov (United States)

    Jin, X; Uchiyama, M; Zhang, Q; Harada, T; Otsuka, K; Shimokawa, T; Niimi, M

    2014-05-01

    Herbal medicines have been used for over 3,000 years in Asian as alternative therapy for their variety effects and have recently become popular in Europe and the United States. In the last 30 years, Japanese herbal medicines were widely used for treatment of diseases after been recognized officially by Japanese government. In this study, we investigated the effect of 34 kinds of traditional Japanese herbal medicines on alloimmune responses in a murine model of cardiac allograft transplantation. CBA mice (H2(k)) underwent transplantation of a C57BL/6 (H2(b)) heart and received oral administration of 2 g/kg/d of the 34 kinds of herbal medicines from the day of transplantation until 7 days afterward. Naïve CBA mice rejected B6 cardiac grafts acutely (median survival time [MST], 7 days). CBA transplant recipients given 2 g/kg/d of Sairei-to (TJ-114) and Tokishakuyaku-san (TJ-23) had prolonged C57BL/6 allograft survival indefinitely (both MSTs > 100 days). Moreover, CBA transplant recipients given Seisinrensiin (TJ-111), Tokishigyakukagoshuyushokyoto (TJ-38), Rikkunshito (TJ-43), Maobushisaishinto (TJ-127), Ninjin-yoei-to (TJ-108), Ryokan-kyomi-shinge-nin-to (TJ-119), Inchingorei-san (TJ-117), Hochuekkito (TJ-41), Kihi-to (TJ-65), and Sinbu-to (TJ-30) had also prolonged C57BL/6 allograft survival significantly (MSTs of 28, 22, 16, 14, 14, 13, 12, 9.5, 9 and 9 days, respectively). However, none of other 22 kinds of herbal medicines could prolong the allograft survival. Furthermore, oral administration of 2 g/kg/d of Daikenchuto (TJ-100) induced sudden death (within 1 minute) in CBA mice. In conclusion, 12 kinds of Japanese herbal medicines prolonged allograft survival and one showed toxic effect in mice. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Peroxisome proliferator-activated receptor γ deficiency in T cells accelerates chronic rejection by influencing the differentiation of CD4+ T cells and alternatively activated macrophages.

    Directory of Open Access Journals (Sweden)

    Xiaofan Huang

    Full Text Available In a previous study, activation of the peroxisome proliferator-activated receptor γ (PPARγ inhibited chronic cardiac rejection. However, because of the complexity of chronic rejection and the fact that PPARγ is widely expressed in immune cells, the mechanism of the PPARγ-induced protective effect was unclear.A chronic rejection model was established using B6.C-H-2bm12KhEg (H-2bm12 mice as donors, and MHC II-mismatched T-cell-specific PPARγ knockout mice or wild type (WT littermates as recipients. The allograft lesion was assessed by histology and immunohistochemistry. T cells infiltrates in the allograft were isolated, and cytokines and subpopulations were detected using cytokine arrays and flow cytometry. Transcription levels in the allograft were measured by RT-PCR. In vitro, the T cell subset differentiation was investigated after culture in various polarizing conditions. PPARγ-deficient regulatory T cells (Treg were cocultured with monocytes to test their ability to induce alternatively activated macrophages (AAM.T cell-specific PPARγ knockout recipients displayed reduced cardiac allograft survival and an increased degree of pathology compared with WT littermates. T cell-specific PPARγ knockout resulted in more CD4+ T cells infiltrating into the allograft and altered the Th1/Th2 and Th17/Treg ratios. The polarization of AAM was also reduced by PPARγ deficiency in T cells through the action of Th2 and Treg. PPARγ-deficient T cells eliminated the pioglitazone-induced polarization of AAM and reduced allograft survival.PPARγ-deficient T cells influenced the T cell subset and AAM polarization in chronic allograft rejection. The mechanism of PPARγ activation in transplantation tolerance could yield a novel treatment without side effects.

  4. Noninvasive detection of rejection of transplanted hearts with indium-111-labeled lymphocytes

    International Nuclear Information System (INIS)

    Eisen, H.J.; Eisenberg, S.B.; Saffitz, J.E.; Bolman, R.M. III; Sobel, B.E.; Bergmann, S.R.

    1987-01-01

    To determine whether cardiac transplant rejection can be detected noninvasively with indium-111 ( 111 In)-labeled lymphocytes, we studied 11 dogs with thoracic heterotopic cardiac transplants without immunosuppression and five dogs with transplants treated with cyclosporine (10 mg/kg/day) and prednisone (1 mg/kg/day). All were evaluated sequentially with gamma scintigraphy after administration of 150 to 350 muCi of autologous 111 In-lymphocytes. Technetium-99m-labeled red blood cells (1 to 3 mCi) were used for correction of radioactivity in the blood pool attributable to circulating labeled lymphocytes. Lymphocyte infiltration was quantified as the ratio of indium in the myocardium of the transplant or native heart compared with that in blood (indium excess, IE). Results were correlated with mechanical and electrical activity of allografts and with histologic findings in sequential biopsy specimens. In untreated dogs (n = 11), IE was 15.5 +/- 7.0 (SD) in transplanted hearts undergoing rejection and 0.4 +/- 1.1 in native hearts on the day before animals were killed. In dogs treated with cyclosporine and prednisone (n = 5), IE was minimal in allografts during the course of immunosuppression (0.8 +/- 0.4) and increased to 22.9 +/- 11.1 after immunosuppression was stopped. Scintigraphic criteria of rejection (IE greater than 2 SD above that in native hearts) correlated with results of biopsies indicative of rejection and appeared before electrophysiologic or mechanical manifestations of dysfunction. Thus infiltration of labeled lymphocytes in allografts, indicative of rejection, is detectable noninvasively by gamma scintigraphy and provides a sensitive approach potentially applicable to clinical monitoring for early detection of rejection and guidance for titration of immunosuppressive measures

  5. Interstitial mononuclear cell infiltrates in chronic rejection of the kidney and correlation with peripheral blood.

    OpenAIRE

    Jeong, H. J.; Hong, S. W.; Kim, Y. S.; Kim, M. S.; Choi, I. H.; Park, K.; Choi, I. J.

    1996-01-01

    To investigate the characteristics of interstitial inflammatory cells and possible involvement of nudelta T cells, 16 renal allograft biopsies showing chronic rejection were stained by immunohistochemical method and correlated with the data of peripheral blood evaluated by flow cytometry. For immunophenotyping, fresh frozen sections were stained with monoclonal antibodies against CD3, CD4, CD8, CD68, CD56, TCRdelta1 and HLA DR. Paraffin embedded tissue was stained with CD45RO, CD20-Cy and CD6...

  6. Increase of peripheral Th17 lymphocytes during acute cellular rejection in liver transplant recipients.

    Science.gov (United States)

    Fan, Hua; Li, Li-Xin; Han, Dong-Dong; Kou, Jian-Tao; Li, Ping; He, Qiang

    2012-12-15

    Although many human inflammatory and autoimmune diseases were previously considered to be mediated by T helper type 1 (Th1) cells, the recently described Th17 cells play dominant roles in several of these diseases. We and others speculated that allograft rejection after organ transplantation may also involve Th17 cells. Episodes of acute rejection occur in 30% of liver transplants. This study aimed to determine the frequency of circulating Th17 cells in patients who had received liver transplants for benign end-stage liver disease and to identify any association between acute rejection episodes and levels of Th17 cells in the peripheral blood. A prospective study compared Th17 cells from 76 consecutive benign end-stage liver disease patients who had undergone orthotopic liver transplantation from 2007 to 2011 with those from 20 age-matched healthy individuals. Peripheral blood samples were collected at different time points within one year after transplant. Blood samples and liver biopsies were also collected at the diagnosis of acute rejection. Percentages of circulating CD4+IL-17+ cells were measured by flow cytometry. The transplant patients were classified into two groups: a rejection group consisting of 17 patients who had an episode of acute rejection, and a non-rejection group comprising the remaining 59 patients with no acute rejection episodes. Percentages of circulating Th17 cells were compared between the two groups and controls. The levels of circulating CD4+IL-17+ T cells in the rejection group were higher during acute rejection than those in the non-rejection group (2.56+/-0.43% versus 1.79+/-0.44%, Pblood was positively correlated with the rejection activity index (r=0.79, P=0.0002). Circulating Th17 cells may be useful as a surrogate marker for predicting acute rejection in liver transplant recipients.

  7. 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%

  8. The Role of the Endothelium during Antibody-Mediated Rejection: From Victim to Accomplice

    Directory of Open Access Journals (Sweden)

    Amy Rachael Cross

    2018-01-01

    Full Text Available Antibody-mediated rejection (AMR of solid organ transplants is characterized by the activation and injury of the allograft endothelium. Histological and transcriptomic studies have associated microvascular inflammation and endothelial lesions with the severity of rejection and poor graft outcomes. The allograft endothelium forms the physical barrier between the donor organ and the recipient; this position directly exposes the endothelium to alloimmune responses. However, endothelial cells are not just victims and can actively participate in the pathogenesis of rejection. In healthy tissues, the endothelium plays a major role in vascular and immune homeostasis. Organ transplantation, however, subjects the endothelium to an environment of inflammation, alloreactive lymphocytes, donor-specific antibodies, and potentially complement activation. As a result, endothelial cells become activated and have modified interactions with the cellular effectors of allograft damage: lymphocytes, natural killer, and myeloid cells. Activated endothelial cells participate in leukocyte adhesion and recruitment, lymphocyte activation and differentiation, as well as the secretion of cytokines and chemokines. Ultimately, highly activated endothelial cells promote pro-inflammatory alloresponses and become accomplices to AMR.

  9. Enhancement by dimethyl myleran of donor type chimerism in murine recipients of bone marrow allografts

    Energy Technology Data Exchange (ETDEWEB)

    Lapidot, T.; Terenzi, A.; Singer, T.S.; Salomon, O.; Reisner, Y. (Weizmann Institute of Science, Rehovot (Israel))

    1989-05-15

    A major problem in using murine models for studies of bone marrow allograft rejection in leukemia patients is the narrow margin in which graft rejection can be analyzed. In mice irradiated with greater than 9 Gy total body irradiation (TBI) rejection is minimal, whereas after administration of 8 Gy TBI, which spares a significant number of clonable T cells, a substantial frequency of host stem cells can also be detected. In current murine models, unlike in humans, bone marrow allograft rejection is generally associated with full autologous hematopoietic reconstitution. In the present study, we investigated the effect of the myeloablative drug dimethyl myleran (DMM) on chimerism status following transplantation of T cell-depleted allogenic bone marrow (using C57BL/6 donors and C3H/HeJ recipients, conditioned with 8 Gy TBI). Donor type chimerism 1 to 2 months post-transplant of 1 to 3 x 10(6) bone marrow cells was markedly enhanced by using DMM one day after TBI and prior to transplantation. Conditioning with cyclophosphamide instead of DMM, in combination with 8 Gy TBI, did not enhance engraftment of donor type cells. Artificial reconstitution of T cells, after conditioning with TBI plus DMM, by adding mature thymocytes, or presensitization with irradiated donor type spleen cells 1 week before TBI and DMM, led to strong graft rejection and consequently to severe anemia. The anti-donor responses in these models were proportional to the number of added T cells and to the number of cells used for presensitization, and they could be neutralized by increasing the bone marrow inoculum.

  10. Enhancement by dimethyl myleran of donor type chimerism in murine recipients of bone marrow allografts

    International Nuclear Information System (INIS)

    Lapidot, T.; Terenzi, A.; Singer, T.S.; Salomon, O.; Reisner, Y.

    1989-01-01

    A major problem in using murine models for studies of bone marrow allograft rejection in leukemia patients is the narrow margin in which graft rejection can be analyzed. In mice irradiated with greater than 9 Gy total body irradiation (TBI) rejection is minimal, whereas after administration of 8 Gy TBI, which spares a significant number of clonable T cells, a substantial frequency of host stem cells can also be detected. In current murine models, unlike in humans, bone marrow allograft rejection is generally associated with full autologous hematopoietic reconstitution. In the present study, we investigated the effect of the myeloablative drug dimethyl myleran (DMM) on chimerism status following transplantation of T cell-depleted allogenic bone marrow (using C57BL/6 donors and C3H/HeJ recipients, conditioned with 8 Gy TBI). Donor type chimerism 1 to 2 months post-transplant of 1 to 3 x 10(6) bone marrow cells was markedly enhanced by using DMM one day after TBI and prior to transplantation. Conditioning with cyclophosphamide instead of DMM, in combination with 8 Gy TBI, did not enhance engraftment of donor type cells. Artificial reconstitution of T cells, after conditioning with TBI plus DMM, by adding mature thymocytes, or presensitization with irradiated donor type spleen cells 1 week before TBI and DMM, led to strong graft rejection and consequently to severe anemia. The anti-donor responses in these models were proportional to the number of added T cells and to the number of cells used for presensitization, and they could be neutralized by increasing the bone marrow inoculum

  11. Magnetic resonance imaging of massive bone allografts with histologic correlation

    International Nuclear Information System (INIS)

    Hoeffner, E.G.; Soulen, R.L.; Ryan, J.R.; Qureshi, F.

    1996-01-01

    The objective of this study was to better understand the MRI appearance of massive bone allografts. The MRI findings of three massive bone allografts imaged in vivo were correlated with the histologic findings following removal of the allografts. A fourth allograft, never implanted, was imaged and evaluated histologically. Allografts were placed for the treatment of primary or recurrent osteosarcoma. The in-vivo allografts have a heterogeneous appearance on MRI which we attribute to the revascularization process. Fibrovascular connective tissue grows into the graft in a patchy, focal fashion, down the medullary canal from the graft-host junction and adjacent to the periosteum. The marrow spaces are initially devoid of normal cellular elements and occupied by fat and gelatinous material. This normal postoperative appearance of massive bone allografts must not be interpreted as recurrent neoplasm or infection in the allograft. Recognition of these complications rests on features outside the marrow. (orig./MG)

  12. Magnetic resonance imaging features of allografts

    International Nuclear Information System (INIS)

    Kattapuram, S.V.; Rosol, M.S.; Rosenthal, D.I.; Palmer, W.E.; Mankin, H.J.

    1999-01-01

    Objective. To investigate the magnetic resonance imaging (MRI) features of allografts at various time intervals after surgery in patients with osteoarticular allografts.Design and patients. Sixteen patients who were treated with osteoarticular allografts and who were followed over time with MRI studies as part of their long-term follow-up were retrospectively selected for this study. T1-weighted images were obtained both before and after gadolinium administration along with T2-weighted images. All images were reviewed by an experienced musculoseletal radiologist, with two other experienced radiologists used for consultation. Imaging studies were organized into three groups for ease of discussion: early postoperative period (2 days to 2 months), intermediate postoperative period (3 months to 2 years), and late postoperative period (greater than 2 years).Results. In the early postoperative period, no gadolinium enhancement of the allograft was visible in any of the MR images. A linear, thin layer of periosteal and endosteal tissue enhancement along the margin of the allograft was visible in images obtained at 3-4 months. This enhancement apeared gradually to increase in images from later periods, and appears to have stabilized in the images obtained approximately 2-3 years after allograft placement. The endosteal enhancement diminished after several years, with examinations conducted between 6 and 8 years following surgery showing minimal endosteal enhancement. However, focal enhancement was noted adjacent to areas of pressure erosion or degenerative cysts. All the cases showed inhomogeneity in the marrow signal (scattered low signal foci on T1 with corresponding bright signal on T2), and a diffuse, inhomogeneous marrow enhancement later on.Conclusion. We have characterized the basic MRI features of osteoarticular allografts in 16 patients who underwent imaging studies at various time points as part of routine follow-up. We believe that the endosteal and periosteal

  13. T-regulatory cells in chronic rejection versus stable grafts.

    Science.gov (United States)

    Al-Wedaie, Fatima; Farid, Eman; Tabbara, Khaled; El-Agroudy, Amgad E; Al-Ghareeb, Sumaya M

    2015-04-01

    Studying regulatory T cells in kidney allograft acceptance versus chronic rejection may help in the understanding of more mechanisms of immune tolerance and, in the future, may enable clinicians to induce immune tolerance and decrease the use of immunosuppressive drugs. The aim of the current study was to evaluate regulatory T cells in kidney transplant patients with stable graft versus transplant with biopsy-proven chronic rejection. The 3 groups that were studied included: kidney transplanted patients with no rejection episodes (n = 43); transplanted patients with biopsy-proven renal rejection (n = 27); and healthy age-matched nontransplanted individuals as controls (n = 42).The percentage of regulatory T cells (CD4+CD25+Foxp3+) in blood was determined by flow cytometry. The regulatory T cell percentage was significantly lower in chronic rejection patients than control or stable graft groups. No significant difference was observed in regulatory T cell percentage between the stable graft and control groups. In the stable graft group, patients on rapamycin had a significantly higher regulatory T cell percentage than patients on cyclosporine. No effect of donor type, infection, or duration after transplant was observed on regulatory T cell percentage. The results of the current study are consistent with previous studies addressing the function of regulatory T cells in inducing immunotolerance after kidney transplant. Considering the established role of regulatory T cells in graft maintenance and our observation of high regulatory T cell percentage in patients receiving rapamycin than cyclosporine, we recommend including rapamycin when possible in immunosuppressive protocols. The findings from the current study on the chronic rejection group support ongoing research of having treatment with regulatory T cells, which may constitute a novel, efficient antirejection therapy in the future.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. A Systematic Review of Failed Anterior Cruciate Ligament Reconstruction With Autograft Compared With Allograft in Young Patients

    Science.gov (United States)

    Wasserstein, David; Sheth, Ujash; Cabrera, Alison; Spindler, Kurt P.

    2015-01-01

    Context: The advantages of allograft anterior cruciate ligament reconstruction (ACLR), which include shorter surgical time, less postoperative pain, and no donor site morbidity, may be offset by a higher risk of failure. Previous systematic reviews have inconsistently shown a difference in failure prevalence by graft type; however, such reviews have never been stratified for younger or more active patients. Objective: To determine whether there is a different ACLR failure prevalence of autograft compared with allograft in young, active patients. Data Sources: EMBASE, MEDLINE, Cochrane trials registry. Study Selection: Comparative studies of allograft versus autograft primary ACL reconstruction in patients 12 points, collegiate or semiprofessional athletes). Study Design: Systematic review with meta-analysis. Level of Evidence: Level 3. Data Extraction: Manual extraction of available data from eligible studies. Quantitative synthesis of failure prevalence and Lysholm score (outcomes in ≥3 studies) and I2 test for heterogeneity. Assessment of study quality using CLEAR NPT and Newcastle-Ottawa Scale (NOS). Results: Seven studies met inclusion criteria (1 level 1; 2 level 2, 4 level 3), including 788 patients treated with autograft tissue and 228 with various allografts. The mean age across studies was 21.7 years (64% male), and follow-up ranged between 24 and 51 months. The pooled failure prevalence was 9.6% (76/788) for autografts and 25.0% (57/228) for allografts (relative risk, 0.36; 95% CI, 0.24-0.53; P < 0.00001; I2 = 16%). The number needed to benefit to prevent 1 failure by using autograft was 7 patients (95% CI, 5-10). No difference between hamstrings autograft and patella tendon autograft was noted. Lysholm score was reported in 3 studies and did not differ between autograft and allograft. Conclusion: While systematic reviews comparing allograft and autograft ACLR have been equivocal, this is the first review to examine young and active patients in whom

  16. Immune response and histology of humoral rejection in kidney transplantation.

    Science.gov (United States)

    González-Molina, Miguel; Ruiz-Esteban, Pedro; Caballero, Abelardo; Burgos, Dolores; Cabello, Mercedes; Leon, Miriam; Fuentes, Laura; Hernandez, Domingo

    2016-01-01

    The adaptive immune response forms the basis of allograft rejection. Its weapons are direct cellular cytotoxicity, identified from the beginning of organ transplantation, and/or antibodies, limited to hyperacute rejection by preformed antibodies and not as an allogenic response. This resulted in allogenic response being thought for decades to have just a cellular origin. But the experimental studies by Gorer demonstrating tissue damage in allografts due to antibodies secreted by B lymphocytes activated against polymorphic molecules were disregarded. The special coexistence of binding and unbinding between antibodies and antigens of the endothelial cell membranes has been the cause of the delay in demonstrating the humoral allogenic response. The endothelium, the target tissue of antibodies, has a high turnover, and antigen-antibody binding is non-covalent. If endothelial cells are attacked by the humoral response, immunoglobulins are rapidly removed from their surface by shedding and/or internalization, as well as degrading the components of the complement system by the action of MCP, DAF and CD59. Thus, the presence of complement proteins in the membrane of endothelial cells is transient. In fact, the acute form of antibody-mediated rejection was not demonstrated until C4d complement fragment deposition was identified, which is the only component that binds covalently to endothelial cells. This review examines the relationship between humoral immune response and the types of acute and chronic histological lesion shown on biopsy of the transplanted organ. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  17. Urinary calprotectin and posttransplant renal allograft injury

    DEFF Research Database (Denmark)

    Tepel, Martin; Borst, Christoffer; Bistrup, Claus

    2014-01-01

    regression showed that higher urinary calprotectin concentrations and older donor age predicted lower eGFR four weeks, 6 months, and 12 months after transplantation. CONCLUSIONS: Urinary calprotectin is an early, noninvasive predictor of immediate renal allograft injury after kidney transplantation.......OBJECTIVE: Current methods do not predict the acute renal allograft injury immediately after kidney transplantation. We evaluated the diagnostic performance of urinary calprotectin for predicting immediate posttransplant allograft injury. METHODS: In a multicenter, prospective-cohort study of 144...... incipient renal transplant recipients, we postoperatively measured urinary calprotectin using an enzyme-linked immunosorbent assay and estimated glomerular filtration rate (eGFR) after 4 weeks, 6 months, and 12 months. RESULTS: We observed a significant inverse association of urinary calprotectin...

  18. Urinary Calprotectin Differentiates Between Prerenal and Intrinsic Acute Renal Allograft Failure.

    Science.gov (United States)

    Seibert, Felix S; Rosenberger, Christian; Mathia, Susanne; Arndt, Robert; Arns, Wolfgang; Andrea, Huppertz; Pagonas, Nikolaos; Bauer, Frederic; Zidek, Walter; Westhoff, Timm H

    2017-02-01

    Urinary calprotectin has recently been identified as a promising biomarker for the differentiation between prerenal and intrinsic acute kidney injury (AKI) in the nontransplant population. The present study investigates whether calprotectin is able to differentiate between these 2 entities in transplant recipients as well. Urinary calprotectin was assessed by enzyme-linked immunosorbent assay in 328 subjects including 125 cases of intrinsic acute allograft failure, 27 prerenal graft failures, 118 patients with stable graft function, and 58 healthy controls. Acute graft failure was defined as AKI stages 1 to 3 (Acute Kidney Injury Network criteria), exclusion criteria were obstructive uropathy, urothelial carcinoma, and metastatic cancer. The clinical differentiation of prerenal and intrinsic graft failure was performed either by biopsy or by a clinical algorithm including response to fluid repletion, history, physical examination, and urine dipstick examination. Reasons for intrinsic graft failure comprised rejection, acute tubular necrosis, urinary tract infection/pyelonephritis, viral nephritis, and interstitial nephritis. Calprotectin concentrations of patients with stable graft function (50.4 ng/mL) were comparable to healthy controls (54.8 ng/mL, P = 0.70) and prerenal graft failure (53.8 ng/mL, P = 0.62). Median urinary calprotectin was 36 times higher in intrinsic AKI (1955 ng/mL) than in prerenal AKI (P renal allograft biopsy specimens confirmed the serological results. Urinary calprotectin is a promising biomarker for the differentiation of prerenal and intrinsic acute renal allograft failure.

  19. [Demonstration and in vitro study of a complex reaction (rejection and facilitation) of the mother towards the embryo in the urodele amphibian Salamandra salamandra L].

    Science.gov (United States)

    Badet, M T; Chateaureynaud-Duprat, P; Voisin, G A

    1975-07-21

    Spleen cells from pregnant (but not from non-pregnant) Salamandra salamandra are cytotoxic in vitro for dissociated epidermal cells from their own embryos. Maternal serum inhibits this cytotoxicity. Analogies and differences are stressed in Salamandra salamandra between allograft rejection mechanisms and immune reactions towards embryos. They may contribute to an explanation of the delayed expulsion of embryos.

  20. In vivo effects of high-dose steroids on nucleic acid content of immunocompetent cells of renal allograft recipients

    International Nuclear Information System (INIS)

    Walle, A.J.; Wong, G.Y.; Suthanthiran, M.; Rubin, A.L.; Stenzel, K.H.

    1988-01-01

    High-dose steroids administered to renal allograft recipients for treatment of acute graft rejection episodes may affect cell cycle progression of peripheral blood mononuclear (PBM) cells. DNA synthesis and cellular DNA and RNA contents of PBM cells were measured in 8 patients during clinically stable periods, and in another 10 patients both during acute rejection episodes and during 7 days of administration of high-dose steroids. Improved renal function documented successful reversal of the rejection episodes in the 10 patients. Compared with the stable patients, the rejecting patients had higher numbers of cells undergoing clonal expansion--namely, higher proportions of G1-cells and of proliferating, or S, G2, and M (SG2M) cells. Steroid treatment had no acute effects on proportions of G1 or SG2M cells in vivo or on incorporation of 3 H thymidine by PBM cells in vitro. However, cells in the prereplicative compartment of the cell cycle (G0/1 cells) had significantly lower RNA content within 7 days of treatment with high doses of steroids. The results suggest that steroids do not acutely influence the posttranscriptional synthesis and the contents of nucleic acids of cells undergoing clonal expansion in vivo. The prereplicative phase of allogeneically stimulated PBM cells of renal allograft recipients may therefore be the cell cycle phase most sensitive to steroids in vivo

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

    Science.gov (United States)

    Maehana, Takeshi; Tanaka, Toshiaki; Kitamura, Hiroshi; Fukuzawa, Nobuyuki; Ishida, Hideki; Harada, Hiroshi; Tanabe, Kazunari; Masumori, Naoya

    2016-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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

  4. Utility of Iron Staining in Identifying the Cause of Renal Allograft Dysfunction in Patients with Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    Yingchun Wang

    2015-01-01

    Full Text Available Sickle cell nephropathy (SCN is associated with iron/heme deposition in proximal renal tubules and related acute tubular injury (ATI. Here we report the utility of iron staining in differentiating causes of renal allograft dysfunction in patients with a history of sickle cell disease. Case 1: the patient developed acute allograft dysfunction two years after renal transplant. Her renal biopsy showed ATI, supported by patchy loss of brush border and positive staining of kidney injury molecule-1 in proximal tubular epithelial cells, where diffuse increase in iron staining (2+ was present. This indicated that ATI likely resulted from iron/heme toxicity to proximal tubules. Electron microscope confirmed aggregated sickle RBCs in glomeruli, indicating a recurrent SCN. Case 2: four years after renal transplant, the patient developed acute allograft dysfunction and became positive for serum donor-specific antibody. His renal biopsy revealed thrombotic microangiopathy (TMA and diffuse positive C4d stain in peritubular capillaries. Iron staining was negative in the renal tubules, implying that TMA was likely associated with acute antibody-mediated rejection (AAMR, type 2 rather than recurrent SCN. These case reports imply that iron staining is an inexpensive but effective method in distinguishing SCN-associated renal injury in allograft kidney from other etiologies.

  5. A selective and potent CXCR3 antagonist SCH 546738 attenuates the development of autoimmune diseases and delays graft rejection

    Directory of Open Access Journals (Sweden)

    Jenh Chung-Her

    2012-01-01

    Full Text Available Abstract Background The CXCR3 receptor and its three interferon-inducible ligands (CXCL9, CXCL10 and CXCL11 have been implicated as playing a central role in directing a Th1 inflammatory response. Recent studies strongly support that the CXCR3 receptor is a very attractive therapeutic target for treating autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis and psoriasis, and to prevent transplant rejection. We describe here the in vitro and in vivo pharmacological characterizations of a novel and potent small molecule CXCR3 antagonist, SCH 546738. Results In this study, we evaluated in vitro pharmacological properties of SCH 546738 by radioligand receptor binding and human activated T cell chemotaxis assays. In vivo efficacy of SCH 546738 was determined by mouse collagen-induced arthritis, rat and mouse experimental autoimmune encephalomyelitis, and rat cardiac transplantation models. We show that SCH 546738 binds to human CXCR3 with a high affinity of 0.4 nM. In addition, SCH 546738 displaces radiolabeled CXCL10 and CXCL11 from human CXCR3 with IC50 ranging from 0.8 to 2.2 nM in a non-competitive manner. SCH 546738 potently and specifically inhibits CXCR3-mediated chemotaxis in human activated T cells with IC90 about 10 nM. SCH 546738 attenuates the disease development in mouse collagen-induced arthritis model. SCH 546738 also significantly reduces disease severity in rat and mouse experimental autoimmune encephalomyelitis models. Furthermore, SCH 546738 alone achieves dose-dependent prolongation of rat cardiac allograft survival. Most significantly, SCH 546738 in combination with CsA supports permanent engraftment. Conclusions SCH 546738 is a novel, potent and non-competitive small molecule CXCR3 antagonist. It is efficacious in multiple preclinical disease models. These results demonstrate that therapy with CXCR3 antagonists may serve as a new strategy for treatment of autoimmune diseases, including rheumatoid arthritis and

  6. Experimental studies on glycerol preserved vascular allografts

    NARCIS (Netherlands)

    Fahner, P.J.

    2014-01-01

    Autologous vein is the conduit of choice in patients with critical peripheral arterial disease who need a vascular reconstruction. However, autologous vein could be of inferior quality or used in prior surgery. Vascular allograft transplantation is an attractive alternative to prosthetic grafts in

  7. Renal Allograft in a Professional Boxer

    Directory of Open Access Journals (Sweden)

    Einollahi Behzad

    2008-01-01

    Full Text Available Significant health benefits result from regular physical activity for kidney transplant recipients. Nevertheless, some adverse effects also have been shown to be associated with highly intensive exercises. We report a kidney transplant professional boxer whose kidney allograft has remained in good health, despite his violent sport activities.

  8. Arthroscopic meniscal allograft transplantation without bone plugs.

    Science.gov (United States)

    Alentorn-Geli, Eduard; Seijas Vázquez, Roberto; García Balletbó, Montserrat; Álvarez Díaz, Pedro; Steinbacher, Gilbert; Cuscó Segarra, Xavier; Rius Vilarrubia, Marta; Cugat Bertomeu, Ramón

    2011-02-01

    Partial or total meniscectomy are common procedures performed at Orthopedic Surgery departments. Despite providing a great relief of pain, it has been related to early onset knee osteoarthritis. Meniscal allograft transplantation has been proposed as an alternative to meniscectomy. The purposes of this study were to describe an arthroscopic meniscal allograft transplantation without bone plugs technique and to report the preliminary results. All meniscal allograft transplantations performed between 2001 and 2006 were approached for eligibility, and a total of 35 patients (involving 37 menisci) were finally engaged in the study. Patients were excluded if they had ipsilateral knee ligament reconstruction or cartilage repair surgery before meniscal transplantation or other knee surgeries after the meniscal transplantation. Scores on Lysholm, Subjective IKDC Form, and Visual Analogue Scale (VAS) scale for pain were obtained at a mean follow-up of 38.6 months and compared to pre-operative data. Data on chondral lesions were obtained during the arthroscopic procedure and through imaging (radiographs and MRI) studies pre-operatively. Two graft failures out of 59 transplants (3.4%) were found. Daily life accidents were responsible for all graft failures. Significant improvements for Lysholm, Subjective IKDC Form, and VAS for pain scores following the meniscal allograft transplantation were found (P lesion, there was no significant interactions for Lysholm (n.s.), Subjective IKDC Form (n.s.), and VAS for pain scores (n.s.). This study demonstrated that an arthroscopic meniscal allograft transplantation without bone plugs improved knee function and symptoms after a total meniscectomy. Improvements were observed independently of the degree of chondral lesion.

  9. Effect of blood transfusions on canine renal allograft survival

    International Nuclear Information System (INIS)

    Van Der Linden, C.J.; Buurman, W.A.; Vegt, P.A.; Greep, J.M.; Jeekel, J.

    1982-01-01

    In this study significantly prolonged canine renal allograft survival has been demonstrated after transfusion of 100 ml of third-party whole blood given peroperatively. Peroperative transfusions of third-party leukocyte-free blood or pure lymphocyte cell suspensions did not influence graft survival. Futhermore, no improvement in graft survival has been found after a peroperative transfuson of irradiated whole blood (2500 rad). These data suggest that delayed graft rejection after blood transfusions can only be expected after the administration of whole blood. The role of competent lymphocytes in whole blood is questionable, since a transfusion of irradiated whole blood in combination with nonirradiated lymphocytes did not lead to prolonged graft survival. Immunosuppression of the recipient directly after transfusion seems to be essential to induce the beneficial effect of blood transfusions. This has been demonstrated for a transfusion of whole blood 14 days before transplantation. A single transfusion of 100 ml of whole blood 14 days before transplantation could effectively prolong graft survival if immunosuppression with azathioprine and prednisone was started on the day of transfusion. No improvement in graft survival has been found with such a transfusion if preoperative immunosuppression has been omitted

  10. Effect of blood transfusions on canine renal allograft survival

    International Nuclear Information System (INIS)

    van der Linden, C.J.; Buurman, W.A.; Vegt, P.A.; Greep, J.M.; Jeekel, J.

    1982-01-01

    In this study significantly prolonged canine renal allograft survival has been demonstrated after transfusion of 100 ml of third-party whole blood given peroperatively. Peroperative transfusions of third-party leukocyte-free blood or pure lymphocyte cell suspensions did not influence graft survival. Furthermore, no improvement in graft survival has been found after a peroperative transfusion of irradiated whole blood (2500 rad). These data suggest that delayed graft rejection after blood transfusions can only be expected after the administration of whole blood. The role of competent lymphocytes in whole blood is questionable, since a transfusion or irradiated whole blood in combination with nonirradiated lymphocytes did not lead to prolonged graft survival. Immunosuppression of the recipient directly after transfusion seems to be essential to induce the beneficial effect of blood transfusions. This has been demonstrated for a transfusion of whole blood 14 days before transplantation. A single transfusion of 100 ml of whole blood 14 days before transplantation could effectively prolong graft survival if immunosuppression with azathioprine and prednisone was started on the day of transfusion. No improvement in graft survival has been found with such a transfusion if preoperative immunosuppression has been omitted

  11. 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

  12. Not All Antibodies Are Created Equal: Factors That Influence Antibody Mediated Rejection

    Directory of Open Access Journals (Sweden)

    Carrie L. Butler

    2017-01-01

    Full Text Available Consistent with Dr. Paul Terasaki’s “humoral theory of rejection” numerous studies have shown that HLA antibodies can cause acute and chronic antibody mediated rejection (AMR and decreased graft survival. New evidence also supports a role for antibodies to non-HLA antigens in AMR and allograft injury. Despite the remarkable efforts by leaders in the field who pioneered single antigen bead technology for detection of donor specific antibodies, a considerable amount of work is still needed to better define the antibody attributes that are associated with AMR pathology. This review highlights what is currently known about the clinical context of pre and posttransplant antibodies, antibody characteristics that influence AMR, and the paths after donor specific antibody production (no rejection, subclinical rejection, and clinical dysfunction with AMR.

  13. Corneal allograft rejection: topical treatment vs. pulsed intravenous methylprednisolone - ten years' result

    OpenAIRE

    Costa, Dácio Carvalho; Castro, Rosane Silvestre de; Camargo, Mariela Soares Ferraz de; Kara-José, Newton

    2008-01-01

    OBJETIVOS: Avaliar a eficácia da associação de pulsoterapia com 500 mg de metilprednisolona intravenosa ao acetato de prednisolona 1% tópico no tratamento do primeiro episódio de rejeição endotelial de transplantes de córnea. MÉTODOS: Estudo caso-controle retrospectivo com 81 sujeitos que apresentaram o primeiro episódio de rejeição endotelial e submetidos à terapia nos primeiros quinze dias dos sintomas. RESULTADOS: 67 sujeitos foram tratados com acetato de prednisolona 1% tópico de 1 em 1 h...

  14. BONE ALLOGRAFTING IN REVISION KNEE ARTHROPLASTY: HISTOLOGICAL CHARACTERISTICS OF STRUCTURAL ALLOGRAFTS 54 MONTHS FOLLOW UP

    Directory of Open Access Journals (Sweden)

    T. A. Kuliaba

    2016-01-01

    Full Text Available Compensation of large bone defects by AORI third type classification is the most difficult problem the audit knee arthroplasty. In this situation, the surgeon have to choose between three possibilities: to use metal cones/sleeves, and, in cases with severely damaged metaepiphysis, to use structural allografts or oncological megaimplants. No doubt, it is interesting to follow the processes that are taking place with massive structural allografts implanted into the human body long time ago. This article presents the case study of the rheumatoid arthritis patient’s treatment with a severe lesion of the knee joint, subjected to repeated revision surgeries, last two of which are made with the use of massive structural allograft of femur. Morphological study of a massive distal femur allograft in 54 months after surgery showed that superficial ingrowth of connective tissue and blood vessels happens on the allograft’s border with its partial restructuring of the bone tissue at the border with the recipient bone. However, the most of allograft remains unchanged even after 54 months after surgery.

  15. Papillary renal cell carcinoma in allograft kidney

    International Nuclear Information System (INIS)

    Roy, Catherine; El Ghali, Sofiane; Buy, Xavier; Gangi, Afshin; Lindner, Veronique

    2005-01-01

    Papillary renal cell carcinoma is a subgroup of malignant renal epithelial neoplasms. Its occurrence in allograft transplanted kidney has not been debated in the literature. We report two pathologically proven cases and discuss the clinical hypothesis for such neoplasms and the aspect on MR images. The paramagnetic effect of the iron associated with an absence of signal coming from calcifications is a plausible explanation for this unusual hypointense appearance on T2-weighted sequence. (orig.)

  16. Late de novo minimal change disease in a renal allograft

    International Nuclear Information System (INIS)

    Madhan, Krishan K.; Camp, Cynric R. E. Temple

    2009-01-01

    Among the causes of the nephrotic syndrome in renal allografts, minimal change disease is a rarity with only few cases described in the medical literature. Most cases described have occurred early in the post-transplant course. There is no established treatment for the condition but prognosis is favorable. We describe a case of minimal change disease that developed 8 years after a successful transplantation of a renal allograft in a middle-aged woman. The nephrotic syndrome was accompanied by deterioration of allograft function. Treatment with mycophenolate mofetil was successful in inducing remission and stabilizing allograft function. (author)

  17. Resistance of Foxp3+ regulatory T cells to Nur77-induced apoptosis promotes allograft survival.

    Directory of Open Access Journals (Sweden)

    Ran Tao

    Full Text Available The NR4A nuclear receptor family member Nur77 (NR4A1 promotes thymocyte apoptosis during negative selection of autoreactive thymocytes, but may also function in mature extrathymic T cells. We studied the effects of over-expression of Nur77 on the apoptosis of murine peripheral T cells, including thymic-derived Foxp3+ regulatory (Treg cells. Overexpression of Nur77 in the T cell lineage decreased numbers of peripheral CD4 and CD8 T cells by approximately 80% compared to wild-type (WT mice. However, the proportions of Treg cells were markedly increased in the thymus (61% of CD4+Foxp3+ singly positive thymocytes vs. 8% in WT and secondary lymphoid organs (40-50% of CD4+Foxp3+ T cells vs. 7-8% in WT of Nur77 transgenic (Nur77Tg mice, and immunoprecipitation studies showed Nur77 was associated with a recently identified HDAC7/Foxp3 transcriptional complex. Upon activation through the T cell receptor in vitro or in vivo, Nur77Tg T cells showed only marginally decreased proliferation but significantly increased apoptosis. Fully allogeneic cardiac grafts transplanted to Nur77Tg mice survived long-term with well-preserved structure, and recipient splenocytes showed markedly enhanced apoptosis and greatly reduced anti-donor recall responses. Allografts in Nur77Tg recipients had significantly increased expression of multiple Treg-associated genes, including Foxp3, Foxp1, Tip60 and HDAC9. Allograft rejection was restored by CD25 monoclonal antibody therapy, indicating that allograft acceptance was dependent upon Treg function in Nur77Tg recipients. These data show that compared to conventional CD4 and CD8 T cells, Foxp3+ Tregs are relatively resistant to Nur77-mediated apoptosis, and that tipping the balance between the numbers of Tregs and responder T cells in the early period post-transplantation can determine the fate of the allograft. Hence, induced expression of Nur77 might be a novel means to achieve long-term allograft survival.

  18. Corneal Graft Rejection Ten Years after Penetrating Keratoplasty in the Cornea Donor Study

    Science.gov (United States)

    Dunn, Steven P.; Gal, Robin L.; Kollman, Craig; Raghinaru, Dan; Dontchev, Mariya; Blanton, Christopher L.; Holland, Edward J; Lass, Jonathan H.; Kenyon, Kenneth R.; Mannis, Mark J; Mian, Shahzad I.; Rapuano, Christopher J.; Stark, Walter J.; Beck, Roy W.

    2015-01-01

    Purpose To assess the effect of donor and recipient factors on corneal allograft rejection and evaluate whether a rejection event was associated with graft failure. Methods 1,090 subjects undergoing penetrating keratoplasty for a moderate risk condition (principally Fuchs’ dystrophy or pseudophakic corneal edema) were followed for up to 12 years. Associations of baseline recipient and donor factors with the occurrence of a rejection event were assessed in univariate and multivariate proportional hazards models. Results Among 651 eyes with a surviving graft at 5 years, the 10-year graft failure (± 99% CI) rates were 12% ± 4% among eyes with no rejection events in the first 5 years, 17% ± 12% in eyes with at least one probable, but no definite rejection event, and 22% ± 20% in eyes with at least one definite rejection event. The only baseline factor significantly associated with a higher risk of definite graft rejection was a preoperative history of glaucoma, particularly when prior glaucoma surgery had been performed and glaucoma medications were being used at time of transplant (10-year incidence 35% ± 23% compared with 14% ± 4% in eyes with no history of glaucoma/intraocular pressure treatment, p=0.008). Conclusion Those patients who experienced a definite rejection event frequently went on to graft failure raising important questions as to how we might change acute and long-term corneal graft management. Multivariate analysis indicated that the prior use of glaucoma medications and glaucoma filtering surgery was a significant risk factor related to a definite rejection event. PMID:25119961

  19. Integrated Kidney Exosome Analysis for the Detection of Kidney Transplant Rejection.

    Science.gov (United States)

    Park, Jongmin; Lin, Hsing-Ying; Assaker, Jean Pierre; Jeong, Sangmoo; Huang, Chen-Han; Kurdi, A; Lee, Kyungheon; Fraser, Kyle; Min, Changwook; Eskandari, Siawosh; Routray, Sujit; Tannous, Bakhos; Abdi, Reza; Riella, Leonardo; Chandraker, Anil; Castro, Cesar M; Weissleder, Ralph; Lee, Hakho; Azzi, Jamil R

    2017-11-28

    Kidney transplant patients require life-long surveillance to detect allograft rejection. Repeated biopsy, albeit the clinical gold standard, is an invasive procedure with the risk of complications and comparatively high cost. Conversely, serum creatinine or urinary proteins are noninvasive alternatives but are late markers with low specificity. We report a urine-based platform to detect kidney transplant rejection. Termed iKEA (integrated kidney exosome analysis), the approach detects extracellular vesicles (EVs) released by immune cells into urine; we reasoned that T cells, attacking kidney allografts, would shed EVs, which in turn can be used as a surrogate marker for inflammation. We optimized iKEA to detect T-cell-derived EVs and implemented a portable sensing system. When applied to clinical urine samples, iKEA revealed high level of CD3-positive EVs in kidney rejection patients and achieved high detection accuracy (91.1%). Fast, noninvasive, and cost-effective, iKEA could offer new opportunities in managing transplant recipients, perhaps even in a home setting.

  20. Differentiation between Acute Skin Rejection in Allotransplantation and T-Cell Mediated Skin Inflammation Based on Gene Expression Analysis

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    Dolores Wolfram

    2015-01-01

    Full Text Available Advances in microsurgical techniques and immunosuppressive medication have rendered transplantation of vascularized composite allografts possible, when autologous tissue is neither available nor sufficient for reconstruction. However, skin rejection and side effects of long-term immunosuppression still remain a major hurdle for wide adoption of this excellent reconstructive technique. Histopathologic changes during acute skin rejection in vascular composite allotransplantation often mimic inflammatory skin disorders and are hard to distinguish. Hence, the identification of diagnostic and therapeutic markers specific for skin rejection is of particular clinical need. Here we present novel markers allowing for early differentiation between rejection in hind limb allotransplantation and contact hypersensitivity. Assessment of Ccl7, Il18, and Il1b expression is most indicative of distinguishing skin rejection from skin inflammatory disorders. Gene expression levels varied significantly across skin types and regions, indicating localization specific mechanism of leukocyte migration and infiltration. Expression of Il12b, Il17a, and Il1b gene expression levels differed significantly between rejection and inflammation, independent of the skin type. In synopsis of the RNA expression profile and previously assessed protein expression, the Il1 family appears as a promising option for accurate skin rejection diagnosis and, as a following step, for development of novel rejection treatments.

  1. 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

  2. Tolerance in a rat cardiac allograft model after short-term treatment with LF 08-0299. Absence of clonal deletion and evidence of CD4+ suppressor cells.

    Science.gov (United States)

    Andoins, C; de Fornel, D; Annat, J; Dutartre, P

    1996-12-15

    LF 08-0299 is a new immunosuppressive compound. In a fully mismatched rat cardiac allograft model (Dark Agouti [DA]-->Lewis [LEW]), long-term unresponsiveness was observed after LF 08-0299 short-term treatment (20 days). Survival of additional cardiac and skin DA allografts, and rejection of third-party (Brown Norway [BN]) skin allografts demonstrated induction of a donor-specific tolerance state. The aim of this study was to investigate mechanisms of cardiac acceptance in this model. LEW rats with long-term surviving heart grafts (LTS LEW) were examined for their immune proliferative and cytotoxic responses toward donors (DA) and third-party (BN) antigens. Normal proliferative responses were observed and limiting dilution analysis did not reveal a reduction of T cytotoxic cell precursors. In our model, tolerance exists despite the presence of cells reactive with donor alloantigens. In vivo adoptive transfer of serum from LTS LEW failed to transfer unresponsiveness, indicating that serum factors do not seem to be involved in tolerance maintenance. Transfer of spleen cells, obtained from LTS LEW, showed specific prolongation of DA cardiac allografts in syngeneic hosts. Moreover, these cells were able to induce the rejection of third-party BN grafts. These results suggest that although LTS LEW possessed suppressor cells, they remained immunocompetent in recognizing and responding to third-party alloantigens. Purified CD4+ cells transferred unresponsiveness to secondary hosts, but CD8+ cells did not. Taken together, these results suggest that tolerance to donor alloantigens after treatment with LF 08-0299 in the rat cardiac allograft model is most likely due to induction of specific CD4+ suppressor cell activity, rather than induction of suppressive serum factor and selective elimination of antidonor helper or cytotoxic cell precursors (clonal deletion).

  3. 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

  4. CHALLENGES IN TREATMENT OF RENAL GRAFT ACUTE ANTIBODY-MEDIATED REJECTION

    Directory of Open Access Journals (Sweden)

    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. 

  5. Lyophilized allografts without pre-treatment with glutaraldehyde are more suitable than cryopreserved allografts for pulmonary artery reconstruction

    Directory of Open Access Journals (Sweden)

    J.R. Olmos-Zúãiga

    2016-01-01

    Full Text Available Various methods are available for preservation of vascular grafts for pulmonary artery (PA replacement. Lyophilization and cryopreservation reduce antigenicity and prevent thrombosis and calcification in vascular grafts, so both methods can be used to obtain vascular bioprostheses. We evaluated the hemodynamic, gasometric, imaging, and macroscopic and microscopic findings produced by PA reconstruction with lyophilized (LyoPA grafts and cryopreserved (CryoPA grafts in dogs. Eighteen healthy crossbred adult dogs of both sexes weighing between 18 and 20 kg were used and divided into three groups of six: group I, PA section and reanastomosis; group II, PA resection and reconstruction with LyoPA allograft; group III, PA resection and reconstruction with CryoPA allograft. Dogs were evaluated 4 weeks after surgery, and the status of the graft and vascular anastomosis were examined macroscopically and microscopically. No clinical, radiologic, or blood-gas abnormalities were observed during the study. The mean pulmonary artery pressure (MPAP in group III increased significantly at the end of the study compared with baseline (P=0.02 and final [P=0.007, two-way repeat-measures analysis of variance (RM ANOVA] values. Pulmonary vascular resistance of groups II and III increased immediately after reperfusion and also at the end of the study compared to baseline. The increase shown by group III vs group I was significant only if compared with after surgery and study end (P=0.016 and P=0.005, respectively, two-way RM ANOVA. Microscopically, permeability was reduced by ≤75% in group III. In conclusion, substitution of PAs with LyoPA grafts is technically feasible and clinically promising.

  6. Lyophilized allografts without pre-treatment with glutaraldehyde are more suitable than cryopreserved allografts for pulmonary artery reconstruction.

    Science.gov (United States)

    Olmos-Zúñiga, J R; Jasso-Victoria, R; Díaz-Martínez, N E; Gaxiola-Gaxiola, M O; Sotres-Vega, A; Heras-Romero, Y; Baltazares-Lipp, M; Baltazares-Lipp, M E; Santillán-Doherty, P; Hernández-Jiménez, C

    2016-02-01

    Various methods are available for preservation of vascular grafts for pulmonary artery (PA) replacement. Lyophilization and cryopreservation reduce antigenicity and prevent thrombosis and calcification in vascular grafts, so both methods can be used to obtain vascular bioprostheses. We evaluated the hemodynamic, gasometric, imaging, and macroscopic and microscopic findings produced by PA reconstruction with lyophilized (LyoPA) grafts and cryopreserved (CryoPA) grafts in dogs. Eighteen healthy crossbred adult dogs of both sexes weighing between 18 and 20 kg were used and divided into three groups of six: group I, PA section and reanastomosis; group II, PA resection and reconstruction with LyoPA allograft; group III, PA resection and reconstruction with CryoPA allograft. Dogs were evaluated 4 weeks after surgery, and the status of the graft and vascular anastomosis were examined macroscopically and microscopically. No clinical, radiologic, or blood-gas abnormalities were observed during the study. The mean pulmonary artery pressure (MPAP) in group III increased significantly at the end of the study compared with baseline (P=0.02) and final [P=0.007, two-way repeat-measures analysis of variance (RM ANOVA)] values. Pulmonary vascular resistance of groups II and III increased immediately after reperfusion and also at the end of the study compared to baseline. The increase shown by group III vs group I was significant only if compared with after surgery and study end (P=0.016 and P=0.005, respectively, two-way RM ANOVA). Microscopically, permeability was reduced by ≤75% in group III. In conclusion, substitution of PAs with LyoPA grafts is technically feasible and clinically promising.

  7. Lyophilized allografts without pre-treatment with glutaraldehyde are more suitable than cryopreserved allografts for pulmonary artery reconstruction

    International Nuclear Information System (INIS)

    Olmos-Zúãiga, J.R.; Jasso-Victoria, R.; Díaz-Martínez, N.E.; Gaxiola-Gaxiola, M.O.; Sotres-Vega, A.; Heras-Romero, Y.; Baltazares-Lipp, M.; Baltazares-Lipp, M.E.; Santillán-Doherty, P.; Hernández-Jiménez, C.

    2015-01-01

    Various methods are available for preservation of vascular grafts for pulmonary artery (PA) replacement. Lyophilization and cryopreservation reduce antigenicity and prevent thrombosis and calcification in vascular grafts, so both methods can be used to obtain vascular bioprostheses. We evaluated the hemodynamic, gasometric, imaging, and macroscopic and microscopic findings produced by PA reconstruction with lyophilized (LyoPA) grafts and cryopreserved (CryoPA) grafts in dogs. Eighteen healthy crossbred adult dogs of both sexes weighing between 18 and 20 kg were used and divided into three groups of six: group I, PA section and reanastomosis; group II, PA resection and reconstruction with LyoPA allograft; group III, PA resection and reconstruction with CryoPA allograft. Dogs were evaluated 4 weeks after surgery, and the status of the graft and vascular anastomosis were examined macroscopically and microscopically. No clinical, radiologic, or blood-gas abnormalities were observed during the study. The mean pulmonary artery pressure (MPAP) in group III increased significantly at the end of the study compared with baseline (P=0.02) and final [P=0.007, two-way repeat-measures analysis of variance (RM ANOVA)] values. Pulmonary vascular resistance of groups II and III increased immediately after reperfusion and also at the end of the study compared to baseline. The increase shown by group III vs group I was significant only if compared with after surgery and study end (P=0.016 and P=0.005, respectively, two-way RM ANOVA). Microscopically, permeability was reduced by ≤75% in group III. In conclusion, substitution of PAs with LyoPA grafts is technically feasible and clinically promising

  8. Lyophilized allografts without pre-treatment with glutaraldehyde are more suitable than cryopreserved allografts for pulmonary artery reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Olmos-Zúãiga, J.R.; Jasso-Victoria, R. [Department of Experimental Surgery, National Institute of Respiratory Diseases ' Ismael Cosío Villegas' , Mexico City (Mexico); Díaz-Martínez, N.E. [Medical and Pharmaceutical Biotechnology, Center for Research and Assistance in Technology and Design of the State of Jalisco, Guadalajara, Jalisco (Mexico); Gaxiola-Gaxiola, M.O. [Laboratory of Morphology, National Institute of Respiratory Diseases ' Ismael Cosío Villegas' , Mexico City (Mexico); Sotres-Vega, A.; Heras-Romero, Y.; Baltazares-Lipp, M. [Department of Experimental Surgery, National Institute of Respiratory Diseases ' Ismael Cosío Villegas' , Mexico City (Mexico); Baltazares-Lipp, M.E. [Hemodynamics and Echocardiography Service, National Institute of Respiratory Diseases ' Ismael Cosío Villegas' , Mexico City (Mexico); Santillán-Doherty, P. [Medical Administration, National Institute of Respiratory Diseases ' Ismael Cosío Villegas' , Mexico City (Mexico); Hernández-Jiménez, C. [Department of Experimental Surgery, National Institute of Respiratory Diseases ' Ismael Cosío Villegas' , Mexico City (Mexico)

    2015-12-04

    Various methods are available for preservation of vascular grafts for pulmonary artery (PA) replacement. Lyophilization and cryopreservation reduce antigenicity and prevent thrombosis and calcification in vascular grafts, so both methods can be used to obtain vascular bioprostheses. We evaluated the hemodynamic, gasometric, imaging, and macroscopic and microscopic findings produced by PA reconstruction with lyophilized (LyoPA) grafts and cryopreserved (CryoPA) grafts in dogs. Eighteen healthy crossbred adult dogs of both sexes weighing between 18 and 20 kg were used and divided into three groups of six: group I, PA section and reanastomosis; group II, PA resection and reconstruction with LyoPA allograft; group III, PA resection and reconstruction with CryoPA allograft. Dogs were evaluated 4 weeks after surgery, and the status of the graft and vascular anastomosis were examined macroscopically and microscopically. No clinical, radiologic, or blood-gas abnormalities were observed during the study. The mean pulmonary artery pressure (MPAP) in group III increased significantly at the end of the study compared with baseline (P=0.02) and final [P=0.007, two-way repeat-measures analysis of variance (RM ANOVA)] values. Pulmonary vascular resistance of groups II and III increased immediately after reperfusion and also at the end of the study compared to baseline. The increase shown by group III vs group I was significant only if compared with after surgery and study end (P=0.016 and P=0.005, respectively, two-way RM ANOVA). Microscopically, permeability was reduced by ≤75% in group III. In conclusion, substitution of PAs with LyoPA grafts is technically feasible and clinically promising.

  9. Patient And Allograft Survival After Transplantation With A Living ...

    African Journals Online (AJOL)

    Departments of Human Anatomy & Surgery, University of Nairobi. BACICGROUND: Late allograft loss remains a key area of concern. This study was aimed at determining the patient and renal allograft outcome and identifying the factors responsible for survival following transplantation with a living-related donor kidney at.

  10. Combining bisphosphonates with allograft bone for implant fixation

    NARCIS (Netherlands)

    Mathijssen, N.M.C.; Buma, P.; Hannink, G.J.

    2014-01-01

    The aim of this review was to discuss the current state of research of combining bisphosphonates with allograft bone for implant fixation. The allograft bone can only be reached by the bisphosphonate once it has been revascularized. However, this can be circumvented by local administration of

  11. Allograft Arthrodesis of the Knee in High-grade Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Teng-Le Huang

    2005-09-01

    Conclusion: Due to the high rate of complications in this study, we conclude that allograft arthrodesis should be left as a salvage or “back-up” reconstructive procedure after resection of osteosarcoma around the knee, unless there are special indications for this procedure. We found allograft fracture to be the most common complication.

  12. Asymptomatic Pulmonary Allograft Kaposi Sarcoma: A Case Report.

    Science.gov (United States)

    Nannini, Nazarena; Rebusso, Alessandro; Lunardi, Francesca; Loy, Monica; Calabrese, Francesca; Battistella, Lucia; Schiavon, Marco; Rea, Federico; Calabrese, Fiorella

    2017-08-01

    Solid-organ transplant recipients are at high risk of developing malignancies. A greater risk of Kaposi sarcoma has been reported in lung recipients in our country, particularly in those from Southern Italy, probably due to the high prevalence of Human herpes virus 8 infection. Kaposi sarcoma affecting only the lung allograft is extremely rare. We describe a case of a lung recipient who developed Kaposi sarcoma only in the graft, 22 months after transplant. The patient, a 65-year-old man from Southern Italy, underwent bilateral lung transplant for idiopathic pulmonary fibrosis in January 2009. He developed mild/moderate acute cellular rejection (≥A2) in 4 of 6 scheduled transbronchial biopsies thus was treated with increased immunosuppressive therapy, shifting from cyclosporine to tacrolimus and mycophenolate mofetil. In July 2010, a high-resolution computed tomography scan showed small bilateral lung nodules, despite a generally good condition. After 2 months, his condition worsened with a severe weight loss. A positron emission tomography scan showed mild metabolic activity in the lesions with no other localizations. In October 2010, a lung biopsy was performed, with results showing typical histologic and immunohistochemical features of Kaposi sarcoma. Molecular tissue evaluations and serologic analyses were positive for Human herpes virus 8. The patient's immunosuppressive therapy was suspended, and he started liposomal doxorubicin treatment; however, after the first cycle, he developed severe respiratory dysfunction. The patient died 27 months after lung transplant for neoplasm. Our report highlights the importance of considering Kaposi sarcoma in the differential diagnosis for lung nodules in lung transplant recipients, even in the absence of any initial specific symptom or cutaneous lesion.

  13. Surgical techniques and radiological findings of meniscus allograft transplantation.

    Science.gov (United States)

    Lee, Hoseok; Lee, Sang Yub; Na, Young Gon; Kim, Sung Kwan; Yi, Jae Hyuck; Lim, Jae Kwang; Lee, So Mi

    2016-08-01

    Meniscus allograft transplantation has been performed over the past 25 years to relieve knee pain and improve knee function in patients with an irreparable meniscus injury. The efficacy and safety of meniscus allograft transplantation have been established in numerous experimental and clinical researches. However, there is a lack of reviews to aid radiologists who are routinely interpreting images and evaluating the outcome of the procedures, and also meniscus allograft transplantation is not widely performed in most hospitals. This review focuses on the indications of the procedure, the different surgical techniques used for meniscus allograft transplantation according to the involvement of the lateral and medial meniscus, and the associated procedures. The postoperative radiological findings and surgical complications of the meniscus allograft transplantation are also described in detail. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Chemical sterilization of allograft dermal tissues.

    Science.gov (United States)

    Phipps, Abigail; Vaynshteyn, Edward; Kowalski, John B; Ngo, Manh-Dan; Merritt, Karen; Osborne, Joel; Chnari, Evangelia

    2017-12-01

    Common terminal sterilization methods are known to alter the natural structure and properties of soft tissues. One approach to providing safe grafts with preserved biological properties is the combination of a validated chemical sterilization process followed by an aseptic packaging process. This combination of processes is an accepted method for production of sterile healthcare products as described in ANSI/AAMI ST67:2011. This article describes the validation of the peracetic acid and ethanol-based (PAAE) chemical sterilization process for allograft dermal tissues at the Musculoskeletal Transplant Foundation (MTF, Edison, NJ). The sterilization capability of the PAAE solution used during routine production of aseptically processed dermal tissue forms was determined based on requirements of relevant ISO standards, ISO 14161:2009 and ISO 14937:2009. The resistance of spores of Bacillus subtilis, Clostridium sporogenes, Mycobacterium terrae, Pseudomonas aeruginosa, Enterococcus faecium, and Staphylococcus aureus to the chemical sterilization process employed by MTF was determined. Using a worst-case scenario testing strategy, the D value was calculated for the most resistant microorganism, Bacillus. The 12D time parameter determined the minimum time required to achieve a SAL of 10 -6 . Microbiological performance qualification demonstrated a complete kill of 10 6 spores at just a quarter of the full cycle time. The validation demonstrated that the PAAE sterilization process is robust, achieves sterilization of allograft dermal tissue to a SAL 10 -6 , and that in combination with aseptic processing secures the microbiological safety of allograft dermal tissue while avoiding structural and biochemical tissue damage previously observed with other sterilization methods such as ionizing irradiation.

  15. Protection against bronchiolitis obliterans syndrome is associated with allograft CCR7+ CD45RA- T regulatory cells.

    Directory of Open Access Journals (Sweden)

    Aric L Gregson

    2010-06-01

    Full Text Available Bronchiolitis obliterans syndrome (BOS is the major obstacle to long-term survival after lung transplantation, yet markers for early detection and intervention are currently lacking. Given the role of regulatory T cells (Treg in modulation of immunity, we hypothesized that frequencies of Treg in bronchoalveolar lavage fluid (BALF after lung transplantation would predict subsequent development of BOS. Seventy BALF specimens obtained from 47 lung transplant recipients were analyzed for Treg lymphocyte subsets by flow cytometry, in parallel with ELISA measurements of chemokines. Allograft biopsy tissue was stained for chemokines of interest. Treg were essentially all CD45RA(-, and total Treg frequency did not correlate to BOS outcome. The majority of Treg were CCR4(+ and CD103(- and neither of these subsets correlated to risk for BOS. In contrast, higher percentages of CCR7(+ Treg correlated to reduced risk of BOS. Additionally, the CCR7 ligand CCL21 correlated with CCR7(+ Treg frequency and inversely with BOS. Higher frequencies of CCR7(+ CD3(+CD4(+CD25(hiFoxp3(+CD45RA(- lymphocytes in lung allografts is associated with protection against subsequent development of BOS, suggesting that this subset of putative Treg may down-modulate alloimmunity. CCL21 may be pivotal for the recruitment of this distinct subset to the lung allograft and thereby decrease the risk for chronic rejection.

  16. Genomic Analysis of Kidney Allograft Injury Identifies Hematopoietic Cell Kinase as a Key Driver of Renal Fibrosis.

    Science.gov (United States)

    Wei, Chengguo; Li, Li; Menon, Madhav C; Zhang, Weijia; Fu, Jia; Kidd, Brian; Keung, Karen L; Woytovich, Christopher; Greene, Ilana; Xiao, Wenzhen; Salem, Fadi; Yi, Zhengzi; He, John Cijiang; Dudley, Joel T; Murphy, Barbara

    2017-05-01

    Renal fibrosis is the common pathway of progression for patients with CKD and chronic renal allograft injury (CAI), but the underlying mechanisms remain obscure. We performed a meta-analysis in human kidney biopsy specimens with CAI, incorporating data available publicly and from our Genomics of Chronic Renal Allograft Rejection study. We identified an Src family tyrosine kinase, hematopoietic cell kinase ( Hck ), as upregulated in allografts in CAI. Querying the Kinase Inhibitor Resource database revealed that dasatinib, a Food and Drug Administration-approved drug, potently binds Hck with high selectivity. In vitro , Hck overexpression activated the TGF-β/Smad3 pathway, whereas HCK knockdown inhibited it. Treatment of tubular cells with dasatinib reduced the expression of Col1a1 Dasatinib also reduced proliferation and α-SMA expression in fibroblasts. In a murine model with unilateral ureteric obstruction, pretreatment with dasatinib significantly reduced the upregulation of profibrotic markers, phosphorylation of Smad3, and renal fibrosis observed in kidneys pretreated with vehicle alone. Dasatinib treatment also improved renal function, reduced albuminuria, and inhibited expression of profibrotic markers in animal models with lupus nephritis and folic acid nephropathy. These data suggest that Hck is a key mediator of renal fibrosis and dasatinib could be developed as an antifibrotic drug. Copyright © 2017 by the American Society of Nephrology.

  17. De Novo Renal Cell Carcinoma in a Kidney Allograft 20 Years after Transplant

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    Masataka Banshodani

    2015-01-01

    Full Text Available Renal cell carcinoma (RCC in a kidney allograft is rare. We report the successful diagnosis and treatment of a de novo RCC in a nonfunctioning kidney transplant 20 years after engraftment. A 54-year-old man received a kidney transplant from his mother when he was 34 years old. After 10 years, chronic rejection resulted in graft failure, and the patient became hemodialysis-dependent. Intravenous contrast-enhanced computed tomography (CT for the evaluation of gastrointestinal symptoms revealed a solid 13 mm tumor in the kidney graft. The tumor was confirmed on ultrasound examination. This tumor had not been detected on a surveillance noncontrast CT scan. Needle biopsy showed that the tumor was an RCC. Allograft nephrectomy was performed. Pathological examination showed that the tumor was a Fuhrman Grade 2 RCC. XY-fluorescence hybridization analysis of the RCC showed that the tumor cells were of donor origin. One year after the surgery, the patient is alive and has no evidence of tumor recurrence. Regardless of whether a kidney transplant is functioning, it should periodically be imaged for RCC throughout the recipient’s lifetime. In our experience, ultrasonography or CT with intravenous contrast is better than CT without contrast for the detection of tumor in a nonfunctioning kidney transplant.

  18. HLA-G Dimers in the Prolongation of Kidney Allograft Survival

    Directory of Open Access Journals (Sweden)

    Maureen Ezeakile

    2014-01-01

    Full Text Available Human leukocyte antigen-G (HLA-G contributes to acceptance of allografts in solid organ/tissue transplantation. Most studies have determined that soluble HLA-G isoforms are systematically detected in serum/plasma of transplanted patients with significantly fewer episodes of acute and/or chronic rejection of allogeneic tissue/organ. Current models of the interactions of HLA-G and its specific receptors explain it as functioning in a monomeric form. However, in recent years, new data has revealed the ability of HLA-G to form disulfide-linked dimeric complexes with high preferential binding and functional activities. Limited data are available on the role of soluble HLA-G dimers in clinical pathological conditions. We describe here the presence of soluble HLA-G dimers in kidney transplant patients. Our study showed that a high level of HLA-G dimers in plasma and increased expression of the membrane-bound form of HLA-G on monocytes are associated with prolongation of kidney allograft survival. We also determined that the presence of soluble HLA-G dimers links to the lower levels of proinflammatory cytokines, suggesting a potential role of HLA-G dimers in controlling the accompanying inflammatory state.

  19. A review: HIV inactivation in allografts

    International Nuclear Information System (INIS)

    Astrid Lobo Gajiwala

    1999-01-01

    This review focuses on the use of 70% ethanol as a virucidal agent with particular reference to human immunodeficiency virus (HIV). The transmission of this virus through allografts is of particular to tissue banks since the screening for HIV antibody of potential donors of tissues does not eliminate the risk of HIV transmission. Seronegetive donors who were in the 'window' period i.e. the time between infection and seroconversion, have been known to transmit HIV. It is suggested that exposure to 70% ethanol be included as a routine step in the banking of tissues whether fresh frozen or freeze-dried

  20. Meniscal allograft transplantation: a meta-analysis

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    De Bruycker Manolito

    2017-01-01

    Full Text Available Purpose: This meta-analysis evaluates the mid- to long-term survival outcome of MAT (meniscal allograft transplantation. Potential prognosticators, with particular focus on chondral status and age of the patient at the time of transplantation, were also analysed. Study design: Meta-analysis. Methods: An online database search was performed using following search string: “meniscal allograft transplantation” and “outcome”. A total of 65 articles were analysed for a total of 3157 performed MAT with a mean follow-up of 5.4 years. Subjective and clinical data was analysed. Results: The subjective and objective results of 2977 patients (3157 allografts were analysed; 70% were male, 30% were female. Thirty-eight percent received an isolated MAT. All other patients underwent at least one concomitant procedure. Lysholm, Knee injury and Osteoarthritis Outcome (KOOS, International Knee Documentation Committee (IKDC and Visual Analogue Scale (VAS scores were analysed. All scores showed a good patient satisfaction at long-term follow-up. The mean overall survival rate was 80.9%. Complication rates were comparable to standard meniscal repair surgery. There was a degenerative evolution in osteoarthritis with at least one grade in 1760 radiographically analysed patients. Concomitant procedures seem to have no effect on the outcome. Age at transplantation is a negative prognosticator. The body mass index (BMI of the patient shows a slightly negative correlation with the outcome of MAT. Conclusions: MAT is a viable solution for the younger patient with chronic pain in the meniscectomised knee joint. The complications are not severe and comparable to meniscal repair. The overall failure rate at final follow-up is acceptable and the allograft heals well in most cases, but MAT cannot be seen as a definitive solution for post-meniscectomy pain. The correct approach to the chronic painful total meniscectomised knee joint thus requires consideration of all

  1. Complications of massive allograft reconstruction for bone tumors

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    Abolhasan Borjian

    2006-11-01

    Full Text Available BACKGROUND: Since the evolution of multi-drug chemotherapy and radiotherapy and new sophisticated surgical techniques, limb salvage and reconstruction, rather than amputation, has become the preferred treatment for patients with bone tumors. One option is allograft replacement. Although allograft has several advantages, it is not without complications. This study was performed to observe these complications in a group of patients treated with allograft replacement for bone tumor resection. The purpose was to gain an overview of the factors predisposing to these complications to minimize their occurrence. METHODS: This retrospective study was performed on patients with benign aggressive and malignant bone tumors undergoing limb reconstruction with allograft between 1997 and 2005 in Al-Zahra and Kashani Hospitals in Isfahan, Iran. Data was collected from patient files, clinical notes, radiographs and a recent physical examination. Complications including local recurrence, fracture of allograft, fixation failure, nonunion, infection, skin necrosis and neurological damage were recorded. RESULTS: Sixty patients including 39 males and 21 females were studied. The mean age of patients was 23 ± 11.7 years. The mean follow-up interval was 28.1 ± 12.4 months (mean ± SD. Complications were allograft fracture in 20%, local recurrence in 16%, fixation failure in 11%, nonunion in 6%, infection in 6%, skin necrosis in 6%, and peroneal nerve palsy in 1% of cases. Most local recurrences (60% were those with a mal-performed biopsy. Most allograft fractures occurred when a short plate was used. CONCLUSIONS: Allograft replacement for bone tumors remains a valid option. To avoid complications, biopsy should be done by a trained surgeon in bone oncology. A long plate is recommended for fixation. Sterility and graft processing must be optimal. Autogenous bone graft must be added at host-allograft junction. KEY WORDS: Bone tumors, bone allograft, limb

  2. 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.

  3. 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.

  4. Total lymphoid irradiation in the treatment of early or recurrent heart transplant rejection

    International Nuclear Information System (INIS)

    Salter, Susan P.; Salter, Merle M.; Kirklin, James K.; Bourge, Robert C.; Naftel, David C.

    1995-01-01

    Purpose: Recurrent acute cardiac allograft rejection is an important cause of repeat hospitalization and a major mode of mortality, particularly during the 6 months immediately following transplant. Total lymphoid irradiation (TLI) has been shown experimentally to induce a state of partial tolerance when administered prior to transplantation. Anecdotal reports of clinical experience have also suggested efficacy of TLI in treatment of recurrent cardiac rejection. The purpose of this study is to evaluate the safety and efficacy of TLI for treatment of early or recurrent heart transplant rejection. Materials and Methods: Between January 1990 and June 1992, 49 patients postallograft cardiac transplant were given courses of TLI for treatment of early or recurrent rejection after conventional therapy with Methylprednisolone, antithymocyte globulin, OKT3, and methotrexate. Two patients failed to complete their therapy and were not evaluated. Two other patients received a second TLI course, making a total of 49 courses delivered. Indications for TLI were early rejection (n = 5), recurrent rejection (n = 38), and recurrent rejection with vasculitis (n = 6). The dose goal of the TLI protocol was 8 Gy in 10 fractions given twice weekly. Three separate fields were used to encompass all major lymph node-bearing areas. The actual mean dose was 7 Gy (range 2.4-8.4 Gy), and the duration of treatment was 8 to 106 days. These variations were secondary to leukopenia or thrombocytopenia. Results: The mean posttransplant follow-up is 15 ± 1.2 months (maximum 27 months). Among patients initiating TLI within 1 month posttransplant (n = 15), the rejection frequency decreased from 1.83 episodes/patient/month pre-TLI to 0.13 episodes/patient/month post-TLI (p < 0.0001). For those who began TLI 1-3 months after transplant (n = 21), rejection decreased from 1.43 to 0.10 episodes/patient/month (p < 0.0001). When TLI was started more than 3 months posttransplant (n = 11), the pre-TLI and post

  5. Adefovir nephrotoxicity in a renal allograft recipient

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    N George

    2015-01-01

    Full Text Available Adefovir dipivoxil, an oral prodrug of adefovir, is used in the treatment of lamivudine-resistant hepatitis B virus (HBV infection. Nephrotoxicity manifesting as proximal renal tubular dysfunction and acute tubular necrosis (ATN were commonly reported in the past, when higher doses were used for the treatment of human immunodeficiency virus infection. However, nephrotoxicity is rare at lower doses that are currently recommended for the treatment of HBV infection. A 31-year-old female was detected to be hepatitis B surface antigen positive months after a kidney transplant. The patient was initiated on lamivudine, but developed resistance after 1 year of treatment, at which time low-dose adefovir was added. The patient developed renal allograft dysfunction after 10 months of starting adefovir. Serum creatinine increased from 1.1 mg/dl to 1.9 mg/dl, along with progressively increasing sub-nephrotic proteinuria. Renal allograft biopsy revealed features of ATN. After discontinuation of adefovir, proteinuria resolved and renal dysfunction improved slowly over the next 2 years. Adefovir-induced nephrotoxicity, although uncommon at lower doses, needs to be considered in the differential diagnosis of renal dysfunction and sub-nephrotic proteinuria occurring in patients receiving adefovir for prolonged periods.

  6. Increased Release Time of Antibiotics from Bone Allografts through a Novel Biodegradable Coating

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    István Hornyák

    2014-01-01

    Full Text Available The use of bone allografts is contraindicated in septic revision surgery due to the high risk of graft reinfection. Antibiotic release from the graft may solve the problem and these combinations can theoretically be used for prevention or even therapy of infection. The present study investigated whether amoxicillin, ciprofloxacin, and vancomycin alone or in combination with chitosan or alginate are suitable for short-term or long-term bone coating. Human bone allografts were prepared from femoral head and lyophilized. Antibiotic coating was achieved by incubating the grafts in antibiotic solution and freeze-drying again. Two biopolymers chitosan and alginate were used for creating sustained-release implantable coatings and the drug release profile was characterized in vitro by spectrophotometry. Using lyophilization with or without chitosan only resulted in short-term release that lasted up to 48 hours. Alginate coating enabled a sustained release that lasted for 8 days with amoxicillin, 28 days with ciprofloxacin coating, and 50 days with vancomycin coating. Using only implantable biodegradable allograft and polymers, a sustained release of antibiotics was achieved with ciprofloxacin and vancomycin for several weeks. Since the calculated daily release of the antibiotic was lower than the recommended IV dose, the calcium alginate coated bone graft can support endoprosthesis revision surgery.

  7. Tc-99m DTPA perfusion scintigraphy and color coded duplex sonography in the evaluation of minimal renal allograft perfusion

    International Nuclear Information System (INIS)

    Bair, H.J.; Platsch, G.; Wolf, F.; Guenter, E.; Becker, D.; Rupprecht, H.; Neumayer, H.H.

    1997-01-01

    Aim: The clinical impact of perfusion scintigraphy versus color coded Duplex sonography was evaluated, with respect to their potential in assessing minimal allograft perfusion in vitally threatened kidney transplants, i.e. oligoanuric allografts suspected to have either severe rejection or thrombosis of the renal vein or artery. Methods: From July 1990 to August 1994 the grafts of 15 out of a total of 315 patients were vitally threatened. Technetium-99m DTPA scintigraphy and color coded Duplex sonography were performed in all patients. For scintigraphic evaluation of transplant perfusion analog scans up to 60 min postinjection, and time-activity curves over the first 60 sec after injection of 370-440 MBq Tc-99m diethylenetriaminepentaacetate acid (DTPA) were used and classified by a perfusion score, the time between renal and iliac artery peaks (TDiff) and the washout of the renogram curve. Additionally, evaluation of excretion function and assessment of vascular or urinary leaks were performed. By color coded Duplex sonography the perfusion in all sections of the graft as well as the vascular anastomoses were examined and the maximal blood flow velocity (Vmax) and the resistive index (RI) in the renal artery were determined by means of the pulsed Doppler device. Pathologic-anatomical diagnosis was achieved by either biopsy or post-explant histology in all grafts. Results: Scintigraphy and color coded Duplex sonography could reliably differentiate minimal (8/15) and not perfused (7/15) renal allografts. The results were confirmed either by angiography in digital subtraction technique (DSA) or the clinical follow up. Conclusion: In summary, perfusion scintigraphy and color coded Duplex sonography are comparable modalities to assess kidney graft perfusion. In clinical practice scintigraphy and colorcoded Doppler sonography can replace digital subtraction angiography in the evaluation of minimal allograft perfusion. (orig.) [de

  8. Early Allograft Dysfunction Is Associated With Higher Risk of Renal Nonrecovery After Liver Transplantation

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    Hani M. Wadei, MD

    2018-04-01

    Full Text Available Abstract. Early allograft dysfunction (EAD identifies allografts with marginal function soon after liver transplantation (LT and is associated with poor LT outcomes. The impact of EAD on post-LT renal recovery, however, has not been studied. Data on 69 primary LT recipients (41 with and 28 without history of renal dysfunction who received renal replacement therapy (RRT for a median (range of 9 (13-41 days before LT were retrospectively analyzed. Primary outcome was renal nonrecovery defined as RRT requirement 30 days from LT. Early allograft dysfunction developed in 21 (30% patients, and 22 (32% patients did not recover renal function. Early allograft dysfunction was more common in the renal nonrecovery group (50% vs 21%, P = 0.016. Multivariate logistic regression analysis demonstrated that EAD (odds ratio, 7.25; 95% confidence interval, 2.0-25.8; P = 0.002 and baseline serum creatinine (odds ratio, 3.37; 95% confidence interval, 1.4-8.1; P = 0.007 were independently associated with renal nonrecovery. History of renal dysfunction, duration of renal dysfunction, and duration of RRT were not related to renal recovery (P > 0.2 for all. Patients who had EAD and renal nonrecovery had the worst 1-, 3-, and 5-year patient survival, whereas those without EAD and recovered renal function had the best outcomes (P < 0.001. Post-LT EAD was independently associated with renal nonrecovery in LT recipients on RRT for a short duration before LT. Furthermore, EAD in the setting of renal nonrecovery resulted in the worst long-term survival. Measures to prevent EAD should be undertaken in LT recipients on RRT at time of LT.

  9. Evaluation of blood flow in Allograft Renal Arteries anastomosed with two different techniques

    International Nuclear Information System (INIS)

    Zomorrodi, A.; Bohluli, A.; Tarzamany, M.K.

    2008-01-01

    Renal artery stenosis in renal transplantation (TRAS) is an avoidable short or long term surgical complication. The etiology is multifactorial, but faulty anastomosis is a major factor. In our transplant center, we evaluated the incidence of TRAS with the use of two different suturing techniques of the anastomosis site between allograft renal and renal and iliac arteries in two groups of renal transplant recipients, group A: 14 patients (6 males and 8 females with age 16 to 59 and mean age of 38 years) in whom allograft arteries were anastomosed with a continuous suture technique and group B: 14 patients (7 males and 7 females with age 32 to 61 and mean age of 46.6 years) in whom the allograft arteries were anastomosed with a combined suture technique (continuous and uninterrupted. Post transplantation, the velocity of blood flow in the renal and iliac arteries at the site of anastomosis was measured by color Doppler ultrasound. The ultrasonographer was blinded to the surgical technique in both study groups. The ratio of the maximum velocity of blood at the site of anastomosis to that in the iliac artery of less than 2.5 was considered as non-significant stenosis, while a ratio of more than 2.5 was considered significant stenosis. In group A there were 9 cases of non-significant stenosis in comparison to 3 cases in group B, while there were no cases of significant stenosis in group A in comparison to 3 cases in group B; the difference was not statistically significant. We conclude that there was no difference in the compared surgical techniques of anastomosis in our study groups. This suggests that other factors such as gentle handling of tissue, enough spatula, margin reversion and comparable diameter of the anastomosed vessels may be more important in the prevention of renal allograft stenosis than the type of suture technique. (author)

  10. The safety of bone allografts used in dentistry: a review.

    Science.gov (United States)

    Holtzclaw, Dan; Toscano, Nicholas; Eisenlohr, Lisa; Callan, Don

    2008-09-01

    Recent media reports concerning "stolen body parts" have shaken the public's trust in the safety of and the use of ethical practices involving human allografts. The authors provide a comprehensive review of the safety aspects of human bone allografts. The authors reviewed U.S. government regulations, industry standards, independent industry association guidelines, company guidelines and scientific articles related to the use of human bone allografts in the practice of dentistry published in the English language. The use of human bone allografts in the practice of dentistry involves the steps of procurement, processing, use and tracking. Rigorous donor screening and aseptic proprietary processing programs have rendered the use of human bone allografts safe and effective as a treatment option. When purchasing human bone allografts for the practice of dentistry, one should choose products accredited by the American Association of Tissue Banks for meeting uniformly high safety and quality control measures. Knowledge of human bone allograft procurement, processing, use and tracking procedures may allow dental clinicians to better educate their patients and address concerns about this valuable treatment option.

  11. SDF-1/CXCR4/CXCR7 is pivotal for vascular smooth muscle cell proliferation and chronic allograft vasculopathy.

    Science.gov (United States)

    Thomas, Michael N; Kalnins, Aivars; Andrassy, Martin; Wagner, Anne; Klussmann, Sven; Rentsch, Markus; Habicht, Antje; Pratschke, Sebastian; Stangl, Manfred; Bazhin, Alexandr V; Meiser, Bruno; Fischereder, Michael; Werner, Jens; Guba, Markus; Andrassy, Joachim

    2015-12-01

    Chronic rejection remains a major obstacle in transplant medicine. Recent studies suggest a crucial role of the chemokine SDF-1 on neointima formation after injury. Here, we investigate the potential therapeutic effect of inhibiting the SDF-1/CXCR4/CXCR7 axis with an anti-SDF-1 Spiegelmer (NOX-A12) on the development of chronic allograft vasculopathy. Heterotopic heart transplants from H-2bm12 to B6 mice and aortic transplants from Balb/c to B6 were performed. Mice were treated with NOX-A12. Control animals received a nonfunctional Spiegelmer (revNOX-A12). Samples were retrieved at different time points and analysed by histology, RT-PCR and proliferation assay. Blockade of SDF-1 caused a significant decrease in neointima formation as measured by intima/media ratio (1.0 ± 0.1 vs. 1.8 ± 0.1, P SDF-1 inhibition (3.42 ± 0.37 vs. 1.67 ± 0.33, P SDF-1/CXCR4/CXCR7 plays a critical role in the development of chronic allograft vasculopathy (CAV). Therefore, pharmacological inhibition of SDF-1 with NOX-A12 may represent a therapeutic option to ameliorate chronic rejection changes. © 2015 Steunstichting ESOT.

  12. Acute antibody-mediated rejection after AB0-incomptible kidney transplantation treated successfully with antigen-specific immunoadsorption

    DEFF Research Database (Denmark)

    Just, Søren Andreas; Marcussen, Niels; Sprogøe, Ulrik

    2009-01-01

    ABO-incompatible kidney transplantation is possible after pre-treatment with rituximab, intravenous immunoglobulin and basiliximab combined with tacrolimus, mycophenolate mofetil and prednisolone. We report on the first patient treated with this protocol who developed acute antibody-mediated reje......ABO-incompatible kidney transplantation is possible after pre-treatment with rituximab, intravenous immunoglobulin and basiliximab combined with tacrolimus, mycophenolate mofetil and prednisolone. We report on the first patient treated with this protocol who developed acute antibody......-mediated rejection (Banff grade II with IgG deposits) caused by ABO antibodies (anti-B). Anti-rejection treatment with anti-B-specific immunoadsorption, intravenous immunoglobulin and methylprednisolone efficiently cleared deposited IgG from the kidney allograft and re-established normal kidney function. We suggest...... that ABO-incompatible kidney transplantation complicated by acute antibody-mediated rejection, caused by ABO antibodies, may successfully be treated with this regime....

  13. Acute antibody-mediated rejection after ABO-incompatible kidney transplantation treated successfully with antigen-specific immunoadsorption

    DEFF Research Database (Denmark)

    Just, Søren Andreas; Marcussen, Niels; Sprogøe, Ulrik

    2010-01-01

    ABO-incompatible kidney transplantation is possible after pre-treatment with rituximab, intravenous immunoglobulin and basiliximab combined with tacrolimus, mycophenolate mofetil and prednisolone. We report on the first patient treated with this protocol who developed acute antibody-mediated reje......ABO-incompatible kidney transplantation is possible after pre-treatment with rituximab, intravenous immunoglobulin and basiliximab combined with tacrolimus, mycophenolate mofetil and prednisolone. We report on the first patient treated with this protocol who developed acute antibody......-mediated rejection (Banff grade II with IgG deposits) caused by ABO antibodies (anti-B). Anti-rejection treatment with anti-B-specific immunoadsorption, intravenous immunoglobulin and methylprednisolone efficiently cleared deposited IgG from the kidney allograft and re-established normal kidney function. We suggest...... that ABO-incompatible kidney transplantation complicated by acute antibody-mediated rejection, caused by ABO antibodies, may successfully be treated with this regime....

  14. 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

  15. Percutaneous fusion of lumbar facet with bone allograft

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    Félix Dolorit Verdecia

    2015-03-01

    Full Text Available OBJECTIVE: To assess the evolution of the cases treated with percutaneous facet fusion with bone allograft in lumbar facet disease. METHOD: Between 2010 and 2014, 100 patients (59 women and 41 men diagnosed with lumbar facet disease underwent surgery. RESULTS: The lumbar facet fusion with bone allograft shows good clinical results, is performed on an outpatient basis, and presents minimal complications and rapid incorporation of the patient to the activities of daily living. CONCLUSIONS: The lumbar facet fusion with bone allograft appears to be an effective treatment for lumbar facet disease.

  16. A neural network approach to the biopsy diagnosis of early acute renal transplant rejection.

    Science.gov (United States)

    Furness, P N; Levesley, J; Luo, Z; Taub, N; Kazi, J I; Bates, W D; Nicholson, M L

    1999-11-01

    To develop and test a neural network to assist in the histological diagnosis of early acute renal allograft rejection. We used three sets of biopsies to train and test the network: 100 'routine' biopsies from Leicester; 21 selected difficult biopsies which had already been evaluated by most of the renal transplant pathologists in the UK, in a study of the Banff classification of allograft pathology and 25 cases which had been classified as 'borderline' according to the Banff classification in a review of transplant biopsies from Oxford. The correct diagnosis for each biopsy was defined by careful retrospective clinical review. Biopsies where this review did not provide a clear diagnosis were excluded. Each biopsy was graded for 12 histological features and the data was entered into a simple single layer perception network, designed using the MATLAB neural network toolbox. Results were compared with logistic regression using the same data, and with 'conventional' histological diagnosis. If the network was trained only with the 100 'routine' cases, its performance with either of the other sets was poor. However, if either of the 'difficult' sets was added to the training group, testing with the other 'difficult' group improved dramatically; 19 of the 21 'Banff' study cases were diagnosed correctly. This was achieved using observations made by a trainee pathologist. The result is better than was achieved by any of the many experienced pathologists who had previously seen these biopsies (maximum 18/21 correct), and is considerably better than that achieved by using logistic regression with the same data. A neural network can provide a considerable improvement in the diagnosis of early acute allograft rejection, though further development work will be needed before this becomes a routine diagnostic tool. The selection of cases used to train the network is crucial to the quality of its performance. There is scope to improve the system further by incorporating clinical

  17. Are the current chronic allograft nephropathy grading systems sufficient to predict renal allograft survival?

    Directory of Open Access Journals (Sweden)

    G.T. Moscoso-Solorzano

    2008-10-01

    Full Text Available A major problem in renal transplantation is identifying a grading system that can predict long-term graft survival. The present study determined the extent to which the two existing grading systems (Banff 97 and chronic allograft damage index, CADI correlate with each other and with graft loss. A total of 161 transplant patient biopsies with chronic allograft nephropathy (CAN were studied. The samples were coded and evaluated blindly by two pathologists using the two grading systems. Logistic regression analyses were used to evaluate the best predictor index for renal allograft loss. Patients with higher Banff 97 and CADI scores had higher rates of graft loss. Moreover, these measures also correlated with worse renal function and higher proteinuria levels at the time of CAN diagnosis. Logistic regression analyses showed that the use of angiotensin-converting enzyme inhibitor (ACEI, hepatitis C virus (HCV, tubular atrophy, and the use of mycophenolate mofetil (MMF were associated with graft loss in the CADI, while the use of ACEI, HCV, moderate interstitial fibrosis and tubular atrophy and the use of MMF were associated in the Banff 97 index. Although Banff 97 and CADI analyze different parameters in different renal compartments, only some isolated parameters correlated with graft loss. This suggests that we need to review the CAN grading systems in order to devise a system that includes all parameters able to predict long-term graft survival, including chronic glomerulopathy, glomerular sclerosis, vascular changes, and severity of chronic interstitial fibrosis and tubular atrophy.

  18. Are the current chronic allograft nephropathy grading systems sufficient to predict renal allograft survival?

    Directory of Open Access Journals (Sweden)

    G.T. Moscoso-Solorzano

    Full Text Available A major problem in renal transplantation is identifying a grading system that can predict long-term graft survival. The present study determined the extent to which the two existing grading systems (Banff 97 and chronic allograft damage index, CADI correlate with each other and with graft loss. A total of 161 transplant patient biopsies with chronic allograft nephropathy (CAN were studied. The samples were coded and evaluated blindly by two pathologists using the two grading systems. Logistic regression analyses were used to evaluate the best predictor index for renal allograft loss. Patients with higher Banff 97 and CADI scores had higher rates of graft loss. Moreover, these measures also correlated with worse renal function and higher proteinuria levels at the time of CAN diagnosis. Logistic regression analyses showed that the use of angiotensin-converting enzyme inhibitor (ACEI, hepatitis C virus (HCV, tubular atrophy, and the use of mycophenolate mofetil (MMF were associated with graft loss in the CADI, while the use of ACEI, HCV, moderate interstitial fibrosis and tubular atrophy and the use of MMF were associated in the Banff 97 index. Although Banff 97 and CADI analyze different parameters in different renal compartments, only some isolated parameters correlated with graft loss. This suggests that we need to review the CAN grading systems in order to devise a system that includes all parameters able to predict long-term graft survival, including chronic glomerulopathy, glomerular sclerosis, vascular changes, and severity of chronic interstitial fibrosis and tubular atrophy.

  19. The Effect of MHC Antigen Matching Between Donors and Recipients on Skin Tolerance of Vascularized Composite Allografts.

    Science.gov (United States)

    Shanmugarajah, K; Powell, H; Leonard, D A; Mallard, C; Albritton, A; Harrington, E; Randolph, M A; Farkash, E; Sachs, D H; Kurtz, J M; Cetrulo, C L

    2017-07-01

    The emergence of skin-containing vascularized composite allografts (VCAs) has provided impetus to understand factors affecting rejection and tolerance of skin. VCA tolerance can be established in miniature swine across haploidentical MHC barriers using mixed chimerism. Because the deceased donor pool for VCAs does not permit MHC antigen matching, clinical VCAs are transplanted across varying MHC disparities. We investigated whether sharing of MHC class I or II antigens between donors and recipients influences VCA skin tolerance. Miniature swine were conditioned nonmyeloablatively and received hematopoietic stem cell transplants and VCAs across MHC class I (n = 3) or class II (n = 3) barriers. In vitro immune responsiveness was assessed, and VCA skin-resident leukocytes were characterized by flow cytometry. Stable mixed chimerism was established in all animals. MHC class II-mismatched chimeras were tolerant of VCAs. MHC class I-mismatched animals, however, rejected VCA skin, characterized by infiltration of recipient-type CD8 + lymphocytes. Systemic donor-specific nonresponsiveness was maintained, including after VCA rejection. This study shows that MHC antigen matching influences VCA skin rejection and suggests that local regulation of immune tolerance is critical in long-term acceptance of all VCA components. These results help elucidate novel mechanisms underlying skin tolerance and identify clinically relevant VCA tolerance strategies. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  20. Bipolar fresh osteochondral allograft of the ankle.

    Science.gov (United States)

    Giannini, Sandro; Buda, Roberto; Grigolo, Brunella; Bevoni, Roberto; Di Caprio, Francesco; Ruffilli, Alberto; Cavallo, Marco; Desando, Giovanna; Vannini, Francesca

    2010-01-01

    Severe post-traumatic ankle arthritis poses a reconstructive challenge in the young and active patient. Bipolar fresh osteochondral allograft (BFOA) may represent an intriguing alternative to arthrodesis and prosthetic replacement. The aim of this study was to describe a lateral trans-malleolar technique for BFOA, and to evaluate the results in a case series. From 2004 to 2006, 32 patients, mean age of 36.8 +/- 8.4 years, affected by ankle arthritis underwent BFOA with a mean followup of 31.2 months. The graft was prepared by specifically designed jigs, including the talus and the tibia with the medial malleolus. The host surfaces were prepared by the same jigs through a lateral approach. The graft was placed and fixed with twist-off screws. Patients were evaluated clinically and radiographically at 2, 4, and 6 month after operation, and at a minimum 24 months followup. A biopsy of the grafted areas was obtained from 7 patients at 1-year followup for histological and immunohistochemical examination. Preoperative AOFAS score was 33.1 +/- 10.9 and postoperatively 69.5 +/- 19.4 (p < 0.0005). Six failures occurred. Cartilage harvests showed hyaline-like histology with a normal collagen component but low proteoglycan presence and a disorganized structure. Samples were positive for MMP-1, MMP-13 and Capsase-3. The use of BFOA represents an intriguing alternative to arthrodesis or arthroplasty. We believe precise allograft sizing, stable fitting and fixation and delayed weightbearing were key factors for a successful outcome. Further research regarding the immunological behavior of transplanted cartilage is needed.

  1. Surgical revascularization induces angiogenesis in orthotopic bone allograft

    NARCIS (Netherlands)

    Willems, Wouter F.; Kremer, Thomas; Friedrich, Patricia; Bishop, Allen T.

    2012-01-01

    Remodeling of structural bone allografts relies on adequate revascularization, which can theoretically be induced by surgical revascularization. We developed a new orthotopic animal model to determine the technical feasibility of axial arteriovenous bundle implantation and resultant angiogenesis. We

  2. Knee extensor mechanism allograft reconstruction following chronic disruption.

    Science.gov (United States)

    Murgier, J; Boisrenoult, P; Pujol, N; Beranger, J S; Tardy, N; Steltzlen, C; Beaufils, P

    2015-11-01

    The management of chronic extensor mechanism disruption can be complex. One of the options is allograft reconstruction. The goal of this study was to present the surgical procedure and provide preliminary results with this technique. The allograft uses the whole extensor mechanism (anterior tibial tubercle, patellar ligament, patella, quadriceps tendon). The native patella can be completely removed if the quality of the bone is poor, otherwise a bone groovecan be created to receive the allograft. The allograft is tightly tensioned with the knee in full extension. This surgical technique was performed 5 times with a minimum follow-up of 1 year. Active extension was recovered in all cases. The mean postoperative KOOS was 55.5 the IKS function score was 68.5 and the IKS knee score was 83. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  3. Deceased donor skin allograft banking: Response and utilization

    Directory of Open Access Journals (Sweden)

    Gore Madhuri

    2010-10-01

    Full Text Available Background: In the absence of xenograft and biosynthetic skin substitutes, deceased donor skin allografts is a feasible option for saving life of patient with extensive burn injury in our country. Aims: The first deceased donor skin allograft bank in India became functional at Lokmanya Tilak Municipal (LTM medical college and hospital on 24 th April 2000. The response of Indian society to this new concept of skin donation after death and the pattern of utilization of banked allografts from 2000 to 2010 has been presented in this study. Settings and Design: This allograft skin bank was established by the department of surgery. The departments of surgery and microbiology share the responsibility of smooth functioning of the bank. Materials and Methods: The response in terms of number of donations and the profile of donors was analyzed from records. Pattern and outcome of allograft utilization was studied from specially designed forms. Results: During these ten years, 262 deceased donor skin allograft donations were received. The response showed significant improvement after counselling was extended to the community. Majority of the donors were above 70 years of age and procurement was done at home for most. Skin allografts from 249 donors were used for 165 patients in ten years. The outcome was encouraging with seven deaths in 151 recipients with burn injuries. Conclusions: Our experience shows that the Indian society is ready to accept the concept of skin donation after death. Use of skin allografts is life saving for large burns. We need to prepare guidelines for the establishment of more skin banks in the country.

  4. Osteochondral and Meniscal Allograft Transplantation in the Football (Soccer) Player

    OpenAIRE

    G?rtz, Simon; Williams, Riley J.; Gersoff, Wayne K.; Bugbee, William D.

    2012-01-01

    Knee injuries are common in football, frequently involving damage to the meniscus and articular cartilage. These injuries can cause significant disability, result in loss of playing time, and predispose players to osteoarthritis. Osteochondral allografting is an increasingly popular treatment option for osteoarticular lesions in athletes. Osteochondral allografts provide mature, orthotopic hyaline cartilage on an osseous scaffold that serves as an attachment vehicle, which is rapidly replaced...

  5. Preservation and sterilization methods of the meniscal allografts: literature review.

    Science.gov (United States)

    Mickiewicz, Patrycja; Binkowski, Marcin; Bursig, Henryk; Wróbel, Zygmunt

    2014-09-01

    Nowadays, there are four types of meniscal allografts known: fresh, cryopreserved, deep-frozen and lyophilized ones but only two of them are widely used in clinical practice. Use of different types of meniscal allografts still remains controversial due to preparation method, their biomechanical properties as well as cost which is connected with processing and storage. The main aim of this review is to present the current status of knowledge concerning meniscal allograft preservation and sterilization, especially the advantages and disadvantages of each method. Authors wanted to show a broad spectrum of methods used and conceptions presented by other authors. The second aim is to gather available information about meniscal preservation and sterilization methods in one paper. Deep-frozen and cryopreserved meniscal allografts are the most frequently used ones in the clinical practice. The use of fresh grafts stays controversial but also has many followers. Lyophilized grafts in turn are not applied at present due to some serious drawbacks including reduction of tensile strength, poor rehydration, graft shrinkage and post-transplantation joint effusion as well as increased risk of meniscal size reduction. An application of sterilizing agents make the meniscal allograft free from the bacteria and viruses, but also it may cause serious structure changes. Therefore, choosing just one ideal method of meniscal allograft preservation and sterilization is complicated and should be based on broad knowledge and experience of surgeon performing the transplantation.

  6. Clinical and functional outcomes of tibial intercalary allograft reconstructions

    Directory of Open Access Journals (Sweden)

    Lucas López Millán

    2012-12-01

    Full Text Available Background The purpose of this study was to evaluate the survival, the complications and the functional outcome of intercalary tibial allografts reconstructions following tumor resections. Methods Intercalary tibia segmental allografts were implanted in 26 consecutive patients after segmental resections. Average follow-up was 6 years. Allograft survival was determined with the Kaplan-Meier method. Function was evaluated with the Musculoskeletal Tumor Society scoring system (MSTS. Results The rate of survival was 84% (CI 95%: 90%- 70% at 5 years and 79% at 10 years (CI 95%: 95%-63%. Allografts were removed in 5 patients (3 due to infections and 2 due to local recurrences. Two patients showed diaphyseal nonunion and 3 had an incomplete fracture, but it was not necessary to remove the allografts. Average MSTS functional score was 29 points (range 27 to 30. Conclusions Despite the incidence of complications, this analysis showed an acceptable survival with excellent functional scores. The use of intercalary allograft clearly has a place in the reconstruction of a segmental defect created by the resection of a tumor in the diaphyseal and/or metaphyseal portion of the tibia.

  7. [Effects of reconstruction with unicondylar osteoarticular allografts with or without prosthesis for bone tumors around knee joint].

    Science.gov (United States)

    Xue, Y S; Fu, J; Guo, Z; Wang, Z; Pei, Y J; Dang, L L; Fan, H B

    2017-04-01

    or prosthesis composite was feasible reconstruction for tumors in distal femoral uni-condyle. It could provide good functional outcomes and also prevent joint degeneration. Similarly, allograft reconstruction was also a reliable technique for proximal tibial defect.

  8. Prevention

    Science.gov (United States)

    ... Error processing SSI file About Heart Disease & Stroke Prevention Heart disease and stroke are an epidemic in ... secondhand smoke. Barriers to Effective Heart Disease & Stroke Prevention Many people with key risk factors for heart ...

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

    Directory of Open Access Journals (Sweden)

    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

  10. Delayed allogeneic skin graft rejection in CD26-deficient mice.

    Science.gov (United States)

    Zhao, Xiangli; Zhang, Kai; Daniel, Peter; Wisbrun, Natali; Fuchs, Hendrik; Fan, Hua

    2018-03-23

    Organ transplantation is an effective therapeutic tool for treating many terminal diseases. However, one of the biggest challenges of transplantation is determining how to achieve the long-term survival of the allogeneic or xenogeneic transplant by, for example, preventing transplant rejection. In the current study, CD26 gene-knockout mice were used to investigate the potential role of CD26/dipeptidyl peptidase-4 (DPPIV) in allogeneic skin graft rejection by tail-skin transplantation. Compared with wild-type (CD26 +/+ ) counterparts, CD26 -/- mice showed reduced necrosis of grafts and delayed graft rejection after skin transplantation. Concentrations of serum IgG, including its subclasses IgG1 and IgG2a, were significantly reduced in CD26 -/- mice during graft rejection. Moreover, after allogeneic skin transplantation, the secretion levels of the cytokines IFN-γ, IL-2, IL-6, IL-4, and IL-13 were significantly reduced, whereas the level of the cytokine IL-10 was increased in the serum of CD26 -/- mice compared with that in the serum of CD26 +/+ mice. Additionally, the concentration of IL-17 in serum and the percentage of cells secreting IL-17 in mouse peripheral blood lymphocytes (MPBLs) were both significantly lower, while the percentage of regulatory T cells (Tregs) was significantly higher in MPBLs of CD26 -/- mice than in those of CD26 +/+ mice. Furthermore, a lower percentage of CD8 + T cells in MPBLs and fewer infiltrated macrophages and T cells in graft tissues of CD26 -/- mice were detected during graft rejection. These results indicate that CD26 is involved in allogeneic skin graft rejection and provides another hint that CD26 deficiency leads to less rejection due to lower activation and proliferation of host immune cells.

  11. In situ expression of platelet-derived growth factor (PDGF-beta) during chronic rejection is abolished by retransplantation.

    Science.gov (United States)

    Yang, H C; McElroy, R J; Kreider, J W; Marshall, R L; Martinie, J B; Diamond, J

    1995-07-01

    We have shown that Fischer 344-->Lewis renal allografts (ALLO) develop chronic rejection which is not detected in Lewis-->Lewis isografts (ISO). The progression of chronic rejection in ALLO can be reversed by retransplantation (RE-TX) of kidneys from ALLO back into syngeneic Fischer 344 recipients. The purpose of this study was to assess the in situ expression of PDGF-beta, a cytokine associated with wound injury, in ISO, ALLO, and RE-TX. In situ PDGF-beta mRNA expression in kidney sections was assessed early (8 weeks) and late (16 weeks) during the development of chronic rejection. Kidneys from ALLO were transplanted back into syngeneic Fischer recipients at 12 weeks and evaluated for PDGF-beta expression 12 weeks later. Differences in glomerular staining were graded quantitatively on a minimum of 25 glomeruli per section with grade 0, no positive cells in the glomerulus; grade 1, 1 or 2 positive cells; grade 2, 3 or more positive cells in a segmental distribution; and grade 3, > 4 positive cells of moderate intensity in a diffuse distribution. According to this grading system, glomerular PDGF-beta mRNA expression in isografts (N = 6) at 8 and 16 weeks after transplantation was 0.09 +/- 0.03 and 0.2 +/- 0.04, respectively. In allografts (N = 6), PDGF-beta mRNA was significantly higher (P < .001) for the same time periods, 1.28 +/- 0.6 and 1.89 +/- 0.08, respectively. In situ expression of PDGF in retransplants (N = 6) at 24 weeks, 0.07 +/- 0.02, was significantly diminished (P < .001) at 24 weeks compared to allografts at 8 or 16 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Inflammatory cytokine TNF-α promotes corneal endothelium apoptosis via upregulating TIPE2 transcription during corneal graft rejection.

    Science.gov (United States)

    Wang, Qun; Wei, Chao; Ma, Li; Wang, Xin; Li, Lin; Zhou, Qingjun; Shi, Weiyun

    2018-02-26

    Endothelial dysfunction accounts for 50% of total corneal transplantation failures, suggesting that corneal endothelial damage is the leading cause of graft failure. Tumor necrosis factor-α (TNF-α) is known to contribute to the negative regulation of corneal transplantation, but how it does so remains unclear. Here, we report a regulatory loop involving TNF-α, TNF-α-induced protein 8 like 2 (TNFAIP8L2 or TIPE2), and apoptosis during corneal graft rejection. We established mice models of penetrating keratoplasty to verify whether the quantification of TNF-α in allogeneic corneas is enhanced through ELISA assay and immunofluorescence staining. In cornea tissues, we obtained corneal endothelium and measured apoptosis of the removed cells. Meanwhile, quantitative real-time PCR and Western blotting were used to detect the mRNA and protein expression of TIPE2. In human corneal endothelial cells, we verified the conclusions through some experiments. By specifically knocking down TIPE2, we detected the importance of TIPE2 in TNF-α-triggered apoptosis. In mice models, TNF-α was higher in the cornea and aqueous humor in allograft group and TNF-α elevation increased the apoptosis of the corneal endothelium. In addition, high levels of TIPE2 were found in allograft rejection models following TNF-α elevation. In human corneal endothelial cells (HCECs), TNF-α clearly augments TIPE2 expression and promotes cell apoptosis through upregulating TIPE2 transcription. Knocking down markedly decreased cell apoptosis. Our study identifies the molecular mechanisms underlying the interplay of TNF-α, TIPE2, and apoptosis during allograft rejection, and it suggests that both TNF-α and TIPE2 might be potential targets for the successfully grafted corneal endothelium.

  13. 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...

  14. Social Causes and Consequences of Rejection Sensitivity

    Science.gov (United States)

    London, Bonita; Downey, Geraldine; Bonica, Cheryl; Paltin, Iris

    2007-01-01

    Predictions from the Rejection Sensitivity (RS) model concerning the social causes and consequences of RS were examined in a longitudinal study of 150 middle school students. Peer nominations of rejection, self-report measures of anxious and angry rejection expectations, and social anxiety, social withdrawal, and loneliness were assessed at two…

  15. Peer Group Rejection and Children's Outgroup Prejudice

    Science.gov (United States)

    Nesdale, Drew; Durkin, Kevin; Maass, Anne; Kiesner, Jeff; Griffiths, Judith; Daly, Josh; McKenzie, David

    2010-01-01

    Two simulation studies examined the effect of peer group rejection on 7 and 9 year old children's outgroup prejudice. In Study 1, children (n = 88) pretended that they were accepted or rejected by their assigned group, prior to competing with a lower status outgroup. Results indicated that rejected versus accepted children showed increased…

  16. On fiber rejection loss in flotation deinking

    Science.gov (United States)

    J.Y. Zhu; Freya Tan

    2005-04-01

    Reducing fiber rejection loss in flotation deinking is very important to conserve natural resources and reduce the cost of secondary fibers in paper recycling. This study examined two aspects of the problem, fiber consistency in the rejection stream and rate of Froth (or wet stream) rejection. Flotation experiments were conducted using both nylon and wood fibers in...

  17. Quadriceps tendon allografts as an alternative to Achilles tendon allografts: a biomechanical comparison.

    Science.gov (United States)

    Mabe, Isaac; Hunter, Shawn

    2014-12-01

    Quadriceps tendon with a patellar bone block may be a viable alternative to Achilles tendon for anterior cruciate ligament reconstruction (ACL-R) if it is, at a minimum, a biomechanically equivalent graft. The objective of this study was to directly compare the biomechanical properties of quadriceps tendon and Achilles tendon allografts. Quadriceps and Achilles tendon pairs from nine research-consented donors were tested. All specimens were processed to reduce bioburden and terminally sterilized by gamma irradiation. Specimens were subjected to a three phase uniaxial tension test performed in a custom environmental chamber to maintain the specimens at a physiologic temperature (37 ± 2 °C) and misted with a 0.9 % NaCl solution. There were no statistical differences in seven of eight structural and mechanical between the two tendon types. Quadriceps tendons exhibited a significantly higher displacement at maximum load and significantly lower stiffness than Achilles tendons. The results of this study indicated a biomechanical equivalence of aseptically processed, terminally sterilized quadriceps tendon grafts with bone block to Achilles tendon grafts with bone block. The significantly higher displacement at maximum load, and lower stiffness observed for quadriceps tendons may be related to the failure mode. Achilles tendons had a higher bone avulsion rate than quadriceps tendons (86 % compared to 12 %, respectively). This was likely due to observed differences in bone block density between the two tendon types. This research supports the use of quadriceps tendon allografts in lieu of Achilles tendon allografts for ACL-R.

  18. Ridge preservation comparing socket allograft alone to socket allograft plus facial overlay xenograft: a clinical and histologic study in humans.

    Science.gov (United States)

    Poulias, Evmenios; Greenwell, Henry; Hill, Margaret; Morton, Dean; Vidal, Ricardo; Shumway, Brian; Peterson, Thomas L

    2013-11-01

    Previous studies of ridge preservation showed a loss of ≈18% or 1.5 mm of crestal ridge width in spite of treatment. The primary aim of this randomized, controlled, masked clinical trial is to compare a socket graft to the same treatment plus a buccal overlay graft, both with a polylactide membrane, to determine if loss of ridge width can be prevented by use of an overlay graft. Twelve patients who served as positive controls received an intrasocket mineralized cancellous allograft (socket group), and 12 patients received the same socket graft procedure plus buccal overlay cancellous xenograft (overlay group). Horizontal ridge dimensions were measured with a digital caliper, and vertical ridge changes were measured from a stent. Before implant placement, at 4 months, a trephine core was obtained for histologic analysis. The mean horizontal ridge width at the crest for the socket group decreased from 8.7 ± 1.0 to 7.1 ± 1.5 mm for a mean loss of 1.6 ± 0.8 mm (P overlay group decreased from 8.4 ± 1.4 to 8.1 ± 1.4 mm for a mean loss of 0.3 ± 0.9 mm (P >0.05). The overlay group was significantly different from the socket group (P overlay group had 40% ± 16% (P >0.05). The overlay treatment significantly prevented loss of ridge width and preserved or augmented the buccal contour. The socket and overlay groups healed with a high percentage of vital bone.

  19. Mannan binding lectin : a two-faced regulator of renal allograft injury?

    NARCIS (Netherlands)

    Damman, Jeffrey; Seelen, Marc A.

    Complement activation plays an important role in the pathogenesis of renal allograft injury after kidney transplantation. There are three known pathways of complement activation, namely, classical, alternative, and lectin pathways. In renal allograft injury, contradictory results were reported about

  20. Comparison of Clinical Outcome of Autograft and Allograft Reconstruction for Anterior Cruciate Ligament Tears

    Directory of Open Access Journals (Sweden)

    Yu-Hua Jia

    2015-01-01

    Conclusions: In the repair of ACL tears, allograft reconstruction is as effective as the autograft reconstruction, but the allograft can lead to more tunnel widening evidently in the tibial tunnel, particularly.

  1. Postoperative rebound of antiblood type antibodies and antibody-mediated rejection after ABO-incompatible living-related kidney transplantation.

    Science.gov (United States)

    Ishida, Hideki; Kondo, Tsunenori; Shimizu, Tomokazu; Nozaki, Taiji; Tanabe, Kazunari

    2015-03-01

    The purpose of this study is to examine whether postoperative antiblood type antibody rebound is attributed to kidney allograft rejection in ABO blood type-incompatible (ABO-I) living-related kidney transplantation (KTx). A total of 191 ABO-I recipients who received ABO-I living-related KTx between 2001 and 2013 were divided into two groups: Group 1 consisted of low rebound [(≦1:32), N = 170] and Group 2 consisted of high rebound [(≧1:64), N = 21], according to the levels of the rebounded antiblood type antibodies within 1 year after transplantation. No prophylactic treatment for rejection was administered for elevated antiblood type antibodies, regardless of the levels of the rebounded antibodies. Within 1 year after transplantation, T-cell-mediated rejection was observed in 13 of 170 recipients (13/170, 8%) in Group 1 and in 2 of 21 recipients (2/21, 10%) in Group 2 (Groups 1 vs. 2, P = 0.432). Antibody-mediated rejection was observed in 15 of 170 recipients (15/170, 9%) and 2 of 21 recipients (2/21, 10%) in Groups 1 and 2, respectively (P = 0.898). In this study, we found no correlation between the postoperative antiblood type antibody rebound and the incidence of acute rejection. We concluded that no treatment is necessary for rebounded antiblood type antibodies. © 2014 Steunstichting ESOT.

  2. Correlation analysis of reject reaction and corneal endothelial cells after penetrating keratoplasty from donation after cardiac death

    Directory of Open Access Journals (Sweden)

    Qian Cao

    2017-01-01

    Full Text Available AIM: To study the relativity between reject reaction from donation after cardiac death(DCDand corneal endothelial cell source of corneal graft after penetrating keratoplasty.METHODS:Totally 28 cases of corneal graft rejection after penetrating keratoplasty with cardiac death donor cornea were analyzed using corneal endothelial microscope at less than 1mo, 2-3mo, 4-6mo, 7-12mo after operation.RESULTS:Coefficient variation of corneal endothelial cell of the 28 cases at less than 1mo,2-3mo, 4-6mo and 7-12mo were 38.23%, 49.56%, 57.18%, 65.04%. Corneal endothelial cell density were 2071.15±311.47, 1771.33±348.18, 1626.59±353.92, 1553.14±307.31. The coefficient variation of corneal endothelial cells was positively correlated with rejection(r=0.95, Pr=-0.93, PCONCLUSION: The corneal endothelial cell coefficient variation increased gradually and the corneal endothelial cell density decreased gradually after DCD corneal allograft rejection. Corneal endothelial cell coefficient variation and corneal endothelial cell density can be used as indicators of early detection of postoperative rejection.

  3. Allograft Reconstruction for the Treatment of Musculoskeletal Tumors of the Upper Extremity

    Directory of Open Access Journals (Sweden)

    Luis A. Aponte-Tinao

    2013-01-01

    Full Text Available In comparison with the lower extremity, there is relatively paucity literature reporting survival and clinical results of allograft reconstructions after excision of a bone tumor of the upper extremity. We analyze the survival of allograft reconstructions in the upper extremity and analyze the final functional score according to anatomical site and type of reconstruction. A consecutive series of 70 allograft reconstruction in the upper limb with a mean followup of 5 years was analyzed, 38 osteoarticular allografts, 24 allograft-prosthetic composites, and 8 intercalary allografts. Kaplan-Meier survival analysis of the allografts was performed, with implant revision for any cause and amputation used as the end points. The function evaluation was performed using MSTS functional score. Sixteen patients (23% had revision surgery for 5 factures, 2 infections, 5 allograft resorptions, and 2 local recurrences. Allograft survival at five years was 79% and 69% at ten years. In the group of patients treated with an osteoarticular allograft the articular surface survival was 90% at five years and 54% at ten years. The limb salvage rate was 98% at five and 10 years. We conclude that articular deterioration and fracture were the most frequent mode of failure in proximal humeral osteoarticular reconstructions and allograft resorption in elbow reconstructions. The best functional score was observed in the intercalary humeral allograft.

  4. Nebulized Pentamidine-Induced Acute Renal Allograft Dysfunction

    Directory of Open Access Journals (Sweden)

    Siddhesh Prabhavalkar

    2013-01-01

    Full Text Available Acute kidney injury (AKI is a recognised complication of intravenous pentamidine therapy. A direct nephrotoxic effect leading to acute tubular necrosis has been postulated. We report a case of severe renal allograft dysfunction due to nebulised pentamidine. The patient presented with repeated episodes of AKI without obvious cause and acute tubular necrosis only on renal histology. Nebulised pentamidine was used monthly as prophylaxis for Pneumocystis jirovecii pneumonia, and administration preceded the creatinine rise on each occasion. Graft function stabilised following discontinuation of the drug. This is the first report of nebulized pentamidine-induced reversible nephrotoxicity in a kidney allograft. This diagnosis should be considered in a case of unexplained acute renal allograft dysfunction.

  5. Prevention

    Science.gov (United States)

    ... Contact Aging & Health A to Z Find a Geriatrics Healthcare Professional Medications & Older Adults Making Your Wishes ... Prevention Hearing Loss Heart Attack High Blood Pressure Nutrition Osteoporosis Shingles Skin Cancer Related News Quitting Smoking, ...

  6. Current and future challenges in therapy for antibody-mediated rejection.

    Science.gov (United States)

    Nair, Nandini; Ball, Timothy; Uber, Patricia A; Mehra, Mandeep R

    2011-06-01

    Antibody-mediated rejection (AMR) continues to present a challenge for the survival of the cardiac allograft. AMR appears to be on the rise, likely secondary to changing trends in clinical practice, including selection of patients for transplantation on mechanical circulatory support and development of more effective combinations of immunosuppressive drugs against acute cellular rejection. Most current strategies are aimed at treating acute AMR, but the treatment of chronic AMR is still not well defined. Clinically, AMR can often be more severe than cellular rejection and more difficult to treat, often not responding to typical protocols of increased immunosuppression. Complex steps involved in the antibody response allows for several potential targets for therapeutic intervention, including suppression of T and B cells, elimination of circulating antibodies, and inhibition of residual antibodies. Existing evidence suggests a multiregimen approach is the best option. Sustenance of accommodation and induction of tolerance could be viewed as viable options if adequate immune surveillance can be achieved in this setting. This review discusses the challenges in treating AMR and provides a critical analysis of current and possible future therapies. Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  7. Porous allograft bone scaffolds: doping with strontium.

    Directory of Open Access Journals (Sweden)

    Yantao Zhao

    Full Text Available Strontium (Sr can promote the process of bone formation. To improve bioactivity, porous allograft bone scaffolds (ABS were doped with Sr and the mechanical strength and bioactivity of the scaffolds were evaluated. Sr-doped ABS were prepared using the ion exchange method. The density and distribution of Sr in bone scaffolds were investigated by inductively coupled plasma optical emission spectrometry (ICP-OES, X-ray photoelectron spectroscopy (XPS, and energy-dispersive X-ray spectroscopy (EDS. Controlled release of strontium ions was measured and mechanical strength was evaluated by a compressive strength test. The bioactivity of Sr-doped ABS was investigated by a simulated body fluid (SBF assay, cytotoxicity testing, and an in vivo implantation experiment. The Sr molar concentration [Sr/(Sr+Ca] in ABS surpassed 5% and Sr was distributed nearly evenly. XPS analyses suggest that Sr combined with oxygen and carbonate radicals. Released Sr ions were detected in the immersion solution at higher concentration than calcium ions until day 30. The compressive strength of the Sr-doped ABS did not change significantly. The bioactivity of Sr-doped material, as measured by the in vitro SBF immersion method, was superior to that of the Sr-free freeze-dried bone and the Sr-doped material did not show cytotoxicity compared with Sr-free culture medium. The rate of bone mineral deposition for Sr-doped ABS was faster than that of the control at 4 weeks (3.28 ± 0.23 µm/day vs. 2.60 ± 0.20 µm/day; p<0.05. Sr can be evenly doped into porous ABS at relevant concentrations to create highly active bone substitutes.

  8. Allografts versus Equine Xenografts in Calcaneal Fracture Repair.

    Science.gov (United States)

    Sonmez, Mehmet Mesut; Armagan, Raffi; Ugurlar, Meric; Eren, Tugrul

    Displaced intra-articular calcaneal fractures are difficult to treat. We determined the functional results and complications of using allografts or equine xenografts in treating these fractures. We reviewed patients seen at our center from May 2011 to December 2014 with Sanders type III or IV unilateral calcaneal fractures treated with locking plates and an additional bone allograft or equine xenograft. A minimum of 1 year after surgery, a history of infection and functional outcomes were assessed using the American Orthopaedic Foot and Ankle Society clinical rating system. Changes in the Gissane angle (GA) and Böhler angle were assessed from radiographs. Of the 91 eligible patients, 15 were lost to follow-up, leaving a sample of 76 patients (42 males): 45 received allografts (19 for type III and 26 for type IV fractures) and 31 received xenografts (20 for type III and 11 for type IV fractures). The mean age was about 40 years in both groups. After ≥1 year of follow-up, the proportion of patients in the American Orthopaedic Foot and Ankle Society scoring categories did not differ significantly between the 2 groups (mean ankle score, 86.5 in the allograft group and 85.1 in the xenograft group), and the American Orthopaedic Foot and Ankle Society functional outcomes were good or excellent in 69% and 68%, respectively (p = .986). The groups did not differ in the incidence of superficial or deep infection (p = 1.000). The Böhler angles were significantly decreased in the xenograft group. Xenografts might be preferred for repairing intra-articular calcaneal fractures because they can perform as well as allografts, avoid donor site morbidities, and are more available and less expensive than allografts. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  9. A Computational Gene Expression Score for Predicting Immune Injury in Renal Allografts.

    Directory of Open Access Journals (Sweden)

    Tara K Sigdel

    Full Text Available Whole genome microarray meta-analyses of 1030 kidney, heart, lung and liver allograft biopsies identified a common immune response module (CRM of 11 genes that define acute rejection (AR across different engrafted tissues. We evaluated if the CRM genes can provide a molecular microscope to quantify graft injury in acute rejection (AR and predict risk of progressive interstitial fibrosis and tubular atrophy (IFTA in histologically normal kidney biopsies.Computational modeling was done on tissue qPCR based gene expression measurements for the 11 CRM genes in 146 independent renal allografts from 122 unique patients with AR (n = 54 and no-AR (n = 92. 24 demographically matched patients with no-AR had 6 and 24 month paired protocol biopsies; all had histologically normal 6 month biopsies, and 12 had evidence of progressive IFTA (pIFTA on their 24 month biopsies. Results were correlated with demographic, clinical and pathology variables.The 11 gene qPCR based tissue CRM score (tCRM was significantly increased in AR (5.68 ± 0.91 when compared to STA (1.29 ± 0.28; p < 0.001 and pIFTA (7.94 ± 2.278 versus 2.28 ± 0.66; p = 0.04, with greatest significance for CXCL9 and CXCL10 in AR (p <0.001 and CD6 (p<0.01, CXCL9 (p<0.05, and LCK (p<0.01 in pIFTA. tCRM was a significant independent correlate of biopsy confirmed AR (p < 0.001; AUC of 0.900; 95% CI = 0.705-903. Gene expression modeling of 6 month biopsies across 7/11 genes (CD6, INPP5D, ISG20, NKG7, PSMB9, RUNX3, and TAP1 significantly (p = 0.037 predicted the development of pIFTA at 24 months.Genome-wide tissue gene expression data mining has supported the development of a tCRM-qPCR based assay for evaluating graft immune inflammation. The tCRM score quantifies injury in AR and stratifies patients at increased risk of future pIFTA prior to any perturbation of graft function or histology.

  10. Experimental study of tissue-engineered cartilage allograft with RNAi chondrocytes in vivo

    Directory of Open Access Journals (Sweden)

    Wang ZH

    2014-05-01

    Full Text Available Zhenghui Wang,1 Xiaoli Li,2 Xi-Jing He,3 Xianghong Zhang,1 Zhuangqun Yang,4 Min Xu,1 Baojun Wu,1 Junbo Tu,5 Huanan Luo,1 Jing Yan11Department of Otolaryngology – Head and Neck Surgery, 2Department of Dermatology, 3Department of Orthopedics, The Second Hospital, Xi’an Jiaotong University, 4Department of Plastic and Burns Surgery, The First Hospital, Xi’an Jiaotong University, 5Department of Oral and Maxillofacial Plastic Surgery, The Stomatological Hospital, Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaPurpose: To determine the effects of RNA interference (RNAi on chondrocyte proliferation, function, and immunological rejection after allogenic tissue-engineered cartilage transplantation within bone matrix gelatin scaffolds.Methods: Seven million rat normal and RNAi chondrocytes were harvested and separately composited with fibrin glue to make the cell suspension, and then transplanted subcutaneously into the back of Sprague Dawley rats after being cultured for 10 days in vitro. Untransplanted animals served as the control group. The allograft and immunological response were examined at 1, 2, 4, 8, and 12 months postoperatively with hematoxylin and eosin histochemical staining, immunohistochemical staining (aggrecan, type II collagen, class I and II major histocompatibility complex, and flow cytometry for peripheral blood cluster of differentiation 4+ (CD4+ and CD8+ T-cells.Results: There was no infection or death in the rats except one, which died in the first week. Compared to the control group, the RNAi group had fewer eukomonocytes infiltrated, which were only distributed around the graft. The ratio of CD4+/CD8+ T-cells in the RNAi group was significantly lower than the normal one (P<0.05. There were many more positively stained chondrocytes and positively stained areas around the cells in the RNAi group, which were not found in the control group.Conclusion: The aggrecanase-1 and aggrecanase-2 RNAi for chondrocytes

  11. Effect of local macrophage depletion on cellular immunity and tolerance evoked by corneal allografts.

    NARCIS (Netherlands)

    Slegers, TP; Rooijen, van N.; Rij, van G.L.; Streilein, JW

    2003-01-01

    Corneal graft rejection can be prevented by local macrophage depletion, via subconjunctival injections with clodronate liposomes. To unravel the underlying immunological mechanism responsible for prolonged graft survival in this circumstance, the effect of this regimen on induction of donor-specific

  12. Early kidney allograft loss - is there scope for improvement?

    Science.gov (United States)

    Ferrari, Paolo

    2018-02-17

    Increased longevity matching using Kidney Donor Profile Index (KDPI) to optimize long-term kidney allograft survival has been central to the effort of appropriate allocation of deceased donor kidneys. The data by Helenterä and co-workers in this issue, who looked at predictors of early allograft loss, should prompt an analysis of whether predictors of short-term graft survival can improve KDPI-based decisions when considering whether to accept or decline a deceased donor kidney offer. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  13. Extended Active Disturbance Rejection Controller

    Science.gov (United States)

    Gao, Zhiqiang (Inventor); Tian, Gang (Inventor)

    2016-01-01

    Multiple designs, systems, methods and processes for controlling a system or plant using an extended active disturbance rejection control (ADRC) based controller are presented. The extended ADRC controller accepts sensor information from the plant. The sensor information is used in conjunction with an extended state observer in combination with a predictor that estimates and predicts the current state of the plant and a co-joined estimate of the system disturbances and system dynamics. The extended state observer estimates and predictions are used in conjunction with a control law that generates an input to the system based in part on the extended state observer estimates and predictions as well as a desired trajectory for the plant to follow.

  14. Prevention

    DEFF Research Database (Denmark)

    Halken, S; Høst, A

    2001-01-01

    , breastfeeding should be encouraged for 4-6 months. In high-risk infants a documented extensively hydrolysed formula is recommended if exclusive breastfeeding is not possible for the first 4 months of life. There is no evidence for preventive dietary intervention neither during pregnancy nor lactation...... populations. These theories remain to be documented in proper, controlled and prospective studies. Breastfeeding and the late introduction of solid foods (>4 months) is associated with a reduced risk of food allergy, atopic dermatitis, and recurrent wheezing and asthma in early childhood. In all infants....... Preventive dietary restrictions after the age of 4-6 months are not scientifically documented....

  15. Reconstruction of an atrophied posterior mandible with the inlay technique and allograft block versus allograft particulate: a case report.

    Science.gov (United States)

    Checchi, Vittorio; Mazzoni, Annalisa; Breschi, Lorenzo; Felice, Pietro

    2015-01-01

    This case report describes the bilateral reconstruction of a severely atrophic posterior mandible in a 30-year-old woman using allograft block versus particulate grafting in the inlay technique. Three months later, four dental implants were placed and bone core biopsy specimens were taken for histologic evaluation. During implant placement, the grafted sites were stable with good clinical osseointegration. The histologic analysis showed the presence of compact bone revealing areas of demarcation between grafted bone, newly formed bone, and bone-regenerated areas. Allografts might serve as an alternative to autogenous and heterologous grafting in posterior mandible augmentation using the inlay technique.

  16. An osteophyte in the tibial plateau is a risk factor for allograft extrusion after meniscus allograft transplantation.

    Science.gov (United States)

    Jeon, Byeongsam; Kim, Jong-Min; Kim, Jong-Min; Lee, Chang-Rack; Kim, Kyung-Ah; Bin, Seong-Il

    2015-05-01

    Osteophytes can be observed on the tibial plateau during meniscus allograft transplantation (MAT). However, no studies to date have evaluated the effect of these osteophytes on meniscus allograft extrusion. Osteophyte excision in the tibial plateau could reduce extrusion of the transplanted meniscus and improve short-term clinical outcomes with meniscus allograft transplantation. Cohort study; Level of evidence, 3. Between October 2004 and July 2012, a total of 323 patients underwent MAT at a single institution. Of these, 88 patients had a peripheral osteophyte in their tibial plateau, and they were enrolled in the study retrospectively. The mean age of the patients was 35.3 years (range, 15-56 years); there were 57 male and 31 female patients. Forty-four patients underwent osteophyte excision concomitantly with MAT and 44 patients underwent MAT only. The 2 groups showed no difference in terms of age, body mass index, time after meniscectomy, and preoperative knee scores. A medial meniscus allograft was transplanted in 13 cases (15%) and a lateral meniscus in 75 (85%). The absolute extrusion and relative percentage of extrusion were measured to evaluate allograft extrusion 12 months after MAT. The modified Lysholm scoring system and the Hospital for Special Surgery score at 2 years after MAT were used to evaluate clinical outcomes. The mean absolute extrusions at 1 year postoperatively in the excision and nonexcision groups were 3.5±1.5 and 5.5±1.6 mm, respectively. The mean relative percentages of extrusion were 34.1%±15.9% and 54.7%±20.7%, respectively. The rates of allograft extrusion (>3 mm) were 28 of 44 (63.6%) and 41 of 44 (93.2%) in the excision and nonexcision groups, respectively. The intergroup differences in absolute extrusion, relative percentage of extrusion, and rate of allograft extrusion were statistically significant (P<.001 for all 3 parameters). There were no significant differences in the clinical outcomes (modified Lysholm or Hospital of

  17. Auditory stimulation of opera music induced prolongation of murine cardiac allograft survival and maintained generation of regulatory CD4+CD25+ cells

    Directory of Open Access Journals (Sweden)

    Uchiyama Masateru

    2012-03-01

    Full Text Available Abstract Background Interactions between the immune response and brain functions such as olfactory, auditory, and visual sensations are likely. This study investigated the effect of sounds on alloimmune responses in a murine model of cardiac allograft transplantation. Methods Naïve CBA mice (H2k underwent transplantation of a C57BL/6 (B6, H2b heart and were exposed to one of three types of music--opera (La Traviata, classical (Mozart, and New Age (Enya--or one of six different single sound frequencies, for 7 days. Additionally, we prepared two groups of CBA recipients with tympanic membrane perforation exposed to opera for 7 days and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment. An adoptive transfer study was performed to determine whether regulatory cells were generated in allograft recipients. Immunohistochemical, cell-proliferation, cytokine, and flow cytometry assessments were also performed. Results CBA recipients of a B6 cardiac graft that were exposed to opera music and Mozart had significantly prolonged allograft survival (median survival times [MSTs], 26.5 and 20 days, respectively, whereas those exposed to a single sound frequency (100, 500, 1000, 5000, 10,000, or 20,000 Hz or Enya did not (MSTs, 7.5, 8, 9, 8, 7.5, 8.5 and 11 days, respectively. Untreated, CBA mice with tympanic membrane perforations and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment rejected B6 cardiac grafts acutely (MSTs, 7, 8 and 8 days, respectively. Adoptive transfer of whole splenocytes, CD4+ cells, or CD4+CD25+ cells from opera-exposed primary allograft recipients resulted in significantly prolonged allograft survival in naive secondary recipients (MSTs, 36, 68, and > 100 days, respectively. Proliferation of splenocytes, interleukin (IL-2 and interferon (IFN-γ production was suppressed in opera-exposed mice, and production of IL-4 and IL-10 from opera-exposed transplant recipients increased

  18. Lamivudine resistance leading to de novo hepatitis B infection in recipients of hepatitis B core antibody positive liver allografts.

    Science.gov (United States)

    Leong, Jennifer; Coty, Patrick; Fiel, M Isabel; Chang, Charissa; Florman, Sander; Schiano, Thomas

    2014-11-01

    Most studies have shown that lamivudine (LAM) prophylaxis is sufficient to prevent hepatitis B virus (HBV) transmission in recipients of hepatitis B core antibody positive (HBcAb(+) ) allografts. However, de novo hepatitis B (DNHB) is known to occur in this patient population. Herein, we report a case series of four liver transplant recipients who developed DNHB after receiving HBcAb(+) allografts due to acquisition of LAM resistance mutations, suggesting that LAM prophylaxis may be suboptimal. A retrospective chart review was performed of all adult liver transplants performed at Mount Sinai from 2001 to 2010. A total of 79 patients received HBcAb(+) allografts for non-hepatitis B-related liver disease. Of these 79 recipients, four patients developed DNHB and were found to have documented LAM resistance. With the increasing use of HBcAb(+) donor livers, we suspect that there will also be a growing number of cases of DNHB due to acquisition of LAM resistance. We suggest that other agents, such as entecavir or tenofovir, be considered for use as prophylaxis in this patient population to decrease this risk. © 2013 The Japan Society of Hepatology.

  19. Comparison between Constrained and Semiconstrained Knee Allograft-Prosthesis Composite Reconstructions

    Directory of Open Access Journals (Sweden)

    German L. Farfalli

    2013-01-01

    Full Text Available Allograft-prosthesis composite (APC can restore capsular and ligamentous tissues of the knee sacrificed in a tumor extirpation. We asked if performing APC would restore knee stability and allow the use of nonconstrained arthroplasty while preventing aseptic loosening. We retrospectively compared 50 knee APCs performed with non-constrained revision knee prosthesis (Group 1 with 36 matched APCs performed with a constrained prosthesis (Group 2. In Group 1, the survival rate was 69% at five and 62% at ten years. Sixteen reconstructions were removed due to complications: eight deep infections, three fractures, two instabilities, one aseptic loosening, one local recurrence, and one nonunion. In Group 2, the survival rate was 80% at five and 53% at ten years. Nine reconstructions were removed: 3 due to deep infections, 3 to fractures, and 3 to aseptic loosening. In both groups, we observed more allograft fractures when the prosthetic stem does not bypass the host-donor osteotomy (. Both groups had mainly good or excellent MSTS functional results. Survival rate and functional scores and aseptic loosening were similar in both groups. A rotating-hinge APC is recommended when host-donor soft tissue reconstruction fails to restore knee instability. The use of a short prosthetic stem has a statistical relationship with APC fractures.

  20. Pre-transplant donor-specific T-cell alloreactivity is strongly associated with early acute cellular rejection in kidney transplant recipients not receiving T-cell depleting induction therapy.

    Directory of Open Access Journals (Sweden)

    Elena Crespo

    Full Text Available Preformed T-cell immune-sensitization should most likely impact allograft outcome during the initial period after kidney transplantation, since donor-specific memory T-cells may rapidly recognize alloantigens and activate the effector immune response, which leads to allograft rejection. However, the precise time-frame in which acute rejection is fundamentally triggered by preformed donor-specific memory T cells rather than by de novo activated naïve T cells is still to be established. Here, preformed donor-specific alloreactive T-cell responses were evaluated using the IFN-γ ELISPOT assay in a large consecutive cohort of kidney transplant patients (n = 90, to assess the main clinical variables associated with cellular sensitization and its predominant time-frame impact on allograft outcome, and was further validated in an independent new set of kidney transplant recipients (n = 67. We found that most highly T-cell sensitized patients were elderly patients with particularly poor HLA class-I matching, without any clinically recognizable sensitizing events. While one-year incidence of all types of biopsy-proven acute rejection did not differ between T-cell alloreactive and non-alloreactive patients, Receiver Operating Characteristic curve analysis indicated the first two months after transplantation as the highest risk time period for acute cellular rejection associated with baseline T-cell sensitization. This effect was particularly evident in young and highly alloreactive individuals that did not receive T-cell depletion immunosuppression. Multivariate analysis confirmed preformed T-cell sensitization as an independent predictor of early acute cellular rejection. In summary, monitoring anti-donor T-cell sensitization before transplantation may help to identify patients at increased risk of acute cellular rejection, particularly in the early phases after kidney transplantation, and thus guide decision-making regarding the use of induction

  1. 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

  2. Could Uric acid have a Pathogenic Role in Chronic Allograft ...

    African Journals Online (AJOL)

    Introduction: Chronic allograft dysfunction (CAD) is the primary cause of chronic graft failure after kidney transplantation. The pathogenesis of CAD involves both antigen-dependent and antigen-independent mechanisms. Serum uric acid could have a role in both mechanisms. Review: Hyperuricemia in subjects with renal ...

  3. Osteoinductive and Osteopromotive Variability among Different Demineralized Bone Allografts.

    Science.gov (United States)

    Wei, Lingfei; Miron, Richard J; Shi, Bin; Zhang, Yufeng

    2015-06-01

    The purpose of this investigation was to compare the osteoinductive and osteopromotive potential of two widely used demineralized freeze-dried bone allografts (DFDBA) (Osteotech® DFDBA and LifeNet® DFDBA). Twenty-seven male Wistar rats (mean body weight 200 g) were treated with either DFDBA from Osteotech and LifeNet or control for femoral and intramuscular defects and assigned to histological analysis at 2, 4, and 8 weeks postimplantation. Hematoxylin and eosin (H&E), Safranin-O, tartrate-resistant acid phosphatase (TRAP), and osteopontin (OPN) staining were performed. Quantitative analysis of mineralized new bone to total volume (BV/TV) was assessed by micro-computed tomography. Both allografts demonstrated osteoinductive potential at 2 weeks as assessed by intramuscular bone formation. LifeNet DFDBA displayed continual new bone formation at 4 and 8 weeks, whereas Osteotech particles were fully resorbed by 4 weeks postimplantation. Femur defects demonstrated significantly greater BV/TV at 4 and 8 weeks with higher expression of OPN staining around LifeNet DFDBA particles. TRAP-positive cells were visible in and around both allograft materials. The results from the present study indicate that variability among allografts exists. In the present, LifeNet DFDBA supported more new bone formation. Further larger animal models or clinical trials are required to validate these findings. © 2013 Wiley Periodicals, Inc.

  4. Noninvasive diagnosis of allograft vascular disease after heart transplantation

    Directory of Open Access Journals (Sweden)

    Fernando Bacal

    2001-01-01

    Full Text Available OBJECTIVE: To determine the predictive values of noninvasive tests for the detection of allograft vascular disease. METHODS: We studied 39 patients with mean ages of 48±13 years and a follow-up period of 86±13 months. The diagnosis of allograft vascular disease was made by cine-coronary arteriography, and it was considered as positive if lesions existed that caused > or = 50% obstruction of the lumen. Patients underwent 24h Holter monitoring, thallium scintigraphy, a treadmill stress test, and dobutamine stress echocardiography. Sensitivity, specificity, and positive and negative predictive values were determined in percentages for each method, as compared with the cine-coronary arteriography results. RESULTS: Allograft vascular disease was found in 15 (38% patients. The Holter test showed 15.4% sensitivity, 95.5% specificity. For the treadmill stress test, sensitivity was 10%, specificity was 100%. When thallium scintigraphy was used, sensitivity was 40%, specificity 95.8%. On echocardiography with dobutamine, we found a 63.6% sensitivity, 91.3% specificity. When the dobutamine echocardiogram was associated with scintigraphy, sensitivity was 71.4%, specificity was 87%. CONCLUSION: In this group of patients, the combination of two noninvasive methods (dobutamine echocardiography and thallium scintigraphy may be a good alternative for the detection of allograft vascular disease in asymptomatic patients with normal ventricular function.

  5. Chronic Renal Allograft Dysfunction: Risk Factors, Immunology and ...

    African Journals Online (AJOL)

    Introduction: Kidney transplantation is the treatment of choice for patients with end-stage renal disease. Despite great progress in surgical aspects and immunosupression therapy, long-term graft survival has not been consistent. Chronic allograft dysfunction (CAD) remains a major cause of late grafts failure. Review: CAD is ...

  6. Effects of Acute Cytomegalovirus Infection on Rat Islet Allograft Survival

    NARCIS (Netherlands)

    Smelt, M. J.; Faas, M. M.; Melgert, B. N.; de Vos, P.; de Haan, Bart; de Haan, Aalzen

    2011-01-01

    Transplantation of pancreatic islets is a promising therapy for the treatment of type 1 diabetes mellitus. However, long-term islet graft survival rates are still unsatisfactory low. In this study we investigated the role of cytomegalovirus (CMV) in islet allograft failure. STZ-diabetic rats

  7. Tuberculosis in a renal allograft recipient presenting with intussusception.

    Science.gov (United States)

    Mohapatra, A; Basu, G; Sen, I; Asirvatham, R; Michael, J S; Pulimood, A B; John, G T

    2012-01-01

    Extra-pulmonary tuberculosis (TB) is more common in renal allograft recipients and may present with dissemination or an atypical features. We report a renal allograft recipient with intestinal TB presenting 3 years after transplantation with persistent fever, weight loss, diarrhea, abdominal pain and mass in the abdomen with intestinal obstruction. He was diagnosed to be having an ileocolic intussusception which on resection showed a granulomatous inflammation with presence of acid-fast bacilli (AFB) typical of Mycobacterium tuberculosis. In addition, AFB was detected in the tracheal aspirate, indicating dissemination. He received anti-TB therapy (ATT) from the fourth postoperative day. However, he developed a probable immune reconstitution inflammatory syndrome (IRIS) with multiorgan failure and died on 11(th) postoperative day. This is the first report of intestinal TB presenting as intussusception in a renal allograft recipient. The development of IRIS after starting ATT is rare in renal allograft recipients. This report highlights the need for a high index of suspicion for diagnosing TB early among renal transplant recipients and the therapeutic dilemma with overwhelming infection and development of IRIS upon reduction of immunosuppression and starting ATT.

  8. Long-term allograft survival after kidney transplantation.

    Science.gov (United States)

    Gómez, E Gómez; Hernández, J P Campos; López, F J Márquez; Garcia, J Ruiz; Montemayor, V Garcia; Curado, F Anglada; Vallejo, M Leva; López, J C Regueiro; Cabello, M D Navarro; Aljama, P; Tapia, M J Requena

    2013-01-01

    Technical and medical advances over the past few years have produced an important increase in the functionality of renal allografts. The aim of this study was to identify the factors associated with allograft survival 15 years after transplantation in our series. A retrospective study of kidney transplantations was carried out at Reina Sofia Hospital in Cordoba from February 1979 to December 1997, with follow-up through June 2012. A subanalysis of the series was undertaken, and Kaplan-Meier analysis and Cox proportional hazards model regression used to achieve the main objective of the study. A total of 487 renal allografts with a mean follow-up of 114 months were studied, of which 37% (n = 180) survived for >15 years. Of the 180 patients, the main causes of graft failure were chronic allograft nephropathy in 29 (66%) and patient death in 13 (29.5%). Multivariate analysis identified the number of HLA mismatches (hazard ratio [HR] 1.25, 95% CI 1.01-1.56), panel reactive antibodies (HR 2.61, 95% CI 1.28-5.26), and delayed graft function (HR 11.25, 95% CI 1.33-95.28) as being significantly associated with graft loss after 15 years. The high immunologic risk of the patients was independently associated with graft loss. Delayed graft function was the most important factor in the speed of graft failure beyond 15 years. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. 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.

  10. 21 CFR 1230.47 - Rejected containers.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rejected containers. 1230.47 Section 1230.47 Food... FEDERAL CAUSTIC POISON ACT Imports § 1230.47 Rejected containers. (a) In all cases where the containers... notification to the importer that the containers must be exported under customs supervision within 3 months...

  11. 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

  12. Liver Transplantation in the Mouse: Insights Into Liver Immunobiology, Tissue Injury and Allograft Tolerance

    Science.gov (United States)

    Yokota, Shinichiro; Yoshida, Osamu; Ono, Yoshihiro; Geller, David A.; Thomson, Angus W.

    2016-01-01

    The surgically-demanding mouse orthotopic liver transplant model was first described in 1991. It has proved a powerful research tool for investigation of liver biology, tissue injury, the regulation of alloimmunity and tolerance induction and the pathogenesis of specific liver diseases. Liver transplantation in mice has unique advantages over transplantation of the liver in larger species, such as the rat or pig, since the mouse genome is well-characterized and there is much greater availability of both genetically-modified animals and research reagents. Liver transplant experiments using various transgenic or gene knockout mice has provided valuable mechanistic insights into the immuno- and pathobiology of the liver and the regulation of graft rejection and tolerance over the past 25 years. The molecular pathways identified in regulation of tissue injury and promotion of liver transplant tolerance provide new potential targets for therapeutic intervention to control adverse inflammatory responses/ immune-mediated events in the hepatic environment and systemically. Conclusion: Orthotopic liver transplantation in the mouse is a valuable model for gaining improved insights into liver biology, immunopathology and allograft tolerance that may result in therapeutic innovation in liver and other diseases. PMID:26709949

  13. Liver Allograft Its Use in Chronic Active Hepatitis With Macronodular Cirrhosis, Hepatitis B Surface Antigen

    Science.gov (United States)

    Corman, Jarques L.; Putnam, Charles W.; Iwatsuki, Shunzaburo; Redeker, Allan G.; Porter, K. A.; Peters, Robert L.; Schröter, Gerhard; Starzl, Thomas E.

    2010-01-01

    A patient suffering from chronic active hepatitis with macronodular cirrhosis, positive for hepatitis B surface antigen (HB,Ag), was treated with an orthoiopic liver allograft. The HB, antigenemia, as measured with several precipltation tests and by complement fixation, became negative after transplantation and remained so for about 2½ months. During the interval, very low Iters of the antigen were detectable by, radioimmunoassay. At about three months after transplantation, she had an attack of acute hepatitis, at which time HB,Ag became detectable by all tests. She recovered, but progressive liver disease developed during the remaining 1½ years of her life. She died of disseminaled nocardiosis and candidiasis with deteriorating hepatic function. The homograft at autopsy, showed no evidence of rejection, but was the site of chronic active liver disease, although of a different pathologic pattern than that affecting her native liver. The differences in histology may reflect the influence of chronic Immunosuppression on the features of chronic active hepatitis. PMID:365134

  14. 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.

  15. 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

  16. mRNA Expression of Interferon Regulatory Factors during Acute Rejection of Liver Transplants in Patients with Autoimmune Hepatitis.

    Science.gov (United States)

    Nasiri, M; Geramizadeh, B; Nabavizadeh, S H; Male-Hosseini, S A; Karimi, M H; Saadat, I

    2018-01-01

    Interferon regulatory factors (IRFs) can play a critical role in the regulation of many facets of innate and adaptive immune responses through transcriptional activation of type I interferons, other proinflammatory cytokines, and chemokines. However, their roles in transplantation immunity still remain to be elucidated. To evaluate the time course of mRNA expression of all 9 members of IRFs family of transcription factors during liver allograft acute rejection. Blood samples of 19 patients with autoimmune hepatitis receiving liver transplants were collected on days 1, 3, 5, and 7 post-transplantation. The patients were followed for 6 months after transplantation and divided into two groups of acute rejection (AR) (n=4) and non-acute rejection (non-AR) (n=15). All of the studied transcription factors were down-regulated in AR-group on days 3, 5, and 7 post-transplantation compared to non-AR group. The mean±SEM IRF5 on day 7 post-transplantation was significantly (p=0.005) lower in AR-group than in non-AR group (0.7±0.21 vs . 1.91±0.27, respectively); expression of other IRFs family members was not significantly different between the two groups on days 3, 5, and 7 post-transplantation. IRF5 may have an important role during the acute rejection of liver transplants.

  17. Therapeutic dilemma in fungal keratitis: administration of steroids for immune rejection early after keratoplasty.

    Science.gov (United States)

    Wang, Ting; Li, Suxia; Gao, Hua; Shi, Weiyun

    2016-08-01

    To investigate the timing and dosage of topical corticosteroid use after keratoplasty for fungal keratitis, and to evaluate the results with regard to anterior segment inflammation, immune rejection, and fungal recurrence. This prospective observational study included a total of 244 patients (244 eyes) who underwent penetrating keratoplasty (PK, 118 patients) or lamellar keratoplasty (LK, 126 patients) for fungal keratitis at the Shandong Eye Hospital between January 2009 and April 2014. Topical administration of steroid eye drops was initiated at 1 week after surgery. Changes in ocular inflammation before and after steroid use, percentages of eyes with fungal recurrence and immune rejection, and the relationship between the timing of local administration of steroids and therapeutic anti-inflammatory effects after keratoplasty were evaluated. The follow-up period was 6 months. Anterior segment inflammation was aggravated within 1 week after surgery, with ocular pain, photophobia, redness, and tearing, but was controlled at 7.51 ± 1.76 days after steroid use. Fungal keratitis recurred in three eyes (1.23 %) at 3 to 5 days after administration of corticosteroids, including two eyes receiving PK and one eye receiving LK. Recurrence was controlled with antifungal medications. Allograft rejection occurred in eight (6.78 %) of 118 patients treated by PK, but did not occur in patients treated by LK. Initiating the use of topical corticosteroids in patients with fungal keratitis 1 week after keratoplasty can aid in rapid control of anterior segment inflammation and reduction of immune rejection, with no increase in the rate of fungal recurrence.

  18. Bortezomib-based treatment of acute antibody-mediated rejection: a case report.

    Science.gov (United States)

    Wang, Q; Li, X L; Xu, X G; Shi, B Y; Zhang, Z M; Li, Z L; Han, Y; Zhou, W Q; Chen, C Q; Cai, M; Zhang, X

    2015-12-22

    Antibody-mediated rejection (AMR) is an important factor affecting survival after renal transplantation. A highly selective proteasome inhibitor, bortezomib, clears activated plasma cells from the body and has important therapeutic effect on AMR. We investigated the effects of bortezomib on AMR in a patient after a second renal transplant. Biopsy confirmed the diagnosis of mixed cellular rejection and AMR. Bortezomib was administered on day 1 (1.3 mg/m(2)), day 4 (1.0 mg/m(2)), and day 8 (1.0 mg/m(2)). On the same days, 250 mg methylprednisolone was administered once, and cyclosporine dose (5 mg·kg(-1)·day(-1)) was reduced by 50%. Oral mycophenolate mofetil and steroid were withdrawn on day 1 of bortezomib treatment. Intermittent double-filtration plasmapheresis was also performed. We monitored parameters, including T lymphocyte subsets, CD139 and CD19 expression, panel reactive antibody (PRA), and serum creatinine concentration. At follow-up 6 months after bortezomib treatment, we observed: 1) serum creatinine stabilized at 130 μM from a peak level of 337 μM; 2) PRA decreased from a maximum of 66.7 to 0%; 3) blood plasma cell percentage rebounded after significantly decreasing following the first dose of bortezomib; 4) in renal allograft biopsy, immunohistochemical staining for C4d shifted from strongly positive to negative, and cellular rejection shifted from type IIA to borderline; and 5) adverse effects such as platelet suppression, hypotension, and grade 3 peripheral neuropathy emerged. Bortezomib effectively treated antibody-mediated renal transplantation rejection in this case study, but clinical trials with large sample sizes are still needed to explore clinical safety and tolerability.

  19. Subclinical antibody-mediated rejection due to anti-human-leukocyte-antigen-DR53 antibody accompanied by plasma cell-rich acute rejection in a patient with cadaveric kidney transplantation.

    Science.gov (United States)

    Katsuma, Ai; Yamamoto, Izumi; Komatsuzaki, Yo; Niikura, Takahito; Kawabe, Mayuko; Okabayashi, Yusuke; Yamakawa, Takafumi; Katsumata, Haruki; Nakada, Yasuyuki; Kobayashi, Akimitsu; Tanno, Yudo; Miki, Jun; Yamada, Hiroki; Ohkido, Ichiro; Tsuboi, Nobuo; Yamamoto, Hiroyasu; Yokoo, Takashi

    2016-07-01

    A 56-year-old man who had undergone cadaveric kidney transplantation 21 months earlier was admitted to our hospital for a protocol biopsy; he had a serum creatinine level of 1.2 mg/dL and no proteinuria. Histological features showed two distinct entities: (i) inflammatory cell infiltration, in the glomerular and peritubular capillaries and (ii) focal, aggressive tubulointerstitial inflammatory cell infiltration, predominantly plasma cells, with mild tubulitis (Banff 13 classification: i2, t1, g2, ptc2, v0, ci1, ct1, cg0, cv0). Immunohistological studies showed mildly positive C4d immunoreactivity in the peritubular capillaries. The patient had donor specific antibody to human-leucocyte-antigen-DR53. We diagnosed him with subclinical antibody-mediated rejection accompanied by plasma cell-rich acute rejection. Both antibody-mediated rejection due to anti- human-leucocyte-antigen -DR53 antibodies and plasma cell-rich acute rejection are known to be refractory and have a poor prognosis. Thus, we started plasma exchange with intravenous immunoglobulin and rituximab for the former and 3 days of consecutive steroid pulse therapy for the latter. Three months after treatment, a follow-up allograft biopsy showed excellent responses to treatment for both histological features. This case report considers the importance of an early diagnosis and appropriate intervention for subclinical antibody-mediated rejection due to donor specific antibody to human-leucocyte-antigen-DR53 and plasma cell-rich acute rejection. © 2016 Asian Pacific Society of Nephrology.

  20. Ankle bipolar fresh osteochondral allograft survivorship and integration: transplanted tissue genetic typing and phenotypic characteristics.

    Science.gov (United States)

    Neri, Simona; Vannini, Francesca; Desando, Giovanna; Grigolo, Brunella; Ruffilli, Alberto; Buda, Roberto; Facchini, Andrea; Giannini, Sandro

    2013-10-16

    Fresh osteochondral allografts represent a treatment option for early ankle posttraumatic arthritis. Transplanted cartilage survivorship, integration, and colonization by recipient cells have not been fully investigated. The aim of this study was to evaluate the ability of recipient cells to colonize the allograft cartilage and to assess allograft cell phenotype. Seventeen ankle allograft samples were studied. Retrieved allograft cartilage DNA from fifteen cases was compared with recipient and donor constitutional DNA by genotyping. In addition, gene expression was evaluated on six allograft cartilage samples by means of real-time reverse transcription-polymerase chain reaction. Histology and immunohistochemistry were performed to support molecular observations. Of fifteen genotyped allografts, ten completely matched to the host, three matched to the donor, and two showed a mixed profile. Gene expression analysis showed that grafted cartilage expressed cartilage-specific markers. The rare persistence of donor cells and the prevailing presence of host DNA in retrieved ankle allografts suggest the ingrowth of recipient cells into the allograft cartilage, presumably migrating from the subchondral bone, in accordance with morphological findings. The expression of chondrogenic markers in some of the samples argues for the acquisition of a chondrocyte-like phenotype by these cells. To our knowledge, this is the first report describing the colonization of ankle allograft cartilage by host cells showing the acquisition of a chondrocyte-like phenotype.

  1. ERROR VS REJECTION CURVE FOR THE PERCEPTRON

    OpenAIRE

    PARRONDO, JMR; VAN DEN BROECK, Christian

    1993-01-01

    We calculate the generalization error epsilon for a perceptron J, trained by a teacher perceptron T, on input patterns S that form a fixed angle arccos (J.S) with the student. We show that the error is reduced from a power law to an exponentially fast decay by rejecting input patterns that lie within a given neighbourhood of the decision boundary J.S = 0. On the other hand, the error vs. rejection curve epsilon(rho), where rho is the fraction of rejected patterns, is shown to be independent ...

  2. Historical and current perspectives on bone marrow transplantation for prevention and treatment of immunodeficiencies and autoimmunities.

    Science.gov (United States)

    Good, R A; Verjee, T

    2001-01-01

    Primary immunodeficiency diseases often fully meet the definition of "experiments of nature." Much of the expanding understanding of the lymphoid systems and immunologic functions generated in recent years has been derived from studying patients with primary, generally genetically determined immunodeficiency diseases, as well as other relatively rare secondary immunodeficiency diseases. Increasing knowledge of immunologic defenses, their interacting cellular and molecular components, the evolving details of sequential stages of cellular differentiation, and the nature and control of the cellular and molecular interactions in immunity have now made it possible to define precisely many primary immunodeficiency diseases in full molecular genetic terms. With this wealth of scientific information based on experimental and clinical research, incredible advances have also been made in using bone marrow transplantation (BMT) often as a curative treatment for immunodeficiency, some 60 to 70 other diseases, leukemias, lymphomas, other cancers, and a rapidly expanding constellation of metabolic diseases or enzyme deficiencies. Also, progress in applying allogeneic BMT to prevent, treat, and cure complex autoimmune diseases, primary immunodeficiency diseases and certain forms of cancers, is considered. Further, mixed BMT (syngeneic plus allogeneic) that establishes a form of stable mixed chimerism has also been employed in animal experiments, which revealed that BMT can be used to treat not only immunodeficiency diseases, but also systemic and organ-specific autoimmune diseases, eg, diabetes and erythematous lupus-like diseases. Moreover, performing BMT in conjunction with organ allografts, eg, thymus or pancreatic transplants, has successfully prevented rejection of these allografts, sometimes without recourse to long-term irradiation or toxic chemical immunosuppressive agents. A crucial role for stromal cells in cellular engineering has now also been realized in animal

  3. Primary arthroplasty in healed osteoarticular allograft in patients with history of primary femoral bone tumors.

    Science.gov (United States)

    Verbeek, Bianca M; Kaiser, Courtney L; Paulino Pereira, Nuno Rui; Hornicek, Francis J; Raskin, Kevin A; Schwab, Joseph H; LozanoCalderón, Santiago A

    2017-12-01

    Roughly 25-35% of patients who are treated with osteoarticular allograft for primary bone sarcomas or aggressive benign bone tumors require surgery in the long-term due to degenerative changes of the articular surface of the allograft. There are three established methods of reconstruction for this complication; a total hip arthroplasty (THA) or total knee arthroplasty (TKA) in the retained osteoarticular allograft, a proximal or distal endoprosthesis after removal of the allograft, and an allograft-prosthesis composite (APC). The aims of this study are 1) to determine the rate of complication and failure of THA/TKA in healed femoral allograft; 2) to compare the methods of revision for allograft degeneration; and 3) to compare the use of arthroplasty in healed allograft to that of arthroplasty in native bone. We included all patients with primary bone sarcomas and locally aggressive primary benign bone tumors treated between 1984 and 2014 with an osteoarticular allograft followed by any subsequent arthroplasty technique as described above. Complications and reasons for failure are described following the classification of Henderson et al. Failure was defined as any complication leading to removal of the initial treatment construct. Failure rates of these groups were compared to primary arthroplasty in a live host bone (Control Group). Complications happened in 25 (61.0%) of the patients with a THA/TKA in the retained allograft, of these, 24 (58.5%) experienced failure, the most common being structural failure/type III (14, 58.3%). Thirteen patients (81.3%) with an endoprosthesis after removal of the allograft experienced complications, all of whom failed. The most common failure modes were aseptic loosening/type II (4, 30.8%) and infection/type IV (5, 38.5%). Complications in patients with an APC were experienced by 12 (85.7%) patients, 11 (78.6%) of whom failed. The most common failure mode was infection/type IV (4, 36.4%). Significantly (p < 0.001) fewer

  4. Irradiation before and donor splenocyte infusion immediately after transplantation induce tolerance to lung, but not heart allografts in miniature swine.

    Science.gov (United States)

    Sommer, Wiebke; Buechler, Gwen; Jansson, Katharina; Avsar, Murat; Knöfel, Ann-Kathrin; Salman, Jawad; Hoeffler, Klaus; Siemeni, Thierry; Gottlieb, Jens; Karstens, Johann H; Jonigk, Danny; Reising, Ansgar; Haverich, Axel; Strüber, Martin; Warnecke, Gregor

    2017-04-01

    Solid organs may differ in their potential to induce and maintain a state of donor-specific tolerance. Previously, we induced stable immunological tolerance in a lung transplantation model in miniature swine. Here, we wished to transfer this established protocol into a heart transplantation model in miniature swine. Heterotopic heart transplantation (HTX) was performed in four and left-sided lung transplantation (LTX) in seven minipigs from gender- and SLA-mismatched donors. All recipients received nonmyeloablative irradiation, donor splenocyte infusion and intravenous pharmacologic immunosuppression for 28 postoperative days. All transplanted hearts were rejected within 95 days. In contrast, four animals of the LTX group developed stable tolerance surviving beyond 500 days, and three further animals rejected 119, 239 and 360 days post-transplantation. In both groups, peripheral blood donor leucocyte chimerism peaked 1 h after reperfusion of the allograft. Importantly, the early chimerism level in the LTX group was significantly higher compared to the HTX group and remained detectable throughout the entire observation period. In conclusion, lungs and hearts vary in their potential to induce a state of tolerance after transplantation in a protocol with pre-operative recipient irradiation and donor splenocyte co-transplantation. This could be due to differential early levels of passenger leucocyte chimerism. © 2017 Steunstichting ESOT.

  5. Long-Term Impact of Cyclosporin Reduction with MMF Treatment in Chronic Allograft Dysfunction: REFERENECE Study 3-Year Follow Up

    Directory of Open Access Journals (Sweden)

    L. Frimat

    2010-01-01

    Full Text Available Calcineurin inhibitor (CNI toxicity contributes to chronic allograft nephropathy (CAN. In the 2-year, randomized, study, we showed that 50% cyclosporin (CsA reduction in combination with mycophenolate mofetil (MMF treatment improves kidney function without increasing the risk for graft rejection/loss. To investigate the long-term effect of this regimen, we conducted a follow up study in 70 kidney transplant patients until 5 years after REFERENCE initiation. The improvement of kidney function was confirmed in the MMF group but not in the control group (CsA group. Four graft losses occurred, 2 in each group (graft survival in the MMF group 95.8% and 90.9% in control group. One death occurred in the control group. There was no statistically significant difference in the occurrence of serious adverse events or acute graft rejections. A limitation is the weak proportion of patient still remaining within the control group. On the other hand, REFERENCE focuses on the CsA regimen while opinions about the tacrolimus ones are still debated. In conclusion, CsA reduction in the presence of MMF treatment seems to maintain kidney function and is well tolerated in the long term.

  6. FOXP3 rs3761549 polymorphism predicts long-term renal allograft function in patients receiving cyclosporine-based immunosuppressive regimen.

    Science.gov (United States)

    Xu, Qin-Xia; Qiu, Xiao-Yan; Jiao, Zheng; Zhang, Ming; Zhong, Ming-Kang

    2018-02-20

    The present study was conducted to determine the effect of FOXP3 single nucleotide polymorphisms (SNPs) on clinical outcomes in CsA-treated renal transplant patients. A total of 166 renal transplant patients with at least 5years of follow-up were included. SNPs of FOXP3 gene (rs3761547, rs3761548, rs3761549, rs2232365 and rs2280883) were detected by Taqman probe technique. The associations of SNPs with acute rejection, CsA-induced nephrotoxicity, pneumonia and post-transplantation estimated glomerular filtration rate (eGFR) were explored. Patients with rs3761549 T/TT genotype showed a more rapid decline in the eGFR level during the 5years following transplantation than those with the C/CC genotype (24.0% vs. 6.3%, P=0.004). All the SNPs and site-site interaction were not related to the occurrence of acute rejection, nephrotoxicity, and pneumonia. FOXP3 rs3761549 was significantly correlated with the renal allograft function. It could be used to predict and improve the outcome of renal transplant patients taking CsA as an immunosuppressant. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. CONVERSION TO TACROLIMUS IN PATIENTS WITH LATE ACUTE AND CHRONIC REJECTION OF TRANSPLANTED KIDNEY

    Directory of Open Access Journals (Sweden)

    E. S. Stolyarevich

    2011-01-01

    Full Text Available Tасrolimus (Tac has been used for rescuing of renal allografts from refractory rejection that occurred during treatment with conventional cyclosporine A (CsA mostly in the early posttransplant period. Less is known about effect of Tac in cases of late acute rejection. Aim of the study was to examine the long-term effects of switching from CyA-based therapy to Tac-based therapy versus continuation of CsA in renal transplant patients with acute rejection occurred 3 month after transplantation or later. In this comparative prospective clinical study 176 patients experiencing a late biopsy-proven acute or active chronic rejection were followed-up for up to 6 months. 61 pati- ents were converted from a CуA-based therapy to the Tac one; in 115 patients CsA-based therapy was continued. During the first month after the rejection episode the median serum creatinine concentration had decreased in both groups (from 0.27 (0.18; 0.4 to 0.25 (0.16; 0.41 mmol/l in the CsA group and from 0.25 (0.18; 0.3 to 0.18 (0.14; 0.25 mmol/l in the Tac group. During the follow-up graft function remained stable in the Tac group 0,17 (0,14; 0,3 mmol/l, while in the CsA group a trend to progression of graft failure was observed 0.33 (0.19; 0.8 mmol/l. The 3-year Kaplan-Meier estimates for graft loss were 57,1% (Tac and 40,9% (CsA, respectively (р < 0.01. Conclusion: early switch from the CsA- to the Tac-based therapy after a late biopsy-confirmed rejection resulted in a significant improvement in the clinical output in renal graft recipients compared to patients for whom the CyA therapy was continued. 

  8. Factors Influencing the Cure Rate in the Corneal Graft Rejection with Survival Analysis

    Directory of Open Access Journals (Sweden)

    Feizi S.

    2009-11-01

    Full Text Available AbstractBackground and Objectives: Immunologic rejection of the transplanted cornea is the major cause of human allograft failure with several risk factors contributing to it. Since in the corneal graft, most individuals do not reject the graft, we used the survival analysis with cure rate for the assessment of the factors influencing the cure rate at the time of data analysis. The main aim of this study was to evaluate the cure rate and assess the risk factors for corneal graft rejection in the keratoconus disease in Labafinejad Hospital, Tehran, Iran. Methods: This was a routine data base study in which the data were gathered from keratoconus patients’ files that had undergone penetrating keratoplasty operation. In the survival analysis, individuals who didn’t reject corneal were considered cured. To study the factors influencing the cure rate, we used the Weibull distribution for survival function and the logistic link function for the cure rate because of their tractability and accuracy.Results: Out of 119 patients 31 patients (26% rejected grafts. Among the factors influencing cure rate, only in vascularization and in persons older than 25 years of age was ameaningful effect on decreasing cure rate. With this cure model, the expected cure rate in the non-vascularization and less than 25 year- old patients was 81, in non-vascularization and more than 25 year- olds it is 64, in the vascularization and less than 25 year- olds, the cure rate is 19 and in the vascularization and more than 25 years of age, the cure rate is 9 percent and the observed cure rate for Kaplan-Meier product limit estimator was 79, 61, 27 and 0 percent, respectively. The results showed that the estimate of cure rate in the survival analysis was near the Kaplan-Meier product-limits estimator.Conclusion: One of the benefits of modeling is its ability to generalize the results; using them in the prediction. According to the results obtained from the fitting cure model

  9. Soaking morselized allograft in bisphosphonate can impair implant fixation

    DEFF Research Database (Denmark)

    Jakobsen, Thomas; Baas, Jørgen; Bechtold, Joan E

    2007-01-01

    The use of impacted, morselized allograft is a well-established way to provide initial stability of revision joint replacements. We investigated whether rinsing morselized allograft in bisphosphonate and subsequently impacting it around experimental titanium-coated implants would further facilitate...... bisphosphonate (alendronate, 2 mg/mL) or saline (control). Unbound alendronate was not rinsed away. During the first surgery, one pair of implants (alendronate and control) was inserted into one humerus. Eight weeks later, a second pair of implants was inserted into the contralateral humerus. The first pair....... Furthermore, the alendronate treatment blocked formation of new bone and inhibited resorption of the graft material. Although limited by the specific dose of alendronate used and the omission of rinsing away excess bisphosphonate, this study warrants caution and calls for further experimental research before...

  10. Total femoral allograft with simultaneous revision total hip and knee arthroplasty: 18 year follow-up

    Directory of Open Access Journals (Sweden)

    Ryan N. Harris, DO

    2015-09-01

    Full Text Available Massive allograft can be a useful option in revision total joint arthroplasty for treatment of significant bone loss. In rare cases, revision hip and knee arthroplasty procedures can be performed simultaneously using massive allograft-prosthetic composites. We present an 18 year follow up of a patient who received a simultaneous revision hip and knee total femoral allograft and discuss recent literature as it relates to this case.

  11. Pyrrhonism and Hume's rejection of induction

    OpenAIRE

    Bogdanovski, Mašan

    2012-01-01

    Sextus' rejection of induction poses a serious problem for Charlotte Stough's classical interpretation of Pyrrhonism. Her explanation of Pyrrhonist action is not available to the classical interpretation, because it implies that a Pyrrhonean has beliefs about his future impressions. In this article, the main premises of Hume's rejection of induction are reconstructed from Sextus' account of commemorative and indicative signs. The Pyrrhonean is not entitled to hold rational beliefs about his f...

  12. X-ray microtomography-based measurements of meniscal allografts.

    Science.gov (United States)

    Mickiewicz, P; Binkowski, M; Bursig, H; Wróbel, Z

    2015-05-01

    X-ray microcomputed tomography (XMT) is a technique widely used to image hard and soft tissues. Meniscal allografts as collagen structures can be imaged and analyzed using XMT. The aim of this study was to present an XMT scanning protocol that can be used to obtain the 3D geometry of menisci. It was further applied to compare two methods of meniscal allograft measurement: traditional (based on manual measurement) and novel (based on digital measurement of 3D models of menisci obtained with use of XMT scanner). The XMT-based menisci measurement is a reliable method for assessing the geometry of a meniscal allograft by measuring the basic meniscal dimensions known from traditional protocol. Thirteen dissected menisci were measured according the same principles traditionally applied in a tissue bank. Next, the same specimens were scanned by a laboratory scanner in the XMT Lab. The images were processed to obtain a 3D mesh. 3D models of allograft geometry were then measured using a novel protocol enhanced by computer software. Then, both measurements were compared using statistical tests. The results showed significant differences (P<0.05) between the lengths of the medial and lateral menisci measured in the tissue bank and the XMT Lab. Also, medial meniscal widths were significantly different (P<0.05). Differences in meniscal lengths may result from difficulties in dissected meniscus measurements in tissue banks, and may be related to the elastic structure of the dissected meniscus. Errors may also be caused by the lack of highlighted landmarks on the meniscal surface in this study. The XMT may be a good technique for assessing meniscal dimensions without actually touching the specimen. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  13. Pancreas Allograft Transplantation in Dogs with Experimental Diabetes Mellitus

    OpenAIRE

    Mendívil Zapata, Rolando; Garmendia, Fausto; Yerén, Cecilia; Torres, William

    2014-01-01

    OBJETIVE : To evaluate the efficacy of pancreatic allograft transplantation (TAP ) in dogs with diabetes mellitus ( DME ) induced by alloxan . METHODS : 63 mongrel dogs were used , of which 33 for the very best experimental conditions , the other 30 were divided into 3 groups of 10 each : a) controls, were only produced DME b ) receptors with DME, the who underwent TAP and c) pancreas donors . RESULTS : The glycemic control was complete in 50% of recipients and partial in 30% , giving an over...

  14. Structural Decoupling and Disturbance Rejection in a Distillation Column

    DEFF Research Database (Denmark)

    Bahar, Mehrdad; Jantzen, Jan; Commault, C.

    1996-01-01

    Introduction, distillation column model, input-output decoupling, disturbance rejection, concluding remarks, references.......Introduction, distillation column model, input-output decoupling, disturbance rejection, concluding remarks, references....

  15. Use of Cortical Strut Allograft After Extended Trochanteric Osteotomy in Revision Total Hip Arthroplasty.

    Science.gov (United States)

    Lim, Chin Tat; Amanatullah, Derek F; Huddleston, James I; Hwang, Katherine L; Maloney, William J; Goodman, Stuart B

    2017-05-01

    Cortical strut allografts restore bone stock and improve postoperative clinical scores after revision total hip arthroplasty (THA). However, use of a cortical strut allograft is implicated in delayed healing of an extended trochanteric osteotomy (ETO). To date, there are no reports directly comparing ETO with or without cortical strut allografts. We reviewed prospectively gathered data on 50 revision THAs performed from 2004-2014 using an ETO. We compared the demographic, radiological, and clinical outcome of patients with (16 hips) and without (34 hips) cortical strut allograft after an ETO. There were no significant differences in Western Ontario McMaster Universities Osteoarthritis Index or Harris Hip Score between the ETOs with and without a cortical strut allograft. Fifteen of the ETOs (94%) with a cortical strut allograft and 31 of the ETOs (91%) without a cortical strut allograft were in situ at final follow-up (P = 1.000). A higher proportion hips with cortical strut allograft (100%, 16 patients) had preoperative Paprosky grade bone loss more than IIIA compared to those without allograft (29%, 10 patients) (P revision THA with ETO does not reduce the rate of union, radiological or clinical outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Quantification of renal allograft perfusion using arterial spin labeling MRI: initial results.

    Science.gov (United States)

    Lanzman, Rotem S; Wittsack, Hans-Jörg; Martirosian, Petros; Zgoura, Panagiota; Bilk, Philip; Kröpil, Patric; Schick, Fritz; Voiculescu, Adina; Blondin, Dirk

    2010-06-01

    To quantify renal allograft perfusion in recipients with stable allograft function and acute decrease in allograft function using nonenhanced flow-sensitive alternating inversion recovery (FAIR)-TrueFISP arterial spin labeling (ASL) MR imaging. Following approval of the local ethics committee, 20 renal allograft recipients were included in this study. ASL perfusion measurement and an anatomical T2-weighted single-shot fast spin-echo (HASTE) sequence were performed on a 1.5-T scanner (Magnetom Avanto, Siemens, Erlangen, Germany). T2-weighted MR urography was performed in patients with suspected ureteral obstruction. Patients were assigned to three groups: group a, 6 patients with stable allograft function over the previous 4 months; group b, 7 patients with good allograft function who underwent transplantation during the previous 3 weeks; group c, 7 allograft recipients with an acute deterioration of renal function. Mean cortical perfusion values were 304.8 +/- 34.4, 296.5 +/- 44.1, and 181.9 +/- 53.4 mg/100 ml/min for groups a, b and c, respectively. Reduction in cortical perfusion in group c was statistically significant. Our results indicate that ASL is a promising technique for nonenhanced quantification of cortical perfusion of renal allografts. Further studies are required to determine the clinical value of ASL for monitoring renal allograft recipients.

  17. Advantages of C2 monitoring to avoid acute rejection in pediatric heart transplant recipients.

    Science.gov (United States)

    Schubert, S; Abdul-Khaliq, H; Lehmkuhl, H B; Hübler, M; Abd El Rahman, M Y; Miera, O; Ewert, P; Weng, Y; Wei, H; Krüdewagen, B; Hetzer, R; Berger, F

    2006-06-01

    Inadequate cyclosporine (CsA) blood levels are a major risk factor for acute rejection in transplant recipients. The CsA trough level (C0 level) measured just before the next dose is commonly used to adjust the oral dosage. However, the 2-hour post-CsA dose concentration (C2 level) is favored as the best single-point correlate of CsA area-under-the-curve concentration and may better reflect the immunosuppressive effect of CsA. Because an adequate C2 level has not yet been defined, this study was performed to assess the value of C2 monitoring for the prevention of acute rejection and to define target levels in pediatric heart transplant recipients. C2 levels were assessed in 50 pediatric heart transplant patients with oral CsA therapy and compared with trough C0 levels using full blood sampling, mass spectrometry and a blinded analysis. Acute graft rejection was detected using intramyocardial electrocardiogram (IMEG) and serial conventional and tissue Doppler echocardiography (TDE). Rejection was confirmed or excluded by endomyocardial biopsy. C2 and not C0 levels were significantly reduced in patients with acute graft rejection (ISHLT Grade > or =2). Patients with a C2 level 600 ng/ml should be the target to prevent acute rejection.

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

    Science.gov (United States)

    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.

  19. Image rejects in general direct digital radiography

    International Nuclear Information System (INIS)

    Hofmann, Bjørn; Rosanowsky, Tine Blomberg; Jensen, Camilla; Wah, Kenneth Hong Ching

    2015-01-01

    The number of rejected images is an indicator of image quality and unnecessary imaging at a radiology department. Image reject analysis was frequent in the film era, but comparably few and small studies have been published after converting to digital radiography. One reason may be a belief that rejects have been eliminated with digitalization. To measure the extension of deleted images in direct digital radiography (DR), in order to assess the rates of rejects and unnecessary imaging and to analyze reasons for deletions, in order to improve the radiological services. All exposed images at two direct digital laboratories at a hospital in Norway were reviewed in January 2014. Type of examination, number of exposed images, and number of deleted images were registered. Each deleted image was analyzed separately and the reason for deleting the image was recorded. Out of 5417 exposed images, 596 were deleted, giving a deletion rate of 11%. A total of 51.3% were deleted due to positioning errors and 31.0% due to error in centering. The examinations with the highest percentage of deleted images were the knee, hip, and ankle, 20.6%, 18.5%, and 13.8% respectively. The reject rate is at least as high as the deletion rate and is comparable with previous film-based imaging systems. The reasons for rejection are quite different in digital systems. This falsifies the hypothesis that digitalization would eliminates rejects. A deleted image does not contribute to diagnostics, and therefore is an unnecessary image. Hence, the high rates of deleted images have implications for management, training, education, as well as for quality

  20. A chronic renal rejection model with a fully MHC-mismatched rat strain combination under immunosuppressive therapy.

    Science.gov (United States)

    Hanaoka, Kaori; Kawato, Yuka; Kubo, Kaori; Nakanishi, Tomonori; Maeda, Masashi; Nakamura, Koji; Hirose, Jun; Noto, Takahisa; Fukahori, Hidehiko; Fujikawa, Akihiko; Miyoshi, Sosuke; Takakura, Shoji; Morokata, Tatsuaki; Higashi, Yasuyuki

    2016-09-01

    The Fischer-to-Lewis (LEW) rat model of kidney transplantation is a widely accepted and well-characterized model of chronic rejection. In contrast to transplantation in a clinical setting, however, the absence of treatment with immunosuppressants and only minor mismatch of major histocompatibility complexes (MHCs) are critical discrepancies. Here, we established a rat model of chronic rejection using fully MHC-mismatched strains in which kidney disease progresses even under immunosuppressive therapy. LEW (RT1(l)) rats were used as donors and Brown Norway (BN, RT1(n)) rats as recipients. Intramuscular administration of 0.1mg/kg of tacrolimus was initiated on the day of transplantation. Post-transplantation, this dose was maintained until Day 9, suspended until Day 28 and then resumed from Day 29. Renal function, histopathology, and levels of donor-specific antibody (DSA) and several biomarkers of renal injury were assessed. On Day 91 post-transplantation, recipients received tacrolimus treatment with short-term suspension exhibited reduced renal function and changes in histology. Those were characteristics of chronic rejection including glomerulosclerosis, interstitial fibrosis, and tubular atrophy in human transplantation recipients. Urinary protein excretion increased in a linear fashion, and elevated levels of several biomarkers of renal injury and DSA were observed even under administration of an immunosuppressant. We established an allograft rejection model with impaired renal function and typical histopathological changes of chronic rejection in fully MHC-mismatched rats by controlling administration of an immunosuppressant. These findings suggest that this model more accurately reflects transplantation in a clinical setting than existing models and enables the evaluation of therapeutic agents. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. A biodegradable, sustained-released, prednisolone acetate microfilm drug delivery system effectively prolongs corneal allograft survival in the rat keratoplasty model.

    Directory of Open Access Journals (Sweden)

    Yu-Chi Liu

    Full Text Available Frequent and long-term use of topical corticosteroids after corneal transplantation is necessary to prevent graft rejection. However, it relies heavily on patient compliance, and sustained therapeutic drug levels are often not achieved with administration of topical eye drops. A biodegradable drug delivery system with a controlled and sustained drug release may circumvent these limitations. In this study, we investigated the efficacy of a prednisolone acetate (PA-loaded poly (d,l-lactide-co-ε-caprolactone (PLC microfilm drug delivery system on promoting the survival of allogeneic grafts after penetrating keratoplasty (PK using a rat model. The drug release profiles of the microfilms were characterized (group 1. Subsequently, forty-eight PK were performed in four experimental groups: syngeneic control grafts (group 2, allogeneic control grafts (group 3, allogeneic grafts with subconjunctivally-implanted PA microfilm (group 4, and allogeneic grafts with PA eye drops (group 5; n = 12 in each. PA-loaded microfilm achieved a sustained and steady release at a rate of 0.006-0.009 mg/day, with a consistent aqueous drug concentration of 207-209 ng/ml. The mean survival days was >28 days in group 2, 9.9±0.8 days in group 3, 26.8±2.7 days in group 4, and 26.4±3.4 days in group 5 (P = 0.023 and P = 0.027 compared with group 3. Statistically significant decrease in CD4+, CD163+, CD 25+, and CD54+ cell infiltration was observed in group 4 and group 5 compared with group 3 (P<0.001. There was no significant difference in the mean survival and immunohistochemical analysis between group 4 and group 5. These results showed that sustained PA-loaded microfilm effectively prolongs corneal allograft survival. It is as effective as conventional PA eye drops, providing a promising clinically applicable alternative for patients undergoing corneal transplantation.

  2. Codominant Role of Interferon-γ- and Interleukin-17-Producing T Cells During Rejection in Full Facial Transplant Recipients.

    Science.gov (United States)

    Borges, T J; O'Malley, J T; Wo, L; Murakami, N; Smith, B; Azzi, J; Tripathi, S; Lane, J D; Bueno, E M; Clark, R A; Tullius, S G; Chandraker, A; Lian, C G; Murphy, G F; Strom, T B; Pomahac, B; Najafian, N; Riella, L V

    2016-07-01

    Facial transplantation is a life-changing procedure for patients with severe composite facial defects. However, skin is the most immunogenic of all transplants, and better understanding of the immunological processes after facial transplantation is of paramount importance. Here, we describe six patients who underwent full facial transplantation at our institution, with a mean follow-up of 2.7 years. Seum, peripheral blood mononuclear cells, and skin biopsy specimens were collected prospectively, and a detailed characterization of their immune response (51 time points) was performed, defining 47 immune cell subsets, 24 serum cytokines, anti-HLA antibodies, and donor alloreactivity on each sample, producing 4269 data points. In a nonrejecting state, patients had a predominant T helper 2 cell phenotype in the blood. All patients developed at least one episode of acute cellular rejection, which was characterized by increases in interferon-γ/interleukin-17-producing cells in peripheral blood and in the allograft's skin. Serum monocyte chemotactic protein-1 level was significantly increased during rejection compared with prerejection time points. None of the patients developed de novo donor-specific antibodies, despite a fourfold expansion in T follicular helper cells at 1 year posttransplantation. In sum, facial transplantation is frequently complicated by a codominant interferon-γ/interleukin-17-mediated acute cellular rejection process. Despite that, medium-term outcomes are promising with no evidence of de novo donor-specific antibody development. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  3. Using intramyocardial electrograms combined with other noninvasive methods for monitoring acute rejection following human heart transplantation.

    Science.gov (United States)

    Jia, Yi-xin; Meng, Xu; Sun, Ling-bo; Han, Jie; Chen, Yang-tian

    2009-01-20

    Acute allograft rejection in heart transplantation remains as one of the major complications. Obligatory graft surveillance is still achieved with the invasive and expensive endomyocardial biopsy (EMB). Our study aimed to study the use of intramyocardial electrograms combined with other noninvasive methods for the monitoring of acute rejection after human heart transplantation. Permanent pacemakers were implanted in 58 patients undergoing heart transplantations. Intramyocardial electrograms (IMEG) were recorded periodically and the results were compared with those from EMBs. The R wave amplitude of the IMEG was used as the index value, the average R wave amplitude at the third week following transplantation was considered as the baseline, and a reduction of > 20% compared with the baseline was regarded as a positive result. EMB was performed in cases of positive IMEG results and also at other times. Other noninvasive methods were used to help the diagnosis. Acute rejection (AR) was defined as International Society of Heart-Lung Transplantation grade IIIA or higher. We obtained 1231 IMEG records and 127 EMBs. Of the total 127 EMBs, 53 were positive, in which there were 42 IMEG positive results and 11 negative, while in the rest 74 negative EMBs, there were 9 IMEG positive results and 65 negative. The sensitivity of IMEG for the diagnosis of AR was 79.2%, and the specificity was 87.8%. The positive predictive value was 82.4% and the negative predictive value was 85.5%. Of the total of 1231 IMEG records, 51 were positive and 1180 were negative. Excluding 11 proved by EMB to be false negative, if the other 1169 were considered as no evidence of rejection, through the other noninvasive methods, AR diagnosed by this noninvasive monitoring strategy, the sensitivity was 79.2%, and the specificity was 99.2%. The positive predictive value was 82.4% and the negative predictive value was 99.1%. IMEG can be used as a noninvasive method for monitoring AR following heart

  4. SWOT analysis of Banff: strengths, weaknesses, opportunities and threats of the international Banff consensus process and classification system for renal allograft pathology.

    Science.gov (United States)

    Mengel, M; Sis, B; Halloran, P F

    2007-10-01

    The Banff process defined the diagnostic histologic lesions for renal allograft rejection and created a standardized classification system where none had existed. By correcting this deficit the process had universal impact on clinical practice and clinical and basic research. All trials of new drugs since the early 1990s benefited, because the Banff classification of lesions permitted the end point of biopsy-proven rejection. The Banff process has strengths, weaknesses, opportunities and threats (SWOT). The strength is its self-organizing group structure to create consensus. Consensus does not mean correctness: defining consensus is essential if a widely held view is to be proved wrong. The weaknesses of the Banff process are the absence of an independent external standard to test the classification; and its almost exclusive reliance on histopathology, which has inherent limitations in intra- and interobserver reproducibility, particularly at the interface between borderline and rejection, is exactly where clinicians demand precision. The opportunity lies in the new technology such as transcriptomics, which can form an external standard and can be incorporated into a new classification combining the elegance of histopathology and the objectivity of transcriptomics. The threat is the degree to which the renal transplant community will participate in and support this process.

  5. Biological effects of rAAV-caAlk2 coating on structural allograft healing

    DEFF Research Database (Denmark)

    Koefoed, Mette; Ito, Hiromu; Gromov, Kirill

    2005-01-01

    Structural bone allografts often fracture due to their lack of osteogenic and remodeling potential. To overcome these limitations, we utilized allografts coated with recombinant adeno-associated virus (rAAV) that mediate in vivo gene transfer. Using beta-galactosidase as a reporter gene, we show...

  6. The renal arterial resistive index and stage of chronic kidney disease in patients with renal allograft

    DEFF Research Database (Denmark)

    Winther, Stine O; Thiesson, Helle C; Poulsen, Lene N

    2012-01-01

    The study investigated the optimal threshold value of renal arterial resistive index as assessed by Doppler ultrasonography determining chronic kidney disease stage 4 or higher in patients with renal allograft.......The study investigated the optimal threshold value of renal arterial resistive index as assessed by Doppler ultrasonography determining chronic kidney disease stage 4 or higher in patients with renal allograft....

  7. Three-dimensional virtual bone bank system for selecting massive bone allograft in orthopaedic oncology.

    Science.gov (United States)

    Wu, Zhigang; Fu, Jun; Wang, Zhen; Li, Xiangdong; Li, Jing; Pei, Yanjun; Pei, Guoxian; Li, Dan; Guo, Zheng; Fan, Hongbin

    2015-06-01

    Although structural bone allografts have been used for years to treat large defects caused by tumour or trauma, selecting the most appropriate allograft is still challenging. The objectives of this study were to: (1) describe the establishment of a visual bone bank system and workflow of allograft selection, and (2) show mid-term follow-up results of patients after allograft implantation. Allografts were scanned and stored in Digital Imaging and Communications in Medicine (DICOM) files. Then, image segmentation was conducted and 3D model reconstructed to establish a visual bone bank system. Based on the volume registration method, allografts were selected after a careful matching process. From November 2010 to June 2013, with the help of the Computer-assisted Orthopaedic Surgery (CAOS) navigation system, the allografts were implanted in 14 patients to fill defects after tumour resection. By combining the virtual bone bank and CAOS, selection time was reduced and matching accuracy was increased. After 27.5 months of follow-up, the mean Musculoskeletal Tumor Society (MSTS) 93 functional score was 25.7 ± 1.1 points. Except for two patients with pulmonary metastases, 12 patents were alive without evidence of disease at the time this report was written. The virtual bone bank system was helpful for allograft selection, tumour excision and bone reconstruction, thereby improving the safety and effectiveness of limb-salvage surgery.

  8. Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapy

    DEFF Research Database (Denmark)

    Ito, Hiromu; Koefoed, Mette; Tiyapatanaputi, Prarop

    2005-01-01

    Structural allograft healing is limited because of a lack of vascularization and remodeling. To study this we developed a mouse model that recapitulates the clinical aspects of live autograft and processed allograft healing. Gene expression analyses showed that there is a substantial decrease in ...

  9. Scapular allograft reconstruction after total scapulectomy: surgical technique and functional results

    NARCIS (Netherlands)

    Capanna, R.; Totti, F.; Geest, I.C.M. van der; Muller, D.A.

    2015-01-01

    HYPOTHESIS: Scapular allograft reconstruction after total scapulectomy preserving the rotator cuff muscles is an oncologically safe procedure and results in good functional outcome with a low complication rate. METHODS: The data of 6 patients who underwent scapular allograft reconstruction after a

  10. The combination of anti-NKG2D and CTLA-4 Ig therapy prolongs islet allograft survival in a murine model.

    Science.gov (United States)

    Pawlick, R; Gala-Lopez, B; Pepper, A R; McCall, M; Ziff, O; Shapiro, A M J

    2014-10-01

    Islet transplantation is an effective means of treating severe type 1 diabetes in patients with life-threatening hypoglycemia. Improvements in glycemic control with correction of HbA1C enhance quality of life irrespective of insulin independence. By antagonizing the Natural Killer Group 2, member D (NKG2D) receptor expression on NK and CD8+ T cells, in combination with blocking CTLA-4 binding sites, we demonstrate a significant delay of graft rejection in islet allotransplant. Anti-NKG2D combined with CTLA-4 Ig (n = 15) results in prolonged allograft survival, with 84.6 ± 10% of the recipients displaying insulin independence compared to controls (n = 10, p < 0.001). The effect of combination therapy on graft survival is superior to treatments alone (CTLA-4 Ig vs. combination p = 0.024, anti-NKG2D vs. combination p < 0.001) indicating an interaction between these pathways. In addition, combination treatment also improves glucose tolerance when compared to controls (n = 10, p = 0.018). Histologically, NKG2D+ cells were significantly decreased within the allograft after 7 days of combination treatment (n = 6, p = 0.029). T cell proliferation was significantly reduced with anti-NKG2D therapy and CD8+ T cell daughter fractions were also significantly decreased with mAb and combination treatment when measured by in vitro mixed lymphocyte reaction (n = 5, p = 0.015, p = 0.005 and p = 0.048). These results demonstrate that inhibition of NKG2D receptors and costimulatory pathways enhance islet allograft survival. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

  11. Campath, calcineurin inhibitor reduction and chronic allograft nephropathy (3C) study: background, rationale, and study protocol

    Science.gov (United States)

    2013-01-01

    Background Kidney transplantation is the best treatment for patients with end-stage renal failure, but uncertainty remains about the best immunosuppression strategy. Long-term graft survival has not improved substantially, and one possible explanation is calcineurin inhibitor (CNI) nephrotoxicity. CNI exposure could be minimized by using more potent induction therapy or alternative maintenance therapy to remove CNIs completely. However, the safety and efficacy of such strategies are unknown. Methods/Design The Campath, Calcineurin inhibitor reduction and Chronic allograft nephropathy (3C) Study is a multicentre, open-label, randomized controlled trial with 852 participants which is addressing two important questions in kidney transplantation. The first question is whether a Campath (alemtuzumab)-based induction therapy strategy is superior to basiliximab-based therapy, and the second is whether, from 6 months after transplantation, a sirolimus-based maintenance therapy strategy is superior to tacrolimus-based therapy. Recruitment is complete, and follow-up will continue for around 5 years post-transplant. The primary endpoint for the induction therapy comparison is biopsy-proven acute rejection by 6 months, and the primary endpoint for the maintenance therapy comparison is change in estimated glomerular filtration rate from baseline to 2 years after transplantation. The study is sponsored by the University of Oxford and endorsed by the British Transplantation Society, and 18 centers for adult kidney transplant are participating. Discussion Late graft failure is a major issue for kidney-transplant recipients. If our hypothesis that minimizing CNI exposure with Campath-based induction therapy and/or an elective conversion to sirolimus-based maintenance therapy can improve long-term graft function and survival is correct, then patients should experience better graft function for longer. A positive outcome could change clinical practice in kidney transplantation. Trial

  12. Ultraviolet light immunomodulation of canine islets for prolongation of allograft survival

    International Nuclear Information System (INIS)

    Kenyon, N.S.; Strasser, S.; Alejandro, R.

    1990-01-01

    Ultraviolet (UV) light treatment of donor islets has been shown to be effective for the prolongation of islet allograft survival in rodent models. This study evaluated UV as an immunomodulator of canine islets. The effects of UV irradiation on islet secretory function in vitro revealed a trend of increasing basal insulin release with increasing doses of UV and a corresponding significant decrease in glucose-mediated insulin release (expressed as percentage of basal fractional insulin release) beginning at UV light exposures of 200-300 J/m2 (n = 3, P less than 0.05). Proliferative responses to UV-irradiated allogeneic peripheral blood leukocytes and islets were significantly decreased by 53-112% (P less than 0.05) in 27 of 29 mixed-lymphocyte cultures and by 35-74% (P less than 0.05) in 4 of 5 mixed-lymphocyte islet culture experiments, respectively, beginning at 200-600 J/m2. Autotransplantation of nonirradiated (n = 8) and irradiated islets (600 J/m2, n = 6) resulted in a 1-mo graft survival rate of 75% for the control group and 50% for the irradiated group. Allotransplantation of irradiated islets (600 J/m2) into either nonimmunosuppressed recipients (1 donor to 1 recipient, n = 8) or recipients of subimmunosuppressive doses of cyclosporin (2 donors to 1 recipient, n = 4) resulted in 100% rejection by day 10. In contrast, when islets were cultured for 24 h postirradiation and transplanted into cyclosporin-treated pancreatectomized recipients (2 donors to 1 recipient), 3 of 7 grafts were prolonged beyond day 10 to days 16, 26, and greater than 100

  13. Vascularized composite allograft transplant survival in miniature swine: is MHC tolerance sufficient for acceptance of epidermis?

    Science.gov (United States)

    Cetrulo, Curtis L; Torabi, Radbeh; Scalea, Joseph R; Shimizu, Akira; Leto Barone, Angelo A; Gillon, Bradford C; Tasaki, Masayuki; Leonard, David A; Cormack, Taylor A; Villani, Vincenzo; Randolph, Mark A; Sachs, David H; Yamada, Kazuhiko

    2013-12-15

    We have previously reported that Massachusetts General Hospital miniature swine, which had accepted class I-mismatched kidneys long-term after 12 days of high-dose cyclosporine A, uniformly accepted donor-major histocompatibility complex (MHC)-matched kidneys without immunosuppression but rejected donor MHC-matched split-thickness skin grafts by day 25, without changes in renal graft function or antidonor in vitro responses. We have now tested whether this "split tolerance" would also be observed for the primarily vascularized skin of vascularized composite allografts (VCAs). Group 1 animals (n=3) received donor MHC-matched VCAs less than 70 days after primary kidney transplant (KTx). Group 2 animals (n=3) received a second donor-matched kidney transplant followed by a donor-matched VCA more than 200 days after primary KTx. Animals in Group 1 lost the epidermis on days 28, 30, and 40, with all other components of the VCAs remaining viable. Histology showed cellular infiltration localized to dermal-epidermal junction. One of three recipients of VCAs in Group 2, accepted all components of the VCA, including epidermis (>200 days). The other two recipients lost only the epidermis on days 45 and 85, with survival of the remainder of the VCA long-term. All tissues of a VCA are accepted long-term on animals tolerant of class I-mismatched kidneys, with the exception of epidermis, the survival of which is markedly prolonged compared with split-thickness skin grafts but not indefinite. Exposure of tolerant animals to second donor-matched kidneys before VCA increases the longevity of the VCA epidermis, suggesting an increase in the immunomodulatory mechanisms associated with tolerance of the kidney.

  14. Three-Dimensional Virtual Bone Bank System Workflow for Structural Bone Allograft Selection: A Technical Report

    Directory of Open Access Journals (Sweden)

    Lucas Eduardo Ritacco

    2013-01-01

    Full Text Available Structural bone allograft has been used in bone defect reconstruction during the last fifty years with acceptable results. However, allograft selection methods were based on 2-dimensional templates using X-rays. Thanks to preoperative planning platforms, three-dimensional (3D CT-derived bone models were used to define size and shape comparison between host and donor. The purpose of this study was to describe the workflow of this virtual technique in order to explain how to choose the best allograft using a virtual bone bank system. We measured all bones in a 3D virtual environment determining the best match. The use of a virtual bone bank system has allowed optimizing the allograft selection in a bone bank, providing more information to the surgeons before surgery. In conclusion, 3D preoperative planning in a virtual environment for allograft selection is an important and helpful tool in order to achieve a good match between host and donor.

  15. Management of chronic allograft dysfunction by switch over to rapamycin.

    Science.gov (United States)

    Sundaram, Varun; Abraham, Georgi; Fathima, Nusrath; Sundaram, Vivek; Reddy, Yogesh N V; Mathew, Milly; Sathiah, Vijaiaboobbathi

    2010-01-01

    The aim of this study was to evaluate the efficacy of conversion from calcineurin inhibitors (CNI)-based to a rapamycin-based immunosuppressive regimen in renal transplant recipients who had allograft dysfunction, in a South Indian population. We analyzed the results of 75 (19.5%) of the 398 renal transplants performed over a five-year period from 2002 to 2007, who were converted from a CNI-based immunosuppression to rapamycin including patients with chronic allograft dysfunction, chronic allograft injury and malignancy. The data analyzed included serial rapamycin levels, serum creatinine, eGFR by nankivel formula, lipid profile, hemoglobin and serum potassium levels. Statistical analysis was performed using student's t test and the Kaplan Meir survival curve was used to predict probability of survival among patients on rapamycin. The mean age of the study patients was 39.6 + or - 12.2 yrs and there was a male predominance (74.6%). Diabetic nephropathy was the predominant cause (36%) of end-stage renal disease (ESRD). Statistical analysis revealed a significant improvement in GFR of 14.6 mL/min and decrease in potassium by 0.7 mmol/L after initiation of rapamycin. There were no significant differences in terms of lipid profile, platelet count, hemoglobin and urine albumin levels. Rapamycin was discontinued in one patient due to hypokalemic nephropathy and in another patient due to delayed wound healing. To our knowledge, this is the first study to provide information on the conversion from a CNI to rapamycin-based immunosuppression in a cohort of Indian renal transplant recipients. In conclusion, the findings of our study confirm that rapamycin-based immunosuppressive regimen improves renal function and graft survival with minimal side effects, in comparison to CNI-based immunosuppression.

  16. Management of chronic allograft dysfunction by switch over to rapamycin

    Directory of Open Access Journals (Sweden)

    Sundaram Varun

    2010-01-01

    Full Text Available The aim of this study was to evaluate the efficacy of conversion from Calcineurin Inhibitors (CNI-based to a rapamycin-based immunosuppressive regimen in renal transplant reci-pients who had allograft dysfunction, in a South Indian population. We analyzed the results of 75 (19.5% of the 398 renal transplants performed over a five-year period from 2002 to 2007, who were converted from a CNI-based immunosuppression to rapamycin including patients with chronic allograft dysfunction, chronic allograft injury and malignancy. The data analyzed included serial rapamycin levels, serum creatinine, eGFR by nankivel formula, lipid profile, hemoglobin and serum potassium levels. Statistical analysis was performed using student′s t test and the Kaplan Meir survival curve was used to predict probability of survival among patients on rapamycin. The mean age of the study patients was 39.6 ± 12.2 yrs and there was a male predominance (74.6%. Diabetic nephropathy was the predominant cause (36% of end-stage renal disease (ESRD. Statistical analysis revealed a significant improvement in GFR of 14.6 mL/min and decrease in potassium by 0.7 mmol/L after initiation of rapamycin. There were no significant differences in terms of lipid profile, platelet count, hemoglobin and urine albumin levels. Rapamycin was discontinued in one patient due to hypokalemic nephropathy and in another patient due to delayed wound healing. To our knowledge, this is the first study to provide information on the conversion from a CNI to rapamycin-based immunosuppression in a cohort of Indian renal transplant recipients. In conclusion, the findings of our study confirm that rapamycin-based immunosuppressive regimen improves renal function and graft survival with mini-mal side effects, in comparison to CNI-based immunosuppression.

  17. Ankle and shoulder joint reconstruction using soft tissue allografts

    International Nuclear Information System (INIS)

    Nather, A.; Singh, G.

    2008-01-01

    Full text: Lateral Collateral Ligament Insufficiency is a common complication of injury to the ankle joint. This needs reconstruction of the torn ligament as the joint instability gives rise to frequent giving way at the ankle joint. It can be reconstructed using autologous peroneus brevis tendon. The authors prefer to reconstruct using deep frozen (-80 degree C) non-gamma irradiated tibialis anterior or tibialis posterior tendon allograft procured by NUH Tissue Bank. The graft must be at least between 18-22 cm long. The procedure employed is a first stage Brostrom Procedure repairing the anterior talo-fibula ligament using Mitek sutures. In the second stage the Calcaneofibular ligament is reconstructed using a figure of eight tendon reconstruction via drill holes in the fibular above and the calcaneum below. Twelve cases have been reconstructed this way with good results. When injury is sustained to the Acromia-clavicular (AC) Joint, for type 3 to 5 AC Joint Dislocation and in manual labourers, reconstruction is needed. The author's preferred method is a 2 stage procedure using deep frozen (-80 degree C), non gamma-irradiated fascia lata allografts procured by NUH Tissue Bank. In the first stage the dislocated AC Joint is reduced and held in position by transfixation using 2 baby Steinmann Pins and repair of torn corac clavicular ligaments. The second stage consisted of reconstruction with rolled-up fascia lata figure of eight allograft tendon between the clavicle and the coracoid process. The 2 pins are removed after 6 weeks and the shoulder mobilised. 10 cases have been done with good results. Two cases showed mild subluxation of the AC joint due to slight loss of the reduction performed during the operation. (Author)

  18. 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.

  19. Multiplexed color-coded probe-based gene expression assessment for clinical molecular diagnostics in formalin-fixed paraffin-embedded human renal allograft tissue.

    Science.gov (United States)

    Adam, Benjamin; Afzali, Bahman; Dominy, Katherine M; Chapman, Erin; Gill, Reeda; Hidalgo, Luis G; Roufosse, Candice; Sis, Banu; Mengel, Michael

    2016-03-01

    Histopathologic diagnoses in transplantation can be improved with molecular testing. Preferably, molecular diagnostics should fit into standard-of-care workflows for transplant biopsies, that is, formalin-fixed paraffin-embedded (FFPE) processing. The NanoString(®) gene expression platform has recently been shown to work with FFPE samples. We aimed to evaluate its methodological robustness and feasibility for gene expression studies in human FFPE renal allograft samples. A literature-derived antibody-mediated rejection (ABMR) 34-gene set, comprised of endothelial, NK cell, and inflammation transcripts, was analyzed in different retrospective biopsy cohorts and showed potential to molecularly discriminate ABMR cases, including FFPE samples. NanoString(®) results were reproducible across a range of RNA input quantities (r = 0.998), with different operators (r = 0.998), and between different reagent lots (r = 0.983). There was moderate correlation between NanoString(®) with FFPE tissue and quantitative reverse transcription polymerase chain reaction (qRT-PCR) with corresponding dedicated fresh-stabilized tissue (r = 0.487). Better overall correlation with histology was observed with NanoString(®) (r = 0.354) than with qRT-PCR (r = 0.146). Our results demonstrate the feasibility of multiplexed gene expression quantification from FFPE renal allograft tissue. This represents a method for prospective and retrospective validation of molecular diagnostics and its adoption in clinical transplantation pathology. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Donor and procurement related issues in vascularized composite allograft transplantation.

    Science.gov (United States)

    McDiarmid, Sue V

    2013-12-01

    To understand the unique requirements of vascularized composite allograft (VCA) donation and procurement practices and the integral role of the established nationwide organ procurement organizations in organ procurement. The recent issuance of a Final Rule (July 2013) by the United States Secretary of Health that redefines VCAs as organs rather than tissues, opens up the potential to formalize policies and procedures, under the auspices of the Organ Procurement and Transplantation Network, that can improve VCA donation, procurement practices, develop allocation algorithms and provide transparent oversight. Improved VCA donation rates, procurement procedures and broader sharing nationwide of VCA donors will have important implications in advancing the emerging field of VCA transplantation.

  1. Femoral revision with impaction allografting and an uncemented femoral component

    DEFF Research Database (Denmark)

    Nickelsen, T N; Erenbjerg, M; Retpen, J B

    2008-01-01

    A technique for uncemented revision of the femoral component which combines impaction allografting and the use of a long-stemmed proximally coated titanium prostheses (Bimetric, Biomet Inc.) is described. The results after a mean follow-up of 112 months are reported. From 1991 to 1995 femoral...... implants 88% had no pain, 10% had slight pain and only 2% had severe pain. Thirty-eight patients had radiographic signs of remodelling of the graft and/or cortical repair. In cases with a successful outcome, the results have been encouraging in relation to clinical performance, regeneration of bone...

  2. Safety and effectiveness of bone allografts in anterior cervical discectomy and fusion surgery.

    Science.gov (United States)

    Miller, Larry E; Block, Jon E

    2011-11-15

    Systematic review. The primary aim of this review was to evaluate clinical and radiographic outcomes in studies of anterior cervical discectomy and fusion (ACDF) using allograft versus ACDF with autograft, ACDF with cage devices, and cervical disc arthroplasty for the treatment of symptomatic cervical disc disease. ACDF remains the standard of care for patients with cervical radiculopathy who are unresponsive to conservative medical care. However, no known study has compared patient outcomes after ACDF with allograft, ACDF with autograft, ACDF with cage, and disc arthroplasty. After applying strict inclusion criteria, 21 comparisons from 20 studies formed the basis for this review. Patient outcomes included neck and arm pain, neck disability index (NDI), physical component summary (PCS), and mental component summary (MCS) scores from the SF-36, radiographic fusion rate, and select adverse events (e.g., wound infection, dysphagia, and adjacent segment degeneration). The four treatment groups included ACDF with allograft (allograft, n = 1341), ACDF with autograft (autograft, n = 568), ACDF with cage (cage, n = 87), and cervical disc arthroplasty (arthroplasty, n = 603). Neck pain was reduced similarly by 63% to 69% in all groups. Comparable improvements were realized in arm pain after ACDF with allograft (75%) or arthroplasty (73%) that were greater than other treatment groups (62-68%). There was notable improvement in neck disability (61-65%) with allograft and arthroplasty after treatment. PCS scores improved with allograft (42%) and arthroplasty (44%). MCS scores improved modestly (16-21%) with allograft and arthroplasty. Fusion rates were 91% for allograft and autograft and 97% for cage. Adverse events were uncommon in all groups. ACDF with allograft, ACDF with autograft, ACDF with cage, and cervical disc arthroplasty show similar improvements in pain, function, and quality of life with correspondingly low adverse event rates. All ACDF procedures result in high

  3. Loss of CD28 on Peripheral T Cells Decreases the Risk for Early Acute Rejection after Kidney Transplantation.

    Directory of Open Access Journals (Sweden)

    Burç Dedeoglu

    Full Text Available End-stage renal disease patients have a dysfunctional, prematurely aged peripheral T-cell system. Here we hypothesized that the degree of premature T-cell ageing before kidney transplantation predicts the risk for early acute allograft rejection (EAR.222 living donor kidney transplant recipients were prospectively analyzed. EAR was defined as biopsy proven acute allograft rejection within 3 months after kidney transplantation. The differentiation status of circulating T cells, the relative telomere length and the number of CD31+ naive T cells were determined as T-cell ageing parameters.Of the 222 patients analyzed, 30 (14% developed an EAR. The donor age and the historical panel reactive antibody score were significantly higher (p = 0.024 and p = 0.039 respectively and the number of related donor kidney transplantation was significantly lower (p = 0.018 in the EAR group. EAR-patients showed lower CD4+CD28null T-cell numbers (p<0.01 and the same trend was observed for CD8+CD28null T-cell numbers (p = 0.08. No differences regarding the other ageing parameters were found. A multivariate Cox regression analysis showed that higher CD4+CD28null T-cell numbers was associated with a lower risk for EAR (HR: 0.65, p = 0.028. In vitro, a significant lower percentage of alloreactive T cells was observed within CD28null T cells (p<0.001.Immunological ageing-related expansion of highly differentiated CD28null T cells is associated with a lower risk for EAR.

  4. Ferrite grade iron oxides from ore rejects

    Indian Academy of Sciences (India)

    Iron oxyhydroxides and hydroxides were synthesized from chemically beneficiated high SiO2/Al2O3 low-grade iron ore (57.49% Fe2O3) rejects and heated to get iron oxides of 96–99.73% purity. The infrared band positions, isothermal weight loss and thermogravimetric and chemical analysis established the chemical ...

  5. Development of enhanced sulfur rejection processes

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, R.H.; Luttrell, G.H.; Adel, G.T.; Richardson, P.E.

    1996-03-01

    Research at Virginia Tech led to the development of two complementary concepts for improving the removal of inorganic sulfur from many eastern U.S. coals. These concepts are referred to as Electrochemically Enhanced Sulfur Rejection (EESR) and Polymer Enhanced Sulfur Rejection (PESR) processes. The EESR process uses electrochemical techniques to suppress the formation of hydrophobic oxidation products believed to be responsible for the floatability of coal pyrite. The PESR process uses polymeric reagents that react with pyrite and convert floatable middlings, i.e., composite particles composed of pyrite with coal inclusions, into hydrophilic particles. These new pyritic-sulfur rejection processes do not require significant modifications to existing coal preparation facilities, thereby enhancing their adoptability by the coal industry. It is believed that these processes can be used simultaneously to maximize the rejection of both well-liberated pyrite and composite coal-pyrite particles. The project was initiated on October 1, 1992 and all technical work has been completed. This report is based on the research carried out under Tasks 2-7 described in the project proposal. These tasks include Characterization, Electrochemical Studies, In Situ Monitoring of Reagent Adsorption on Pyrite, Bench Scale Testing of the EESR Process, Bench Scale Testing of the PESR Process, and Modeling and Simulation.

  6. Waste heat rejection from geothermal power stations

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, R.C.

    1978-12-01

    This study of waste heat rejection from geothermal power stations is concerned only with the heat rejected from the power cycle. The heat contained in reinjected or otherwise discharged geothermal fluids is not included with the waste heat considered here. The heat contained in the underflow from the flashtanks in such systems is not considered as part of the heat rejected from the power cycle. By following this definition of the waste heat to be rejected, various methods of waste heat dissipation are discussed without regard for the particular arrangement to obtain heat from the geothermal source. Recent conceptual design studies made for 50-MW(e) geothermal power stations at Heber and Niland, California, are of particular interst. The former uses a flashed-steam system and the latter a binary cycle that uses isopentane. In last-quarter 1976 dollars, the total estimated capital costs were about $750/kW and production costs about 50 mills/kWhr. If wet/dry towers were used to conserve 50% of the water evaporation at Heber, production costs would be about 65 mills/kWhr.

  7. Music genre recognition with risk and rejection

    DEFF Research Database (Denmark)

    Sturm, Bob L.

    2013-01-01

    We explore risk and rejection for music genre recognition (MGR) within the minimum risk framework of Bayesian classification. In this way, we attempt to give an MGR system knowledge that some misclassifications are worse than others, and that deferring classification to an expert may be a better...

  8. Antimyosin imaging in cardiac transplant rejection

    International Nuclear Information System (INIS)

    Johnson, L.L.; Cannon, P.J.

    1991-01-01

    Fab fragments of antibodies specific for cardiac myosin have been labeled with indium-111 and injected intravenously into animals and into patients with heart transplants. The antibodies, developed by Khaw, Haber, and co-workers, localize in cardiac myocytes that have been damaged irreversibly by ischemia, myocarditis, or the rejection process. After clearance of the labeled antibody from the cardiac blood pool, planar imaging or single photon emission computed tomography is performed. Scintigrams reveal the uptake of the labeled antimyosin in areas of myocardium undergoing transplant rejection. In animal studies, the degree of antimyosin uptake appears to correlate significantly with the degree of rejection assessed at necropsy. In patients, the correlation between scans and pathologic findings from endomyocardial biopsy is not as good, possibly because of sampling error in the endomyocardial biopsy technique. The scan results at 1 year correlate with either late complications (positive) or benign course (negative). Current limitations of the method include slow blood clearance, long half-life of indium-111, and hepatic uptake. Overcoming these limitations represents a direction for current research. It is possible that from these efforts a noninvasive approach to the diagnosis and evaluation of cardiac transplantation may evolve that will decrease the number of endomyocardial biopsies required to evaluate rejection. This would be particularly useful in infants and children. 31 references

  9. Accept & Reject Statement-Based Uncertainty Models

    NARCIS (Netherlands)

    E. Quaeghebeur (Erik); G. de Cooman; F. Hermans (Felienne)

    2015-01-01

    textabstractWe develop a framework for modelling and reasoning with uncertainty based on accept and reject statements about gambles. It generalises the frameworks found in the literature based on statements of acceptability, desirability, or favourability and clarifies their relative position. Next

  10. Neural Mechanisms of the Rejection-Aggression Link.

    Science.gov (United States)

    Chester, David S; Lynam, Donald R; Milich, Richard; DeWall, C Nathan

    2018-03-28

    Social rejection is a painful event that often increases aggression. However, the neural mechanisms of this rejection-aggression link remain unclear. A potential clue may be that rejected people often recruit the ventrolateral prefrontal cortex's (VLPFC) self-regulatory processes to manage the pain of rejection. Using functional MRI, we replicated previous links between rejection and activity in the brain's mentalizing network, social pain network, and VLPFC. VLPFC recruitment during rejection was associated with greater activity in the brain's reward network (i.e., the ventral striatum) when individuals were given an opportunity to retaliate. This retaliation-related striatal response was associated with greater levels of retaliatory aggression. Dispositionally aggressive individuals exhibited less functional connectivity between the ventral striatum and the right VLPFC during aggression. This connectivity exerted a suppressing effect on dispositionally aggressive individuals' greater aggressive responses to rejection. These results help explain how the pain of rejection and reward of revenge motivate rejected people to behave aggressively.

  11. Radiation sterilisation of tissue allografts for transplant surgery

    International Nuclear Information System (INIS)

    Phillips, G.O.

    1994-01-01

    The application of ionising radiation to sterilise biological tissues is an extension of their use for the sterilisation of other medical products and pharmaceuticals. This paper describes the effects of radiation on biological tissues, both at the macro- and molecular level. Changes in mechanical and other physical properties can accompany irradiation. These are shown to be due to the glycosamino-glycan component (hyaluronic acid), rather than to the collagen fibrils. Fast reaction methods are used to identify the mechanism of the radiation degradation processes. Methods by which tissues can be protected from these undesirable effects are discussed. The application of radiation sterilisation to human tissues used in transplant surgery is described, and the practical methods of processing given. Such radiation sterilised allografts now have wide application, with more than 500,000 used each year. The IAEA programme in this field has extended the application to 13 countries of the Asia and Pacific Region. Such Tissue Banks are also established with the support of IAEA in Africa and South America. The allografts can now be produced in developing countries in a readily available form, at low cost, and reduce the need for costly imported alternatives. (author). 45 refs., 19 figs., 3 tabs

  12. Comparative Effectiveness of Bone Grafting Using Xenograft Freeze-Dried Cortical Bovine, Allograft Freeze-Dried Cortical New Zealand White Rabbit, Xenograft Hydroxyapatite Bovine, and Xenograft Demineralized Bone Matrix Bovine in Bone Defect of Femoral Diaphysis of White Rabbit: Experimental Study In Vivo

    Directory of Open Access Journals (Sweden)

    Ferdiansyah Mahyudin

    2017-01-01

    Full Text Available Autogenous bone graft is gold standard in treating bone defects, but it might have difficulty in corporation and rejection reaction. This study is to compare the effectiveness among freeze-dried xenograft, freeze-dried allograft, hydroxyapatite xenograft, and demineralized bone matrix xenograft as bone graft to fill bone defect in femoral diaphysis of white rabbit. Thirty male New Zealand white rabbits were distributed into five groups. Bone defect was filled correspondingly with xenograft freeze-dried cortical bovine, allograft freeze-dried cortical New Zealand white rabbit, xenograft hydroxyapatite bovine, and xenograft demineralized bone matrix bovine. No graft was used in control group. VEGF, osteoblast, and woven bone were higher in allograft freeze-dried cortical New Zealand white rabbit (mean 5.6625 (p<0.05 and xenograft demineralized bone matrix bovine (mean 5.2475 (p<0.05 with calcification of woven bone was already seen in week 2 in the latter group. There was a decrease of woven bone (mean 4.685 (p<0.05 fibrous tissue (mean 41.07 (p<0.05 in xenograft demineralized bone matrix bovine. The Immunoglobulin-G was elevated in control and all study groups but not significantly (p=0.07855. Bone healing process in xenograft demineralized bone matrix bovine is more effective than in xenograft hydroxyapatite bovine, allograft freeze-dried New Zealand white rabbit, xenograft freeze-dried cortical bovine, and control.

  13. Femoral head allograft disinfection system using moderate heat

    International Nuclear Information System (INIS)

    Knaepler, H.; Von Garrel, T.

    1999-01-01

    The employment of a reliable thermal viral inactivation process, which minimally manipulates tissues, for surgically retrieved femoral head allografts addresses the increased concerns with virus transmissibility while minimizing the loss of biological properties. The newest European and German surgical bone banking guidelines have incorporated the use of independently validated then-nal viral inactivation methods in place of repeat serological testing of donor. Our investigations have shown that heat treatment at 80 degree C for a minimum of 10 minutes provides safe, good quality cancellous bone allografts and increases the cost-effectiveness and simplicity of managing a hospital frozen femoral head bone bank. Human femoral head centers were contaminated with different vegetative bacterial and viral suspensions. A core temperature of 80 degree C for 10 minutes was sufficient to fully inactivate 3 x 106 ml Staphylococcus aureus and Streptococcus faecalis, and >5 loglo steps of cytomeglia (herpes group), polio (enterovirus), and yellow fever (arbovirus) viruses. A one hour treatment in a water bath set at 80 degree sufficient to fully inactivate E. coli, proteus vulgaris, and Pseudomonas aerog. vegetative suspensions; 20 minutes was sufficient to fully inactivate the D antigen (rhesus factor) but had no effect on A or B antigens. Several biomechanical and biological properties of bone following a one hour treatment in a water bath set at 80 degree C were investigated. Employing compression and tension tests, 80 degree C treated human and porcine cancellous bone blocks showed reductions in properties ranging from 8-19% compared to untreated control groups. Osteointegration at 3 months following treatment of explanted and then reimplanted autograft rat diaphyseal segment was 15% less than untreated controls. Subsequently, a thermal disinfection system for femoral heads from living donors (Lobator Marburg Bone Bank System, Telos GmbH, Hungen, Germany) was developed. A

  14. To Accept or Reject? The Impact of Adolescent Rejection Sensitivity on Early Adult Romantic Relationships.

    Science.gov (United States)

    Hafen, Christopher A; Spilker, Ann; Chango, Joanna; Marston, Emily S; Allen, Joseph P

    2014-03-01

    Successfully navigating entry into romantic relationships is a key task in adolescence, which sensitivity to rejection can make difficult to accomplish. This study uses multi-informant data from a community sample of 180 adolescents assessed repeatedly from age 16 to 22. Individuals with elevated levels of rejection sensitivity at age 16 were less likely to have a romantic partner at age 22, reported more anxiety and avoidance when they did have relationships, and were observed to be more negative in their interactions with romantic partners. In addition, females whose rejection sensitivity increased during late adolescence were more likely to adopt a submissive pattern within adult romantic relationships, further suggesting a pattern in which rejection sensitivity forecasts difficulties.

  15. Analysis of AHG-PRA and ELISA-PRA in kidney transplant patients with acute rejection episodes.

    Science.gov (United States)

    Kaufman, Arnauld; de Souza Pontes, Luciane Faria; Queiroz Marques, Maria Teresa; Sampaio, José Cavaliere; de Moraes Sobrino Porto, Luís Cristóvão; de Moraes Souza, Edison Régio

    2003-01-01

    Many centers determined a significant correlation between post-transplant anti-HLA antibodies production and clinical outcome. In order to confirm this correlation and ascertain the sequential appearance of anti-HLA antibodies, we compared the ELISA (ELISA-PRA) and the anti-human globulin enhanced complement-dependent lymphocytotoxicity panel-reactive antibodies test (AHG-PRA) with the occurrence of acute rejection episodes. Thirty patients who underwent kidney transplantation between December 1998 and October 1999 were assayed. One pre-transplant and 10 post-transplant serum samples were tested from each recipient except from one of them who lost his graft on the 1 week post-transplant. The diagnosis of acute rejection episode was based on classical criteria (fever, graft swelling and tenderness, oliguria, weight gain) and a rapid rise in serum creatinine levels, confirmed by an allograft biopsy graded by the Banff working classification. The 322 pre- and post-transplant serum specimens were tested by AHG-PRA methodology and 298 of them by the ELISA-PRA. The agreement coefficient (kappa) for both methodologies was 0.63. There were 27 acute rejection episodes in 19 patients. AHG-PRA results were significantly correlated (Hazard ratio=10.06; P=0.006) with this occurrence. These data were not confirmed with the ELISA-PRA procedure. Our results suggest that a routine post-transplant AHG-PRA test offers an early risk assessment of acute rejection episodes and may be a useful method for monitoring the kidney transplant evolution.

  16. Treatment options for renal cell carcinoma in renal allografts: a case series from a single institution.

    Science.gov (United States)

    Swords, Darden C; Al-Geizawi, Samer M; Farney, Alan C; Rogers, Jeffrey; Burkart, John M; Assimos, Dean G; Stratta, Robert J

    2013-01-01

    Renal cell carcinoma (RCC) is more common in renal transplant and dialysis patients than the general population. However, RCC in transplanted kidneys is rare, and treatment has previously consisted of nephrectomy with a return to dialysis. There has been recent interest in nephron-sparing procedures as a treatment option for RCC in allograft kidneys in an effort to retain allograft function. Four patients with RCC in allograft kidneys were treated with nephrectomy, partial nephrectomy, or radiofrequency ablation. All of the patients are without evidence of recurrence of RCC after treatment. We found nephron-sparing procedures to be reasonable initial options in managing incidental RCCs diagnosed in functioning allografts to maintain an improved quality of life and avoid immediate dialysis compared with radical nephrectomy of a functioning allograft. However, in non-functioning renal allografts, radical nephrectomy may allow for a higher chance of cure without the loss of transplant function. Consequently, radical nephrectomy should be utilized whenever the allograft is non-functioning and the patient's surgical risk is not prohibitive. © 2013 John Wiley & Sons A/S.

  17. Utility of an allograft tendon for scoliosis correction via the costo-transverse foreman.

    Science.gov (United States)

    Sun, Dong; McCarthy, Michael; Dooley, Adam C; Ramakrishnaiah, Raghu H; Shelton, R Shane; McLaren, Sandra G; Skinner, Robert A; Suva, Larry J; McCarthy, Richard E

    2017-01-01

    Current convex tethering techniques for treatment of scoliosis have centered on anterior convex staples or polypropylene tethers. We hypothesized that an allograft tendon tether inserted via the costo-transverse foramen would correct an established spinal deformity. In the pilot study, six 8-week-old pigs underwent allograft tendon tethering via the costo-transverse foreman or sham to test the strength of the transplanted tendon to retard spine growth. After 4 months, spinal deformity in three planes was induced in all animals with allograft tendons. In the treatment study, the allograft tendon tether was used to treat established scoliosis in 11 8-week-old pigs (spinal deformity > 50°). Once the deformity was observed (4 months) animals were assigned to either no treatment group or allograft tendon tether group and progression assessed by monthly radiographs. At final follow-up, coronal Cobb angle and maximum vertebral axial rotation of the treatment group was significantly smaller than the non-treatment group, whereas sagittal kyphosis of the treatment group was significantly larger than the non-treatment group. In sum, a significant correction was achieved using a unilateral allograft tendon spinal tether, suggesting that an allograft tendon tethering approach may represent a novel fusion-less procedure to correct idiopathic scoliosis. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:183-192, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  18. Electrocardiographic Characteristics of Potential Organ Donors and Associations with Cardiac Allograft Utilization

    Science.gov (United States)

    Khush, Kiran K.; Menza, Rebecca; Nguyen, John; Goldstein, Benjamin A.; Zaroff, Jonathan G.; Drew, Barbara J.

    2012-01-01

    Background Current regulations require that all cardiac allograft offers for transplantation must include an interpreted 12-lead electrocardiogram (ECG). However, little is known about the expected ECG findings in potential organ donors, or the clinical significance of any identified abnormalities in terms of cardiac allograft function and suitability for transplantation. Methods and Results A single experienced reviewer interpreted the first ECG obtained after brainstem herniation in 980 potential organ donors managed by the California Transplant Donor Network from 2002-2007. ECG abnormalities were summarized, and associations between specific ECG findings and cardiac allograft utilization for transplantation were studied. ECG abnormalities were present in 51% of all cases reviewed. The most common abnormalities included voltage criteria for left ventricular hypertrophy (LVH), prolongation of the corrected QT interval (QTc), and repolarization changes (ST/T wave abnormalities). Fifty seven percent of potential cardiac allografts in this cohort were accepted for transplantation. LVH on ECG was a strong predictor of allograft non-utilization. No significant associations were seen between QTc prolongation, repolarization changes and allograft utilization for transplantation, after adjusting for donor clinical variables and echocardiographic findings. Conclusions We have performed the first comprehensive study of ECG findings in potential donors for cardiac transplantation. Many of the common ECG abnormalities seen in organ donors may result from the heightened state of sympathetic activation that occurs after brainstem herniation, and are not associated with allograft utilization for tr