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Sample records for acute antibody-mediated rejection

  1. Acute antibody-mediated rejection in pancreas and kidney transplantation

    NARCIS (Netherlands)

    Kort, Hanneke de

    2013-01-01

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

  2. 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

  3. 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. 

  4. 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

    -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....

  5. 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

    -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....

  6. Rituximab in the treatment of refractory late acute antibody-mediated rejection: Our initial experience

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    M Surendra

    2016-01-01

    Full Text Available Antibody-mediated rejection (AMR is not uncommon after renal transplantation and is harder to handle compared to cell-mediated rejection. When refractory to conventional therapies, rituximab is an attractive option. This study aims to examine the effectiveness of rituximab in refractory late acute AMR. This is a retrospective study involving nine renal transplant recipients. Four doses of rituximab were administered at weekly interval for 4 weeks, at a dose of 375 mg/m 2. The mean age of patients was 35.3 ± 7.38 years. The median period between transplantation and graft dysfunction was 30 ± 20 months. Mean serum creatinine at the time of discharge after transplantation and at the time of acute AMR diagnosis was 1.14 ± 0.19 mg/dl and 2.26 ± 0.57 mg/dl, respectively. After standard therapy, it was 2.68 ± 0.62 mg/dl. One patient died of Pseudomonas sepsis and three patients progressed to end-stage renal disease (ESRD. Four biopsies showed significant plasma cell infiltrations. Mean serum creatinine among non-ESRD patients at the end of 1 year progressed from 2.3 ± 0.4 to 3.8 ± 1.2 mg/dl (P value 0.04. eGFR prior to therapy and at the end of 1 year were 34.4 ± 6.18 and 20.8 ± 7.69 ml/min (P value 0.04, respectively. Only one patient showed improvement in graft function in whom donor-specific antibody (DSA titers showed significant improvement. Rituximab may not be effective in late acute AMR unlike in early acute AMR. Monitoring of DSA has a prognostic role in these patients and plasma cell rich rejection is associated with poor prognosis.

  7. Plasma C4d+ Endothelial Microvesicles Increase in Acute Antibody-Mediated Rejection.

    Science.gov (United States)

    Tower, Cindy M; Reyes, Morayma; Nelson, Karen; Leca, Nicolae; Kieran, Niamh; Muczynski, Kimberly; Jefferson, Jonathan A; Blosser, Christopher; Kukla, Aleksandra; Maurer, David; Chandler, Wayne; Najafian, Behzad

    2017-09-01

    Antibody-mediated rejection (AMR) is a major cause of kidney allograft loss. Currently, AMR diagnosis relies on biopsy which is an invasive procedure. A noninvasive biomarker of acute AMR could lead to early diagnosis and treatment of this condition and improve allograft outcome. Microvesicles are membrane-bound vesicles released from the cell surface after injury. We hypothesized that because AMR is associated with allograft endothelial injury and C4d deposition, plasma microvesicles positive for endothelial (CD144) marker and C4d are increased in this condition. We studied microvesicle concentration in the plasma of 95 kidney transplant patients with allograft dysfunction and compared with 23 healthy volunteers. Biopsy diagnosis and scoring was performed using Banff classification. In the 28 subjects with AMR, the density of C4d+/CD144+ microvesicles was on average 11-fold (P = 0.002) higher than transplant recipients with no AMR and 24-fold (P = 0.008) than healthy volunteers. Densities of C4d+ and C4d+/annexin V+ (C4d+/AVB+) microvesicles were also increased in AMR patients compared with no AMR and healthy subjects. C4d+/AVB+ microvesicles correlated with AMR biopsy severity. Nine patients with acute AMR that received treatment showed a mean 72% decrease (P = 0.01) in C4d+/CD144+ microvesicle concentration compared with pretreatment values. Quantification of plasma C4d+ microvesicles provides information about presence of AMR, its severity and response to treatment in transplant patients.

  8. Rituximab-Related Late-Onset Neutropenia in Kidney Transplant Recipients Treated for Antibody-Mediated Acute Rejection.

    Science.gov (United States)

    Ahmadi, Fatemeh; Dashti-Khavidaki, Simin; Khatami, Mohammad-Reza; Lessan-Pezeshki, Mahboob; Khalili, Hossein; Khosravi, Malihe

    2017-08-01

    Kidney transplant is a new area for use of rituximab, which is being used to treat acute antibody-mediated rejection or as an induction agent in ABO- or HLA-incompatible grafts. We report on late-onset neutropenia in rituximab-treated kidney transplant recipients with antibody-mediated rejection. This observational prospective study was performed on kidney transplant recipients with clinically suspicious or biopsy-proven antibody-mediated rejection treated with plasmapheresis plus intravenous immunoglobulin with (cases) or without (controls) rituximab. Compared with none of the controls, 4 of 6 patients (66.7%) in the rituximab-treated group experienced late-onset neutropenia 35 to 93 days after the last dose of rituximab. The course of neutropenia was complicated by endocarditis in 1 patient, resulting in his death just because of a lack of valvular surgery. Increased use of rituximab to treat antibody-mediated rejection among kidney transplant recipients requires attention to its late-onset adverse event, neutropenia. Although asymptomatic in some patients, kidney transplant recipients treated concomitantly with plasmapheresis and mycophenolate mofetil are predisposed to hypogammaglobulinemia, and monitoring of patients for infections is required.

  9. Histological long-term outcomes from acute antibody-mediated rejection following ABO-compatible liver transplantation.

    Science.gov (United States)

    Del Bello, Arnaud; Danjoux, Marie; Congy-Jolivet, Nicolas; Lavayssière, Laurence; Esposito, Laure; Muscari, Fabrice; Kamar, Nassim

    2017-04-01

    Acute antibody-mediated rejection (aAMR) is an unusual complication after orthotopic ABO-compatible liver transplantation. To date, the clinical and histological long-term outcomes after aAMR are not well known. Herein, we describe nine cases of aAMR that occurred in our liver-transplant center between 2008 and 2016, with an initial and reevaluation liver biopsy available for reexamination. Two patients presented with aAMR at 10.5 (10, 11) days post-transplantation, caused by preformed donor-specific antibodies. Seven other recipients developed de novo donor-specific antibodies and aAMR at 11.2 (3-24) months post-transplantation. Eight of the nine patients received a B-cell targeting agent (rituximab, with or without plasma exchange), associated with polyclonal antibodies (three patients) or intravenous immunoglobulins (three patients). At the last follow up (i.e. 21 [4-90] months post-aAMR), seven patients were alive, including two patients with normal liver tests. Grafts' survival was 66%. A liver biopsy performed at 11.5 (5-48.5) months after the first biopsy showed no significant improvement in aAMR score (from 2 ± 1.3 to 1.6 ± 1.5, P = 0.6), a significant improvement in chronic AMR score (from 37 ± 9 to 25 ± 8, P = 0.003) and an increase in the Metavir score (1.2 ± 0.6 to 2.1 ± 0.9, P = 0.03). In this study, a B-cell-depleting agent seemed to improve the prognosis of aAMR in selected cases, but several patients kept active lesions antibody-mediated rejection. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

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

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    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

  11. Significance of complement split product C4d in ABO-compatible liver allograft: diagnosing utility in acute antibody mediated rejection.

    Science.gov (United States)

    Ali, Sharif; Ormsby, Adrian; Shah, Veena; Segovia, Maria C; Kantz, Kristin L; Skorupski, Sharon; Eisenbrey, A Bradley; Mahan, Meredith; Huang, Mary Ann Y

    2012-01-01

    Diagnosis of liver allograft antibody-mediated rejection (AMR) is difficult and requires a constellation of clinical, laboratory and histologic features that support the disease and exclude other causes. Histologic features of AMR may intermix with those of biliary obstruction, preservation/reperfusion injury, and graft ischemia. Tissue examination for complement degradation product 4d (C4d) has been proved to support this diagnosis in other allografts. For this reason, we conducted a retrospective review of all ABO compatible/identical re-transplanted liver patients with primary focus on identifying AMR as a possible cause of graft failure and to investigate the utility of C4d in liver allograft specimens. We reviewed 193 liver samples obtained from 53 consecutive ABO-compatible re-transplant patients. 142 specimens were stained with C4d. Anti-donor antibody screening and identification was determined by Luminex100 flow cytometry. For the study analysis, patients were stratified into 3 groups according to time to graft failure: group A, patients with graft failure within 0-7 days (n=7), group B within 8-90 days (n=13) and C >90 days (n=33). Two patients (3.7%) met the diagnostic criteria of acute AMR. Both patients experienced rapid decline of graft function with presence of donor specific antibodies (DSA), morphologic evidence of humoral rejection and C4d deposition in liver specimens. C4d-positive staining was identified in different medical liver conditions i.e., acute cellular rejection (52%), chronic ductopenic rejection (50%), recurrent liver disease (48%), preservation injury (18%), and hepatic necrosis (54%). Univariate analysis showed no significant difference of C4d-positive staining among the 3 patients groups, or patients with DSA (P>.05). In conclusion, AMR after ABO-compatible liver transplantation is an uncommon cause of graft failure. Unlike other solid organ allografts, C4d-positive staining is not a rugged indicator of humoral rejection, thus

  12. Acute Antibody-Mediated Rejection in Presence of MICA-DSA and Successful Renal Re-Transplant with Negative-MICA Virtual Crossmatch.

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    Yingzi Ming

    Full Text Available The presence of donor-specific alloantibodies (DSAs against the MICA antigen results in high risk for antibody-mediated rejection (AMR of a transplanted kidney, especially in patients receiving a re-transplant. We describe the incidence of acute C4d+ AMR in a patient who had received a first kidney transplant with a zero HLA antigen mismatch. Retrospective analysis of post-transplant T and B cell crossmatches were negative, but a high level of MICA alloantibody was detected in sera collected both before and after transplant. The DSA against the first allograft mismatched MICA*018 was in the recipient. Flow cytometry and cytotoxicity tests with five samples of freshly isolated human umbilical vein endothelial cells demonstrated the alloantibody nature of patient's MICA-DSA. Prior to the second transplant, a MICA virtual crossmatch and T and B cell crossmatches were used to identify a suitable donor. The patient received a second kidney transplant, and allograft was functioning well at one-year follow-up. Our study indicates that MICA virtual crossmatch is important in selection of a kidney donor if the recipient has been sensitized with MICA antigens.

  13. Antibody-Mediated Rejection: An Evolving Entity in Heart Transplantation

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    Sharon Chih

    2012-01-01

    Full Text Available Antibody-mediated rejection (AMR is gaining increasing recognition as a major complication after heart transplantation, posing a significant risk for allograft failure, cardiac allograft vasculopathy, and poor survival. AMR results from activation of the humoral immune arm and the production of donor-specific antibodies (DSA that bind to the cardiac allograft causing myocardial injury predominantly through complement activation. The diagnosis of AMR has evolved from a clinical diagnosis involving allograft dysfunction and the presence of DSA to a primarily pathologic diagnosis based on histopathology and immunopathology. Treatment for AMR is multifaceted, targeting inhibition of the humoral immune system at different levels with emerging agents including proteasome and complement inhibitors showing particular promise. While there have been significant advances in our current understanding of the pathogenesis, diagnosis, and treatment of AMR, further research is required to determine optimal diagnostic tools, therapeutic agents, and timing of treatment.

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

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    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.

  15. Antibody-Mediated Rejection in Sensitized Nonhuman Primates: Modeling Human Biology.

    Science.gov (United States)

    Burghuber, C K; Kwun, J; Page, E J; Manook, M; Gibby, A C; Leopardi, F V; Song, M; Farris, A B; Hong, J J; Villinger, F; Adams, A B; Iwakoshi, N N; Knechtle, S J

    2016-06-01

    We have established a model of sensitization in nonhuman primates and tested two immunosuppressive regimens. Animals underwent fully mismatched skin transplantation, and donor-specific antibody (DSA) response was monitored by flow cross-match. Sensitized animals subsequently underwent kidney transplantation from their skin donor. Immunosuppression included tacrolimus, mycophenolate, and methylprednisolone. Three animals received basiliximab induction; compared with nonsensitized animals, they showed a shorter mean survival time (4.7 ± 3.1 vs. 187 ± 88 days). Six animals were treated with T cell depletion (anti-CD4/CD8 mAbs), which prolonged survival (mean survival time 21.6 ± 19.0 days). All presensitized animals showed antibody-mediated rejection (AMR). In two of three basiliximab-injected animals, cellular rejection (ACR) was prominent. After T cell depletion, three of six monkeys experienced early acute rejection within 8 days with histological evidence of thrombotic microangiopathy and AMR. The remaining three monkeys survived 27-44 days, with mixed AMR and ACR. Most T cell-depleted animals experienced a rebound of DSA that correlated with deteriorating kidney function. We also found an increase in proliferating memory B cells (CD20(+) CD27(+) IgD(-) Ki67(+) ), lymph node follicular helper T cells (ICOS(+) PD-1(hi) CXCR5(+) CD4(+) ), and germinal center (GC) response. Depletion controlled cell-mediated rejection in sensitized nonhuman primates better than basiliximab, yet grafts were rejected with concomitant DSA rise. This model provides an opportunity to test novel desensitization strategies. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  16. Late antibody-mediated rejection after ABO-incompatible kidney transplantation during Gram-negative sepsis

    NARCIS (Netherlands)

    A. de Weerd (Annelies); A.G. Vonk (Alieke); H. van der Hoek (Hans); M. van Groningen (Marian); W. Weimar (Willem); M.G.H. Betjes (Michiel); M. Agteren (Madelon)

    2014-01-01

    textabstractBackground: The major challenge in ABO-incompatible transplantation is to minimize antibody-mediated rejection. Effective reduction of the anti-ABO blood group antibodies at the time of transplantation has made ABO-incompatible kidney transplantation a growing practice in our hospital

  17. The Complement System and Antibody-Mediated Transplant Rejection.

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    Stites, Erik; Le Quintrec, Moglie; Thurman, Joshua M

    2015-12-15

    Complement activation is an important cause of tissue injury in patients with Ab-mediated rejection (AMR) of transplanted organs. Complement activation triggers a strong inflammatory response, and it also generates tissue-bound and soluble fragments that are clinically useful markers of inflammation. The detection of complement proteins deposited within transplanted tissues has become an indispensible biomarker of AMR, and several assays have recently been developed to measure complement activation by Abs reactive to specific donor HLA expressed within the transplant. Complement inhibitors have entered clinical use and have shown efficacy for the treatment of AMR. New methods of detecting complement activation within transplanted organs will improve our ability to diagnose and monitor AMR, and they will also help guide the use of complement inhibitory drugs. Copyright © 2015 by The American Association of Immunologists, Inc.

  18. Long-term experience of plasmapheresis in antibody-mediated rejection in renal transplantation.

    LENUS (Irish Health Repository)

    Brown, C M

    2009-11-01

    Antibody-mediated rejection (AMR) continues to pose a serious challenge in renal transplantation with potentially devastating consequences. Treatment options for this condition include plasmapheresis, high-dose intravenous immunoglobulin (IVIG), plasmapheresis with low-dose IVIG, and the use of rituximab (anti-CD20 chimeric antibody). We previously reported on the short-term outcome of plasmapheresis as a rescue therapy for AMR in our centre. We now report on the long-term follow up.

  19. Antibody-Mediated Rejection in Heart Transplantation: Case Presentation with a Review of Current International Guidelines

    Directory of Open Access Journals (Sweden)

    Octavio E. Pajaro

    2011-01-01

    Full Text Available Antibody-mediated rejection (AMR (humoral rejection of cardiac allografts remains difficult to diagnose and treat. Interest in AMR of cardiac allografts has increased over the last decade as it has become apparent that untreated humoral rejection threatens graft and patient survival. An international and multidisciplinary consensus group has formulated guidelines for the diagnosis and treatment of AMR and established that identification of circulating or donor-specific antibodies is not required and that asymptomatic AMR, that is, biopsy-proven AMR without cardiac dysfunction is a real entity with worsened prognosis. Strict criteria for the diagnosis of cardiac AMR have not been firmly established, although the diagnosis relies heavily on tissue pathological findings. Therapy remains largely empirical. We review an unfortunate experience with one of our patients and summarize recommended criteria for the diagnosis of AMR and potential treatment schemes with a focus on current limitations and the need for future research and innovation.

  20. Antibody-mediated rejection in heart transplantation: case presentation with a review of current international guidelines.

    Science.gov (United States)

    Pajaro, Octavio E; Jaroszewski, Dawn E; Scott, Robert L; Kalya, Anantharam V; Tazelaar, Henry D; Arabia, Francisco A

    2011-01-01

    Antibody-mediated rejection (AMR) (humoral rejection) of cardiac allografts remains difficult to diagnose and treat. Interest in AMR of cardiac allografts has increased over the last decade as it has become apparent that untreated humoral rejection threatens graft and patient survival. An international and multidisciplinary consensus group has formulated guidelines for the diagnosis and treatment of AMR and established that identification of circulating or donor-specific antibodies is not required and that asymptomatic AMR, that is, biopsy-proven AMR without cardiac dysfunction is a real entity with worsened prognosis. Strict criteria for the diagnosis of cardiac AMR have not been firmly established, although the diagnosis relies heavily on tissue pathological findings. Therapy remains largely empirical. We review an unfortunate experience with one of our patients and summarize recommended criteria for the diagnosis of AMR and potential treatment schemes with a focus on current limitations and the need for future research and innovation.

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

    Science.gov (United States)

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

    2015-07-01

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

  2. INTRAVENOUS IMMUNOGLOBULIN ADMINISTRATION FOR DESENSITIZATION BEFORE RENAL TRANSPLANTATION AND MANAGING ANTIBODY-MEDIATED REJECTION

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    A. I. Sushkov

    2011-01-01

    Full Text Available Much attention has been placed recently in transplantation in highly HLA-sensitized patients. In attempts to remove these antibodies and enable successful renal transplantation, several approaches have been developed. Intravenous immunoglobulin (IVIG was found to be effective in the treatment of autoimmune and inflammatory disorders (e. g. Kawasaki disease, Guillain-Barre syndrome. Recently, a beneficial effect of IVIG on the reduc- tion of anti-HLA antibodies was described. The anti-inflammatory effect of IVIG provides hopeful opportunities in antibody-mediated rejection (AMR management. There are several protocols of IVIG administration for pre-transplant desensitization and AMR treatment: high-dose IVIG, low-dose IVIG + plasmapheresis, IVIG + plasmapheresis + rituximab. These advancements have enabled transplantation in patients previously considered untransplantable and in concert with new diagnostic techniques has resulted in new approaches to management of AMR. 

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

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    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.

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

    Science.gov (United States)

    Cross, Amy Rachael; Glotz, Denis; Mooney, Nuala

    2018-01-01

    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.

  5. Relationship Between Albuminuria During the First Year and Antibody-Mediated Rejection in Protocol Biopsies in Kidney Transplant Recipients.

    Science.gov (United States)

    Belmar Vega, L; Rodrigo Calabia, E; Gómez Román, J J; Ruiz San Millán, J C; Martín Penagos, L; Arias Rodríguez, M

    2016-11-01

    Antibody-mediated rejection is the main cause of deterioration of kidney transplants and frequently is detected only by means of protocol biopsies. The aim of this study was to relate the presence of albuminuria throughout the 1st year to the histologic findings detected by 1-year protocol biopsies in kidney graft recipients. Retrospective observational study of 86 protocol biopsies 1 year after transplantation. Albuminuria was measured at 3, 6, 9, and 12 months in urine samples and expressed as albumin/creatinine (mg/g). Analysis of biopsies, reflected according to the Banff criteria, the following categories: fibrosis and tubular atrophy, 35 (40.7%); cellular rejection, 13 (15.1%); antibody-mediated rejection, 8 (9.3%); chronic glomerulopathy, 10 (11.6%); normal, 14 (16.3%); recurrence, 1 (1.2%); and other, 5 (5.8%). The proportions of patients with albuminuria for Banff scale scores (0 vs ≥1, respectively) at 6 and 12 months, respectively, after transplantation, were: for marker glomerulitis, 45.5% versus 59.3% (P = .021) and 36.4% versus 70.4% (P albuminuria after renal transplantation is common, especially in patients with proteinuria. Persistent albuminuria after transplantation, even at low levels, can be indicative of subclinical antibody-mediated rejection. Additional broader studies to relate the albuminuria to histologic changes observed in protocol biopsies are required. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. 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.

  7. Coincidence of cellular and antibody mediated rejection in heart transplant recipients - preliminary report.

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    Zakliczyński, Michał; Nożyński, Jerzy; Konecka-Mrówka, Dominika; Babińska, Agnieszka; Flak, Bożena; Hrapkowicz, Tomasz; Zembala, Marian

    2014-03-01

    Antibody mediated rejection (AMR) can significantly influence the results of orthotopic heart transplantation (OHT). However, AMR and cellular rejection (CR) coexistence is poorly described. Therefore we performed a prospective pilot study to assess AMR/CR concomitance in endomyocardial biopsies (EMBs) obtained electively in 27 OHT recipients (21 M/6 F, 45.4 ± 14.4 y/o). Biopsy samples were paraffin embedded and processed typically with hematoxylin/eosin staining to assess CR, and, if a sufficient amount of material remained, treated with immunohistochemical methods to localize particles C3d and C4d as markers of antibody dependent complement activation. With this approach 80 EMBs, including 41 (51%) harvested within the first month after OHT, were qualified for the study. Among them 14 (18%) were C3d+, 37 (46%) were C4d+, and 12 (15%) were both C3d and C4d positive. At least one C3d+, C4d+, and C3d/C4d+ EMB was found in 10 (37%), 17 (63%), and 8 (30%) patients, respectively. Among 37 CR0 EMBs C3d was observed in 4 (11%), C4d in 17 (46%), and both C3d/C4d in 3 (8%) cases. Among 28 CR1 EMBs C3d was observed in 3 (11%), C4d in 11 (39%), and C3d/C4d in 3 (11%) cases. Among 15 CR2 EMBs C3d was observed in 7 (47%), C4d in 9 (60%), and C3d/C4d in 6 (40%) cases. Differences in C3d and C3d/C4d occurrence between grouped CR0-1 EMBs and CR2 EMBs (7/65 - 11% vs. 7/15 - 47%; 6/65 - 9% vs. 6/15 - 40%) were significant (p = 0.0035 and p = 0.0091, respectively, χ(2) test). In conclusion, apparently frequent CR and AMR coexistence demonstrated in this preliminary study warrants further investigation in this field.

  8. Coincidence of cellular and antibody mediated rejection in heart transplant recipients – preliminary report

    Science.gov (United States)

    Nożyński, Jerzy; Konecka-Mrówka, Dominika; Babińska, Agnieszka; Flak, Bożena; Hrapkowicz, Tomasz; Zembala, Marian

    2014-01-01

    Antibody mediated rejection (AMR) can significantly influence the results of orthotopic heart transplantation (OHT). However, AMR and cellular rejection (CR) coexistence is poorly described. Therefore we performed a prospective pilot study to assess AMR/CR concomitance in endomyocardial biopsies (EMBs) obtained electively in 27 OHT recipients (21 M/6 F, 45.4 ± 14.4 y/o). Biopsy samples were paraffin embedded and processed typically with hematoxylin/eosin staining to assess CR, and, if a sufficient amount of material remained, treated with immunohistochemical methods to localize particles C3d and C4d as markers of antibody dependent complement activation. With this approach 80 EMBs, including 41 (51%) harvested within the first month after OHT, were qualified for the study. Among them 14 (18%) were C3d+, 37 (46%) were C4d+, and 12 (15%) were both C3d and C4d positive. At least one C3d+, C4d+, and C3d/C4d+ EMB was found in 10 (37%), 17 (63%), and 8 (30%) patients, respectively. Among 37 CR0 EMBs C3d was observed in 4 (11%), C4d in 17 (46%), and both C3d/C4d in 3 (8%) cases. Among 28 CR1 EMBs C3d was observed in 3 (11%), C4d in 11 (39%), and C3d/C4d in 3 (11%) cases. Among 15 CR2 EMBs C3d was observed in 7 (47%), C4d in 9 (60%), and C3d/C4d in 6 (40%) cases. Differences in C3d and C3d/C4d occurrence between grouped CR0-1 EMBs and CR2 EMBs (7/65 – 11% vs. 7/15 – 47%; 6/65 – 9% vs. 6/15 – 40%) were significant (p = 0.0035 and p = 0.0091, respectively, χ2 test). In conclusion, apparently frequent CR and AMR coexistence demonstrated in this preliminary study warrants further investigation in this field. PMID:26336395

  9. Antibody-Mediated Rejection of the Heart in the Setting of Autoimmune Demyelinating Polyneuropathy: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Kathryn J. Lindley

    2012-01-01

    Full Text Available Background. Antibody-mediated rejection (AMR is caused by the production of donor-specific antibodies (DSA which lead to allograft injury in part via complement activation. The inflammatory demyelinating polyneuropathies (IDP are inflammatory disorders of the nervous system, involving both cellular and humoral immune mechanisms directed against myelin. Case Report. A 58-year-old man five years after heart transplant presented with progressive dyspnea, imbalance, dysphagia, and weakness. Nerve conduction studies and electromyogram were consistent with IDP. Plasmapheresis and high-dose steroids resulted in improvement in neurologic symptoms. Within two weeks, he was readmitted with anasarca and acute renal failure, requiring intravenous furosemide and inotropic support. Echocardiogram and right heart catheterization revealed reduced cardiac function and elevated filling pressures. DSA was positive against HLA DR53, and endomyocardial biopsy revealed grade 1R chronic inflammation, with strong capillary endothelial immunostaining for C4d. Plasmapheresis and intravenous immunoglobulin (IVIG were initiated. His anasarca and renal failure subsequently resolved, echocardiogram showed improved function off inotropes, and anti-DR53 MFI was reduced by 57%. Conclusions. This is an example of a single immune-mediated process causing concurrent IDP and AMR. The improvement in cardiac function and neurologic symptoms with plasmapheresis, IVIG, and high-dose steroids argues for a unifying antibody-mediated mechanism.

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

    Directory of Open Access Journals (Sweden)

    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

  11. The 2013 International Society for Heart and Lung Transplantation Working Formulation for the standardization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation

    DEFF Research Database (Denmark)

    Berry, Gerald J; Burke, Margaret M; Andersen, Claus Yding

    2013-01-01

    -2012 to develop a Working Formulation for the pathologic diagnosis, grading, and reporting of cardiac antibody-mediated rejection. The diagnostic criteria for its morphologic and immunopathologic components are enumerated, illustrated, and described in detail. Numerous challenges and unresolved clinical......, immunologic, and pathologic questions remain to which a Working Formulation may facilitate answers....

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

    Directory of Open Access Journals (Sweden)

    Silvia Pineda

    2017-12-01

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

  13. Noninvasive Imaging of Acute Renal Allograft Rejection by Ultrasound Detection of Microbubbles Targeted to T-lymphocytes in Rats.

    NARCIS (Netherlands)

    Grabner, A.; Kentrup, D.; Mühlmeister, M.; Pawelski, H.; Biermann, C.; Bettinger, T.; Pavenstadt, H.; Schlatter, E.; Tiemann, K.; Reuter, S.

    2016-01-01

    PURPOSE: We propose CD3-antibody-mediated contrast-enhanced ultrasonography using human T-lymphocytes for image-based diagnosis of acute allograft rejection (AR) established in a rat renal transplantation model. MATERIALS AND METHODS: 15 minutes after tail vein injection of 30 x 10(6) human

  14. Plasma Exosomes From HLA-Sensitized Kidney Transplant Recipients Contain mRNA Transcripts Which Predict Development of Antibody-Mediated Rejection.

    Science.gov (United States)

    Zhang, Hao; Huang, Edmund; Kahwaji, Joseph; Nast, Cynthia C; Li, Ping; Mirocha, James; Thomas, David L; Ge, Shili; Vo, Ashley A; Jordan, Stanley C; Toyoda, Mieko

    2017-10-01

    Sensitization to HLA remains a significant immunologic barrier to successful transplantation. Identifying immune mechanisms responsible for antibody-mediated rejection (AMR) is an important goal. Here, we explored the possibility of predicting the risk for AMR by measuring mRNA transcripts of AMR-associated genes in plasma exosomes from kidney transplant patients. Total RNA was extracted from exosomes purified from 152 ethylenediaminetetraacetic acid-plasma samples of 64 patients (18 AMR, 8 cell-mediated rejection [CMR], 38 no rejection in desensitized [DES] and non-DES control groups) for reverse transcription into cDNA, preamplification and then real time quantitative polymerase chain reaction (qPCR) for 21 candidate genes. The mRNA transcript levels of each gene were calculated. Comparisons were made among 4 patient groups for each gene and also for a gene combination score based on selected genes. Among 21 candidate genes, we identified multiple genes (gp130, CCL4, TNFα, SH2D1B, CAV1, atypical chemokine receptor 1 [duffy blood group]) whose mRNA transcript levels in plasma exosomes significantly increased among AMR compared with CMR and/or control patients. A gene combination score calculated from 4 genes of gp130, SH2D1B, TNFα, and CCL4 was significantly higher in the AMR than the CMR (P exosomes may contain information indicating clinical conditions of kidney transplant patients. mRNA transcript profiles based on gp130, SH2D1B, TNFα, and CCL4 in plasma exosomes may be used to predict on-going and/or imminent AMR.

  15. Antibody-mediated rejection after ABO-incompatible pediatric living donor liver transplantation for propionic acidemia: A case report.

    Science.gov (United States)

    Honda, Masaki; Sakamoto, Seisuke; Sakamoto, Rieko; Matsumoto, Shirou; Irie, Tomoaki; Uchida, Koushi; Shimata, Keita; Kawabata, Seiichi; Isono, Kaori; Hayashida, Shintaro; Yamamoto, Hidekazu; Endo, Fumio; Inomata, Yukihiro

    2016-09-01

    We herein present the case of a four-yr-old boy with PA who developed AMR after ABO-incompatible LDLT despite undergoing B cell desensitization using rituximab. Although the CD19+ lymphocyte count decreased to 0.1% nine days after the administration of rituximab, he developed a high fever which was accompanied by arthralgia due to a streptococcal infection 13 days after rituximab prophylaxis. After the clearance of the infection, he underwent ABO-incompatible LDLT 36 days after the administration of rituximab. The CD19+ lymphocyte count just prior to LDLT was 1.2%. He developed AMR five days after LDLT, and the antidonor-type IgM and IgG antibody titers increased to 1:1024 and 1:1024, respectively. He was treated by plasma exchange, IVIG, steroid pulse therapy, and rituximab re-administration; however, his liver dysfunction continued. Despite intensive treatment, he died due to complicated abdominal hernia, acute renal failure, and ARDS. This case suggests that a streptococcal infection may induce the activation of innate immune responses; thus, additional desensitization therapy should be considered prior to ABO-incompatible LDLT if B cell reactivation is suspected. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. MiR-142-5p and miR-486-5p as biomarkers for early detection of chronic antibody-mediated rejection in kidney transplantation.

    Science.gov (United States)

    Iwasaki, Kenta; Yamamoto, Takayuki; Inanaga, Yukiko; Hiramitsu, Takahisa; Miwa, Yuko; Murotani, Kenta; Narumi, Shuji; Watarai, Yoshihiko; Katayama, Akio; Uchida, Kazuharu; Kobayashi, Takaaki

    2017-02-01

    De novo donor-specific HLA antibody (DSA) would not necessarily contribute to chronic antibody-mediated rejection (CAMR) in kidney transplantation. Here, we investigated whether PBMC miRNAs could be predictable biomarkers for CAMR. Microarray profiling of 435 mature miRNAs in pooled samples was conducted. Individual analysis revealed that miR-142-5p was significantly (p biomarkers to evaluate immune response and kidney allograft status.

  17. The Effect of Combination Therapy with Rituximab and Intravenous Immunoglobulin on the Progression of Chronic Antibody Mediated Rejection in Renal Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Gun Hee An

    2014-01-01

    Full Text Available The treatment for chronic active antibody-mediated rejection (CAMR remains controversial. We investigated the efficacy of rituximab (RTX and intravenous immunoglobulin (IVIg for CAMR. Eighteen patients with CAMR were treated with RTX (375 mg/m2 and IVIg (0.4 g/kg for 4 days. The efficacy of RTX/IVIg combination therapy (RIT was assessed by decline in estimated glomerular filtration rate per month (ΔeGFR before and after RIT. Patients were divided into responder and nonresponder groups based on decrease and no decrease in ΔeGFR, respectively, and their clinical and histological characteristics were compared. Response rate to RIT was 66.7% (12/18, and overall ΔeGFR decreased significantly to 0.4± 1.7 mL·min−1·1.73 m−2 per month 6 months after RIT compared to that observed 6 months before RIT (1.8±1.0, P<0.05. Clinical and histological features between the 12 responders and the 6 nonresponders were not significantly different, but nonresponders had a significantly higher proteinuria levels at the time of RIT (2.5±2.5 versus 7.0±3.5 protein/creatinine (g/g, P<0.001. The effect of the RIT on ΔeGFR had dissipated in all patients by 1 year post-RIT. Thus, RIT delayed CAMR progression, and baseline proteinuria level was a prognostic factor for response to RIT.

  18. HLA-C antibodies in women with recurrent miscarriage suggests that antibody mediated rejection is one of the mechanisms leading to recurrent miscarriage

    NARCIS (Netherlands)

    Meuleman, T.; van Beelen, E.; Kaaja, R. J.; van Lith, J. M. M.; Claas, F. H. J.; Bloemenkamp, K. W. M.

    2016-01-01

    HLA-C is the only polymorphic classical HLA I antigen expressed on trophoblast cells. It is known that higher incidence of C4d deposition on trophoblast cells is present in women with recurrent miscarriage. C4d is a footprint of antibody-mediated classical complement activation. Therefore, this

  19. HLA-C antibodies in women with recurrent miscarriage suggests that antibody mediated rejection is one of the mechanisms leading to recurrent miscarriage

    NARCIS (Netherlands)

    Meuleman, T; van Beelen, E; Kaaja, R J; van Lith, J M M; Claas, F H J; Bloemenkamp, K W M

    HLA-C is the only polymorphic classical HLA I antigen expressed on trophoblast cells. It is known that higher incidence of C4d deposition on trophoblast cells is present in women with recurrent miscarriage. C4d is a footprint of antibody-mediated classical complement activation. Therefore, this

  20. Ultrastructural basis of acute renal allograft rejection

    NARCIS (Netherlands)

    V.D. Vuzevski (Vojislav)

    1976-01-01

    textabstractAn attempt was made: I. to demonstrate the evolution and the time of onset of the ultrastructural morphological changes in the renal parenchyma and blood vessels, as well as the ultrastructural feature of the interstitial cellular infiltration in acute rejection of kidney allografts; 2.

  1. THE DIAGNOSIS OF LIVER ALLOGRAFT ACUTE REJECTION IN LIVER BIOPSIES

    Directory of Open Access Journals (Sweden)

    L. V. Shkalova

    2011-01-01

    Full Text Available We performed histological examination of 80 liver allograft biopsies, the diagnosis of acute rejection was proved in 34 cases. Histological changes in liver biopsies in different grades of acute rejection were estimated according to Banff classification 1995, 1997 and were compared with current literature data. The article deals with the question of morphological value of grading acute rejection on early and late, also we analyze changes in treat- ment tactics after morphological verification of liver allograft acute rejection

  2. HLA-C antibodies in women with recurrent miscarriage suggests that antibody mediated rejection is one of the mechanisms leading to recurrent miscarriage.

    Science.gov (United States)

    Meuleman, T; van Beelen, E; Kaaja, R J; van Lith, J M M; Claas, F H J; Bloemenkamp, K W M

    2016-08-01

    HLA-C is the only polymorphic classical HLA I antigen expressed on trophoblast cells. It is known that higher incidence of C4d deposition on trophoblast cells is present in women with recurrent miscarriage. C4d is a footprint of antibody-mediated classical complement activation. Therefore, this study hypothesize that antibodies against HLA-C may play a role in the occurrence of unexplained consecutive recurrent miscarriage. Present case control study compared the incidence of HLA-C specific antibodies in 95 women with at least three consecutive miscarriages and 105 women with uneventful pregnancy. In the first trimester of the next pregnancy, presence and specificity of HLA antibodies were determined and their complement fixing ability. The incidence of HLA antibodies was compared with uni- and multivariate logistic regression models adjusting for possible confounders. Although in general a higher incidence of HLA antibodies was found in women with recurrent miscarriage 31.6% vs. in control subjects 9.5% (adjusted OR 4.3, 95% CI 2.0-9.5), the contribution of antibodies against HLA-C was significantly higher in women with recurrent miscarriage (9.5%) compared to women with uneventful pregnancy (1%) (adjusted OR 11.0, 95% CI 1.3-89.0). In contrast to the control group, HLA-C antibodies in the recurrent miscarriage group were more often able to bind complement. The higher incidence of antibodies specific for HLA-C in women with recurrent miscarriage suggests that HLA-C antibodies may be involved in the aetiology of unexplained consecutive recurrent miscarriage. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. 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.

  4. Acute appendicitis mistaken as acute rejection in renal transplant recipients.

    Directory of Open Access Journals (Sweden)

    Talwalkar N

    1994-01-01

    Full Text Available Case histories of 2 renal transplant recipients are reported who had presenting features of fever, leukocytosis and pain/tenderness over right iliac fossa and were diagnosed to be due to acute appendicitis rather than more commonly suspected acute rejection episode which has very similar features. Diagnosis of acute appendicitis was suspected on the basis of rectal examination and later confirmed by laparotomy. The purpose of this communication is to emphasize the need for proper diagnosis in patient with such presentation; otherwise wrong treatment may be received.

  5. Impacts of donor-specific anti-HLA antibodies and antibody-mediated rejection on outcomes after intestinal transplantation in children.

    Science.gov (United States)

    Petit, L-M; Rabant, M; Canioni, D; Suberbielle-Boissel, C; Goulet, O; Chardot, C; Lacaille, F

    2017-03-01

    AMR is a risk factor for graft failure after SBTx. We studied impact of DSAs and AMR in 22 children transplanted between 2008 and 2012 (11 isolated SBTx, 10 liver inclusive Tx, and one modified multivisceral Tx). Three patients never developed DSA, but DSAs were found in seven in the pre-Tx period and de novo post-Tx in 19 children. Pathology revealed cellular rejection (15/19), with vascular changes and C4d+. Patients were treated with IV immunoglobulins, plasmapheresis, and steroids. Rescue therapy included antithymocyte globulins, rituximab, eculizumab, and bortezomib. Pathology and graft function normalized in 13 patients, graft loss occurred in two, and death in seven. At the end of the follow-up, 15 children were alive (68%), 13 with functioning graft (59%). Prognosis factors for poor outcome after Tx were the presence of symptoms at AMR suspicion (P +.033). DSAs were often found following SBTx, mostly de novo. Resistant ACR or severe AMR is still difficult to differentiate, with a high need for immunosuppression in both. DSAs may precede development of severe disease and pathology features on the graft: relationship and correlation need to be better investigated with larger groups before and after Tx. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. 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

  7. Fractal analysis of heart graft acute rejection microscopic images.

    Science.gov (United States)

    Pijet, M; Nozynski, J; Konecka-Mrowka, D; Zakliczynski, M; Hrapkowicz, T; Zembala, M

    2014-10-01

    Endomyocardial biopsy to evaluate rejection in the transplanted heart is accepted at the "gold standard." The complexity of microscopic images suggested using digital methods for precise evaluating of acute rejection episodes with numerical representation. The aim of the present was study to characterize digitally acute rejection of the transplanted heart using complexity/fractal image analysis. Biopsy samples harvested form 40 adult recipients after orthotropic heart transplantation were collected and rejection grade was evaluated according to the International Society for Heart and Lung Transplantation (0, 1a, 1b, or 3a) at transverse and longitudinal sections. Fifteen representative digital microscope images from each grade were collected and analyzed after Sobel edge detection and binarization. Only mean fractal dimension showed a progressive and significant increase and correlation based on rejection grade using longitudinal sections. Lacunarity and number of foreground pixels showed unequivocal results. Mean fractal diameter could serve as auxiliary digital parameter for grading of acute rejection in the transplanted heart.

  8. Alteration of Cardiac Deformation in Acute Rejection in Pediatric Heart Transplant Recipients.

    Science.gov (United States)

    Chanana, Nitin; Van Dorn, Charlotte S; Everitt, Melanie D; Weng, Hsin Yi; Miller, Dylan V; Menon, Shaji C

    2017-04-01

    The objective of this study is to assess changes in cardiac deformation during acute cellular- and antibody-mediated rejection in pediatric HT recipients. Pediatric HT recipients aged ≤18 years with at least one episode of biopsy-diagnosed rejection from 2006 to 2013 were included. Left ventricular systolic S (SS) and SR (SSr) data were acquired using 2D speckle tracking on echocardiograms obtained within 12 h of right ventricular endomyocardial biopsy. A mixed effect model was used to compare cardiac deformation during CR (Grade ≥ 1R), AMR (pAMR ≥ 2), and mixed rejection (CR and AMR positive) versus no rejection (Grade 0R and pAMR 0 or 1). A total of 20 subjects (10 males, 50%) with 71 rejection events (CR 35, 49%; AMR 21, 30% and mixed 15, 21%) met inclusion criteria. The median time from HT to first biopsy used for analysis was 5 months (IQR 0.25-192 months). Average LV longitudinal SS and SSr were reduced significantly during rejection (SS: -17.2 ± 3.4% vs. -10.7 ± 4.5%, p < 0.001 and SSr: -1.2 ± 0.2 s(- 1) vs. -0.9 ± 0.3 s(- 1); p < 0.001) and in all rejection types. Average LV short-axis radial SS was reduced only in CR compared to no rejection (p = 0.04), while average LV circumferential SS and SSr were reduced significantly in AMR compared to CR (SS: 18.9 ± 4.2% vs. 20.8 ± 8.8%, p = 0.03 and SSr: 1.35 ± 0.8 s(- 1) vs. 1.54 ± 0.9 s(- 1); p = 0.03). In pediatric HT recipients, LV longitudinal SS and SSr were reduced in all rejection types, while LV radial SS was reduced only in CR. LV circumferential SS and SSr further differentiated between CR and AMR with a significant reduction seen in AMR as compared to CR. This novel finding suggests mechanistic differences between AMR- and CR-induced myocardial injury which may be useful in non-invasively predicting the type of rejection in pediatric HT recipients.

  9. Acute rejection and humoral sensitization in lung transplant recipients.

    Science.gov (United States)

    Martinu, Tereza; Chen, Dong-Feng; Palmer, Scott M

    2009-01-15

    Despite the recent introduction of many improved immunosuppressive agents for use in transplantation, acute rejection affects up to 55% of lung transplant recipients within the first year after transplant. Acute lung allograft rejection is defined as perivascular or peribronchiolar mononuclear inflammation. Although histopathologic signs of rejection often resolve with treatment, the frequency and severity of acute rejections represent the most important risk factor for the subsequent development of bronchiolitis obliterans syndrome (BOS), a condition of progressive airflow obstruction that limits survival to only 50% at 5 years after lung transplantation. Recent evidence demonstrates that peribronchiolar mononuclear inflammation (also known as lymphocytic bronchiolitis) or even a single episode of minimal perivascular inflammation significantly increase the risk for BOS. We comprehensively review the clinical presentation, diagnosis, histopathologic features, and mechanisms of acute cellular lung rejection. In addition, we consider emerging evidence that humoral rejection occurs in lung transplantation, characterized by local complement activation or the presence of antibody to donor human leukocyte antigens (HLA). We discuss in detail methods for HLA antibody detection as well as the clinical relevance, the mechanisms, and the pathologic hallmarks of humoral injury. Treatment options for cellular rejection include high-dose methylprednisolone, antithymocyte globulin, or alemtuzumab. Treatment options for humoral rejection include intravenous immunoglobulin, plasmapheresis, or rituximab. A greater mechanistic understanding of cellular and humoral forms of rejection and their role in the pathogenesis of BOS is critical in developing therapies that extend long-term survival after lung transplantation.

  10. 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.

  11. Right Ventricular Dysfunction as an Echocardiographic Measure of Acute Rejection Following Heart Transplantation in Children.

    Science.gov (United States)

    Aggarwal, Sanjeev; Blake, Jennifer; Sehgal, Swati

    2017-03-01

    Noninvasive biomarkers of acute allograft rejection (AAR) following orthotopic heart transplantation (OHT) are needed. The aim of this study was to investigate the accuracy of echocardiographic (ECHO) right ventricular (RV) global functional and resistance indices in the detection of AAR. This retrospective chart review included children with biopsy-proven AAR (grade ≥ 2R cellular or CD4 + antibody-mediated rejection) following OHT and an ECHO within 12 h of the biopsy. ECHO measures: (a) ratio of systolic to diastolic duration (S/D), (b) RV myocardial performance index (MPI) and (c) tricuspid regurgitant gradient to RV outflow tract velocity time integral ratio (TRG/VTI), were derived at baseline, during AAR and at two follow-ups. Sixteen patients [56% male, mean (SD) age at OHT 3.5 (4.3) years] had 16 AAR episodes. S/D (1.15 vs. 1.60, p < 0.01), RV MPI (0.19 vs. 0.39, p < 0.01) and TRG/VTI (1.05 vs. 1.7, p = 0.01) deteriorated during AAR and, except for diastolic duration, improved significantly at first follow-up. The negative predictive values for S/D, RV MPI and TRG/VTI at cutoffs of 1.3, 0.31 and 1.3 were 97, 97 and 87%, respectively. RV S/D, MPI and TRG/VTI deteriorated during AAR. Their excellent negative predictive values suggest that their incorporation in surveillance may obviate the need for routine biopsies.

  12. Salivary cortisol in response to acute social rejection and acceptance by peers.

    Science.gov (United States)

    Blackhart, Ginette C; Eckel, Lisa A; Tice, Dianne M

    2007-07-01

    Past research indicates that social rejection predicts a wide range of psychological problems (e.g., depression), but laboratory studies examining self-reports of negative affect after social rejection have reported inconsistent results. Salivary cortisol was measured before and after a social rejection/acceptance manipulation for objective assessment of psychological distress subsequent to peer rejection. Rejected participants were predicted to show significantly greater salivary cortisol than accepted or control participants. The present research also examined several factors that may moderate the relationship between acute rejection and cortisol. As predicted, rejected participants exhibited significantly higher cortisol than accepted or control participants. Defensiveness moderated the relationship between rejection and cortisol; highly defensive rejected participants showed significantly lower cortisol than less defensive rejected participants after peer rejection. Results indicate that social rejection causes psychological distress, but highly defensive individuals appear to be less susceptible than less defensive individuals to increases in salivary cortisol after acute social rejection.

  13. Multiquadrant Subtenon Triamcinolone Injection for Acute Corneal Graft Rejection: A Case Report

    Directory of Open Access Journals (Sweden)

    Sunali Goyal

    2017-05-01

    Full Text Available Background: We report a case of reversal of an acute corneal graft rejection following multiquadrant subtenon triamcinolone injection. Case Presentation: A 19-year-old woman who had acute corneal graft rejection failed to show resolution of the graft rejection after standard treatment with systemic, intravenous, and topical steroids. The graft rejection, however, responded to injection of triamcinolone in multiple subtenon quadrants. Conclusions: For corneal graft rejection, multiquadrant subtenon triamcinolone injections may be a safe adjunct to systemic treatment.

  14. Rejection

    National Research Council Canada - National Science Library

    Black, Mary

    2007-01-01

    .... [...]my long term favourite story comes from Ireland, where in the chaotic, jobless mid-1980s one friend applied for everything going and then wallpapered his bathroom with the rejection letters...

  15. 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.

  16. Increased C4d in post-reperfusion biopsies and increased donor specific antibodies at one-week post transplant are risk factors for acute rejection in mild to moderately sensitized kidney transplant recipients

    Science.gov (United States)

    Djamali, Arjang; Muth, Brenda; Ellis, Thomas M.; Mohamed, Maha; Fernandez, Luis; Miller, Karen; Bellingham, Janet; Odorico, Jon; Mezrich, Joshua; Pirsch, John; D’Alessandro, Tony; Vidyasagar, Vijay; Hofmann, R. Michael; Torrealba, Jose; Kaufman, Dixon; Foley, David

    2013-01-01

    In order to define the intensity of immunosuppression, we examined risk factors for acute rejection in desensitization protocols that use baseline donor specific antibody levels measured as mean fluorescence intensity (MFImax). The study included 146 patients transplanted with a negative flow crossmatch and a mean follow-up of 18 months with the majority (83%) followed for at least 1 year. At the time of transplant, mean calculated panel reactive antibody and MFImax ranged from 10.3% to 57.2%, and 262 to 1691, respectively, between low and high-risk protocols. Mean MFImax increased significantly from transplant to one-week and one-year. The incidence of acute rejection (mean 1.65 months) as a combination of clinical and subclinical rejection was 32% including 14% cellular, 12% antibody-mediated and 6% mixed rejection. In regression analyses, only C4d staining in post-reperfusion biopsies (hazard ratio 3.3, confidence interval 1.71 to 6.45) and increased donor specific antibodies at 1 week post-transplant were significant predictors of rejection. A rise in MFImax by 500 was associated with a 2.8-fold risk of rejection. Thus, C4d staining in post-reperfusion biopsies and an early rise in donor specific antibodies after transplantation are risk factors for rejection in moderately sensitized patients. PMID:23447068

  17. Shotgun Proteomics Identifies Proteins Specific for Acute Renal Transplant Rejection

    Energy Technology Data Exchange (ETDEWEB)

    Sigdel, Tara K.; Kaushal, Amit; Gritsenko, Marina A.; Norbeck, Angela D.; Qian, Weijun; Xiao, Wenzhong; Camp, David G.; Smith, Richard D.; Sarwal, Minnie M.

    2010-01-04

    Acute rejection (AR) remains the primary risk factor for renal transplant outcome; development of non-invasive diagnostic biomarkers for AR is an unmet need. We used shotgun proteomics using LC-MS/MS and ELISA to analyze a set of 92 urine samples, from patients with AR, stable grafts (STA), proteinuria (NS), and healthy controls (HC). A total of 1446 urinary proteins were identified along with a number of NS specific, renal transplantation specific and AR specific proteins. Relative abundance of identified urinary proteins was measured by protein-level spectral counts adopting a weighted fold-change statistic, assigning increased weight for more frequently observed proteins. We have identified alterations in a number of specific urinary proteins in AR, primarily relating to MHC antigens, the complement cascade and extra-cellular matrix proteins. A subset of proteins (UMOD, SERPINF1 and CD44), have been further cross-validated by ELISA in an independent set of urine samples, for significant differences in the abundance of these urinary proteins in AR. This label-free, semi-quantitative approach for sampling the urinary proteome in normal and disease states provides a robust and sensitive method for detection of urinary proteins for serial, non-invasive clinical monitoring for graft rejection after

  18. Changes in the serum levels of interleukin-17/interleukin-23 during acute rejection in liver transplantation.

    Science.gov (United States)

    Fábrega, Emilio; López-Hoyos, Marcos; San Segundo, David; Casafont, Fernando; Pons-Romero, Fernando

    2009-06-01

    Interleukin-23 (IL-23) and T helper 17 (Th17) cells have been cast as major players in autoimmunity, but their role in transplantation immunity remains to be specified. The aim of our study was to investigate the time course of serum levels of IL-23 and IL-17 during hepatic allograft rejection. Serum levels of IL-23 and IL-17 were determined in 20 healthy subjects and 50 hepatic transplant recipients. These patients were divided into 2 groups: group I was composed of 15 patients with acute rejection, and group II was composed of 35 patients without acute rejection. Samples were collected on days 1 and 7 after liver transplantation and on the day of liver biopsy. The concentrations of IL-23 were similar for the rejection group and nonrejection group at early postoperative times. We observed a significant increase in serum IL-23 levels in the rejection group when a diagnosis of acute rejection had been established. Similarly to IL-23, at the diagnosis of acute rejection, the concentration of IL-17 was significantly higher in the rejection group versus the nonrejection group. The whole transplant group, including those with stable graft function, had higher serum levels of IL-23 and IL-17 than the controls during the entire postoperative period. In conclusion, IL-23 and IL-17 are up-regulated during acute hepatic rejection. These findings suggest a role for Th17 cells in human liver allograft rejection. (c) 2009 AASLD.

  19. Biopsy-proven acute cellular rejection as an efficacy endpoint of randomized trials in liver transplantation: a systematic review and critical appraisal.

    Science.gov (United States)

    Rodríguez-Perálvarez, Manuel; Rico-Juri, Jose M; Tsochatzis, Emmanuel; Burra, Patrizia; De la Mata, Manuel; Lerut, Jan

    2016-09-01

    Biopsy-proven acute cellular rejection (ACR) is the primary efficacy endpoint in most randomized trials evaluating immunosuppression in liver transplantation. However, ACR is not a major cause of graft loss, and a certain grade of immune activation may be even beneficial for long-term graft acceptance. Validated criteria to select candidates for liver biopsy are lacking, and routine clinical practice relies on liver tests, which are inaccurate markers of ACR. Indeed, both the agreement among clinicians to select candidates for liver biopsy and the correlation between the clinical suspicion of ACR and histological findings are poor. In randomized trials evaluating immunosuppression protocols, this concern grows exponentially due to the open-label and multicenter nature of most studies. Therefore, biopsy-proven ACR is a suboptimal efficacy endpoint given its limited impact on prognosis and the heterogeneous diagnosis, which may increase the risk of bias. Chronic rejection and/or graft loss would be more appropriate endpoints, but would certainly require larger studies with prolonged surveillances. An objective method to select candidates for liver biopsy is therefore urgently needed, and only severe episodes of histological ACR should be considered as potentially harmful. Emerging surrogate markers of ACR and antibody-mediated rejection require further investigation to determine their clinical role. © 2015 Steunstichting ESOT.

  20. Cellular mechanisms underlying acute graft rejection: time for reassessment

    NARCIS (Netherlands)

    Alegre, Maria-Luisa; Florquin, Sandrine; Goldman, Michel

    2007-01-01

    Rejection of transplanted organs depends on an orchestrated immune response to histocompatibility antigens expressed by the grafted tissue. Effector mechanisms primarily responsible for the rejection process classically involve type 1 helper CD4(+) T cells, cytotoxic CD8(+) T cells and antibodies.

  1. Selective treatment of early acute rejection after liver transplantation : Effects on liver, infection rate, and outcome

    NARCIS (Netherlands)

    Klompmaker, IJ; Gouw, ASH; Haagsma, EB; TenVergert, EM; Verwer, R; Slooff, MJH

    To evaluate the results of selective treatment of biopsy-proven mild acute rejection episodes, we retrospectively studied 1-week liver biopsies of 103 patients with a primary liver graft in relation to liver function tests. The overall incidence of rejection was 35 %. In four patients the biopsy

  2. Relationship between acute rejection and cyclosporine or mycophenolic acid levels in Japanese heart transplantation.

    Science.gov (United States)

    Wada, Kyoichi; Takada, Mitsutaka; Ueda, Takashi; Ochi, Hiroyuki; Kotake, Takeshi; Morishita, Hideki; Hanatani, Akihisa; Nakatani, Takeshi

    2007-03-01

    Cyclosporine (CsA), Mycophenolate mofetil (MMF) and prednisolone (PSL) are widely used for the prevention of acute rejection after heart transplantation. Recently, the serum concentration - time curves (AUC) of CsA and MMF have been demonstrated to be precise predictors of acute rejection. Fourteen heart transplant patients were treated concomitantly with CsA, MMF, and PSL between May 1999 and November 2005 at the National Cardiovascular Center and of them 3 had acute rejection episodes [International Society for Heart & Lung Transplantation grade 3a]. Two patients (man in his 30 s; woman in her 40 s) had acute rejection with a mycophenolic acid (MPA) AUC(0-12 h) cardiac allograft rejection even if the MMF was temporarily stopped. These 3 patients were investigated to evaluate the relationship between acute rejection and pharmacokinetic parameters, including the CsA C0, C2, AUC(0-4 h) and MPA AUC(0-12 h). The findings suggest that a high CsA AUC(0-4 h) may prevent rejection of a cardiac allograft, even if MMF is stopped or drastically reduced.

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

    Science.gov (United States)

    Roedder, Silke; Sigdel, Tara; Hsieh, Szu-Chuan; Cheeseman, Jennifer; Metes, Diana; Macedo, Camila; Reed, Elaine F.; Gritsch, H. A.; Zeevi, Adriana; Shapiro, Ron; Kirk, Allan D.; Sarwal, Minnie M.

    2017-01-01

    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) 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. PMID:29164120

  4. 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.

  5. Impact of the addition of maintenance steroids to a rapid steroid discontinuation immunosuppressive protocol following acute renal transplant rejection.

    Science.gov (United States)

    Arora, Swati; Marcus, Richard J; Dikkala, Sudharani; Sureshkumar, Kalathil K

    2009-12-01

    Rapid steroid discontinuation immunosuppressive protocols are increasingly used in renal transplant. The optimal immunosuppressive regimen in patients who develop acute rejection while on a rapid steroid discontinuation protocol is less clear. We examined our experience of adding maintenance steroid therapy in renal transplant recipients who developed 1 or more acute rejection episode while on a rapid steroid discontinuation protocol. The outcome of 145 patients who underwent renal transplant from 2002 to 2007 and initiated a rapid steroid discontinuation protocol was analyzed. Patients were divided into the following 5 groups: (i): acute rejection X 1 and no maintenance steroids, (ii): acute rejection X 1 and started on maintenance steroids, (iii): acute rejection X 2 and no maintenance steroids (iv): acute rejection X 2 and started on maintenance steroids, and (v): no acute rejection Compared with patients with no acute rejection, graft survival was significantly inferior in patients who experienced 2 or more acute rejection episodes-whether they were started on maintenance steroids (P = .003) or not (P = .006) - but was similar in patients who experienced only 1 episode of acute rejection, and were started either on maintenance steroids (P = .87) or were continued on the rapid steroid discontinuation protocol (P = .69). In patients who sustained 2 episodes of acute rejection, addition of maintenance steroids had no impact on graft survival (P = .97). More than 1 episode of acute rejection in renal transplant recipients on rapid steroid discontinuation protocol is associated with poor, long-term, graft survival, which remains unchanged despite starting maintenance steroids. The use of maintenance steroids may not have a positive impact on graft survival after acute rejection.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Ultrasound molecular imaging of acute cardiac transplantation rejection using nanobubbles targeted to T lymphocytes.

    Science.gov (United States)

    Liu, Jinfeng; Chen, Yihan; Wang, Guohua; Lv, Qing; Yang, Yali; Wang, Jing; Zhang, Pingyu; Liu, Jie; Xie, Yu; Zhang, Li; Xie, Mingxing

    2018-02-08

    Clinical surveillance of acute heart transplantation rejection requires repeated invasive endomyocardial biopsies and noninvasive diagnostic techniques are desperately needed. It is acknowledged that T lymphocyte infiltration is the central process of acute rejection. We hypothesized that ultrasound molecular imaging with T lymphocyte-targeted nanobubbles could be used to detect acute rejection in heart transplantation. In this study, nanobubbles bearing anti-CD3 antibody (NB CD3 ) or isotype antibody (NB con ) were prepared and characterized. There was significant adhesion of NB CD3 to T lymphocytes compared with NB con in vitro. The signal intensity of the adherent NB CD3 was significantly higher than that of the NB con in allograft rats, but not significantly different in isograft rats. Furthermore, the signal intensity of NB CD3 in allograft rats was significantly higher than that in isograft rats, indicating more T lymphocyte infiltration in allograft rats compared with isograft rats. These results were further confirmed by immunohistochemistry examination, and the signal intensity of NB CD3 was positively correlated with the number of T lymphocytes in allograft rats. In summary, ultrasound molecular imaging with T lymphocyte-targeted nanobubbles can detect T lymphocyte infiltration in acute rejection and could be used as a noninvasive method in acute rejection detection after cardiac transplantation. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Priscila Cilene León Bueno de Camargo

    2014-08-01

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

  9. T cell immunohistochemistry refines lung transplant acute rejection diagnosis and grading.

    Science.gov (United States)

    Cheng, Lin; Guo, Haizhou; Qiao, Xinwei; Liu, Quan; Nie, Jun; Li, Jinsong; Wang, Jianjun; Jiang, Ke

    2013-10-14

    Lung transplant volume has been increasing. However, inaccurate and uncertain diagnosis for lung transplant rejection hurdles long-term outcome due to, in part, interobserver variability in rejection grading. Therefore, a more reliable method to facilitate diagnosing and grading rejection is warranted. Rat lung grafts were harvested on day 3, 7, 14 and 28 post transplant for histological and immunohistochemical assessment. No immunosuppressive treatment was administered. We explored the value of interstitial T lymphocytes quantification by immunohistochemistry and compared the role of T cell immunohistochemistry with H&E staining in diagnosing and grading lung transplant rejection. Typical acute rejection from grade A1 to A4 was found. Rejection severity was heterogeneously distributed in one-third transplanted lungs (14/40): lesions in apex and center were more augmented than in the base and periphery of the grafts, respectively. Immunohistochemistry showed profound difference in T lymphocyte infiltration among grade A1 to A4 rejections. The coincidence rate of H&E and immunohistochemistry was 77.5%. The amount of interstitial T lymphocyte infiltration increased gradually with the upgrading of rejection. The statistical analysis demonstrated that the difference in the amount of interstitial T lymphocytes between grade A2 and A3 was not obvious. However, T lymphocytes in lung tissue of grade A4 were significantly more abundant than in other grades. Rejection severity was heterogeneously distributed within lung grafts. Immunohistochemistry improves the sensitivity and specificity of rejection diagnosis, and interstitial T lymphocyte quantitation has potential value in diagnosing and monitoring lung allograft rejection. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1536075282108217.

  10. 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.

  11. Delta Neutrophil Index as a Marker for Differential Diagnosis between Acute Graft Pyelonephritis and Acute Graft Rejection.

    Directory of Open Access Journals (Sweden)

    Dong Ho Shin

    Full Text Available The delta neutrophil index (DNI is the fraction of circulating immature granulocytes, which reflect infectious and/or septic condition. Acute graft pyelonephritis (AGPN versus acute graft rejection is a frequently encountered diagnostic and therapeutic dilemma in kidney transplant recipients, but little is known about the clinical usefulness of DNI value in the differentiation of the two conditions.A total of 90 episodes of AGPN or acute graft rejection were evaluated at the Kangdong Sacred Heart Hospital between 2008 and 2014. We performed retrospective analysis of demographic, clinical, and laboratory parameters data. Receiver operating curves (ROC and multivariate logistic regression were conducted to ascertain the utility of DNI in discriminating between AGPN and acute graft rejection.AGPN group had significantly higher DNI values than acute graft rejection group (2.9% vs. 1.9%, P < 0.001. The area under the ROC curve for DNI value to discriminate between AGPN and acute graft rejection was 0.85 (95% confidence interval [CI]; 0.76-0.92, P < 0.001. A DNI value of 2.7% was selected as the cut-off value for AGPN, and kidney transplant recipients with a DNI value ≥ 2.7% were found to be at a higher risk of infection than those with a DNI < 2.7% (odd ratio [OR] 40.50; 95% CI 8.68-189.08; P < 0.001. In a multivariate logistic regression analysis, DNI was a significant independent factor for predicting AGPN after adjusting age, sex, log WBC count, log neutorphil count, log lymphocyte count, CRP concentration, and procalcitonin concentration (OR 4.32; 95% CI 1.81-10.34, P < 0.001.This study showed that DNI was an effective marker to differentiate between AGPN and acute graft rejection. Thus, these finding suggest that DNI may be a useful marker in the management of these patients.

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

    Science.gov (United States)

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

    2013-10-21

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

  13. Local production of interleukin-6 during acute rejection in human renal allografts

    NARCIS (Netherlands)

    Raasveld, M. H.; Weening, J. J.; Kerst, J. M.; Surachno, S.; ten Berge, R. J.

    1993-01-01

    Interleukin-6 is involved in T-cell activation and possibly plays a role in the pathogenesis of acute rejection of transplanted organs. This is indicated by elevated levels of interleukin-6 in serum and urine of renal allograft recipients, and elevated amounts of mRNA for interleukin-6 in all

  14. 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

  15. DISTINCT PHENOTYPES OF INFILTRATING CELLS DURING ACUTE AND CHRONIC LUNG REJECTION IN HUMAN HEART-LUNG TRANSPLANTS

    NARCIS (Netherlands)

    WINTER, JB; CLELLAND, C; GOUW, ASH; PROP, J

    1995-01-01

    To differentiate between acute and chronic lung rejection in an early stage, phenotypes of infiltrating inflammatory cells were analyzed in 34 transbronchial biopsies (TBBs) of 24 patients after heart-lung transplantation. TBBs were taken during during acute lung rejection and chronic lung

  16. Serum Levels of Interleukin-34 During Acute Rejection in Liver Transplantation.

    Science.gov (United States)

    San Segundo, D; Ruiz, P; Irure, J; Arias-Loste, M T; Cuadrado, A; Puente, A; Casafont, F; López-Hoyos, M; Crespo, J; Fábrega, E

    2016-11-01

    Accumulating evidence indicates that interleukin (IL)-34 participates in T-cell homeostasis and tolerance due to the ability of IL-34 to trigger apoptosis of Th1, Th17, and Tc1 cells, but spare Th2 cells and Treg. In addition, IL-34 exerts anti-inflammatory effects by impairing leukocyte adhesion and transendothelial migration, and reducing the secretion of proinflammatory cytokines. The aim of our study was to investigate the time course of serum levels of IL-34 during hepatic allograft rejection. Serum levels of IL-34 were determined in 20 healthy subjects and 45 hepatic transplant recipients. These patients were divided into 2 groups: group I was composed of 15 patients with acute rejection, and group II was composed of 30 patients without acute rejection. Samples were collected on days 1 and 7 after liver transplantation and on the day of liver biopsy. The concentrations of IL-34 were higher in the rejection group vs nonrejection group during the entire postoperative period. The whole transplant group, including those with stable graft function, showed higher IL-34 serum levels than the controls at all times after liver transplantation. Our preliminary results could be related to the recent finding that IL-34 may play an immune-suppressive role in liver transplantation. In our case, although we must be cautious with serum data, increased IL-34 would help to control alloresponse during rejection and protect from graft lost. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Presumed serum sickness following thymoglobulin treatment of acute cellular rejection of a cardiac allograft.

    Science.gov (United States)

    Ratushny, Vladimir; Capell, Brian C; Rosenbach, Misha

    2017-09-01

    Serum sickness is a hypersensitivity reaction to proteins in antiserum derived from nonhuman animal sources and can be seen in patients being treated with antiserum to prevent transplant rejection. Serum sickness may display variable clinical presentations. Because cutaneous findings may be the initial symptom in some cases, it is important for dermatologists to be able to recognize this condition given its potentially life-threatening symptoms. We present a case of a 35-year-old man with presumed serum sickness after receiving thymoglobulin for the treatment of acute cellular rejection of a heart transplant. The clinical presentation, laboratory findings, and treatment options are reviewed.

  18. IL-15 is decreased upon CsA and FK506 treatment of acute rejection following heart transplantation in mice.

    Science.gov (United States)

    Yu, Zhiyong; Zhou, Xiaoping; Yu, Songfeng; Xie, Haiyang; Zheng, Shusen

    2015-01-01

    The aim of this study was to investigate the effect of cyclosporine A (CsA) and tacrolimus (FK506) on interleukin-15 (IL-15) production during acute rejection following heart transplantation in mice. Inbred male Balb/c (H‑2d) and C57BL/6 (H-2b) mice were used to establish a heterotopic intra-abdominal cardiac transplantation model. The mice were divided in four groups: syngeneic control, allogeneic acute rejection, allogeneic rejection treated with CsA, and allogeneic rejection treated with FK506. The expression of IL-15, IL-2, and tumor necrosis factor-α (TNF-α) was measured using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. A low level of IL-15 was detected in transplanted hearts of the control group, with a significant increase observed in the allogeneic acute rejection group. Compared to the allogeneic acute rejection group, IL-15 expression was significantly decreased in the CsA- and FK506-treated allogeneic rejection groups. The TNF-α expression pattern was similar to that of IL-15 in all groups. IL-2 expression was increased in the allogeneic acute rejection group and was inhibited in mice treated with CsA and FK506. In conclusion, increased IL-15 expression in rejected murine heart grafts may be reduced by CsA and FK506 in vivo.

  19. Impact of animal strain on gene expression in a rat model of acute cardiac rejection

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    Norsworthy Kelly J

    2009-06-01

    Full Text Available Abstract Background The expression levels of many genes show wide natural variation among strains or populations. This study investigated the potential for animal strain-related genotypic differences to confound gene expression profiles in acute cellular rejection (ACR. Using a rat heart transplant model and 2 different rat strains (Dark Agouti, and Brown Norway, microarrays were performed on native hearts, transplanted hearts, and peripheral blood mononuclear cells (PBMC. Results In heart tissue, strain alone affected the expression of only 33 probesets while rejection affected the expression of 1368 probesets (FDR 10% and FC ≥ 3. Only 13 genes were affected by both strain and rejection, which was Conclusion In ACR, genetic background has a large impact on the transcriptome of immune cells, but not heart tissue. Gene expression studies of ACR should avoid study designs that require cross strain comparisons between leukocytes.

  20. Transfer of tolerance to collagen type V suppresses Th-17 lymphocyte mediated acute lung transplant rejection

    Science.gov (United States)

    Braun, Ruedi K.; Molitor-Dart, Melanie; Wigfield, Christopher; Xiang, Zhuzai; Fain, Sean B.; Jankowska-Gan, Ewa; Seroogy, Christine M.; Burlingham, William J.; Wilkes, David S.; Brand, David D.; Torrealba, Jose; Love, Robert B.

    2009-01-01

    Background Rat lung allograft rejection is mediated by collagen type V (col(V)) specific Th17 cells. Adoptive transfer of these cells is sufficient to induce rejection pathology in isografts, whereas tolerance to col(V) suppresses allograft rejection. We therefore tested if regulatory T cells from tolerant rats could suppress the Th17 mediated rejection in the syngeneic model of lung transplantation. Methods Rats were subjected to syngeneic left lung transplantation and acute rejection was induced by adoptive transfer of lymph node cells from col(V)-immunized rats. Tolerance was induced by intravenous (iv) injection of col(V) and spleen lymphocytes were used for adoptive transfer. CD4+ T cells were depleted using magnetic beads. Lung isografts were analyzed using micro-PET imaging and histochemistry. The transvivo delayed type hypersensitivity (TV-DTH) assay was used to analyze the Th17 response. Results Adoptive co-transfer of col(V)-specific effector cells with cells from col(V) tolerized rats suppressed severe vasculitis and bronchiolitis with parenchymal inflammation, and the expression of IL-17 transcripts in mediastinal lymph nodes induced by effector cells alone. Analysis by TV-DTH showed that the reactivity to col(V) was dependent on the presence of TNF-α and IL-17, but not IFN-γ. Depletion of CD4+ T cells from the suppressor cell population abrogated the col(V)-specific protection. Conclusion Th17 mediated acute rejection after lung transplantation is ameliorated by CD4+ col(V)-specific regulatory T cells. The mechanism for this Th17 suppression is consistent with tolerance induction to col(V). The goal of transplantation treatment therefore should target Th17 development and not suppression of T cell activation by suppressing IL-2. PMID:20029330

  1. Successful Treatment of T Cell-Mediated Acute Rejection with Delayed CTLA4-Ig in Mice

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    James S. Young

    2017-09-01

    Full Text Available Clinical observations that kidney transplant recipients receiving belatacept who experienced T cell-mediated acute rejection can be successfully treated and subsequently maintained on belatacept-based immunosuppression suggest that belatacept is able to control memory T cells. We recently reported that treatment with CTLA4-Ig from day 6 posttransplantation successfully rescues allografts from acute rejection in a BALB/c to C57BL/6 heart transplant model, in part, by abolishing B cell germinal centers and reducing alloantibody titers. Here, we show that CTLA4-Ig is additionally able to inhibit established T cell responses independently of B cells. CTLA4-Ig inhibited the in vivo cytolytic activity of donor-specific CD8+ T cells, and the production of IFNγ by graft-infiltrating T cells. Delayed CTLA4-Ig treatment did not reduce the numbers of graft-infiltrating T cells nor prevented the accumulation of antigen-experienced donor-specific memory T cells in the spleen. Nevertheless, delayed CTLA4-Ig treatment successfully maintained long-term graft acceptance in the majority of recipients that had experienced a rejection crisis, and enabled the acceptance of secondary BALB/c heart grafts transplanted 30 days after the first transplantation. In summary, we conclude that delayed CTLA4-Ig treatment is able to partially halt ongoing T cell-mediated acute rejection. These findings extend the functional efficacy of CTLA4-Ig therapy to effector T cells and provide an explanation for why CTLA4-Ig-based immunosuppression in the clinic successfully maintains long-term graft survival after T cell-mediated rejection.

  2. Association of Endothelial Nitric Oxide Synthase Gene Polymorphisms With Acute Rejection in Liver Transplant Recipients.

    Science.gov (United States)

    Azarpira, Negar; Namazi, Soha; Malahi, Sayan; Kazemi, Kourosh

    2016-06-01

    Polymorphisms of the endothelial nitric oxide synthase gene have been associated with altered endothelial nitric oxide synthase activity. The purpose of this study was to investigate the relation between endothelial nitric oxide synthase -786T/C and 894G/T polymorphism and their haplotypes on the occurrence of acute rejection episodes in liver transplant recipients. We conducted a case control study in which 100 liver transplant recipients and 100 healthy controls were recruited from Shiraz Transplant Center. The patients used triple therapy including tacrolimus, mycophenolate mofetil, and prednisolone for immunosuppression maintenance. DNA was extracted from peripheral blood and endothelial nitric oxide synthase polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism. Patients included 60 men and 40 women (mean age, 32.35 ± 10.2 y). There was a significant association of endothelial nitric oxide synthase 894G/T and acute rejection episode. The GT* gen-otype and acute rejection episodes had a significant association (odds ratio, 2.42; 95% confidence interval, 0.97-6.15; P = .03). The GG and GT* genotype and T* allele frequency were significantly different between patients and control subjects (P = .001). Haplotype TT* was higher in recipients than control subjects (odds ratio, 2.17; 95% confidence interval, 1.12-4.25; P = .01). Haplotype TG was higher in the control group (odds ratio, 0.62; 95% confidence interval, 0.40-0.96; P = .02). Our results suggest a relation between different endothelial nitric oxide synthase geno-types and risk of acute rejection episodes. However, further study is necessary to determine genetic susceptibility for transplant patients.

  3. Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection.

    Science.gov (United States)

    Stewart, Susan; Winters, Gayle L; Fishbein, Michael C; Tazelaar, Henry D; Kobashigawa, Jon; Abrams, Jacki; Andersen, Claus B; Angelini, Annalisa; Berry, Gerald J; Burke, Margaret M; Demetris, Anthony J; Hammond, Elizabeth; Itescu, Silviu; Marboe, Charles C; McManus, Bruce; Reed, Elaine F; Reinsmoen, Nancy L; Rodriguez, E Rene; Rose, Alan G; Rose, Marlene; Suciu-Focia, Nicole; Zeevi, Adriana; Billingham, Margaret E

    2005-11-01

    In 1990, an international grading system for cardiac allograft biopsies was adopted by the International Society for Heart Transplantation. This system has served the heart transplant community well, facilitating communication between transplant centers, especially with regard to patient management and research. In 2004, under the direction of the International Society for Heart and Lung Transplantation (ISHLT), a multidisciplinary review of the cardiac biopsy grading system was undertaken to address challenges and inconsistencies in its use and to address recent advances in the knowledge of antibody-mediated rejection. This article summarizes the revised consensus classification for cardiac allograft rejection. In brief, the revised (R) categories of cellular rejection are as follows: Grade 0 R--no rejection (no change from 1990); Grade 1 R--mild rejection (1990 Grades 1A, 1B and 2); Grade 2 R--moderate rejection (1990 Grade 3A); and Grade 3 R--severe rejection (1990 Grades 3B and 4). Because the histologic sub-types of Quilty A and Quilty B have never been shown to have clinical significance, the "A" and "B" designations have been eliminated. Recommendations are also made for the histologic recognition and immunohistologic investigation of acute antibody-mediated rejection (AMR) with the expectation that greater standardization of the assessment of this controversial entity will clarify its clinical significance. Technical considerations in biopsy processing are also addressed. This consensus revision of the Working Formulation was approved by the ISHLT Board of Directors in December 2004.

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

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    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.

  5. Inhibition of histone methyltransferase EZH2 ameliorates early acute renal allograft rejection in rats.

    Science.gov (United States)

    Li, Long; Zhang, Yi; Xu, Ming; Rong, Ruiming; Wang, Jina; Zhu, Tongyu

    2016-10-26

    Although histone methyltransferases EZH2 has been proved to have significant regulatory effect on the immune rejection after hematopoietic stem cell transplantation, its role in solid-organ transplantation remains uncovered. In this study, we investigate whether histone methylation regulation can impact renal allograft rejection in rat models. Allogeneic rat renal transplantation model (Wistar to Lewis) was established, and the recipients were administrated with EZH2 inhibitor DZNep after transplantation. Renal allografts and peripheral blood were collected on day 5 after transplantation for histological examination and mechanism investigation. We found that inhibition of EZH2 by DZNep after transplantation significantly ameliorated acute rejection (AR), with decreased histological injury and reduced inflammatory infiltration in renal allografts. Attenuation of AR was due to the prohibited activation of alloreactive T cells, the subsequent impaired production of inflammatory cytokines, and also the elevated apoptosis of alloreactive T cells in both renal allografts and periphery. However, inhibition of EZH2 did not increase the regulatory T cells during the AR. Disruption of EZH2 by DZNep suppressed the immune responses of alloreactive T cells and ameliorated AR of renal allografts. This suggests a therapeutic potential of targeting histone methyltransferases EZH2 in treating allograft rejection after solid organ transplantation.

  6. Serum levels of interleukin-9 during acute rejection in liver transplantation.

    Science.gov (United States)

    Fábrega, E; López-Hoyos, M; San Segundo, D; Casafont, F; Angel Mieses, M; Sampedro, B; Pons-Romero, F

    2012-01-01

    Interleukin-9 (IL-9) has been cast as a player in autoimmunity, but its role in liver transplantation remains to be clarified. The aim of our study was to investigate the time course of IL-9 serum levels during hepatic allograft rejection. IL-9 serum levels were determined in 34 healthy subjects and 50 hepatic transplant recipients. The patients were divided into two groups: group I was composed of 15 patients with acute rejection episodes, and group II, 35 patients free of this problem. Samples were collected on days 1 and 7 after liver transplantation and on the day of liver biopsy. The concentrations of IL-9 were similar in the rejection and nonrejection groups over the entire postoperative period. The whole transplant group, including those with stable graft function, showed higher IL-9 serum levels than the controls at all times after liver transplantation. These preliminary results suggest a lack of participation of IL-9 in human liver allograft rejection. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  7. Nebulized cyclosporine for prevention of acute pulmonary allograft rejection in the rat: pharmacokinetic and histologic study.

    Science.gov (United States)

    Blot, F; Tavakoli, R; Sellam, S; Epardeau, B; Faurisson, F; Bernard, N; Becquemin, M H; Frachon, I; Stern, M; Pocidalo, J J

    1995-01-01

    With regard to limiting the systemic effects of cyclosporine A and obtaining better control of acute pulmonary allograft rejection, local immunosuppressive therapy with aerosolized cyclosporine A seems of interest. Given the in situ immunologic mechanisms of acute rejection, as well as the anatomic structure of the lung, this therapy is feasible as previously described by others. The aim of our study is to determine the pharmacokinetic parameters of nebulized cyclosporine A and the best modalities of administration. In a pharmacokinetic study, the cyclosporine A was given either by intramuscular injection (10 mg/kg) or by aerosol at 10 and 25 mg/kg doses; 70 rats were killed at 25 and 50 minutes and 2, 4, 6, 8, 12, 24, or 48 hours after cyclosporine A administration. Cyclosporine A levels were measured in whole blood and in the lung. The areas under the concentration time curves were determined. Twenty-four lung transplantations were then performed. The rats were killed on postoperative day 9. Acute rejection was scored on a scale of 0 to 4, and cyclosporine A trough levels were measured in the lung and in the blood. With a jet nebulizer, the mass median aerodynamic diameter was 2.5 microns, with a standard geometric deviation of 2.3. In blood, the area under the concentration curve was greater for intramuscular (80.6 ng.hr/ml) than for aerosol administrations at 10 (15.1 ng.hr/ml) and 25 mg/kg (41.0 ng.hr/ml) doses. In the lungs, the area under the concentration curve was greater for the aerosol route at 25 mg/kg doses (588 ng.hr/mg) than for the low-dose (200 ng.hr/mg) or intramuscular administration (200 ng.hr/mg). The lung targeting index of cyclosporine A (ratio area under the concentration curve-lungs/area under the concentration curve-blood) was greater for both aerosol administrations than for the intramuscular route. In the study of the prevention of acute rejection, rats without immunosuppression (n = 6), rats receiving daily doses of cyclosporine A

  8. Antibody-mediated resistance against plant pathogens.

    Science.gov (United States)

    Safarnejad, Mohammad Reza; Jouzani, Gholamreza Salehi; Tabatabaei, Meisam; Tabatabaie, Meisam; Twyman, Richard M; Schillberg, Stefan

    2011-01-01

    Plant diseases have a significant impact on the yield and quality of crops. Many strategies have been developed to combat plant diseases, including the transfer of resistance genes to crops by conventional breeding. However, resistance genes can only be introgressed from sexually-compatible species, so breeders need alternative measures to introduce resistance traits from more distant sources. In this context, genetic engineering provides an opportunity to exploit diverse and novel forms of resistance, e.g. the use of recombinant antibodies targeting plant pathogens. Native antibodies, as a part of the vertebrate adaptive immune system, can bind to foreign antigens and eliminate them from the body. The ectopic expression of antibodies in plants can also interfere with pathogen activity to confer disease resistance. With sufficient knowledge of the pathogen life cycle, it is possible to counter any disease by designing expression constructs so that pathogen-specific antibodies accumulate at high levels in appropriate sub-cellular compartments. Although first developed to tackle plant viruses and still used predominantly for this purpose, antibodies have been targeted against a diverse range of pathogens as well as proteins involved in plant-pathogen interactions. Here we comprehensively review the development and implementation of antibody-mediated disease resistance in plants. Copyright © 2011 Elsevier Inc. All rights reserved.

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

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    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.

  10. Acute Rejection in Renal Transplant Patients of a Hospital in Bogota, Colombia.

    Science.gov (United States)

    García, P; Huerfano, M; Rodríguez, M; Caicedo, A; Berrío, F; Gonzalez, C

    2016-01-01

    Renal transplantation is the best treatment for end stage renal disease. Acute graft rejection is one of the main complications and may influence graft survival. To determine the incidence and features of acute cellular rejection (ACR) episodes confirmed by biopsy. We studied a cohort of 175 patients who underwent renal transplantation between 2004 and 2012 to determine the cumulative incidence of ACR confirmed by biopsy and to identify the associated risk factors using multivariate analysis. The one-year patient survival was 96.6%; the graft survival was 93.7%. The incidence of ACR within one year was 14.3%, of which 46% were observed within 6 months following transplantation. The most frequently observed ACR type was 1B according to the Banff classification system (42%). A relationship between ACR and receipt of a kidney from expanded criteria donors was observed, both in univariate and adjusted multiple log-binomial regression analyses, but only 6.3% of patients received extended criteria donor kidneys. No other relationships between variables were found. ACR frequency in this study was similar to that of other cohorts reported previously. We need a bigger sample of renal transplants from expanded criteria donors, PRA and DSA test to support the results.

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

    Directory of Open Access Journals (Sweden)

    Elizabeth Hollis

    2017-03-01

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

  12. 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.

  13. A Five-Gene Peripheral Blood Diagnostic Test for Acute Rejection in Renal Transplantation

    Science.gov (United States)

    Li, Li; Khatri, Purveshkumar; Sigdel, Tara K.; Tran, Tim; Ying, Lihua; Vitalone, Matthew; Chen, Amery; Hsieh, Szu-chuan; Dai, Hong; Zhang, Meixia; Naesens, Maarten; Zarkhin, Valeriya; Sansanwal, Poonam; Chen, Rong; Mindrinos, Michael; Xiao, Wenzhong; Benfield, Mark; Ettenger, Robert; Dharnidharka, Vikas; Mathias, Robert; Portale, Anthony; McDonald, Ruth; Harmon, William; Kershaw, David; Vehaskari, V. Matti; Kamil, Elaine; Baluarte, H. Jorge; Warady, Brad; Davis, Ron; Butte, Atul J.; Salvatierra, Oscar; Sarwal, Minnie

    2012-01-01

    Monitoring of renal graft status through peripheral blood (PB) rather than invasive biopsy is important as it will lessen the risk of infection and other stresses, while reducing the costs of rejection diagnosis. Blood gene biomarker panels were discovered by microarrays at a single center and subsequently validated and cross-validated by QPCR in gthe NIH SNSO1 randomized study from 12 US pediatric transplant programs. A total of 367 unique human PB samples, each paired with a graft biopsy for centralized, blinded phenotype classification, were analyzed (115 acute rejection (AR), 180 stable and 72 other causes of graft injury). Of the differentially expressed genes by microarray, Q-PCR analysis of a five gene-set (DUSP1, PBEF1, PSEN1, MAPK9 and NKTR) classified AR with high accuracy. A logistic regression model was built on independent training-set (n=47) and validated on independent test-set (n=198)samples, discriminating AR from STA with 91% sensitivity and 94% specificity and AR from all other non-AR phenotypes with 91% sensitivity and 90% specificity. The 5-gene set can diagnose AR potentially avoiding the need for invasive renal biopsy. These data support the conduct of a prospective study to validate the clinical predictive utility of this diagnostic tool. PMID:23009139

  14. Analysis of leukocyte activation during acute rejection of pulmonary allografts in noninfected and cytomegalovirus-infected rats.

    Science.gov (United States)

    Steinmüller, C; Steinhoff, G; Bauer, D; You, X M; Denzin, H; Franke-Ullmann, G; Hausen, B; Bruggemann, C; Wagner, T O; Lohmann-Matthes, M L; Emmendörffer, A

    1997-01-01

    After human lung transplantation acute rejection and cytomegalovirus (CMV) infections may occur, probably contributing to the development of chronic rejection. We established a model of subacute allograft rejection in rats to analyze leukocyte activation and effects of a CMV infection. Histoincompatible lung transplants (BN/LEW) without immunosuppression (group A) and lungs of initially immunosuppressed animals (group B) were analyzed. The production of inflammatory mediators (interleukin-6, tumor necrosis factor alpha, nitric oxides) and the expression of MHC class II antigens by alveolar and lung tissue macrophages were significantly enhanced during the alloresponse. In recipients without immunosuppression (group A) allograft necrosis was detected by day 6, whereas group B allografts were fully rejected by day 25. In allografts of immunosuppressed, CMV-infected animals (group C) the CMV infection was clearly aggravated and the number of activated lung tissue macrophages was increased when compared with noninfected allografts or isografts. The subacute model provides the advantage of allowing us to study mechanisms of acute rejection without the effects of reperfusion injury. Furthermore these findings underline the role of inflammatory mediators produced by macrophages during rejection.

  15. DISTURBANCE OF THE CARDIOMYOCYTE’S MACROMOLECULAR STRUCTURE IN HEART ALLOGRAFTS AS A SIGN OF CHRONIC REJECTION

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    A. G. Kupriyanova

    2012-01-01

    Full Text Available Chronic rejection, especially cardiac allograft vasculopathy, is a major limiting factor for long-term transplant survival. This process affects not only the blood vessels, but also cardiomyocytes. However, there are extremely few reports on the evaluation of their macromolecular structure state. The aim of the study was to evaluate the structural proteins of cardiomyocytes (actin, myosin, troponin I, titin, desmin, vinculin of heart allografts in different periods after the operation (from 6 days to 15 years. Major changes of macromolecular structure were revealed in late period after transplantation (6 months – 15 years. The contribution of humoral immune response in the process of chronic cardiac allograft rejection was observed: in eight of twelve recipients episodes of acute humoral rejection had been repeatedly registered; disorders of the expression of 5 proteins out of 6 characterized were found in recipients with recurrent and persistent antibody-mediated rejection

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

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    Lan Zhu

    2016-01-01

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

  17. Interleukin-17 positive cells accumulate in renal allografts during acute rejection and are independent predictors of worse graft outcome

    NARCIS (Netherlands)

    Yapici, Ünsal; Kers, Jesper; Bemelman, Fréderike J.; Roelofs, Joris J. T. H.; Groothoff, Jaap W.; van der Loos, Chris M.; van Donselaar-van der Pant, Karlijn A. M. I.; Idu, Mirza M.; Claessen, Nike; ten Berge, Ineke J. M.; Florquin, Sandrine

    2011-01-01

    Interleukin-17 (IL-17) plays an important role in the regulation of cellular and humoral immune responses. Recent studies suggest a role for IL-17 in transplantation. Our study investigated whether quantifying IL-17(+) cells in renal transplant biopsies during acute rejection could have additional

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

    Science.gov (United States)

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

    2017-01-01

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

  19. Evaluation of Digital PCR as a Technique for Monitoring Acute Rejection in Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    Hyeseon Lee

    2017-03-01

    Full Text Available Early detection and proper management of kidney rejection are crucial for the long-term health of a transplant recipient. Recipients are normally monitored by serum creatinine measurement and sometimes with graft biopsies. Donor-derived cell-free deoxyribonucleic acid (cfDNA in the recipient's plasma and/or urine may be a better indicator of acute rejection. We evaluated digital PCR (dPCR as a system for monitoring graft status using single nucleotide polymorphism (SNP-based detection of donor DNA in plasma or urine. We compared the detection abilities of the QX200, RainDrop, and QuantStudio 3D dPCR systems. The QX200 was the most accurate and sensitive. Plasma and/or urine samples were isolated from 34 kidney recipients at multiple time points after transplantation, and analyzed by dPCR using the QX200. We found that donor DNA was almost undetectable in plasma DNA samples, whereas a high percentage of donor DNA was measured in urine DNA samples, indicating that urine is a good source of cfDNA for patient monitoring. We found that at least 24% of the highly polymorphic SNPs used to identify individuals could also identify donor cfDNA in transplant patient samples. Our results further showed that autosomal, sex-specific, and mitochondrial SNPs were suitable markers for identifying donor cfDNA. Finally, we found that donor-derived cfDNA measurement by dPCR was not sufficient to predict a patient's clinical condition. Our results indicate that donor-derived cfDNA is not an accurate predictor of kidney status in kidney transplant patients.

  20. Association between donor-specific antibodies and acute rejection and resolution in small bowel and multivisceral transplantation.

    Science.gov (United States)

    Tsai, Hsin-Lin; Island, Eddie R; Chang, Jei-Wen; Gonzalez-Pinto, Ignacio; Tryphonopoulos, Panagiotis; Nishida, Seigo; Selvaggi, Gennaro; Tekin, Akin; Moon, Jang; Levi, David; Woodle, E Steve; Ruiz, Phillip; Weppler, Debbie; Lee, Oscar K S; Tzakis, Andreas G

    2011-09-27

    Donor-specific antibodies (DSA) are associated with acute kidney graft rejection, but their role in small bowel/multivisceral allograft remains unclear. We carried out a prospective study to understand the impact of DSA in the setting of intestinal allograft rejection. Thirteen patients (15 grafts) were serially evaluated for DSA levels pre- and posttransplant. DSA was determined by Luminex and the results were interpreted as fluorescence intensity (FI), with FI more than 3000 considered positive. The clinical rejection episodes in allografts were significantly associated with the presence of DSA (P=0.041).We obtained 291 biopsy samples from graft ileum and date-matched DSA assay reports. Sixty-three (21.65%) of the biopsies showed acute rejection. The appearance of DSA were preformed (n=5, anti-human leukocyte antigen class II=3, anti-class I and II=2), de novo (n=4, 15.25±4.72 days after transplantation, anti-class II=1, and anti-class I and II=3) and never (n=6). Among the 63 biopsies, 30(47.6%) had significant correlations with positive DSA (kappa=0.30, Ptransplantation patients, there was a high incidence of DSA. The presence of DSA should alert the clinical team of a higher risk of rejection, and reduction of the FI is clinically associated with resolution. Serial endoscopy guided biopsies combined with simultaneous DSA measurement in postintestinal transplantation follow-up is an effective means of screening for cellular and humoral-based forms of acute rejection.

  1. Belatacept for prevention of acute rejection in adult patients who have had a kidney transplant: an update

    Directory of Open Access Journals (Sweden)

    Wojciechowski D

    2012-11-01

    Full Text Available David Wojciechowski, Flavio VincentiKidney Transplant Service, University of California, San Francisco, CA, USAAbstract: In June 2011, the US Food and Drug Administration approved belatacept for the prophylaxis of organ rejection in adult kidney transplant recipients. This review discusses the use of belatacept for the prevention of acute rejection as part of a maintenance immunosuppression regimen. Belatacept is a selective costimulation blocker designed to provide effective immunosuppression while avoiding the toxicities associated with calcineurin inhibitors. Phase III trial data have demonstrated that belatacept is noninferior to cyclosporine in 1-year patient and allograft survival. Three-year data demonstrate an ongoing improvement in mean measured glomerular filtration rate in belatacept-treated versus cyclosporine-treated patients. However, the rate of acute rejection was higher in belatacept-treated patients compared with cyclosporine. Specifically, there was a higher incidence of Banff type II rejections in patients treated with belatacept. Despite the higher Banff grade, rejections on belatacept were not associated with other factors associated with poor outcomes, such as the development of donor-specific antibodies or reduced estimated glomerular filtration rate. One safety issue that must be considered when using belatacept is the potential for increased risk of post-transplant lymphoproliferative disease. There were more cases of post-transplant lymphoproliferative disease in belatacept-treated patients, especially in recipients seronegative for Epstein–Barr virus or patients treated with lymphocyte-depleting agents. Therefore, belatacept can be recommended for use in Epstein–Barr virus antibody-positive recipients.Keywords: belatacept, kidney transplant, acute rejection

  2. Acute cellular rejection is a risk factor for bronchiolitis obliterans syndrome independent of post-transplant baseline FEV1

    DEFF Research Database (Denmark)

    Burton, C.M.; Iversen, M.; Carlsen, J.

    2009-01-01

    maximum FEV(1) occurred at a median 183 days post-transplant. Freedom from BOS was 81%, 53%, 38% and 15%, and cumulative incidence of BOS was 18%, 43%, 57% and 77% at 1, 3, 5 and 10 years post-transplantation, respectively. Acute cellular rejection was independently associated with an increased cause......-specific hazard of BOS (hazard ratio 1.4, confidence interval 1.1 to 1.8, p = 0.009). The absolute value of baseline FEV(1) was a significant confounder in all survival and competing risk analyses of BOS (p rejection remains...

  3. Multifactorial aspects of antibody-mediated blood cell destruction

    NARCIS (Netherlands)

    Kapur, R.

    2014-01-01

    The research described in this thesis focuses on diseases of antibody-mediated blood cell destruction via FcγRs on phagocytes, in particular regarding platelets in fetal or neonatal alloimmune thrombocytopenia (FNAIT) and red blood cells (RBC) in hemolytic disease of the fetus and newborn (HDFN).

  4. Transfer of tolerance to collagen type V suppresses T-helper-cell-17 lymphocyte-mediated acute lung transplant rejection.

    Science.gov (United States)

    Braun, Ruedi K; Molitor-Dart, Melanie; Wigfield, Christopher; Xiang, Zhuzai; Fain, Sean B; Jankowska-Gan, Ewa; Seroogy, Christine M; Burlingham, William J; Wilkes, David S; Brand, David D; Torrealba, Jose; Love, Robert B

    2009-12-27

    Rat lung allograft rejection is mediated by collagen type V (col(V)) specific T-helper-cell 17 (Th17) cells. Adoptive transfer of these cells is sufficient to induce rejection pathology in isografts, whereas tolerance to col(V) suppresses allograft rejection. Therefore, we tested whether regulatory T cells from tolerant rats could suppress the Th17-mediated rejection in the syngeneic model of lung transplantation. Rats were subjected to syngeneic left lung transplantation, and acute rejection was induced by adoptive transfer of lymph node cells from col(V)-immunized rats. Tolerance was induced by intravenous injection of col(V), and spleen lymphocytes were used for adoptive transfer. CD4+ T cells were depleted using magnetic beads. Lung isografts were analyzed using micro-positron emission tomography imaging and histochemistry. The transvivo delayed type hypersensitivity assay was used to analyze the Th17 response. Adoptive cotransfer of col(V)-specific effector cells with cells from col(V)-tolerized rats suppressed severe vasculitis and bronchiolitis with parenchymal inflammation, and the expression of interleukin (IL)-17 transcripts in mediastinal lymph nodes induced by effector cells alone. Analysis by transvivo delayed type hypersensitivity showed that the reactivity to col(V) was dependent on the presence of tumor necrosis factor-alpha and IL-17 but not interferon-gamma. Depletion of CD4+ T cells from the suppressor cell population abrogated the col(V)-specific protection. Th17-mediated acute rejection after lung transplantation is ameliorated by CD4+ col(V)-specific regulatory T cells. The mechanism for this Th17 suppression is consistent with tolerance induction to col(V). The goal of transplantation treatment, therefore, should target Th17 development and not suppression of T-cell activation by suppressing IL-2.

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

    Directory of Open Access Journals (Sweden)

    Dai Yong

    2008-01-01

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

  6. 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...... 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...... observers evaluated 168 endomyocardial biopsy specimens according to the Stanford Classification and 100 endomyocardial biopsy specimens according to the International Grading System. The evaluation was carried out blindly. Kappa values of 54.1% and 51.5%, respectively, were obtained, both significantly...

  7. Impact of longitudinal exposure to mycophenolic acid on acute rejection in renal-transplant recipients using a joint modeling approach.

    OpenAIRE

    Daher-Abdi, Zeinab; Essig, Marie; Rizopoulos, Dimitris; Le Meur, Yannick; Prémaud, Aurélie; Woillard, Jean-Baptiste; Rerolle, Jean-Philippe; Marquet, Pierre; Rousseau, Annick

    2013-01-01

    International audience; This study aimed to investigate the association between longitudinal exposure to mycophenolic acid (MPA) and acute rejection (AR) risk in the first year after renal transplantation, and to propose MPA exposure targets conditionally to this association. A joint model, adjusted for monitoring strategy (fixed-dose versus concentration-controlled) and recipient age, was developed; it combined a mixed-effects model to describe the whole pattern of MPA exposure (i.e. area un...

  8. Acute Rejection After Kidney Transplantation Associates With Circulating MicroRNAs and Vascular Injury

    Science.gov (United States)

    Bijkerk, Roel; Florijn, Barend W.; Khairoun, Meriem; Duijs, Jacques M. G. J.; Ocak, Gurbey; de Vries, Aiko P.J.; Schaapherder, Alexander F.; Mallat, Marko J. K.; de Fijter, Johan W.; Rabelink, Ton J.; van Zonneveld, Anton Jan; Reinders, Marlies E. J.

    2017-01-01

    Background Acute rejection (AR) of kidney transplants is associated with the loss of endothelial integrity, microvascular rarefaction and, ultimately, graft dysfunction. Circulating angiogenic microRNAs (miRNAs) may serve as markers for microvascular injury. Here, we investigated the short- and long-term effects of AR after kidney transplantation on systemic vascular injury and the associated circulating miRNA profile. Methods Systemic vascular injury was determined by measuring capillary tortuosity and density within the oral mucosa as well as by assessing circulating levels of angiopoietin-2/angiopoietin-1 ratio, vascular endothelial growth factor and soluble thrombomodulin. After a pilot study, we selected 48 miRNAs to assess the AR- and microvascular injury associated circulating miRNAs. Results In stable transplant recipients (n = 25) and patients with AR (n = 13), which were also studied longitudinally (1, 6, and 12 months post-AR), we found an AR-associated increase in markers of systemic vascular injury, of which vascular endothelial growth factor and soluble thrombomodulin normalized within 1 year after AR. Of the 48 selected miRNAs, 8 were either decreased (miR-135a, miR-199a-3p, and miR-15a) or increased (miR-17, miR-140-3p, miR-130b, miR-122 and miR-192) in AR. Of these, miR-130b, miR-199a, and miR-192 associated with markers of vascular injury, whereas miR-140-3p, miR-130b, miR-122, and miR-192 normalized within 1 year after AR. Conclusions AR after kidney transplantation is characterized by systemic microvascular injury and associates with specific circulating miRNA levels. PMID:28706977

  9. Kidney allograft survival after acute rejection, the value of follow-up biopsies.

    Science.gov (United States)

    El Ters, M; Grande, J P; Keddis, M T; Rodrigo, E; Chopra, B; Dean, P G; Stegall, M D; Cosio, F G

    2013-09-01

    Kidney allografts are frequently lost due to alloimmunity. Still, the impact of early acute rejection (AR) on long-term graft survival is debated. We examined this relationship focusing on graft histology post-AR and assessing specific causes of graft loss. Included are 797 recipients without anti-donor antibodies (DSA) at transplant who had 1 year protocol biopsies. 15.2% of recipients had AR diagnosed by protocol or clinical biopsies. Compared to no-AR, all histologic types of AR led to abnormal histology in 1 and 2 years protocol biopsies, including more fibrosis + inflammation (6.3% vs. 21.9%), moderate/severe fibrosis (7.7% vs. 13.5%) and transplant glomerulopathy (1.4% vs. 8.3%, all p < 0.0001). AR were associated with reduced graft survival (HR = 3.07 (1.92-4.94), p < 0.0001). However, only those AR episodes followed by abnormal histology led to reduced graft survival. Early AR related to more late alloimmune-mediated graft losses, particularly transplant glomerulopathy (31% of losses). Related to this outcome, recipients with AR were more likely to have new DSA class II 1 year posttransplant (no-AR, 11.1%; AR, 21.2%, p = 0.039). In DSA negative recipients, early AR often leads to persistent graft inflammation and increases the risk of new DSA II production. Both of these post-AR events are associated with increased risk of graft loss. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

  10. Activation of polymorphonuclear leukocyte oxygen radical production during acute lung rejection in dogs: inhibition by an antiadhesion molecule monoclonal antibody.

    Science.gov (United States)

    Cale, A R; Katzmann, J A; Tazelaar, H D; Miller, V M; McGregor, C G

    1993-01-01

    Monoclonal antibodies against leukocyte adhesion molecules reduce the severity of reperfusion injury and, in some cases, prevent acute allograft rejection. These effects are assumed to be due to prevention of leukocyte-endothelial adhesion. Experiments were designed to study activation of polymorphonuclear leukocytes during acute rejection of canine single lung allografts and to test the ability of an anti-beta 2-integrin monoclonal antibody (R15.7/H4) to regulate leukocyte metabolism independent of leukocyte-endothelial adhesion. Peripheral blood polymorphonuclear leukocytes were obtained by Ficoll-Hypaque centrifugation from unoperated control dogs (n = 10), from dogs with a single lung autotransplant (n = 4), and from dogs after single lung allotransplantation during unmodified rejection (n = 12). Oxygen radicals were measured with luminal-enhanced chemiluminescence of unstimulated polymorphonuclear leukocytes, polymorphonuclear leukocytes stimulated by opsonized-zymosan, and polymorphonuclear leukocytes incubated with anti-beta 2-integrin beta-chain (CD18) monoclonal antibodies before exposure to opsonized zymosan. Polymorphonuclear leukocyte viability was unaffected by the monoclonal antibodies. Polymorphonuclear leukocytes from unoperated and autotransplant dogs did not produce oxygen radicals unless stimulated by opsonized zymosan. Polymorphonuclear leukocytes from rejecting animals produced oxygen radicals in the absence of zymosan, and when stimulated, production of oxygen radicals was significantly greater than that of polymorphonuclear leukocytes from unoperated and autotransplant dogs. Production of oxygen radicals was inhibited significantly by the monoclonal antibodies in polymorphonuclear leukocytes from all three groups. This study shows that rejection activates polymorphonuclear leukocytes and increases the potential to produce activated oxygen species. In addition to inhibiting leukocyte adhesion to endothelial cells, anti-beta 2-integrin

  11. Administration of Antithymocyte Globulin (Rabbit) to Treat a Severe, Mixed Rejection Episode in a Pregnant Renal Transplant Recipient.

    Science.gov (United States)

    Kutzler, Heather L; Ye, Xiaoyi; Rochon, Caroline; Martin, Spencer T

    2016-04-01

    Pregnancy in solid organ transplant recipients carries numerous risks to the mother such as increased risk of rejection, gestational diabetes mellitus, and preeclampsia. The developing fetus is subjected to risks such as birth defects, preterm delivery, and low birth weight. Typically, these risks can be managed through intensive, multidisciplinary prenatal care and a proper immunosuppressive regimen. In the setting of rejection, however, little data are available to suggest safe and effective treatment of acute cellular rejection, antibody-mediated rejection, or mixed rejection episodes in the pregnant solid organ transplant recipient. We describe the first case, to our knowledge, in which antithymocyte globulin (rabbit) was used to successfully treat a pregnant renal transplant recipient who experienced a mixed rejection episode. A 22-year-old, African American woman with stage 6 chronic kidney disease received a deceased donor renal transplant after undergoing hemodialysis for 3 years. Her maintenance immunosuppressive regimen at the time of transplantation consisted of tacrolimus, prednisone, and mycophenolate mofetil. Despite counseling efforts on the importance of having a planned pregnancy after kidney transplantation so that her immunosuppressive medications could be optimized, the patient became pregnant 12 months later; her mycophenolate mofetil was changed to azathioprine to reduce the risk of fetal deformities or death. Three months later, the patient was admitted for biopsy of her transplanted kidney and was evaluated for possible kidney rejection. After confirmation of a mixed 1B acute cellular rejection and antibody-mediated rejection episode, the patient decided to pursue resolution of her rejection episode and continue the pregnancy despite the potential risks to the fetus. She was treated with high-dose corticosteroids, intravenous immunoglobulin, plasmapheresis, and antithymocyte globulin (rabbit). Twenty-nine months after transplantation, the

  12. 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

  13. High Tacrolimus Clearance Is a Risk Factor for Acute Rejection in the Early Phase After Renal Transplantation.

    Science.gov (United States)

    Egeland, Erlend Johannessen; Robertsen, Ida; Hermann, Monica; Midtvedt, Karsten; Størset, Elisabet; Gustavsen, Marte Theie; Reisæter, Anna Varberg; Klaasen, Rolf; Bergan, Stein; Holdaas, Hallvard; Hartmann, Anders; Åsberg, Anders

    2017-08-01

    Patients with high tacrolimus clearance eliminate more drug within a dose interval compared with those with low clearance. Delays in dosing time will result in transient periods of lower concentrations in high versus low clearance patients. Transient subtherapeutic tacrolimus concentrations may induce acute rejection episodes. A retrospective study in all renal transplant patients treated with tacrolimus at our center from 2009 to 2013 was conducted. The association between individually estimated tacrolimus clearance (daily tacrolimus dose [mg]/trough concentration [μg/L]) and biopsy-proven acute rejection (BPAR) the first 90 days posttransplantation was investigated. In total, 638 patients treated with oral tacrolimus were included in the analysis. Eighty-five (13.3%) patients experienced BPAR. Patients were stratified into 4 groups per their estimated clearance. The patients in the high clearance group had significantly higher incidence of BPAR (20.6%) with a hazard ratio of 2.39 (95% confidence interval, 1.30-4.40) compared with the low clearance group. Clearance estimate (as a continuous variable) showed a hazard ratio of 2.25 (95% confidence interval, 1.70-2.99) after adjusting for other risk factors. There were no significant differences in neither trough concentrations the first week after transplantation nor time to target trough concentration between patients later experiencing BPAR or not. High estimated clearance is significantly associated with increased risk of BPAR the first 90 days posttransplantation and may predict an increased risk of rejection in the early phase after renal transplantation.

  14. Profile of the Pleximmune blood test for transplant rejection risk prediction

    Science.gov (United States)

    Sindhi, Rakesh; Ashokkumar, Chethan; Higgs, Brandon W; Levy, Samantha; Soltys, Kyle; Bond, Geoffrey; Mazariegos, George; Ranganathan, Sarangarajan; Zeevi, Adriana

    2016-01-01

    Summary The Pleximmune™ test (Plexision Inc., Pittsburgh, PA, USA) is the first cell-based test approved by the US FDA, which predicts acute cellular rejection in children with liver- or intestine transplantation. The test addresses an unmet need to improve management of immunosuppression, which incurs greater risks of opportunistic infections and Epstein–Barr virus-induced malignancy during childhood. High-dose immunosuppression and recurrent rejection after intestine transplantation also result in a 5-year graft loss rate of up to 50%. Such outcomes seem increasingly unacceptable because children can experience rejection-free survival with reduced immunosuppression. Pleximmune test sensitivity and specificity for predicting acute cellular rejection is 84% and 81% respectively in training set–validation set testing of 214 children. Among existing gold standards, the biopsy detects but cannot predict rejection. Anti-donor antibodies, which presage antibody-mediated injury, reflect late-stage allosensitization as a downstream effect of engagement between recipient and donor cells. Therefore, durable graft and patient outcomes also require an accurate management of cellular immune responses in clinical practice. PMID:26760313

  15. Nitric oxide production and nitric oxide synthase expression in acute human renal allograft rejection

    NARCIS (Netherlands)

    Albrecht, EWJA; van Goor, H; Tiebosch, ATMG; Moshage, H; Tegzess, Adam; Stegeman, CA

    2000-01-01

    Background Nitric oxide (NO) is produced by nitric oxide synthases (NOS), which are either constitutively expressed in the kidney or inducible, in resident and infiltrating cells during inflammation and allograft rejection. NO is rapidly degraded to the stable end products nitrite and nitrate, which

  16. Complement in Non-Antibody-Mediated Kidney Diseases

    Directory of Open Access Journals (Sweden)

    Andrea Angeletti

    2017-07-01

    Full Text Available The complement system is part of the innate immune response that plays important roles in protecting the host from foreign pathogens. The complement components and relative fragment deposition have long been recognized to be strongly involved also in the pathogenesis of autoantibody-related kidney glomerulopathies, leading to direct glomerular injury and recruitment of infiltrating inflammation pathways. More recently, unregulated complement activation has been shown to be associated with progression of non-antibody-mediated kidney diseases, including focal segmental glomerulosclerosis, C3 glomerular disease, thrombotic microangiopathies, or general fibrosis generation in progressive chronic kidney diseases. Some of the specific mechanisms associated with complement activation in these diseases were recently clarified, showing a dominant role of alternative activation pathway. Over the last decade, a growing number of anticomplement agents have been developed, and some of them are being approved for clinical use or already in use. Therefore, anticomplement therapies represent a realistic choice of therapeutic approaches for complement-related diseases. Herein, we review the complement system activation, regulatory mechanisms, their involvement in non-antibody-mediated glomerular diseases, and the recent advances in complement-targeting agents as potential therapeutic strategies.

  17. Pathogenesis and mechanisms of antibody-mediated hemolysis.

    Science.gov (United States)

    Flegel, Willy A

    2015-07-01

    The clinical consequences of antibodies to red blood cells (RBCs) have been studied for a century. Most clinically relevant antibodies can be detected by sensitive in vitro assays. Several mechanisms of antibody-mediated hemolysis are well understood. Such hemolysis after transfusion is reliably avoided in a donor-recipient pair, if one individual is negative for the cognate antigen to which the other has the antibody. Mechanisms of antibody-mediated hemolysis were reviewed based on a presentation at the Strategies to Address Hemolytic Complications of Immune Globulin Infusions Workshop addressing intravenous immunoglobulin (IVIG) and ABO antibodies. The presented topics included the rates of intravascular and extravascular hemolysis; immunoglobulin (Ig)M and IgG isoagglutinins; auto- and alloantibodies; antibody specificity; A, B, A,B, and A1 antigens; A1 versus A2 phenotypes; monocytes-macrophages, other immune cells, and complement; monocyte monolayer assay; antibody-dependent cell-mediated cytotoxicity; and transfusion reactions due to ABO and other antibodies. Several clinically relevant questions remained unresolved, and diagnostic tools were lacking to routinely and reliably predict the clinical consequences of RBC antibodies. Most hemolytic transfusion reactions associated with IVIG were due to ABO antibodies. Reducing the titers of such antibodies in IVIG may lower the frequency of this kind of adverse event. The only way to stop these events is to have no anti-A or anti-B in the IVIG products. © 2015 AABB.

  18. Is lymphocytic bronchiolitis a marker of acute rejection? An analysis of 2,697 transbronchial biopsies after lung transplantation.

    Science.gov (United States)

    Burton, Christopher M; Iversen, Martin; Scheike, Thomas; Carlsen, Jørn; Andersen, Claus B

    2008-10-01

    Guidelines for the diagnosis and grading of lymphocytic bronchiolitis (LB) have been available for more than a decade, but agreement is lacking concerning the clinical implications of this histologic finding. Study goals were to describe the overall prevalence and incidence of LB in a consecutive cohort of lung transplant recipients and identify risk factors for the onset, frequency, and severity of LB. A retrospective analysis was done of 2,697 transbronchial biopsy (TBB) specimens obtained during the first 2 years after transplantation from 299 consecutive patients who underwent transplantation between 1996 and 2006. Full diameter membranous bronchioli were missing in approximately 30% of TBB specimens. The proportion of patients demonstrating LB remained constant during follow-up (trend test, p = 0.2). The cumulative incidence of LB (>or=B2) was 33%, 53%, 62%, and 68% at 1-, 3-, 6-, and 12-months, respectively. Approximately one-quarter and one-half of the patients had a second episode of >or=B2 within 3 months and 2-years of transplantation, respectively. Exposure to LB during the first 2 years after transplantation was independently associated with the frequency and/or severity of acute cellular rejection (p bronchiolitis obliterans (odds ratio, 3.3, 95% confidence interval, 1.5-6.9, p = 0.001). The frequency and severity of LB was associated with the occurrence and severity of acute cellular rejection.

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

    Directory of Open Access Journals (Sweden)

    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. Structural basis for antibody-mediated neutralization of Lassa virus.

    Science.gov (United States)

    Hastie, Kathryn M; Zandonatti, Michelle A; Kleinfelter, Lara M; Heinrich, Megan L; Rowland, Megan M; Chandran, Kartik; Branco, Luis M; Robinson, James E; Garry, Robert F; Saphire, Erica Ollmann

    2017-06-02

    The arenavirus Lassa causes severe hemorrhagic fever and a significant disease burden in West Africa every year. The glycoprotein, GPC, is the sole antigen expressed on the viral surface and the critical target for antibody-mediated neutralization. Here we present the crystal structure of the trimeric, prefusion ectodomain of Lassa GP bound to a neutralizing antibody from a human survivor at 3.2-angstrom resolution. The antibody extensively anchors two monomers together at the base of the trimer, and biochemical analysis suggests that it neutralizes by inhibiting conformational changes required for entry. This work illuminates pH-driven conformational changes in both receptor-binding and fusion subunits of Lassa virus, illustrates the unique assembly of the arenavirus glycoprotein spike, and provides a much-needed template for vaccine design against these threats to global health. Copyright © 2017, American Association for the Advancement of Science.

  1. Antibody-mediated Prevention of Fusarium Mycotoxins in the Field

    Directory of Open Access Journals (Sweden)

    Yu-Cai Liao

    2008-10-01

    Full Text Available Fusarium mycotoxins directly accumulated in grains during the infection of wheat and other cereal crops by Fusarium head blight (FHB pathogens are detrimental to humans and domesticated animals. Prevention of the mycotoxins via the development of FHB-resistant varieties has been a challenge due to the scarcity of natural resistance against FHB pathogens. Various antibodies specific to Fusarium fungi and mycotoxins are widely used in immunoassays and antibody-mediated resistance in planta against Fusarium pathogens has been demonstrated. Antibodies fused to antifungal proteins have been shown to confer a very significantly enhanced Fusarium resistance in transgenic plants. Thus, antibody fusions hold great promise as an effective tool for the prevention of mycotoxin contaminations in cereal grains. This review highlights the utilization of protective antibodies derived from phage display to increase endogenous resistance of wheat to FHB pathogens and consequently to reduce mycotoxins in field. The role played by Fusarium-specific antibody in the resistance is also discussed.

  2. Serum exosomal protein profiling for the non-invasive detection of cardiac allograft rejection.

    Science.gov (United States)

    Kennel, Peter J; Saha, Amit; Maldonado, Dawn A; Givens, Raymond; Brunjes, Danielle L; Castillero, Estibaliz; Zhang, Xiaokan; Ji, Ruiping; Yahi, Alexandre; George, Isaac; Mancini, Donna M; Koller, Antonius; Fine, Barry; Zorn, Emmanuel; Colombo, Paolo C; Tatonetti, Nicholas; Chen, Emily I; Schulze, P Christian

    2017-07-19

    Exosomes are cell-derived circulating vesicles that play an important role in cell-cell communication. Exosomes are actively assembled and carry messenger RNAs, microRNAs and proteins. The "gold standard" for cardiac allograft surveillance is endomyocardial biopsy (EMB), an invasive technique with a distinct complication profile. The development of novel, non-invasive methods for the early diagnosis of allograft rejection is warranted. We hypothesized that the exosomal proteome is altered in acute rejection, allowing for a distinction between non-rejection and rejection episodes. Serum samples were collected from heart transplant (HTx) recipients with no rejection, acute cellular rejection (ACR) and antibody-mediated rejection (AMR). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of serum exosome was performed using a mass spectrometer (Orbitrap Fusion Tribrid). Principal component analysis (PCA) revealed a clustering of 3 groups: (1) control and heart failure (HF); (2) HTx without rejection; and (3) ACR and AMR. A total of 45 proteins were identified that could distinguish between groups (q < 0.05). Comparison of serum exosomal proteins from control, HF and non-rejection HTx revealed 17 differentially expressed proteins in at least 1 group (q < 0.05). Finally, comparisons of non-rejection HTx, ACR and AMR serum exosomes revealed 15 differentially expressed proteins in at least 1 group (q < 0.05). Of these 15 proteins, 8 proteins are known to play a role in the immune response. Of note, the majority of proteins identified were associated with complement activation, adaptive immunity such as immunoglobulin components and coagulation. Characterizing of circulating exosomal proteome in different cardiac disease states reveals unique protein expression patterns indicative of the respective pathologies. Our data suggest that HTx and allograft rejection alter the circulating exosomal protein content. Exosomal protein analysis could be a novel approach

  3. 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...... or reactivated EBV infection (PREBV) was correlated to acute rejection (treated with OKT3; P

  4. New formulations of tacrolimus and prevention of acute and chronic rejections in adult kidney-transplant recipients.

    Science.gov (United States)

    Jouve, Thomas; Rostaing, Lionel; Malvezzi, Paolo

    2017-07-01

    ​Introduction: As tolerance is not yet achievable, the kidney-transplanted-patients have to take on a daily-basis immunosuppressive drugs in order to avoid acute rejection-AR-. The cornerstone of immunosuppression relies on tacrolimus-therapy which is potentially nephrotoxic. Areas Covered: We identified from the studies published in the recent years those who were reporting on AR in de novo kidney-transplant recipients under tacrolimus-based therapy, as well as those who reported on the attempt to minimize tacrolimus-therapy. There are many formulations of tacrolimus: immediate-release (Prograf®), slow-release (Advagraf®), or extended-release (Envarsus®). All demonstrate a very good efficacy in preventing AR episodes. Studies in which tacrolimus was minimized or even weaned-off have shown that it was unsafe, i.e. in resulting in AR episode and/or de novo donor-specific alloantibodies. Recent data show that Tacrobell®, a generic of tacrolimus, was as efficient as Prograf® in the short- and long-term. Expert-opinion: Tacrolimus-based immunosuppression is very effective in preventing rejection in kidney-transplant recipients. It might be associated with nephrotoxicity, that can be reduced by avoiding tacrolimus trough levels too high in the long-term. Conversely, tacrolimus ultraminimization should not be attempted.

  5. Donor and recipient genetic variants in NLRP3 associate with early acute rejection following kidney transplantation

    NARCIS (Netherlands)

    Dessing, Mark C.; Kers, Jesper; Damman, Jeffrey; Navis, Gerjan J.; Florquin, Sandrine; Leemans, Jaklien C.

    2016-01-01

    NLRP3 (NOD-like receptor family, pyrin domain containing 3) is a member of the inflammasome family and is of special interest in renal disease. Experimental studies have shown that Nlrp3 plays a significant role in the induction of renal damage and dysfunction in acute and chronic renal injury.

  6. Association of high HLA-E expression during acute cellular rejection and numbers of HLA class I leader peptide mismatches with reduced renal allograft survival.

    Science.gov (United States)

    Guberina, Hana; Rebmann, Vera; Wagner, Bettina; da Silva Nardi, Fabiola; Dziallas, Phillip; Dolff, Sebastian; Bienholz, Anja; Wohlschlaeger, Jeremias; Bankfalvi, Agnes; Heinemann, Falko M; Witzke, Oliver; Zoet, Yvonne M; Claas, Frans H J; Horn, Peter A; Kribben, Andreas; Doxiadis, Ilias I N

    2017-03-01

    Non-classical Human Leukocyte Antigen (HLA)-E preferentially presents leader peptides derived from classical HLA-class I molecules. HLA-E can trigger opposed immune responses by interacting with inhibitory NKG2A or by activating NKG2C receptors on NK and T-cells. We studied the impact of HLA-E on renal allograft survival during acute cellular rejection. HLA-E expression was up-regulated in acute cellular rejection (ACR) biopsies (n=12) compared to biopsies from 13 renal allografts with no rejection-signs. HLA-E up-regulation was correlated with numbers of HLA-class I leader peptide mismatches (p=0.04). CD8+ and CD56+ infiltrating cells correlated with HLA-E expression (pleader peptides might represent additional targets for immune-activating responses. Copyright © 2016 Elsevier GmbH. All rights reserved.

  7. Doppler ultrasound of the hepatic artery and vein performed daily in the first two weeks after orthotopic liver transplantation - Useful for the diagnosis of acute rejection?

    NARCIS (Netherlands)

    Kok, T; Haagsma, EB; Klompmaker, IJ; Zwaveling, JH; Peeters, PMJG; Bijleveld, CMA; Meerman, L; Slooff, MJH

    RATIONALE AND OBJECTIVES. To analyze changes in Doppler ultrasound variables in relation to liver biopsy findings for the diagnosis of acute rejection after orthotopic liver transplantation (OLT), the authors performed in a prospective study 316 Doppler ultrasound examinations in the first 2 weeks

  8. 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.

  9. High-mobility group box 1 accelerates early acute allograft rejection via enhancing IL-17+ γδ T-cell response.

    Science.gov (United States)

    Xia, Quansong; Duan, Lihua; Shi, Lifeng; Zheng, Fang; Gong, Feili; Fang, Min

    2014-04-01

    Th17 and γδ T cells are the dominant IL-17-producing cell. We previously reported that high-mobility group box 1 (HMGB1) is critical in inducing IL-17-producing alloreactive T cells during early stage of acute allograft rejection. However, the role of γδ T cells during this process and its implication in HMGB1-mediated allograft rejection are not fully understood. Here, we use a murine model of cardiac allograft transplantation to further study the role of HMGB1 and IL-17-producing γδ T cells in acute allograft rejection. It was found that the expression of HMGB1 was increased in allograft, while blockade of HMGB1 suppressed IL-17(+) γδ T-cell response and inhibited the gene transcription of IL-23 and IL-1β. Furthermore, in vitro HMGB1 indirectly promoted the development of IL-17(+) γδ T cells by stimulating dendritic cells to produce IL-23 and IL-1β, meanwhile depletion of γδ T cells in vivo prolonged allograft survival and reduced the level of IL-17 in serum. In conclusion, our findings inferred that increased HMGB1 expression could enhance IL-17(+) γδ T-cell response by promoting the secretion of IL-23 and IL-1β, while IL-17(+) γδ T cells contribute to the early stage of acute allograft rejection. © 2014 Steunstichting ESOT.

  10. Molecular mechanism of antibody-mediated activation of β-galactosidase

    National Research Council Canada - National Science Library

    Vinothkumar, Kutti R; McMullan, Greg; Henderson, Richard

    2014-01-01

    Binding of a single-chain Fv antibody to Escherichia coli β-galactosidase (β-gal) is known to stabilize the enzyme and activate several inactive point mutants, historically called antibody-mediated enzyme formation mutants...

  11. Impact of longitudinal exposure to mycophenolic acid on acute rejection in renal-transplant recipients using a joint modeling approach.

    Science.gov (United States)

    Daher Abdi, Z; Essig, M; Rizopoulos, D; Le Meur, Y; Prémaud, A; Woillard, J B; Rérolle, J P; Marquet, P; Rousseau, A

    2013-06-01

    This study aimed to investigate the association between longitudinal exposure to mycophenolic acid (MPA) and acute rejection (AR) risk in the first year after renal transplantation, and to propose MPA exposure targets conditionally to this association. A joint model, adjusted for monitoring strategy (fixed-dose versus concentration-controlled) and recipient age, was developed; it combined a mixed-effects model to describe the whole pattern of MPA exposure (i.e. area under the concentration-time curve (AUC)) and a survival model. MPA AUC thresholds were determined using time-dependent receiver-operating characteristics (ROC) curves. Data from 490 adult renal-transplant recipients, representative of the general population of adult renal-transplant patients (i.e. including patients considered at low immunological risk-enrolled in the OPERA trial as well as second renal transplant and patients co-treated by either cyclosporine or tacrolimus), were analyzed. A significant association was found between the longitudinal exposure to MPA (MPA AUCs=f(t)) and AR (p=0.0081), and validated by bootstrapping. A significant positive correlation was observed between time post-transplantation and ROC thresholds which increased in average from 35 mg h/L in the first days to 41 mg h/L beyond six months post-transplantation (papproach which recognizes the repeated measures in a same patient, this study supports the association between MPA exposure and AR. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Infiltration of Macrophages Correlates with Severity of Allograft Rejection and Outcome in Human Kidney Transplantation.

    Directory of Open Access Journals (Sweden)

    Tobias Bergler

    Full Text Available Despite substantial progress in recent years, graft survival beyond the first year still requires improvement. Since modern immunosuppression addresses mainly T-cell activation and proliferation, we studied macrophage infiltration into the allografts of 103 kidney transplant recipients during acute antibody and T-cell mediated rejection. Macrophage infiltration was correlated with both graft function and graft survival until month 36 after transplantation.Macrophage infiltration was significantly elevated in antibody-mediated and T-cell mediated rejection, but not in kidneys with established IFTA. Treatment of rejection with steroids was less successful in patients with more prominent macrophage infiltration into the allografts. Macrophage infiltration was accompanied by increased cell proliferation as well as antigen presentation. With regard to the compartmental distribution severity of T-cell-mediated rejection was correlated to the amount of CD68+ cells especially in the peritubular and perivascular compartment, whereas biopsies with ABMR showed mainly peritubular CD68 infiltration. Furthermore, severity of macrophage infiltration was a valid predictor of resulting creatinine values two weeks as well as two and three years after renal transplantation as illustrated by multivariate analysis. Additionally performed ROC curve analysis showed that magnitude of macrophage infiltration (below vs. above the median was a valid predictor for the necessity to restart dialysis. Having additionally stratified biopsies in accordance to the magnitude of macrophage infiltration, differential CD68+ cell infiltration was reflected by striking differences in overall graft survival.The differences in acute allograft rejection have not only been reflected by different magnitudes of macrophage infiltration, but also by compartment-specific infiltration pattern and subsequent impact on resulting allograft function as well as need for dialysis initiation. There is

  13. Normalizing Rejection.

    Science.gov (United States)

    Conn, Vicki S; Zerwic, Julie; Jefferson, Urmeka; Anderson, Cindy M; Killion, Cheryl M; Smith, Carol E; Cohen, Marlene Z; Fahrenwald, Nancy L; Herrick, Linda; Topp, Robert; Benefield, Lazelle E; Loya, Julio

    2016-02-01

    Getting turned down for grant funding or having a manuscript rejected is an uncomfortable but not unusual occurrence during the course of a nurse researcher's professional life. Rejection can evoke an emotional response akin to the grieving process that can slow or even undermine productivity. Only by "normalizing" rejection, that is, by accepting it as an integral part of the scientific process, can researchers more quickly overcome negative emotions and instead use rejection to refine and advance their scientific programs. This article provides practical advice for coming to emotional terms with rejection and delineates methods for working constructively to address reviewer comments. © The Author(s) 2015.

  14. Hyperosmolar nonketotic hyperglycemic coma induced by methylprednisolone pulse therapy for acute rejection after liver transplantation: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Zhou J

    2014-12-01

    Full Text Available Jian Zhou,* Weiqiang Ju,* Xiaopeng Yuan, Xiaofeng Zhu, Dongping Wang, Xiaoshun HeOrgan Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China *These authors contributed equally to this work Abstract: Hyperosmolar nonketotic hyperglycemic coma (HNKHC is a serious, rare complication induced by methylprednisolone (MP pulse therapy for acute rejection after orthotopic liver transplantation (OLT. Herein, we report an unusual case of a 58-year-old woman who experienced acute rejection at 30 months after OLT, only one case in which HNKHC resulted in MP pulse therapy for acute rejection in all 913 recipients in our center. The general morbidity of HNKHC was 1.09‰ in this study. HNKHC is characterized by rapid onset, rapid progression, and a lack of specific clinical manifestations. High-dose MP management was a clear risk factor. The principle of treatment included rapid rehydration, low-dose insulin infusion, and correcting disorders of electrolytes and acidosis. In conclusion, clinicians considering MP pulse therapy after OLT should be alert to the occurrence of HNKHC. Keywords: liver transplantation, complications, hyperosmolar nonketotic hyperglycemic coma, methylprednisolone pulse therapy, principle of treatment

  15. HEart trAnsplantation Registry of piTie-Salpetriere University Hospital

    Science.gov (United States)

    2018-01-08

    Cardiac Transplant Disorder; Cardiac Death; Heart Failure; Acute Cellular Graft Rejection; Antibody-Mediated Graft Rejection; Cardiac Allograft Vasculopathy; Heart Transplant Rejection; Immune Tolerance

  16. Delayed Graft Function in Kidney Transplants: Time Evolution, Role of Acute Rejection, Risk Factors, and Impact on Patient and Graft Outcome

    Directory of Open Access Journals (Sweden)

    Martin Chaumont

    2015-01-01

    Full Text Available Background. Although numerous risk factors for delayed graft function (DGF have been identified, the role of ischemia-reperfusion injury and acute rejection episodes (ARE occurring during the DGF period is ill-defined and DGF impact on patient and graft outcome remains controversial. Methods. From 1983 to 2014, 1784 kidney-only transplantations from deceased donors were studied. Classical risk factors for DGF along with two novel ones, recipient’s perioperative saline loading and residual diuresis, were analyzed by logistic regression and receiver operating characteristic (ROC curves. Results. Along with other risk factors, absence of perioperative saline loading increases acute rejection incidence (OR = 1.9 [1.2–2.9]. Moreover, we observed two novel risk factors for DGF: patient’s residual diuresis ≤500 mL/d (OR = 2.3 [1.6–3.5] and absence of perioperative saline loading (OR = 3.3 [2.0–5.4]. Area under the curve of the ROC curve (0.77 [0.74–0.81] shows an excellent discriminant power of our model, irrespective of rejection. DGF does not influence patient survival (P=0.54. However, graft survival is decreased only when rejection was associated with DGF (P<0.001.  Conclusions. Perioperative saline loading efficiently prevents ischemia-reperfusion injury, which is the predominant factor inducing DGF. DGF per se has no influence on patient and graft outcome. Its incidence is currently close to 5% in our centre.

  17. Time elapsed after transplantation influences the relationship between the number of regulatory T cells in lung allograft biopsies and subsequent acute rejection episodes

    DEFF Research Database (Denmark)

    Krustrup, Dorrit; Iversen, Martin; Martinussen, Torben

    2014-01-01

    levels of Tregs/mm2. For biopsies taken 0.5 and 1month after transplantation, a significant correlation between Tregs/mm2 and the degree of acute rejection was found, and logistic regression analysis using updated values for Tregs/mm2 showed a significant relationship between Tregs/mm2 at 2weeks and an A...... indicating a narrow therapeutic window for induction of tolerance by specifically targeting T-cells. The results also indirectly indicate that Tregs early after transplantation could have an impact on the long-term outcome....

  18. A pilot study of steroid-free immunosuppression in the prevention of acute rejection in renal allograft recipients.

    Science.gov (United States)

    Cole, E; Landsberg, D; Russell, D; Zaltzman, J; Kiberd, B; Caravaggio, C; Vasquez, A R; Halloran, P

    2001-09-15

    Corticosteroids have been a mainstay of rejection prophylaxis for several decades, despite the multiple adverse effects of long-term use, including weight gain, hyperlipidemia, diabetes, hypertension, and bone disease. The detrimental effect of steroids on the metabolic profile begins in the early posttransplantation period, and the complete avoidance of steroids in transplantation would therefore be optimal. We hypothesized that the addition of mycophenolate mofetil (MMF) and a humanized monoclonal anti-CD25 antibody (daclizumab) to a cyclosporine (CsA microemulsion)-based immunosuppression protocol would permit transplantation without steroids. Steroid-free renal transplantation was attempted in 57 patients treated with daclizumab, MMF, and CsA. Twenty-eight patients received kidneys from living donors; the remaining 29 received cadaveric grafts. At 1 year, patient and graft survival were 95% and 89%, respectively. Fourteen patients (25%) experienced rejections, of which 13 were readily reversed with steroids; 1 patient required OKT3. Mean serum creatinine at 12 months for patients not experiencing rejection was 149+/-58 micromol/L, compared with 158+/-102 micromol/L for those experiencing rejection. Five patients required hospitalization for infection; no patients developed lymphoproliferative disease. At baseline, 17 patients required 3 or more antihypertensive medications, compared with 2 patients at 1 year. Three of 43 nondiabetic patients developed diabetes during the study. There was no significant reduction in lumbar or femoral bone density. On the basis of these positive results, we believe steroid avoidance with this immunosuppressive regimen merits further study.

  19. 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

  20. Indium-111 myosin-specific antibodies and technetium-99m pyrophosphate in the detection of acute cardiac rejection of transplanted hearts. Studies in a heterotopic rat heart model

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Kan (Mie Univ., Tsu (Japan). School of Medicine); Ueda, Keisuke (Saitama Univ. (Japan). Dept. of Surgery); Scheffel, U.; Ravert, H.; Wagner, H.N. Jr. (Johns Hopkins Medical Institutions, Baltimore, MD (USA). Dept. of Radiology); LaFrance, N.D. (Du Pont (E.I.) Co., Inc., North Billerica, MA (USA)); Baumgartner, W.A.; Reitz, B.A.; Herskowitz, A. (Johns Hopkins Medical Institutions, Baltimore, MD (USA). Dept. of Surgery)

    1991-07-01

    {sup 111}In-labelled myosin-specific antibodies were evaluated as an indicator of early changes in acute rejection in a rat heart heterotopic transplant model. Uptake of antibodies was measured in allograft and isograft hearts of animals undergoing different regimens of cyclosporine treatment and compared with the uptake of technetium 99m pyrophosphate. The data were correlated with histological estimation of the severity of myocyte necrosis and sign of early rejection (venous cuffing and endocardial inflammation, indicators of perivascular infiltrate and intermyocyte extension, respectively). Myocyte necrosis in transplanted hearts was reflected by increases in technetium 99m pyrophosphate accumulation (r=0.88) but was poorly correlated with labelled antibody uptake (r=0.58). There was no positive correlation between the degree of early cardiac rejection and uptake of either of the radiopharmaceuticals: accumulation of the labeled antibodies paradoxically declined with increased histological severity scores, whereas that of technetium 99m pyrophosphate remained unchanged. Cyclosporine treatment augmented the uptake of labelled antibodies in transplanted hearts. This may be due to alterations in plasma membrane permeability brought about by the drug, resulting in a rise in antibody binding to intracellular myosin. (orig.).

  1. 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

  2. Suppression of acute and chronic cardiac allograft rejection in mice by inhibition of chemokine receptor 5 in combination with cyclosporine A.

    Science.gov (United States)

    Li, Jun; Xia, Jiahong; Zhang, Kailun; Xu, Lei

    2009-11-01

    Inhibition of chemokine receptor 5 (CCR5), a chemokine receptor expressed on activated T cells, is an effective antiviral therapy in patients with HIV infection, but its efficacy in modulating inflammation and immunity is only just beginning to be investigated. In this study we examined the inhibition of CCR5 in combination with the treatment with cyclosporine A in acute and chronic rejection in cardiac transplantation. Eighty fully MHC-mismatched murine cardiac allograft models were randomized to four groups. Recipients in group A were treated with anti-CCR5 mAb and CsA, mice in group B were given anti-CCR5 mAb alone, animals in group C were administered only CsA, and group D were the control group with PBS. Acute and chronic rejection was investigated on day 7 and day 45 post-transplant, respectively. Allografts treated with anti-CCR5 mAb plus CsA showed significantly prolonged survival (44.73 +/- 0.258 d, P cardiac graft failure that has not been obviated by conventional immunosuppressive agents.

  3. Orthogonal Comparison of Molecular Signatures of Kidney Transplants With Subclinical and Clinical Acute Rejection: Equivalent Performance Is Agnostic to Both Technology and Platform.

    Science.gov (United States)

    Kurian, S M; Velazquez, E; Thompson, R; Whisenant, T; Rose, S; Riley, N; Harrison, F; Gelbart, T; Friedewald, J J; Charette, J; Brietigam, S; Peysakhovich, J; First, M R; Abecassis, M M; Salomon, D R

    2017-08-01

    We performed orthogonal technology comparisons of concurrent peripheral blood and biopsy tissue samples from 69 kidney transplant recipients who underwent comprehensive algorithm-driven clinical phenotyping. The sample cohort included patients with normal protocol biopsies and stable transplant (sTx) function (n = 25), subclinical acute rejection (subAR, n = 23), and clinical acute rejection (cAR, n = 21). Comparisons between microarray and RNA sequencing (RNA-seq) signatures were performed and demonstrated a strong correlation between the blood and tissue compartments for both technology platforms. A number of shared differentially expressed genes and pathways between subAR and cAR in both platforms strongly suggest that these two clinical phenotypes form a continuum of alloimmune activation. SubAR is associated with fewer or less expressed genes than cAR in blood, whereas in biopsy tissues, this clinical phenotype demonstrates a more robust molecular signature for both platforms. The discovery work done in this study confirms a clear ability to detect gene expression profiles for sTx, subAR, and cAR in both blood and biopsy tissue, yielding equivalent predictive performance that is agnostic to both technology and platform. Our data also provide strong biological insights into the molecular mechanisms underlying these signatures, underscoring their logistical potential as molecular diagnostics to improve clinical outcomes following kidney transplantation. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  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. Association of the Number of HLA-DR Mismatches With Early Post-transplant Acute Cellular Rejection Among Heart Transplantation Recipients: A Cohort Study in Japanese Population.

    Science.gov (United States)

    Nitta, D; Kinugawa, K; Imamura, T; Iino, J; Endo, M; Amiya, E; Hatano, M; Kinoshita, O; Nawata, K; Ono, M; Komuro, I

    Although many risk factors are reported about graft rejection after heart transplantation (HTx), the effect of HLA mismatch (MM) still remains unknown, especially in the Japanese population. The aim of the present study was to investigate the influence of HLA MM on graft rejection among HTx recipients in Japan. We retrospectively investigated the association of the number of HLA MM including class I (A, B) and class II (DR) (for each locus MM: 0 to 2, total MM: 0 to 6) and the incidence of moderate to severe acute cellular rejection (ACR) confirmed by endomyocardial biopsy (International Society for Heart and Lung Transplantation grade ≥ 3A/2R) within 1 year after HTx. Between 2007 and 2014, we had 49 HTx cases in our institute. After excluding those with insufficient data and positive donor-specific antigen, finally 35 patients were enrolled. Moderate to severe ACR was observed in 16 (45.7%) patients. The number of HLA-DR MM was significantly associated with the development of ACR (ACR+: 1.50 ± 0.63, ACR-: 1.11 ± 0.46, P = .029). From univariate analysis, DR MM = 2 was the only independent risk factor for ACR episodes (P = .017). The frequency of ACR within 1 year was significantly higher in those with DR MM = 2 (DR MM = 0 to 1: 0.3 ± 0.47, DR MM = 2: 1.17 ± 1.34 times, P = .007). The number of HLA-DR MMs was associated with the development and recurrence of ACR episodes among HTx recipients within 1 year after transplantation in Japanese population. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. Sepiapterin decreases acute rejection and apoptosis in cardiac transplants independently of changes in nitric oxide and inducible nitric-oxide synthase dimerization.

    Science.gov (United States)

    Pieper, Galen M; Ionova, Irina A; Cooley, Brian C; Migrino, Raymond Q; Khanna, Ashwani K; Whitsett, Jennifer; Vásquez-Vivar, Jeannette

    2009-06-01

    Tetrahydrobiopterin (BH(4)), a cofactor of inducible nitric-oxide synthase (iNOS), is an important post-translational regulator of NO bioactivity. We examined whether treatment of cardiac allograft recipients with sepiapterin [S-(-)-2-amino-7,8-dihydro-6-(2-hydroxy-1-oxopropyl)-4-(1H)-pteridinone], a precursor of BH(4), inhibited acute rejection and apoptosis in cardiac transplants. Heterotopic cardiac transplantation was performed in Wistar-Furth donor to Lewis recipient strain rats. Recipients were treated daily after transplantation with 10 mg/kg sepiapterin. Grafts were harvested on post-transplant day 6 for analysis of BH(4) (high-performance liquid chromatography), expression of inflammatory cytokines (reverse transcription- and real-time polymerase chain reaction), iNOS (Western blots), and NO (Griess reaction and NO analyzer). Histological rejection grade was scored, and graft function was determined by echocardiography. Apoptosis, protein nitration, and oxidative stress were determined by immunohistochemistry. Treatment of allografts with sepiapterin increased cardiac BH(4) levels by 3-fold without changing protein levels of GTP cyclohydrolase, the enzyme that regulates de novo BH(4) synthesis. Sepiapterin decreased inflammatory cell infiltrate and significantly inhibited histological rejection scores and apoptosis similar in magnitude to cyclosporine. Sepiapterin also decreased nitrative and oxidative stress. Sepiapterin caused a smaller increase in left ventricular mass versus untreated allografts but without improving fractional shortening. Sepiapterin did not alter tumor necrosis factor-alpha and interferon-gamma expression, whereas it decreased interleukin (IL)-2 expression. Sepiapterin did not change total iNOS protein or monomer levels, or plasma and tissue NO metabolites levels. It is concluded that the mechanism(s) of antirejection are due in part to decreased apoptosis, protein nitration, and oxidation of cardiomyocytes, which seems to be

  7. Antibody-Mediated Neutralization of Pertussis Toxin-Induced Mitogenicity of Human Peripheral Blood Mononuclear Cells

    OpenAIRE

    Scott H Millen; Bernstein, David I.; Connelly, Beverly; Ward, Joel I.; Chang, Swei-Ju; Weiss, Alison A.

    2004-01-01

    Antibody-mediated neutralization of pertussis toxin-induced proliferation of human peripheral blood mononuclear cells (PBMC) was assessed using alamarBlue and compared with results from the Chinese hamster ovary (CHO) cell assay using sera from vaccinated adults and convalescent children. Neutralization values for the CHO assay were similar for vaccinated and convalescent subjects; however. the convalescent group had higher titers in the PBMC assay. Results for pertussis toxin neutralization ...

  8. Acute Rejection Rates and Graft Outcomes According to Induction Regimen among Recipients of Kidneys from Deceased Donors Treated with Tacrolimus and Mycophenolate

    Science.gov (United States)

    Jaikaransingh, Vishal; MacConmara, Malcolm P.; Parekh, Justin R.; Levea, Swee-Ling; Ariyamuthu, Venkatesh K.; Zhang, Song; Gao, Ang; Ayvaci, Mehmet U.S.; Sandikci, Burhaneddin; Rajora, Nilum; Ahmed, Vaqar; Lu, Christopher Y.; Mohan, Sumit; Vazquez, Miguel A.

    2016-01-01

    Background and objectives IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent for induction therapy in renal transplantation. However, this remains controversial in deceased donor renal transplantation (DDRT) maintained on tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids. Design, setting, participants, & measurements We studied the United Network for Organ Sharing Registry for patients receiving DDRT from 2000 to 2012 maintained on TAC/MPA at transplantation hospital discharge (n=74,627) to compare outcomes of IL2-RA and other induction agents. We initially divided the cohort into two groups on the basis of steroid use at the time of discharge: steroid (n=59,010) versus no steroid (n=15,617). Each group was stratified into induction categories: IL2-RA, rabbit antithymocyte globulin (r-ATG), alemtuzumab, and no induction. The main outcomes were incidence of acute rejection within the first year and overall graft failure (defined as graft failure and/or death) post-transplantation. Propensity score (PS), specifically inverse probability of treatment weight, analysis was used to minimize selection bias caused by nonrandom assignment of induction therapies. Results Median (25th, 75th percentiles) follow-up times were 3.9 (1.1, 5.9) and 3.2 (1.1, 4.9) years for steroid and no steroid groups, respectively. Acute rejection within the first year and overall graft failure within 5 years of transplantation were more common in the no induction category (13.3%; P<0.001 and 28%; P=0.01, respectively) in the steroid group and the IL2-RA category (11.1%; P=0.16 and 27.4%; P<0.001, respectively) in the no steroid group. Compared with IL2-RA, PS–weighted and covariate–adjusted multivariable logistic and Cox analyses showed that outcomes in the steroid group were similar among induction categories, except that acute rejection was significantly lower with r-ATG (odds ratio [OR], 0.68; 95% confidence interval [95% CI], 0.62 to 0.74). In the no

  9. 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.

  10. 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

  11. The kSORT Assay to Detect Renal Transplant Patients at High Risk for Acute Rejection: Results of the Multicenter AART Study

    Science.gov (United States)

    Hsieh, Sue; Dai, Hong; Bestard, Oriol; Metes, Diana; Zeevi, Andrea; Gritsch, Albin; Cheeseman, Jennifer; Macedo, Camila; Peddy, Ram; Medeiros, Mara; Vincenti, Flavio; Asher, Nancy; Salvatierra, Oscar; Shapiro, Ron; Kirk, Allan; Reed, Elaine; Sarwal, Minnie M.

    2014-01-01

    Background Development of noninvasive molecular assays to improve disease diagnosis and patient monitoring is a critical need. In renal transplantation, acute rejection (AR) increases the risk for chronic graft injury and failure. Noninvasive diagnostic assays to improve current late and nonspecific diagnosis of rejection are needed. We sought to develop a test using a simple blood gene expression assay to detect patients at high risk for AR. Methods and Findings We developed a novel correlation-based algorithm by step-wise analysis of gene expression data in 558 blood samples from 436 renal transplant patients collected across eight transplant centers in the US, Mexico, and Spain between 5 February 2005 and 15 December 2012 in the Assessment of Acute Rejection in Renal Transplantation (AART) study. Gene expression was assessed by quantitative real-time PCR (QPCR) in one center. A 17-gene set—the Kidney Solid Organ Response Test (kSORT)—was selected in 143 samples for AR classification using discriminant analysis (area under the receiver operating characteristic curve [AUC] = 0.94; 95% CI 0.91–0.98), validated in 124 independent samples (AUC = 0.95; 95% CI 0.88–1.0) and evaluated for AR prediction in 191 serial samples, where it predicted AR up to 3 mo prior to detection by the current gold standard (biopsy). A novel reference-based algorithm (using 13 12-gene models) was developed in 100 independent samples to provide a numerical AR risk score, to classify patients as high risk versus low risk for AR. kSORT was able to detect AR in blood independent of age, time post-transplantation, and sample source without additional data normalization; AUC = 0.93 (95% CI 0.86–0.99). Further validation of kSORT is planned in prospective clinical observational and interventional trials. Conclusions The kSORT blood QPCR assay is a noninvasive tool to detect high risk of AR of renal transplants. Please see later in the article for the Editors' Summary PMID

  12. The kSORT assay to detect renal transplant patients at high risk for acute rejection: results of the multicenter AART study.

    Directory of Open Access Journals (Sweden)

    Silke Roedder

    2014-11-01

    Full Text Available Development of noninvasive molecular assays to improve disease diagnosis and patient monitoring is a critical need. In renal transplantation, acute rejection (AR increases the risk for chronic graft injury and failure. Noninvasive diagnostic assays to improve current late and nonspecific diagnosis of rejection are needed. We sought to develop a test using a simple blood gene expression assay to detect patients at high risk for AR.We developed a novel correlation-based algorithm by step-wise analysis of gene expression data in 558 blood samples from 436 renal transplant patients collected across eight transplant centers in the US, Mexico, and Spain between 5 February 2005 and 15 December 2012 in the Assessment of Acute Rejection in Renal Transplantation (AART study. Gene expression was assessed by quantitative real-time PCR (QPCR in one center. A 17-gene set--the Kidney Solid Organ Response Test (kSORT--was selected in 143 samples for AR classification using discriminant analysis (area under the receiver operating characteristic curve [AUC] = 0.94; 95% CI 0.91-0.98, validated in 124 independent samples (AUC = 0.95; 95% CI 0.88-1.0 and evaluated for AR prediction in 191 serial samples, where it predicted AR up to 3 mo prior to detection by the current gold standard (biopsy. A novel reference-based algorithm (using 13 12-gene models was developed in 100 independent samples to provide a numerical AR risk score, to classify patients as high risk versus low risk for AR. kSORT was able to detect AR in blood independent of age, time post-transplantation, and sample source without additional data normalization; AUC = 0.93 (95% CI 0.86-0.99. Further validation of kSORT is planned in prospective clinical observational and interventional trials.The kSORT blood QPCR assay is a noninvasive tool to detect high risk of AR of renal transplants. Please see later in the article for the Editors' Summary.

  13. The first 24 h: targeting the window of opportunity for antibody-mediated protection against HIV-1 transmission.

    Science.gov (United States)

    Lewis, George K

    2016-11-01

    I will review evidence that antibodies protect against HIV-1 transmission in a short window of opportunity, involving neutralization, Fc-mediated effector function, or both. The last decade witnessed a dramatic progress in the understanding of antibody-mediated protection against HIV-1, including active and passive immunization studies in nonhuman primates; association between reduced infection risk and the specificities and function of antibodies in the RV144 clinical trial; identification of potent, broadly neutralizing antibodies; high-resolution structural studies of the HIV-1 envelope trimer; and an increasing appreciation that Fc-mediated effector function is critical to protection against transmission for neutralizing and nonneutralizing antibodies. Less information is known about how antibodies protect in situ, except that they must do in the first 24 h after exposure. New evidence suggests that antibodies protect in an acute innate immune environment involving the NXLRX1 inflammasome and transforming growth factor beta (TGF-β) that favors infection and rapid dissemination of CCR6RORγ Th17 cells. These recent findings set the stage for understanding how antibodies can prevent the transmission of HIV-1. In this context, antibodies must prevent infection in an innate immune environment that strongly favors transmission. This information is key for the development of a vaccine against HIV-1.

  14. Analysis of Sera of Recipients with Allograft Rejection Indicates That Keratin 1 Is the Target of Anti-Endothelial Antibodies

    OpenAIRE

    Xuli Guo; Juan Hu; Weiguang Luo; Qizhi Luo; Jing Guo; Fang Tian; Yingzi Ming; Yizhou Zou

    2017-01-01

    Anti-endothelial cell antibodies (AECAs) are usually directed against the surface antigens on the vascular endothelial cells. Clinical studies suggest a pathogenic role for nonhuman leukocyte antigen in antibody-mediated rejection; however, the antigens on the donor vascular endothelium that serve as the first-line targets for an immune response during allograft rejection have not been fully identified. Here, we used immunoprecipitation and mass spectrometry to identify antigens from the sera...

  15. Basiliximab treatment for steroid-resistant rejection in pediatric patients following liver transplantation for acute liver failure.

    Science.gov (United States)

    Shigeta, Takanobu; Sakamoto, Seisuke; Uchida, Hajime; Sasaki, Kengo; Hamano, Ikumi; Kanazawa, Hiroyuki; Fukuda, Akinari; Kawai, Toshinao; Onodera, Masafumi; Nakazawa, Atsuko; Kasahara, Mureo

    2014-12-01

    An IL-2 receptor antagonist, basiliximab, decreases the frequency of ACR in liver transplant (LT) recipients as induction therapy. The aim of this study was to evaluate the effectiveness of basiliximab against SRR as rescue therapy in pediatric LT patients with ALF. Forty pediatric ALF patients underwent LT between November 2005 and July 2013. Among them, seven patients suffering from SRR were enrolled in this study. The median age at LT was 10 months (6-12 months). SRR was defined as the occurrence of refractory rejection after more than two courses of steroid pulse therapy. Basiliximab was administered to all patients. The withdrawal of steroids without deterioration of the liver function was achieved in six patients treated with basiliximab therapy without patient mortality, although one patient developed graft loss and required retransplantation for veno-occlusive disease. The pathological examinations of liver biopsies in the patients suffering from SRR revealed severe centrilobular injuries, particularly fibrosis within one month after LT. We demonstrated the effectiveness and safety of rescue therapy consisting of basiliximab for SRR in pediatric LT recipients with ALF. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Urinary metabolomics for noninvasive detection of borderline and acute T cell-mediated rejection in children after kidney transplantation.

    Science.gov (United States)

    Blydt-Hansen, T D; Sharma, A; Gibson, I W; Mandal, R; Wishart, D S

    2014-10-01

    The goal of this study was to evaluate the utility of urinary metabolomics for noninvasive diagnosis of T cell-mediated rejection (TCMR) in pediatric kidney transplant recipients. Urine samples (n = 277) from 57 patients with surveillance or indication kidney biopsies were assayed for 134 unique metabolites by quantitative mass spectrometry. Samples without TCMR (n = 183) were compared to borderline tubulitis (n = 54) and TCMR (n = 30). Partial least squares discriminant analysis identified distinct classifiers for TCMR (area under receiver operating characteristic curve [AUC] = 0.892; 95% confidence interval [CI] 0.827-0.957) and borderline tubulitis (AUC = 0.836; 95% CI 0.781-0.892), respectively. Application of the TCMR classifier to borderline tubulitis samples yielded a discriminant score (-0.47 ± 0.33) mid-way between TCMR (-0.20 ± 0.34) and No TCMR (-0.80 ± 0.32) (p metabolomics is a sensitive, specific and noninvasive tool for TCMR identification that is superior to serum creatinine, with minimal confounding by other allograft injury processes. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

  17. 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 number of lymphocytes expressing FoxP3 in transbronchial biopsies from lung allografts with the FoxP3 expression in bronchoalveolar lavage fluid (BALF). In addition, we aimed to correlate the number of FoxP3+ cells in transbronchial biopsies with the degree of acute cellular rejection in lung allografts....

  18. Kidney Intragraft Homing of De Novo Donor-Specific HLA Antibodies Is an Essential Step of Antibody-Mediated Damage but Not Per Se Predictive of Graft Loss.

    Science.gov (United States)

    Nocera, A; Tagliamacco, A; Cioni, M; Innocente, A; Fontana, I; Barbano, G; Carrea, A; Ramondetta, M; Sementa, A; Basso, S; Quartuccio, G; Klersy, C; Bertocchi, M; Verrina, E; Garibotto, G; Ghiggeri, G M; Cardillo, M; Comoli, P; Ginevri, F

    2017-03-01

    Donor-specific HLA antibody (DSA)-mediated graft injury is the major cause of kidney loss. Among DSA characteristics, graft homing has been suggested as an indicator of severe tissue damage. We analyzed the role of de novo DSA (dnDSA) graft homing on kidney transplantation outcome. Graft biopsy specimens and parallel sera from 48 nonsensitized pediatric kidney recipients were analyzed. Serum samples and eluates from graft biopsy specimens were tested for the presence of dnDSAs with flow bead technology. Intragraft dnDSAs (gDSAs) were never detected in the absence of serum dnDSAs (sDSAs), whereas in the presence of sDSAs, gDSAs were demonstrated in 72% of biopsy specimens. A significantly higher homing capability was expressed by class II sDSAs endowed with high mean fluorescence intensity and C3d- and/or C1q-fixing properties. In patients with available sequential biopsy specimens, we detected gDSAs before the appearance of antibody-mediated rejection. In sDSA-positive patients, gDSA positivity did not allow stratification for antibody-mediated graft lesions and graft loss. However, a consistent detection of skewed unique DSA specificities was observed over time within the graft, likely responsible for the damage. Our results indicate that gDSAs could represent an instrumental tool to identify, among sDSAs, clinically relevant antibody specificities requiring monitoring and possibly guiding patient management. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  19. Different IVIG glycoforms affect in vitro inhibition of anti-ganglioside antibody-mediated complement deposition.

    Directory of Open Access Journals (Sweden)

    Makoto Sudo

    Full Text Available Intravenous immunoglobulin (IVIG is the first line treatment for Guillain-Barré syndrome and multifocal motor neuropathy, which are caused by anti-ganglioside antibody-mediated complement-dependent cytotoxicity. IVIG has many potential mechanisms of action, and sialylation of the IgG Fc portion reportedly has an anti-inflammatory effect in antibody-dependent cell-mediated cytotoxicity models. We investigated the effects of different IVIG glycoforms on the inhibition of antibody-mediated complement-dependent cytotoxicity. Deglycosylated, degalactosylated, galactosylated and sialylated IgG were prepared from IVIG following treatment with glycosidases and glycosyltransferases. Sera from patients with Guillain-Barré syndrome, Miller Fisher syndrome and multifocal motor neuropathy associated with anti-ganglioside antibodies were used. Inhibition of complement deposition subsequent to IgG or IgM autoantibody binding to ganglioside, GM1 or GQ1b was assessed on microtiter plates. Sialylated and galactosylated IVIGs more effectively inhibited C3 deposition than original IVIG or enzyme-treated IVIGs (agalactosylated and deglycosylated IVIGs. Therefore, sialylated and galactosylated IVIGs may be more effective than conventional IVIG in the treatment of complement-dependent autoimmune diseases.

  20. Increasing the sensitivity of reverse phase protein arrays by antibody-mediated signal amplification

    Directory of Open Access Journals (Sweden)

    Brase Jan C

    2010-06-01

    Full Text Available Abstract Background Reverse phase protein arrays (RPPA emerged as a useful experimental platform to analyze biological samples in a high-throughput format. Different signal detection methods have been described to generate a quantitative readout on RPPA including the use of fluorescently labeled antibodies. Increasing the sensitivity of RPPA approaches is important since many signaling proteins or posttranslational modifications are present at a low level. Results A new antibody-mediated signal amplification (AMSA strategy relying on sequential incubation steps with fluorescently-labeled secondary antibodies reactive against each other is introduced here. The signal quantification is performed in the near-infrared range. The RPPA-based analysis of 14 endogenous proteins in seven different cell lines demonstrated a strong correlation (r = 0.89 between AMSA and standard NIR detection. Probing serial dilutions of human cancer cell lines with different primary antibodies demonstrated that the new amplification approach improved the limit of detection especially for low abundant target proteins. Conclusions Antibody-mediated signal amplification is a convenient and cost-effective approach for the robust and specific quantification of low abundant proteins on RPPAs. Contrasting other amplification approaches it allows target protein detection over a large linear range.

  1. 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

  2. Clinical significance of the ratio between FOXP3 positive regulatory T cell and interleukin-17 secreting cell in renal allograft biopsies with acute T-cell-mediated rejection

    Science.gov (United States)

    Chung, Byung H; Oh, Hye J; Piao, Shang G; Hwang, Hyeon S; Sun, In O; Choi, Sun R; Park, Hoon S; Choi, Bum S; Choi, Yeong J; Park, Cheol W; Kim, Yong-Soo; Cho, Mi-La; Yang, Chul W

    2012-01-01

    The aim of this study is to investigate the clinical significance of the ratio between interleukin-17 (IL-17) secreting cell and FOXP3-positive regulatory T cell (FOXP3+ Treg) infiltration in renal allograft tissues with acute T-cell-mediated rejection (ATCMR). Fifty-six patients with biopsy-proven ATCMR were included. Infiltration of FOXP3+ Treg and IL-17-secreting cells was evaluated with immunostaining for FOXP3 or IL-17 on the biopsy specimens, and the patients were divided into the FOXP3 high group (Log FOXP3/IL-17 > 0·45) or the IL-17 high group (Log FOXP3/IL-17 IL-17 high group, allograft function was significantly decreased compared with the FOXP3 high group (P IL-17 high group was higher than the FOXP3 high group (P IL-17 high group than in the FOXP3 high group (all indicators, P IL-17 high group showed lower 1-year (54% versus 90%, P IL-17 ratio was a significant predictor for allograft outcome. The FOXP3/IL-17 ratio is a useful indicator for representing the severity of tissue injury, allograft dysfunction and for predicting the clinical outcome of ATCMR. PMID:22444300

  3. Higher tacrolimus trough levels on days 2-5 post-renal transplant are associated with reduced rates of acute rejection.

    LENUS (Irish Health Repository)

    O'Seaghdha, C M

    2011-04-06

    We analyzed the association between whole-blood trough tacrolimus (TAC) levels in the first days post-kidney transplant and acute cellular rejection (ACR) rates. Four hundred and sixty-four consecutive, deceased-donor kidney transplant recipients were included. All were treated with a combination of TAC, mycophenolate mofetil and prednisolone. Patients were analyzed in four groups based on quartiles of the mean TAC on days 2 and 5 post-transplant: Group 1: median TAC 11 ng\\/mL (n = 122, range 2-13.5 ng\\/mL), Group 2: median 17 ng\\/mL (n = 123, range 14-20 ng\\/mL), Group 3: median 24 ng\\/mL (n = 108, range 20.5-27 ng\\/mL) and Group 4: median 33.5 ng\\/mL (n = 116, range 27.5-77.5 ng\\/mL). A graded reduction in the rates of ACR was observed for each incremental days 2-5 TAC. The one-yr ACR rate was 24.03% (95% CI 17.26-32.88), 22.20% (95% CI 15.78-30.70), 13.41% (95% CI 8.15-21.63) and 8.69% (95% CI 4.77-15.55) for Groups 1-4, respectively (p = 0.003). This study suggests that higher early TACs are associated with reduced rates of ACR at one yr.

  4. 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...

  5. Antibody-mediated enhancement of Wesselsbron virus in P388D1 cells.

    Science.gov (United States)

    Fagbami, A H; Halstead, S B

    1986-01-01

    Antibody-mediated enhancement of Wesselsbron virus was investigated in P388D1 cell cultures. Virus infection was enhanced in culture by various dilutions of homologous and heterologous flavivirus antibody. Highest enhancement ratios and enhancing antibody titres were obtained with the homologous antibody. Enhancement of Wesselsbron virus infection in P388D1 cultures was also dependent on the multiplicity of infection (MOI) used; cultures infected at the lowest MOI produced the highest enhancement ratios. Of the four heterologous flavivirus IMAF tested for ability to enhance Wesselsbron virus infection, Potiskum virus antibody produced highest fold enhancement and possessed the highest enhancing antibody titre. Zika, Uganda S and Dakar bat IMAF produced lower fold enhancement and had lower enhancing antibody titres.

  6. Treatment of refractory antibody mediated autoimmune disorders with an anti-CD20 monoclonal antibody (rituximab)

    Science.gov (United States)

    Arzoo, K; Sadeghi, S; Liebman, H

    2002-01-01

    Patients: Because of its novel mechanism of action, rituximab was used to treat three patients with refractory systemic antibody mediated autoimmune disorders. The first patient, a 71 year old woman with idiopathic type II mixed essential cryoglobulinaemia, had both dermatological and neurological manifestations with marked renal disease attributed to her cryoglobulinaemia. Patient 2, a 73 year old woman with Goodpasture's syndrome, was refractory to conventional treatment (cyclophosphamide, prednisone, plasmapheresis). She had persistent haemoptysis and haematuria and positive antiglomerular basement membrane antibodies. The third patient, a 75 year old man with primary biliary cirrhosis, myelodysplasia, and systemic immune complex vasculitis, had progressive renal insufficiency, a macular erythematous rash, and severe thrombocytopenia. Results: Treatment with rituximab resolved all clinical and laboratory manifestations in the three patients. Conclusions: Rituximab may be an important therapeutic agent for the treatment of patients refractory or intolerant to corticosteroid or cytotoxic treatment, or both. PMID:12228164

  7. Antibody-mediated modulation of cytokinins in tobacco: organ-specific changes in cytokinin homeostasis.

    Science.gov (United States)

    Gelová, Zuzana; Ten Hoopen, Petra; Novák, Ondrej; Motyka, Václav; Pernisová, Markéta; Dabravolski, Siarhei; Didi, Vojtech; Tillack, Isolde; Okleštková, Jana; Strnad, Miroslav; Hause, Bettina; Haruštiaková, Danka; Conrad, Udo; Janda, Lubomír; Hejátko, Jan

    2017-12-23

    Cytokinins comprise a group of phytohormones with an organ-specific mode of action. Although the mechanisms controlling the complex networks of cytokinin metabolism are partially known, the role of individual cytokinin types in the maintenance of cytokinin homeostasis remains unclear. Utilizing the overproduction of single-chain Fv antibodies selected for their ability to bind trans-zeatin riboside and targeted to the endoplasmic reticulum, we post-synthetically modulated cytokinin ribosides, the proposed transport forms of cytokinins. We observed asymmetric activity of cytokinin biosynthetic genes and cytokinin distribution in wild-type tobacco seedlings with higher cytokinin abundance in the root than in the shoot. Antibody-mediated modulation of cytokinin ribosides further enhanced the relative cytokinin abundance in the roots and induced cytokinin-related phenotypes in an organ-specific manner. The activity of cytokinin oxidase/dehydrogenase in the roots was strongly up-regulated in response to antibody-mediated formation of the cytokinin pool in the endoplasmic reticulum. However, we only detected a slight decrease in the root cytokinin levels. In contrast, a significant decrease of cytokinins occurred in the shoot. We suggest the roots as the main site of cytokinin biosynthesis in tobacco seedlings. Conversely, cytokinin levels in the shoot seem to depend largely on long-range transport of cytokinin ribosides from the root and their subsequent metabolic activation. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  8. Age-specific risk of renal graft loss from late acute rejection or noncompliance in the adolescent and young adult period.

    Science.gov (United States)

    Ritchie, Angus G; Clayton, Philip A; McDonald, Stephen P; Kennedy, Sean E

    2017-04-27

    To identify if an age-specific high-risk window for graft loss is present in Australia and New Zealand and identify the aetiology for such graft loss using the ANZDATA registry. Retrospective cohort analysis of all renal transplants performed in Australia and New Zealand during 1985-2010 in which the graft survived >3 months and the patient spent at least some time aged 10-30y inclusive while the graft was functioning. Calculation of adjusted hazard ratio (aHR) for graft loss according to age, sex, race, cause of end-stage kidney disease, transition, era of transplantation, donor type and Human Leucocyte Antigen mismatch calculated using an extended Cox proportional hazards model. Analysis of age-specific aHR of graft loss from any cause or late acute rejection (LAR) or non-compliance. 3289 grafts in 3048 recipients were included. 757 grafts failed including 110 (15%) from LAR or non-compliance. Age was strongly associated with graft loss from LAR or non-compliance (p risk of graft loss from LAR or non-compliance was significantly increased from 16-24y, peaking at 19-21y (aHR 11.3, 95%CI 1.5-84.3, p non-compliance (aHR 3.5, 95%CI 2.1-5.6), whereas paediatric-to-adult transition with a functioning transplant was not (aHR 1.2, 95%CI 0.4-3.5, p = 0.68). The high risk of graft loss during adolescence and young adulthood is primarily due to LAR or non-compliance. The elevated risk continues well into the 20s and is independent of paediatric-to-adult transition. This article is protected by copyright. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Multiparametric cardiovascular magnetic resonance surveillance of acute cardiac allograft rejection and characterisation of transplantation-associated myocardial injury: a pilot study.

    Science.gov (United States)

    Miller, Christopher A; Naish, Josephine H; Shaw, Steven M; Yonan, Nizar; Williams, Simon G; Clark, David; Bishop, Paul W; Ainslie, Mark P; Borg, Alex; Coutts, Glyn; Parker, Geoffrey J M; Ray, Simon G; Schmitt, Matthias

    2014-07-20

    Serial surveillance endomyocardial biopsies are performed in patients who have recently undergone heart transplantation in order to detect acute cardiac allograft rejection (ACAR) before symptoms occur, however the biopsy process is associated with a number of limitations. This study aimed to prospectively and longitudinally evaluate the performance of multiparametric cardiovascular magnetic resonance (CMR) for detecting and monitoring ACAR in the early phase post-transplant, and characterize graft recovery following transplantation. All patients receiving a heart transplant at a single UK centre over a period of 25 months were approached within one month of transplantation. Multiparametric CMR was prospectively performed on the same day as biopsy on four separate occasions (6 weeks, 10 weeks, 15 weeks and 20 weeks post-transplant). CMR included assessment of global and regional ventricular function, myocardial tissue characterization (T1 mapping, T2 mapping, extracellular volume, LGE) and pixel-wise absolute myocardial blood flow quantification. CMR parameters were compared with biopsy findings. As is standard, grade 2R or higher ACAR was considered significant. 88 CMR-matched biopsies were performed in 22 patients. Eight (9%) biopsies in 5 patients demonstrated significant ACAR. Significant ACAR was associated with a reduction in circumferential strain (-12.7±2.5% vs. -13.7±3.6%, p=0.047) but there was considerable overlap between groups. Whilst trends were observed between ACAR and proposed CMR markers of oedema, particularly after adjusting for primary graft dysfunction, differences were not significant. Significant improvements were seen in markers of graft structure and contractility, oedema and microvascular function over the period studied, although few parameters normalised. This study provides novel insight into the myocardial injury associated with transplantation, and its recovery, however multiparametric CMR was not able to accurately detect ACAR

  11. CD47-signal regulatory protein-α (SIRPα) interactions form a barrier for antibody-mediated tumor cell destruction

    NARCIS (Netherlands)

    Zhao, Xi Wen; van Beek, Ellen M.; Schornagel, Karin; van der Maaden, Hans; van Houdt, Michel; Otten, Marielle A.; Finetti, Pascal; van Egmond, Marjolein; Matozaki, Takashi; Kraal, Georg; Birnbaum, Daniel; van Elsas, Andrea; Kuijpers, Taco W.; Bertucci, Francois; van den Berg, Timo K.

    2011-01-01

    Monoclonal antibodies are among the most promising therapeutic agents for treating cancer. Therapeutic cancer antibodies bind to tumor cells, turning them into targets for immune-mediated destruction. We show here that this antibody-mediated killing of tumor cells is limited by a mechanism involving

  12. Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses

    Science.gov (United States)

    McRaven, Michael D; Sawant, Sheetal; Gurley, Thaddeus C; Xu, Thomas T.; Dennison, S. Moses; Liao, Hua-Xin; Chenine, Agnès-Laurence; Alam, S. Munir; Haynes, Barton F.; Tomaras, Georgia D.

    2016-01-01

    Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine

  13. Antibody-Mediated Extreme Insulin Resistance: A Report of Three Cases.

    Science.gov (United States)

    Kim, Han Na; Fesseha, Betiel; Anzaldi, Laura; Tsao, Allison; Galiatsatos, Panagis; Sidhaye, Aniket

    2018-01-01

    Type 2 diabetes mellitus is characterized by relative insulin deficiency and insulin resistance. Features suggesting severe insulin resistance include acanthosis nigricans, hyperandrogenism, weight loss, and recurrent hospital admissions for diabetic ketoacidosis. In rare circumstances, hyperglycemia persists despite administration of massive doses of insulin. In these cases, it is important to consider autoimmune etiologies for insulin resistance, such as type B insulin resistance and insulin antibody-mediated extreme insulin resistance, which carry high morbidity and mortality if untreated. Encouragingly, immunomodulatory regimens have recently been published that induce remission at high rates. We describe 3 cases of extreme insulin resistance mediated by anti-insulin receptor autoantibodies or insulin autoantibodies. All cases were effectively treated with an immunomodulatory regimen. Although cases of extreme insulin resistance are rare, it is important to be aware of autoimmune causes, recognize suggestive signs and symptoms, and pursue appropriate diagnostic evaluation. Prompt treatment with immunomodulators is key to restoring euglycemia in patients with autoimmune etiologies of insulin resistance. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Influence of type I IFN signaling on anti-MOG antibody-mediated demyelination.

    Science.gov (United States)

    Berg, Carsten Tue; Khorooshi, Reza; Asgari, Nasrin; Owens, Trevor

    2017-06-24

    Antibodies with specificity for myelin oligodendrocyte glycoprotein (MOG) are implicated in multiple sclerosis and related diseases. The pathogenic importance of anti-MOG antibody in primary demyelinating pathology remains poorly characterized. The objective of this study is to investigate whether administration of anti-MOG antibody would be sufficient for demyelination and to determine if type I interferon (IFN) signaling plays a similar role in anti-MOG antibody-mediated pathology, as has been shown for neuromyelitis optica-like pathology. Purified IgG2a monoclonal anti-MOG antibody and mouse complement were stereotactically injected into the corpus callosum of wild-type and type I IFN receptor deficient mice (IFNAR1-KO) with and without pre-established experimental autoimmune encephalomyelitis (EAE). Anti-MOG induced complement-dependent demyelination in the corpus callosum of wild-type mice and did not occur in mice that received control IgG2a. Deposition of activated complement coincided with demyelination, and this was significantly reduced in IFNAR1-KO mice. Co-injection of anti-MOG and complement at onset of symptoms of EAE induced similar levels of callosal demyelination in wild-type and IFNAR1-KO mice. Anti-MOG antibody and complement was sufficient to induce callosal demyelination, and pathology was dependent on type I IFN. Induction of EAE in IFNAR1-KO mice overcame the dependence on type I IFN for anti-MOG and complement-mediated demyelination.

  15. Structural insight into antibody-mediated antagonism of the Glucagon-like peptide-1 Receptor

    Science.gov (United States)

    Hennen, Stephanie; Kodra, János T.; Soroka, Vladyslav; Krogh, Berit O.; Wu, Xiaoai; Kaastrup, Peter; Ørskov, Cathrine; Rønn, Sif G.; Schluckebier, Gerd; Barbateskovic, Silvia; Gandhi, Prafull S.; Reedtz-Runge, Steffen

    2016-01-01

    The Glucagon-like peptide-1 receptor (GLP-1R) is a member of the class B G protein-coupled receptor (GPCR) family and a well-established target for the treatment of type 2 diabetes. The N-terminal extracellular domain (ECD) of GLP-1R is important for GLP-1 binding and the crystal structure of the GLP-1/ECD complex was reported previously. The first structure of a class B GPCR transmembrane (TM) domain was solved recently, but the full length receptor structure is still not well understood. Here we describe the molecular details of antibody-mediated antagonism of the GLP-1R using both in vitro pharmacology and x-ray crystallography. We showed that the antibody Fab fragment (Fab 3F52) blocked the GLP-1 binding site of the ECD directly and thereby acts as a competitive antagonist of native GLP-1. Interestingly, Fab 3F52 also blocked a short peptide agonist believed to engage primarily the transmembrane and extracellular loop region of GLP-1R, whereas functionality of an allosteric small-molecule agonist was not inhibited. This study has implications for the structural understanding of the GLP-1R and related class B GPCRs, which is important for the development of new and improved therapeutics targeting these receptors. PMID:27196125

  16. Antibody-mediated neutralization of myelin-associated EphrinB3 accelerates CNS remyelination.

    Science.gov (United States)

    Syed, Yasir A; Zhao, Chao; Mahad, Don; Möbius, Wiebke; Altmann, Friedrich; Foss, Franziska; González, G A; Sentürk, Aycan; Acker-Palmer, Amparo; Lubec, Gert; Lilley, Kathryn; Franklin, Robin J M; Nave, Klaus-A; Kotter, Mark R N

    2016-02-01

    Remyelination in multiple sclerosis (MS) lesions often remains incomplete despite the presence of oligodendrocyte progenitor cells (OPCs). Amongst other factors, successful remyelination depends on the phagocytic clearance of myelin debris. However, the proteins in myelin debris that act as potent and selective inhibitors on OPC differentiation and inhibit CNS remyelination remain unknown. Here, we identify the transmembrane signalling protein EphrinB3 as important mediator of this inhibition, using a protein analytical approach in combination with a primary rodent OPC assay. In the presence of EphrinB3, OPCs fail to differentiate. In a rat model of remyelination, infusion of EphrinB3 inhibits remyelination. In contrast, masking EphrinB3 epitopes using antibodies promotes remyelination. Finally, we identify EphrinB3 in MS lesions and demonstrate that MS lesion extracts inhibit OPC differentiation while antibody-mediated masking of EphrinB3 epitopes promotes it. Our findings suggest that EphrinB3 could be a target for therapies aiming at promoting remyelination in demyelinating disease.

  17. Failure to down-regulate intragraft cytokine mRNA expression shortly after clinical heart transplantation is associated with high incidence of acute rejection

    NARCIS (Netherlands)

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

    BACKGROUND: Brain-death, ischemia and reperfusion damage have been implicated as initial factors that lead to a cascade of immunologic events that result in allograft rejection in experimental animals. Cytokines are thought to play a central role in this process. Therefore, we evaluated intragraft

  18. Silane-modified surfaces in specific antibody-mediated cell recognition.

    Science.gov (United States)

    Sterzynska, Karolina; Budna, Joanna; Frydrych-Tomczak, Emilia; Hreczycho, Grzegorz; Malinska, Agnieszka; Maciejewski, Hieronim; Zabel, Maciej

    2014-01-01

    The immobilization of antibodies on various surfaces has been the subject of advanced research in various immunoassay-based diagnostic devices. The physical and chemical stabilities of the immobilized antibodies on a solid surface still cause many problems because upon immobilizing antibody molecules, the antigen-binding ability usually decreases. The silanization of surfaces with organosilanes carrying chemically active groups such as (3-aminopropyl) triethoxysilane (APTES) can accommodate these antigen-binding molecules in an appropriate orientation so that their functionality and binding activity are essentially retained. In this study, n-butyltrimethoxysilane (BMS) and 3-(octafluoropentyloxy)-propyltriethoxysilane (OFPOS) were used as "blocking silanes". The aims of this study were to compare the effectiveness of specific antibody binding of APTES, APTES + BMS and APTES + OFPOS and to characterize the modified surfaces by contact angle measurements and immunofluorescence measurements prior to and after immobilizing proteins. Additionally, we have evaluated the functionality of the immobilized antibodies by their abilities to bind EpCAM-positive human colon adenocarcinoma cell line (LoVo) and EpCAM-negative mouse embryonic fibroblast cell line (3T3). Cell enumeration was conducted on the basis of DAPI-positive signals and recorded using a confocal laser scanning biological microscope. The results of our study showed that the immobilization capability and reactivity of APTES, APTES + BMS and APTES + OFPOS differ. The modification of APTES with unreactive silanes (BMS,OFPOS) is recommended to improve the antibody binding efficiency. However, using OFPOS resulted in more effective antibody and cell binding, and it appears to be the most useful compound in specific antibody-mediated cell recognition.

  19. Neuropathogenesis of Zika Virus Infection : Potential Roles of Antibody-Mediated Pathology

    Science.gov (United States)

    Tsunoda, Ikuo; Omura, Seiichi; Sato, Fumitaka; Kusunoki, Susumu; Fujita, Mitsugu; Park, Ah-Mee; Hasanovic, Faris; Yanagihara, Richard; Nagata, Satoshi

    2017-01-01

    Zika virus (ZIKV) is an enveloped, positive-sense, single-stranded RNA virus that belongs to the genus Flavivirus, family Flaviviridae, which includes many human and animal pathogens, such as dengue virus (DENV), West Nile virus, and Japanese encephalitis virus. In the original as well as subsequent experimental and clinical reports, ZIKV seems to have moderate neurotropism (in animal models) and neurovirulence (in human fetuses), but no neuroinvasiveness (in human adults). Intrauterine ZIKV infection (viral pathology) has been linked to an increased incidence of microcephaly, while increased Guillain-Barré syndrome (GBS) following ZIKV infection is likely immune-mediated (immunopathology). Clinically, in ZIKV infection, antibodies against other flaviviruses, such as DENV, have been detected; these antibodies can cross-react with ZIKV without ZIKV neutralization. In theory, such non-neutralizing antibodies are generated at the expense of decreased production of neutralizing antibodies (“antigenic sin”), leading to poor viral clearance, while the non-neutralizing antibodies can also enhance viral replication in Fc receptor (FcR)-bearing cells via antibody-dependent enhancement (ADE). Here, we propose three potential roles of the antibody-mediated pathogenesis of ZIKV infection: 1) cross-reactive antibodies that recognize ZIKV and neural antigens cause GBS; 2) ZIKV-antibody complex is transported transplacentally via neonatal FcR (FcRn), resulting in fetal infection; and 3) ZIKV-antibody complex is taken up at peripheral nerve endings and transported to neurons in the central nervous system (CNS), by which the virus can enter the CNS without crossing the blood-brain barrier. PMID:28428682

  20. Use of tacrolimus in rescue therapy of acute and chronic rejection in liver transplantation Uso de tacrolimus na terapia de resgate de rejeições agudas e crônicas no transplante de fígado

    Directory of Open Access Journals (Sweden)

    Fabricio Ferreira Coelho

    2003-01-01

    Full Text Available PURPOSE: To study the indications and results of tacrolimus as rescue therapy for acute cellular or chronic rejection in liver transplantation. PATIENTS AND METHODS: Eighteen liver transplant recipients who underwent rescue therapy with tacrolimus between March 1995 and August 1999 were retrospectively studied. The treatment indication, patients, and graft situation were recorded as of October 31st, 1999. The response to tacrolimus was defined as patient survival with a functional graft and histological reversal of acute cellular, or for chronic rejection, bilirubin serum levels decreasing to up to twice the upper normal limit. RESULTS: Fourteen cases (77.8% presented a good response. The response rate for the different indications was: (1 acute cellular + sepsis - 0/1 case; (2 recurrent acute cellular - 1/1 case; (3 OKT3-resistant acute cellular - 2/2 cases; (4 steroid-resistant acute cellular + active viral infection - 3/3 cases; (5 chronic rejection - 8/11 cases (72.7% response rate. The 4 patients who did not respond died. CONCLUSION: Tacrolimus rescue therapy was successful in most cases of acute cellular and chronic rejection in liver transplantation.OBJETIVO: Estudar os critérios de indicação e o resultado do uso de tacrolimus na terapia de resgate de rejeições agudas ou crônicas no transplante de fígado. CASUÍSTICA E MÉTODO: Foram estudados 18 pacientes transplantados de fígado, submetidos a terapia de resgate com tacrolimus entre março de 1995 e agosto de 1999. Foram registradas a indicação do tratamento e a situação de pacientes e enxertos em 31/10/1999. Considerou-se "respondendores" pacientes vivos, com enxerto funcionante e regressão histológica da terapia de resgate de rejeições agudas, ou com bilirrubina até 2 vezes o valor normal, no caso de terapia de resgate de rejeições crônicas. RESULTADO: Observou-se resposta em 14 casos (77,8%. A taxa de resposta nas diferentes indicações foi: (1 terapia de resgate

  1. Delayed hyperacute rejection in a patient who developed clostridium difficile infection after ABO-incompatible kidney transplantation

    Directory of Open Access Journals (Sweden)

    Gerald S Lipshutz

    2010-11-01

    the surface of bacterial cell wall occurring before the firm establishment of accommodation can trigger the onset of acute antibody-mediated rejection. We herein report a case of delayed hyperacute rejection in an A1 to O, ABO incompatible transplant recipient following an episode of Clostridium difficile infection.Keywords: ABO incompatible transplantation, delayed hyperacute rejection, kidney transplantation, Clostridium difficile infection

  2. Analysis of Sera of Recipients with Allograft Rejection Indicates That Keratin 1 Is the Target of Anti-Endothelial Antibodies

    Directory of Open Access Journals (Sweden)

    Xuli Guo

    2017-01-01

    Full Text Available Anti-endothelial cell antibodies (AECAs are usually directed against the surface antigens on the vascular endothelial cells. Clinical studies suggest a pathogenic role for nonhuman leukocyte antigen in antibody-mediated rejection; however, the antigens on the donor vascular endothelium that serve as the first-line targets for an immune response during allograft rejection have not been fully identified. Here, we used immunoprecipitation and mass spectrometry to identify antigens from the sera of kidney transplant recipients who were experiencing antibody-mediated rejection. Keratin 1 (KRT1 was identified as a novel antigenic target expressed on endothelial cells. To validate our finding, we produced recombinant proteins representing the three most common alleles of KRT1. The serum used for immunoprecipitation showed a strong reaction to KRT1 recombinants in western blot and ELISA. In the kidney transplant cohort, more AECA-positive recipients than AECA-negative recipients had KRT1 antibodies (32.2% versus 11.9%, p=0.002. Sera from 255 renal recipients were tested by ELISA. Of the 77 recipients with deteriorating graft function (serum creatinine > 120 μmol/L, 23 had anti-KRT1 antibodies. KRT1-IgG positivity was, therefore, associated with a higher risk of kidney transplant rejection (29.9% (23/77 versus 16.9% (30/178, p=0.0187. A better understanding of this antigenic target will improve long-term allograft survival.

  3. Analysis of Sera of Recipients with Allograft Rejection Indicates That Keratin 1 Is the Target of Anti-Endothelial Antibodies.

    Science.gov (United States)

    Guo, Xuli; Hu, Juan; Luo, Weiguang; Luo, Qizhi; Guo, Jing; Tian, Fang; Ming, Yingzi; Zou, Yizhou

    2017-01-01

    Anti-endothelial cell antibodies (AECAs) are usually directed against the surface antigens on the vascular endothelial cells. Clinical studies suggest a pathogenic role for nonhuman leukocyte antigen in antibody-mediated rejection; however, the antigens on the donor vascular endothelium that serve as the first-line targets for an immune response during allograft rejection have not been fully identified. Here, we used immunoprecipitation and mass spectrometry to identify antigens from the sera of kidney transplant recipients who were experiencing antibody-mediated rejection. Keratin 1 (KRT1) was identified as a novel antigenic target expressed on endothelial cells. To validate our finding, we produced recombinant proteins representing the three most common alleles of KRT1. The serum used for immunoprecipitation showed a strong reaction to KRT1 recombinants in western blot and ELISA. In the kidney transplant cohort, more AECA-positive recipients than AECA-negative recipients had KRT1 antibodies (32.2% versus 11.9%, p = 0.002). Sera from 255 renal recipients were tested by ELISA. Of the 77 recipients with deteriorating graft function (serum creatinine > 120 μmol/L), 23 had anti-KRT1 antibodies. KRT1-IgG positivity was, therefore, associated with a higher risk of kidney transplant rejection (29.9% (23/77) versus 16.9% (30/178), p = 0.0187). A better understanding of this antigenic target will improve long-term allograft survival.

  4. Antiglomerular basement membrane antibody-mediated glomerulonephritis after intranasal cocaine use.

    Science.gov (United States)

    Peces, R; Navascués, R A; Baltar, J; Seco, M; Alvarez, J

    1999-01-01

    We report a case of rapidly progressive glomerulonephritis due to antiglomerular basement membrane (anti-GBM) antibodies that progressed to end-stage renal disease in a 35-year-old man who used intranasal cocaine on an occasional basis. In contrast to many prior reports of acute renal failure occurring with cocaine-associated rhabdomyolysis, this patient did not have any evidence of acute muscle damage and myoglobin release. Circulating anti-GBM antibodies and renal biopsy with linear IgG and C3 deposits confirmed the diagnosis of anti-GBM disease. The possibility of anti-GBM must be considered in the differential diagnosis of acute renal failure in cocaine addicts. This unusual combination raises complex questions regarding the pathogenesis of this type of renal injury.

  5. Successful reversal of acute vascular rejection and cyclosporine-associated nephrotoxicity in renal allograft with combined sirolimus and mycophenolate mofetil as immunotherapy.

    Science.gov (United States)

    Ołdakowska-Jedynak, U; Paczek, L; Mucha, K; Foroncewicz, B; Perkowska-Ptasińska, A

    2006-01-01

    Cyclosporine (CsA) has substantially improved patient and graft survival rates in solid organ transplantation. In clinical studies, sirolimus has been shown to be as effective as CsA to maintain survival of renal and cardiac allografts without causing nephrotoxicity. Herein we describe a patient with biopsy-proven CsA-associated nephrotoxicity and refractory renal allograft rejection who was converted from steroids, CsA, and azathioprine to steroids, sirolimus (RAPA), and low-dose mycophenolate mofetil (MMF). The follow-up period was 60 months. We observed substantial improvement, even normalization in renal function. Our patient did not give consent to repeat biopsy after conversion. We also observed a beneficial effect of CsA withdrawal on blood pressure control. The spectrum of adverse events induced by sirolimus seemed to be mild relative to the potency of the immunosuppressive effect. The excellent response to combined RAPA and MMF in this patient was probably due to "concerted actions" of these agents on both B- and T-cell functions. The combination enhanced therapeutic efficacy while minimizing the toxicity of individual drugs used in the regimen. These findings suggest that sirolimus, when used as a base therapy in combination with low-dose MMF in a renal allograft recipient, may be an alternative to CsA-based therapy, providing potent immunosuppression of a renal allograft. Sirolimus administration facilitated steroids dose reduction.

  6. Heavy Proteinuria as a Manifestation of Acute Allograft Rejection Presenting Early after Kidney Transplantation: A Retrospective, Single-Center Case Series

    Science.gov (United States)

    2009-01-01

    Abstract: The differential diagnosis of heavy proteinuria presenting early after kidney transplantation has generally included de novo or recurrent...SUPPLEMENTARY NOTES 14. ABSTRACT The differential diagnosis of heavy proteinuria presenting early after kidney transplantation has generally included de novo...26 The Open Transplantation Journal, 2009, 3, 26-30 1874-4184/09 2009 Bentham Open Open Access Heavy Proteinuria as a Manifestation of Acute

  7. Kidney intragraft donor-specific antibodies as determinant of antibody-mediated lesions and poor graft outcome.

    Science.gov (United States)

    Bachelet, T; Couzi, L; Lepreux, S; Legeret, M; Pariscoat, G; Guidicelli, G; Merville, P; Taupin, J-L

    2013-11-01

    Allograft pathology, antibody-tissue interaction as demonstrated by C4d deposition and serological evidence of donor-specific antibodies (DSA) are the cardinal diagnostic features of antibody-mediated lesions (AML) in kidney transplantation. However, discrepancy between histological and serological findings is common, and more reliable diagnostic tools are called for. Here, we asked whether the in situ detection of DSA could serve as marker for AML. To that end, we applied the anti-HLA single antigen flow bead assay to eluates from 51 needle core graft biopsies performed for cause. Intragraft antibody profiles were correlated to serum DSA (sDSA), histological data and transplant outcome. The prevalence and the mean number of intragraft DSA (gDSA) were lower than that of sDSA (15/51 gDSA+ vs. 37/51 sDSA+ patients; 1.64 gDSA vs. 2.24 sDSA per patient). DSA were detected in all anti-HLA antibody-positive biopsies (15/15). The presence of gDSA was significantly associated with (1) microcirculation lesions taken individually (g, cg) and analyzed in functional clusters (ptc + g + cg > 0, cg + mm > 0), (2) C4d positivity and (3) a worse short-term transplant outcome (p = 0.05). These associations were not found for patients presenting only sDSA. Taken together, these results indicate that gDSA is a severity marker of antibody-mediated pathogenic process. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

  8. Acute myeloid leukemia after kidney transplantation: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Francesca Cardarelli

    Full Text Available Abstract The incidence of malignancy is greater in kidney transplant recipients compared to the general population, though the higher risk is not equally distributed to all types of cancers. In face of the increased longevity of renal transplant recipients, certain cancers, such as acute leukemias, are becoming more prevalent. Acute myeloid leukemia (AML typically presents with cytopenias and infections, both common findings after kidney transplantation. Therefore, the diagnosis of AML may be initially overlooked in these patients. We report the case of a 33-year-old man who presented with fever, pancytopenia and acute worsening of his renal allograft function 9 years after a living unrelated kidney transplant. After initial negative infectious work-up, a kidney biopsy revealed C4d-positive antibody-mediated rejection in combination with scattered atypical inflammatory cells. A subsequent bone marrow biopsy confirmed AML. He underwent successful induction chemotherapy with daunorubucin and cytarabine and ultimately achieved a complete remission. However, he developed a Page kidney with worsening renal function and abdominal pain three weeks after biopsy in the setting of chemotherapy-induced thrombocytopenia. Herein, we discuss the prevalence, risk factors, presentation and management of leukemia after kidney transplantation.

  9. [Effect of emodin on rejection of liver transplantation in rats].

    Science.gov (United States)

    Jing, He; Lin, Shengzhang; Yang, Xiao

    2009-06-01

    To investigate the mechanism of Emodin on the role of acute rejection in rat liver transplantation. Forty-eight pairs of orthotopic liver transplantation model were established with inbred rats which were randomly divided into 3 groups: Control group (BN --> BN), acute rejection group (Lewis --> BN) and emodin group (Lewis --> BN). Six recipients in each group were randomly collected and contents of TNF-alpha and IL-10 in the peripheral blood were detected with ELISA on Day 1, 3, 5 and 7 separately after transplantation and histopathological evaluation was made to detect the differences among groups after the livers were taken out on day 7. The other 10 in each group were protected to evaluate the animation and life time. The average meso-life time in emodin group (25.6 days) is significantly longer (P < 0.05) than acute rejection group (10.9 days). Compared with the acute rejection group, Emodin group shows up less rejection in the histopathological evaluation (P < 0.01), less TNF-alpha (P < 0.05) and a significant up-regulation of IL-10 in the peripheral blood (P < 0.05 after day 3). Emodin can inhibit the acute rejection of liver transplantation in rats model effectively and it may play the role with reduction of TNF-alpha and upregulation of IL-10.

  10. Incidence, risk factors, and outcome of antithymocyte globulin treatment of steroid-resistant rejection after liver transplantation

    NARCIS (Netherlands)

    Bijleveld, CGE; Klompmaker, IJ; vandenBerg, AP; Gouw, ASH; Hepkema, BG; Haagsma, EB; Slooff, MJH

    1996-01-01

    We retrospectively analyzed the incidence and outcome of steroid-resistant rejection (SRR) during the first 6 months after OLT in 126 patients receiving triple immunosuppression. A total of 95 patients either did not experience acute rejection at all or had acute rejection that subsided without

  11. Phagocytic cells contribute to the antibody-mediated elimination of pulmonary-infected SARS coronavirus.

    Science.gov (United States)

    Yasui, Fumihiko; Kohara, Michinori; Kitabatake, Masahiro; Nishiwaki, Tetsu; Fujii, Hideki; Tateno, Chise; Yoneda, Misako; Morita, Kouichi; Matsushima, Kouji; Koyasu, Shigeo; Kai, Chieko

    2014-04-01

    While the 2002-2003 outbreak of severe acute respiratory syndrome (SARS) resulted in 774 deaths, patients who were affected with mild pulmonary symptoms successfully recovered. The objective of the present work was to identify, using SARS coronavirus (SARS-CoV) mouse infection models, immune factors responsible for clearing of the virus. The elimination of pulmonary SARS-CoV infection required the activation of B cells by CD4(+) T cells. Furthermore, passive immunization (post-infection) with homologous (murine) anti-SARS-CoV antiserum showed greater elimination efficacy against SARS-CoV than that with heterologous (rabbit) antiserum, despite the use of equivalent titers of neutralizing antibodies. This distinction was mediated by mouse phagocytic cells (monocyte-derived infiltrating macrophages and partially alveolar macrophages, but not neutrophils), as demonstrated both by adoptive transfer from donors and by immunological depletion of selected cell types. These results indicate that the cooperation of anti-SARS-CoV antibodies and phagocytic cells plays an important role in the elimination of SARS-CoV. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Limitations of Murine Models for Assessment of Antibody-Mediated Therapies or Vaccine Candidates against Staphylococcus epidermidis Bloodstream Infection

    Science.gov (United States)

    Zhang, Jinrong; Kesselly, Augustus; Lam, Hubert; Kleanthous, Harry; Yethon, Jeremy A.

    2016-01-01

    Staphylococcus epidermidis is normally a commensal colonizer of human skin and mucus membranes, but, due to its ability to form biofilms on indwelling medical devices, it has emerged as a leading cause of nosocomial infections. Bacteremia or bloodstream infection is a frequent and costly complication resulting from biofilm fouling of medical devices. Our goal was to develop a murine model of S. epidermidis infection to identify potential vaccine targets for the prevention of S. epidermidis bacteremia. However, assessing the contribution of adaptive immunity to protection against S. epidermidis challenge was complicated by a highly efficacious innate immune response in mice. Naive mice rapidly cleared S. epidermidis infections from blood and solid organs, even when the animals were immunocompromised. Cyclophosphamide-mediated leukopenia reduced the size of the bacterial challenge dose required to cause lethality but did not impair clearance after a nonlethal challenge. Nonspecific innate immune stimulation, such as treatment with a Toll-like receptor 4 (TLR4) agonist, enhanced bacterial clearance. TLR2 signaling was confirmed to accelerate the clearance of S. epidermidis bacteremia, but TLR2−/− mice could still resolve a bloodstream infection. Furthermore, TLR2 signaling played no role in the clearance of bacteria from the spleen. In conclusion, these data suggest that S. epidermidis bloodstream infection is cleared in a highly efficient manner that is mediated by both TLR2-dependent and -independent innate immune mechanisms. The inability to establish a persistent infection in mice, even in immunocompromised animals, rendered these murine models unsuitable for meaningful assessment of antibody-mediated therapies or vaccine candidates. PMID:26857577

  13. Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials.

    Science.gov (United States)

    Gilbert, Peter B; Juraska, Michal; deCamp, Allan C; Karuna, Shelly; Edupuganti, Srilatha; Mgodi, Nyaradzo; Donnell, Deborah J; Bentley, Carter; Sista, Nirupama; Andrew, Philip; Isaacs, Abby; Huang, Yunda; Zhang, Lily; Capparelli, Edmund; Kochar, Nidhi; Wang, Jing; Eshleman, Susan H; Mayer, Kenneth H; Magaret, Craig A; Hural, John; Kublin, James G; Gray, Glenda; Montefiori, David C; Gomez, Margarita M; Burns, David N; McElrath, Julie; Ledgerwood, Julie; Graham, Barney S; Mascola, John R; Cohen, Myron; Corey, Lawrence

    2017-01-01

    Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been developed as potential agents for prevention of HIV-1 infection. The HIV Vaccine Trials Network and the HIV Prevention Trials Network are conducting the Antibody Mediated Prevention (AMP) trials to assess whether, and how, intravenous infusion of the anti-CD4 binding site bnAb, VRC01, prevents HIV-1 infection. These are the first test-of-concept studies to assess HIV-1 bnAb prevention efficacy in humans. The AMP trials are two parallel phase 2b HIV-1 prevention efficacy trials conducted in two cohorts: 2700 HIV-uninfected men and transgender persons who have sex with men in the United States, Peru, Brazil, and Switzerland; and 1500 HIV-uninfected sexually active women in seven countries in sub-Saharan Africa. Participants are randomized 1:1:1 to receive an intravenous infusion of 10 mg/kg VRC01, 30 mg/kg VRC01, or a control preparation every 8 weeks for a total of 10 infusions. Each trial is designed (1) to assess overall prevention efficacy (PE) pooled over the two VRC01 dose groups vs. control and (2) to assess VRC01 dose and laboratory markers as correlates of protection (CoPs) against overall and genotype- and phenotype-specific infection. Each AMP trial is designed to have 90% power to detect PE > 0% if PE is ≥ 60%. The AMP trials are also designed to identify VRC01 properties (i.e., concentration and effector functions) that correlate with protection and to provide insight into mechanistic CoPs. CoPs are assessed using data from breakthrough HIV-1 infections, including genetic sequences and sensitivities to VRC01-mediated neutralization and Fc effector functions. The AMP trials test whether VRC01 can prevent HIV-1 infection in two study populations. If affirmative, they will provide information for estimating the optimal dosage of VRC01 (or subsequent derivatives) and identify threshold levels of neutralization and Fc effector functions associated with high-level protection, setting a benchmark

  14. Private Information and Insurance Rejections.

    Science.gov (United States)

    Hendren, Nathaniel

    2013-09-01

    Across a wide set of non-group insurance markets, applicants are rejected based on observable, often high-risk, characteristics. This paper argues that private information, held by the potential applicant pool, explains rejections. I formulate this argument by developing and testing a model in which agents may have private information about their risk. I first derive a new no-trade result that theoretically explains how private information could cause rejections. I then develop a new empirical methodology to test whether this no-trade condition can explain rejections. The methodology uses subjective probability elicitations as noisy measures of agents beliefs. I apply this approach to three non-group markets: long-term care, disability, and life insurance. Consistent with the predictions of the theory, in all three settings I find significant amounts of private information held by those who would be rejected; I find generally more private information for those who would be rejected relative to those who can purchase insurance; and I show it is enough private information to explain a complete absence of trade for those who would be rejected. The results suggest private information prevents the existence of large segments of these three major insurance markets.

  15. Primary HHV 6 infection after liver transplantation with acute graft rejection and multi-organ failure: successful treatment with a 2.5-fold dose of cidofovir and reduction of immunosuppression

    NARCIS (Netherlands)

    Dohna-Schwake, C.; Fiedler, M.; Gierenz, N.; Gerner, P.; Ballauf, A.; Breddemann, A.; Laer, S.; Baba, H.A.; Hoyer, P.F.

    2011-01-01

    HHV type 6 has been reported with enhanced pathogenicity in immunocompromised patients. Herein, we report about a two-yr-old girl who experienced primary HHV 6 infection after liver transplantation. She clinically presented with graft rejection and necrotic hepatitis as well as high fever,

  16. Explaining the paradoxical rejection-aggression link: the mediating effects of hostile intent attributions, anger, and decreases in state self-esteem on peer rejection-induced aggression in youth

    NARCIS (Netherlands)

    Reijntjes, A.; Thomaes, S.; Kamphuis, J.H.; Bushman, B.J.; Orobio de Castro, B.; Telch, M.J.

    2011-01-01

    People are strongly motivated to feel accepted by others. Yet when faced with acute peer rejection they often aggress against the very peers they desire acceptance from, which may lead to further rejection. The present experiment tests three potential mediators of aggressive responses to acute peer

  17. Explaining the paradoxical rejection-aggression link: The mediating effects of hostile intent attributions, anger, and decreases in state self-esteem on peer rejection-induced aggression in youth

    NARCIS (Netherlands)

    Reijntjes, A.H.A.; Thomaes, S.C.E.; Kamphuis, J.H.; Bushman, B. J.; Orobio de Castro, B.; Telch, M.J.

    2011-01-01

    People are strongly motivated to feel accepted by others. Yet when faced with acute peer rejection they often aggress against the very peers they desire acceptance from, which may lead to further rejection. The present experiment tests three potential mediators of aggressive responses to acute peer

  18. Explaining the paradoxical rejection-aggression link: The mediating effects of hostile intent attributions, anger, and decreases in state self-esteem on peer rejection-related aggression in youth

    NARCIS (Netherlands)

    Reijntjes, A.; Thomaes, S.; Kamphuis, J.H.; Bushman, B.J.; Orobio de Castro, B.; Telch, M. J.

    2011-01-01

    People are strongly motivated to feel accepted by others. Yet when faced with acute peer rejection they often aggress against the very peers they desire acceptance from, which may lead to further rejection. The present experiment tests three potential mediators of aggressive responses to acute peer

  19. [Flow cytometry controlled induction therapy with ATG and noninvasive monitoring of rejection--a modern management concept after heart transplantation].

    Science.gov (United States)

    Wagner, F M; Tugtekin, S M; Matschke, K; Platzbecker, U; Gulielmos, V; Schüler, S

    1998-01-01

    We introduce our concept of non-invasive transplant monitoring. The introduction of individualized immunosuppression by means of flow cytometry leads to a lower incidence of acute graft rejection and preserves immuncompetence. With the simultaneous use of echocardiography and intramyocardial electrogram (IMEG) acute graft rejections can be safely identified without using any invasive method.

  20. Low CD4/CD8 Ratio in Bronchus-Associated Lymphoid Tissue Is Associated with Lung Allograft Rejection.

    Science.gov (United States)

    Shenoy, K V; Solomides, C; Cordova, F; Rogers, T J; Ciccolella, D; Criner, G J

    2012-01-01

    Background. Bronchus-associated lymphoid tissue (BALT) has been associated with lung allograft rejection in rat transplant models. In human transplant recipients, BALT has not been linked to clinically significant rejection. We hypothesize that the immunohistochemical composition of BALT varies with the presence of acute lung allograft rejection. Methods. We retrospectively examined 40 human lung allograft recipients transplanted from 3/1/1999 to 6/1/2008. Patients were grouped by frequency and severity of acute rejection based on International Society of Heart Lung Transplant (ISHLT) criteria. Transbronchial biopsies were reviewed for BALT by a blinded pathologist. BALT if present was immunohistochemically stained to determine T-and B-cell subpopulations. Results. BALT presence was associated with an increased frequency of acute rejection episodes in the first year after transplantation. Patients with a lower CD4/CD8 ratio had an increased rejection rate; however, BALT size or densities of T-cell and B-cell subpopulations did not correlate with rejection rate. Conclusion. The presence of BALT is associated with an increased frequency of rejection one year after transplant. The lower the CD4/CD8 ratio, the more acute rejection episodes occur in the first year after transplantation. The immunohistochemical composition of BALT may predict patients prone to frequent episodes of acute cellular rejection.

  1. Low CD4/CD8 Ratio in Bronchus-Associated Lymphoid Tissue Is Associated with Lung Allograft Rejection

    Directory of Open Access Journals (Sweden)

    K. V. Shenoy

    2012-01-01

    Full Text Available Background. Bronchus-associated lymphoid tissue (BALT has been associated with lung allograft rejection in rat transplant models. In human transplant recipients, BALT has not been linked to clinically significant rejection. We hypothesize that the immunohistochemical composition of BALT varies with the presence of acute lung allograft rejection. Methods. We retrospectively examined 40 human lung allograft recipients transplanted from 3/1/1999 to 6/1/2008. Patients were grouped by frequency and severity of acute rejection based on International Society of Heart Lung Transplant (ISHLT criteria. Transbronchial biopsies were reviewed for BALT by a blinded pathologist. BALT if present was immunohistochemically stained to determine T-and B-cell subpopulations. Results. BALT presence was associated with an increased frequency of acute rejection episodes in the first year after transplantation. Patients with a lower CD4/CD8 ratio had an increased rejection rate; however, BALT size or densities of T-cell and B-cell subpopulations did not correlate with rejection rate. Conclusion. The presence of BALT is associated with an increased frequency of rejection one year after transplant. The lower the CD4/CD8 ratio, the more acute rejection episodes occur in the first year after transplantation. The immunohistochemical composition of BALT may predict patients prone to frequent episodes of acute cellular rejection.

  2. Does borderline kidney allograft rejection always require treatment?

    Science.gov (United States)

    Németh, Dorottya; Ovens, Jörg; Opelz, Gerhard; Sommerer, Claudia; Döhler, Bernd; Becker, Luis E; Gross, Marie-Luise; Waldherr, Rüdiger; Mieth, Markus; Sadeghi, Mahmoud; Schmidt, Jan; Langer, Robert M; Zeier, Martin; Süsal, Caner

    2010-08-27

    Borderline rejection (Bord-R) is a frequent diagnosis in renal transplantation, and there is increasing evidence that regulatory T lymphocytes are involved in its pathogenesis. Current histopathologic practice does not differentiate between graft-protecting and -damaging T lymphocytes, and patients with Bord-R routinely receive rejection treatment. We analyzed Treg-associated forkhead box P3 (Foxp3) gene expression in Bord-R and more severe forms of acute rejection episodes (ARE). Foxp3 transcripts were measured in 520 serial peripheral blood samples from 177 kidney graft recipients obtained during the first 20 days posttransplantation. The highest Foxp3 transcripts were observed in patients with Bord-R or without rejection and the lowest in patients with ARE. Patients with Bord-R on posttransplant days 5 to 7 showed an increased Foxp3 transcript level of 156%, which increased to 302% by posttransplant days 14 to 16. In contrast, patients with ARE demonstrated significantly lower Foxp3 gene expression than that observed in Bord-R, nonrejectors, or acute tubular necrosis patients (P=0.001, PBord-R. This finding questions the appropriateness of rejection treatment in all patients with the histopathologic diagnosis "Bord-R".

  3. The Relationship of Anti-MICA Antibodies and MICA Expression with Heart Allograft Rejection

    National Research Council Canada - National Science Library

    Suarez-Alvarez, B; Lopez-Vazquez, A; Gonzalez, M. Zapico; Fdez-Morera, J. L; Diaz-Molina, B; Blanco-Gelaz, M. A; Pascual, D; Martinez-Borra, J; Muro, M; Alvarez-Lopez, M. R; Lopez-Larrea, C

    2007-01-01

    The role of MICA antibodies in acute heart allograft rejection was examined utilizing 190 pre- and post-transplant serum samples from 44 patients collected during the first year after transplantation...

  4. Association between a gain-of-function variant of PTPN22 and rejection in liver transplantation.

    Science.gov (United States)

    Dullin, Raphael; Koch, Martina; Sterneck, Martina; Nashan, Björn; Thude, Hansjörg

    2015-02-01

    The protein tyrosine phosphatase nonreceptor 22 gene (PTPN22) encodes a strong T-cell regulator called lymphoid protein tyrosine phosphatase. Previously, PTPN22 was described as a susceptibility gene for autoimmunity because it contains single nucleotide polymorphisms (SNPs) associated with several autoimmune diseases. One SNP (rs2476601; 1858G>A) has emerged as a particularly potent risk factor for autoimmunity. We address the question whether PTPN22 polymorphisms are also associated with acute rejection after liver transplantation. We investigated the influence of six PTPN22 SNPs on the susceptibility to acute liver allograft rejection. Consequently, we carried out a retrospective study genotyping 345 German liver recipients at six SNP loci, which include rs2488457 (-1123G>C), rs33996649 (788C>T), rs2476601 (1858G>A), rs1310182 (-852A>G), rs1217388 (-2200G>A), rs3789604 (64434T>G). Our study enrolled 165 recipients who did not develop rejection, 123 who showed one rejection episode, and 57 patients who suffered from multiple acute rejections after transplantation. The 1858A allele containing genotypes (GA+AA) and the 1858A allele had a significantly higher frequency in the group of patients with multiple rejection episodes (35.1% and 18.4%) compared to rejection-free patients (15.8% and 7.9%; P=0.022 and 0.023). In contrast, we could not detect any association between rejection and the other tested SNPs. Additionally, we identified one haplotype contributing to risk of multiple rejections, however, exhibiting no stronger impact than the 1858A allele alone. We conclude that the 1858G>A SNP may confer susceptibility to multiple acute liver transplant rejections in the German population.

  5. The Effect of Cortex/Medulla Proportions on Molecular Diagnoses in Kidney Transplant Biopsies: Rejection and Injury Can Be Assessed in Medulla.

    Science.gov (United States)

    Madill-Thomsen, K S; Wiggins, R C; Eskandary, F; Böhmig, G A; Halloran, P F

    2017-08-01

    Histologic assessment of kidney transplant biopsies relies on cortex rather than medulla, but for microarray studies, the proportion cortex in a biopsy is typically unknown and could affect the molecular readings. The present study aimed to develop a molecular estimate of proportion cortex in biopsies and examine its effect on molecular diagnoses. Microarrays from 26 kidney transplant biopsies divided into cortex and medulla components and processed separately showed that many of the most significant differences were in glomerular genes (e.g. NPHS2, NPHS1, CLIC5, PTPRO, PLA2R1, PLCE1, PODXL, and REN). Using NPHS2 (podocin) to estimate proportion cortex, we examined whether proportion cortex influenced molecular assessment in the molecular microscope diagnostic system. In 1190 unselected kidney transplant indication biopsies (Clinicaltrials.govNCT01299168), only 11% had Molecular scores for antibody-mediated rejection, T cell-mediated rejection, and injury were independent of proportion cortex. Rejection was diagnosed in many biopsies that were mostly or all medulla. Agreement in molecular diagnoses in paired cortex/medulla samples (23/26) was similar to biological replicates (32/37). We conclude that NPHS2 expression can estimate proportion cortex; that proportion cortex has little influence on molecular diagnosis of rejection; and that, although histology cannot assess medulla, rejection does occur in medulla as well as cortex. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  6. Nucleic Acid Drugs for Prevention of Cardiac Rejection

    Directory of Open Access Journals (Sweden)

    Jun-ichi Suzuki

    2009-01-01

    Full Text Available Heart transplantation has been broadly performed in humans. However, occurrence of acute and chronic rejection has not yet been resolved. Several inflammatory factors, such as cytokines and adhesion molecules, enhance the rejection. The graft arterial disease (GAD, which is a type of chronic rejection, is characterized by intimal thickening comprised of proliferative smooth muscle cells. Specific treatments that target the attenuation of acute rejection and GAD formation have not been well studied in cardiac transplantation. Recent progress in the nucleic acid drugs, such as antisense oligodeoxynucleotides (ODNs to regulate the transcription of disease-related genes, has important roles in therapeutic applications. Transfection of cis-element double-stranded DNA, named as “decoy,” has been also reported to be a useful nucleic acid drug. This decoy strategy has been not only a useful method for the experimental studies of gene regulation but also a novel clinical strategy. In this paper, we reviewed the experimental results of NF-κB, E2F, AP-1, and STAT-1 decoy and other ODNs using the experimental heart transplant models.

  7. Rejection sensitivity and symptom severity in patients with borderline personality disorder: effects of childhood maltreatment and self-esteem.

    Science.gov (United States)

    Bungert, Melanie; Liebke, Lisa; Thome, Janine; Haeussler, Katrin; Bohus, Martin; Lis, Stefanie

    2015-01-01

    Interpersonal dysfunction in Borderline Personality Disorder (BPD) is characterized by an 'anxious preoccupation with real or imagined abandonment' (DSM-5). This symptom description bears a close resemblance to that of rejection sensitivity, a cognitive affective disposition that affects perceptions, emotions and behavior in the context of social rejection. The present study investigates the level of rejection sensitivity in acute and remitted BPD patients and its relation to BPD symptom severity, childhood maltreatment, and self-esteem. Data were obtained from 167 female subjects: 77 with acute BPD, 15 with remitted BPD, and 75 healthy controls who were matched with the patients for age and education. The instruments used for assessment were the Rejection Sensitivity Questionnaire, the short version of the Borderline Symptom List, the Childhood Trauma Questionnaire, and the Rosenberg Self-Esteem Scale. Both acute and remitted BPD patients had higher scores on the Rejection Sensitivity Questionnaire than did healthy controls. Lower self-esteem was found to be positively correlated with both increased BPD symptom severity and higher rejection sensitivity, and mediated the relation between the two. History of childhood maltreatment did not correlate with rejection sensitivity, BPD symptom severity, or self-esteem. Our findings support the hypothesis that rejection sensitivity is an important component in BPD, even for remitted BPD patients. Level of self-esteem appears to be a relevant factor in the relationship between rejection sensitivity and BPD symptom severity. Therapeutic interventions for BPD would do well to target rejection sensitivity.

  8. Perturbations in the Urinary Exosome in Transplant Rejection

    Energy Technology Data Exchange (ETDEWEB)

    Sigdel, Tara K.; NG, Yolanda; Lee, Sangho; Nicora, Carrie D.; Qian, Weijun; Smith, Richard D.; Camp, David G.; Sarwal, Minnie M.

    2015-01-05

    Background: Urine exosomes, vesicles exocytosed into urine by all renal epithelial cell types, occur under normal physiologic and disease states. Exosome contents may mirror disease-specific proteome perturbations in kidney injury. Analysis methodologies for the exosomal fraction of the urinary proteome were developed and for comparing the urinary exosomal fraction versus unfractionated proteome for biomarker discovery. Methods: Urine exosomes were isolated by centrifugal filtration from mid-stream, second morning void, urine samples collected from kidney transplant recipients with and without biopsy matched acute rejection. The proteomes of unfractionated whole urine (Uw) and urine exosomes (Uexo) underwent mass spectrometry-based quantitative proteomics analysis. The proteome data were analyzed for significant differential protein abundances in acute rejection (AR). Results: Identifications of 1018 and 349 proteins, Uw and Uexo fractions, respectively, demonstrated a 279 protein overlap between the two urinary compartments with 25%(70) of overlapping proteins unique to Uexoand represented membrane bound proteins (p=9.31e-7). Of 349 urine exosomal proteins identified in transplant patients 220 were not previously identified in the normal urine exosomal fraction. Uexo proteins (11), functioning in the inflammatory / stress response, were more abundant in patients with biopsy-confirmed acute rejection, 3 of which were exclusive to Uexo. Uexo AR-specific biomarkers (8) were also detected in Uw, but since they were observed at significantly lower abundances in Uw, they were not significant for AR in Uw. Conclusions: A rapid urinary exosome isolation method and quantitative measurement of enriched Uexo proteins was applied. Urine proteins specific to the exosomal fraction were detected either in unfractionated urine (at low abundances) or by Uexo fraction analysis. Perturbed proteins in the exosomal compartment of urine collected from kidney transplant patients were

  9. Recurrent and de novo glomerulonephritis following renal transplantation: higher rates of rejection and lower graft survival.

    Science.gov (United States)

    Mirioglu, Safak; Caliskan, Yasar; Goksoy, Yagmur; Gulcicek, Sibel; Ozluk, Yasemin; Sarihan, Irem; Seyahi, Nurhan; Kilicaslan, Isin; Turkmen, Aydin; Sever, Mehmet Sukru

    2017-12-01

    In this retrospective study with case-control design, we aimed to determine the clinical and pathological characteristics of post-transplant glomerulonephritis (GN), and their effects on transplant recipients. One hundred and twenty renal transplant recipients with biopsy-proven recurrent or de novo primary GN were compared with two matched control groups including 120 transplant recipients with nonrecurrent primary GN (nonrecurrent GN group) and 120 transplant recipients with non-GN etiology (non-GN group). Primary outcome was allograft loss, and secondary outcomes were biopsy-confirmed cellular or antibody-mediated rejection. In recurrent/de novo GN, nonrecurrent GN and non-GN groups, 54.2% (n = 65), 16.7% (n = 20) and 8.3% (n = 10) of patients reached primary outcome after a median follow-up of 96 (IQR: 56-149) months, respectively. Allograft loss was significantly higher in recurrent/de novo GN group compared to nonrecurrent GN and non-GN groups (p < 0.001). At 10 years, allograft loss rates in recurrent/de novo GN group were 54.2% for focal segmental glomerulosclerosis, 53.2% for membranoproliferative glomerulonephritis, and 33.4% for IgA nephropathy cases. Biopsy-confirmed rejection rate was significantly higher in the recurrent/de novo GN group (n = 25, 20.8%) compared to non-GN (n = 8, 6.7%) group (p = 0.001). Recurrent/de novo GN is associated with higher risk of rejection and worse allograft survival.

  10. 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…

  11. 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…

  12. 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...

  13. Estudo das alterações das citocinas inflamatórias na rejeição aguda do transplante intestinal em ratos Cytokine participation in the acute rejection of intestinal transplantation in rats

    Directory of Open Access Journals (Sweden)

    André Dong Won Lee

    2004-06-01

    patients with short bowel syndrome, aiming the reintroduction of oral diet. However, the major obstacle in this procedure is the strong rejection. Delay in rejection diagnosis may be irreversible and lethal. AIM: To define method for early diagnosis of rejection based on the presence of interleucin-6 (IL-6 e interferon- gamma (IFN-gamma from intestinal allograft. MATERIAL AND METHODS: Isogenic rats Brown-Norway (BN and Lewis (LEW were submitted to intestinal heterotopic allotransplantation and divided in two groups: LEW donor to LEW recipient isograft group (C and BN donor to LEW recipient allograft group (Tx. According to the day of sacrifice, Tx group were subdivided in three subgroups with eight animals each as follow: Tx3- sacrificed at third postoperative day (POD, Tx5 - sacrificed at fifth POD and Tx7 - sacrificed at seventh POD. Eight animals from control group were subdivided in three moments according to the time of biopsy from the graft as follow: C³ - biopsy at third POD; C5 - biopsy at fifth POD and C7 - biopsy at seventh POD. All animals from control group were sacrificed at seventh POD. Rejection parameters were compared between the control groups (C3 vs C5, C3 vs C7 and C5 vs C7, and allograft group (Tx3 vs Tx5, Tx3 vs Tx7 and Tx5 vs Tx7. The same parameters were analyzed between the control group and allograft groups ( C3 vs Tx3, C5 vs Tx5 and C7 vs Tx7. RESULTS: In C group no statistical significant difference regarding the immunoexpression of the cytokines, while in Tx group, immunoexpression of IL-6 and IFN-gamma were remarkable since the fifth postoperative day.

  14. Collagen Sponge Functionalized with Chimeric Anti-BMP-2 Monoclonal Antibody Mediates Repair of Critical-Size Mandibular Continuity Defects in a Nonhuman Primate Model

    Directory of Open Access Journals (Sweden)

    Yilin Xie

    2017-01-01

    Full Text Available Antibody-mediated osseous regeneration (AMOR has been introduced by our research group as a tissue engineering approach to capture of endogenous growth factors through the application of specific monoclonal antibodies (mAbs immobilized on a scaffold. Specifically, anti-Bone Morphogenetic Protein- (BMP- 2 mAbs have been demonstrated to be efficacious in mediating bone repair in a number of bone defects. The present study sought to investigate the application of AMOR for repair of mandibular continuity defect in nonhuman primates. Critical-sized mandibular continuity defects were created in Macaca fascicularis locally implanted with absorbable collagen sponges (ACS functionalized with chimeric anti-BMP-2 mAb or isotype control mAb. 2D and 3D analysis of cone beam computed tomography (CBCT imaging demonstrated increased bone density and volume observed within mandibular continuity defects implanted with collagen scaffolds functionalized with anti-BMP-2 mAb, compared with isotype-matched control mAb. Both CBCT imaging and histologic examination demonstrated de novo bone formation that was in direct apposition to the margins of the resected bone. It is hypothesized that bone injury may be necessary for AMOR. This is evidenced by de novo bone formation adjacent to resected bone margins, which may be the source of endogenous BMPs captured by anti-BMP-2 mAb, in turn mediating bone repair.

  15. Collagen Sponge Functionalized with Chimeric Anti-BMP-2 Monoclonal Antibody Mediates Repair of Critical-Size Mandibular Continuity Defects in a Nonhuman Primate Model

    Science.gov (United States)

    Xie, Yilin; Su, Yingying; Tang, Jianxia; Goh, Bee Tin; Saigo, Leonardo; Zhang, Chunmei; Wang, Jinsong; Khojasteh, Arash; Wang, Songlin

    2017-01-01

    Antibody-mediated osseous regeneration (AMOR) has been introduced by our research group as a tissue engineering approach to capture of endogenous growth factors through the application of specific monoclonal antibodies (mAbs) immobilized on a scaffold. Specifically, anti-Bone Morphogenetic Protein- (BMP-) 2 mAbs have been demonstrated to be efficacious in mediating bone repair in a number of bone defects. The present study sought to investigate the application of AMOR for repair of mandibular continuity defect in nonhuman primates. Critical-sized mandibular continuity defects were created in Macaca fascicularis locally implanted with absorbable collagen sponges (ACS) functionalized with chimeric anti-BMP-2 mAb or isotype control mAb. 2D and 3D analysis of cone beam computed tomography (CBCT) imaging demonstrated increased bone density and volume observed within mandibular continuity defects implanted with collagen scaffolds functionalized with anti-BMP-2 mAb, compared with isotype-matched control mAb. Both CBCT imaging and histologic examination demonstrated de novo bone formation that was in direct apposition to the margins of the resected bone. It is hypothesized that bone injury may be necessary for AMOR. This is evidenced by de novo bone formation adjacent to resected bone margins, which may be the source of endogenous BMPs captured by anti-BMP-2 mAb, in turn mediating bone repair. PMID:28401163

  16. Stimulation of Fas agonistic antibody-mediated apoptosis by heparin-like agents suppresses Hsp27 but not Bcl-2 protective activity.

    Science.gov (United States)

    Manero, Florence; Ljubic-Thibal, Vesna; Moulin, Maryline; Goutagny, Nadège; Yvin, Jean-Claude; Arrigo, André-Patrick

    2004-01-01

    We report that in Jurkat T cells or freshly isolated T lymphocytes, physiological concentrations of high-molecular weight sulfated polysaccharides such as heparin, heparan sulfate, and dextran sulfate significantly increased the percentage of cell death induced by Fas IgM agonistic antibody. The phenomenon was caspase dependent and P53 independent and correlated with an increased accessibility of cell surface Fas receptors. We also observed that the Fas IgM agonistic antibody-dependent formation of sodium dodecyl sulfate (SDS)-resistant large structures containing Fas receptor was decreased in the presence of heparin-like agents. In contrast, the different agents had no effect when cell death was triggered by FasL, the natural ligand of Fas that does not generate SDS-resistant forms of Fas. Interestingly, the synergistic effect of heparin-like agents toward Fas IgM agonistic antibody-mediated cell death abolished Hsp27 antiapoptotic activity but did not alter much the protection generated by Bcl-2 expression.

  17. Induction Therapy, Rejection, and Graft Outcomes in Pediatric and Adolescent Kidney Transplant Recipients.

    Science.gov (United States)

    Mincham, Christine Marie; Wong, Germaine; Teixeira-Pinto, Armando; Kennedy, Sean; Alexander, Stephen; Larkins, Nicholas; Lim, Wai H

    2017-09-01

    Although the clinical benefit of interleukin-2-receptor antibody (IL-2RAb) induction in reducing the risk of acute rejection in adult kidney transplant recipients is well established, a similar benefit in pediatric recipients remains controversial. The aim of this study is to evaluate the efficacy of IL-2RAb in reducing acute rejection in pediatric and adolescent recipients aged 21 years or younger using Australia and New Zealand Dialysis and Transplant registry. The association between IL-2RAb induction and risk of acute rejection was examined using adjusted logistic regression and propensity score analyses, whereby the associations between induction, graft loss, and incident cancer were examined using adjusted Cox regression analysis. There were 658 recipients followed up for a median of 5.5 years between 2001 and 2012. The use of IL-2RAb induction was associated with adjusted odds ratios of 0.61 (95% confidence interval [CI], 0.41-0.91; P = 0.007) for any rejection and 0.57 (95% CI, 0.35-0.92; P = 0.020) for early rejection occurring in the first 6 months after transplant. These associations were attenuated in the propensity score analysis but remained statistically significant with adjusted odds ratio of 0.65 (95% CI, 0.49-0.87) for any rejection and 0.64 (95% CI, 0.44-0.93) for early rejection. There were no associations between induction, graft loss, and incident cancer. Induction treatment of IL-2RAb in pediatric and adolescent kidney transplant recipients is associated with at least a 40% reduction in the odds of acute rejection, independent of age, era, immunological status, and initial immunosuppression.

  18. Profile of the Pleximmune blood test for transplant rejection risk prediction

    OpenAIRE

    Sindhi, Rakesh; Ashokkumar, Chethan; Higgs, Brandon W; Levy, Samantha; Soltys, Kyle; Bond, Geoffrey; Mazariegos, George; Ranganathan, Sarangarajan; Zeevi, Adriana

    2016-01-01

    The Pleximmune? test (Plexision Inc., Pittsburgh, PA, USA) is the first cell-based test approved by the US FDA, which predicts acute cellular rejection in children with liver- or intestine transplantation. The test addresses an unmet need to improve management of immunosuppression, which incurs greater risks of opportunistic infections and Epstein?Barr virus-induced malignancy during childhood. High-dose immunosuppression and recurrent rejection after intestine transplantation also result in ...

  19. Recurrence and rejection in liver transplantation for primary sclerosing cholangitis

    Science.gov (United States)

    Fosby, Bjarte; Karlsen, Tom H; Melum, Espen

    2012-01-01

    Primary sclerosing cholangitis (PSC) is a chronic progressive inflammatory disease affecting the bile ducts, leading to fibrosis and eventually cirrhosis in most patients. Its etiology is unknown and so far no effective medical therapy is available. Liver transplantation (LTX) is the only curative treatment and at present PSC is the main indication for LTX in the Scandinavian countries. Close to half of the PSC patients experience one or more episodes of acute cellular rejection (ACR) following transplantation and approximately 1/5 of the transplanted patients develop recurrent disease in the graft. In addition, some reports indicate that ACR early after LTX for PSC can influence the risk for recurrent disease. For these important post-transplantation entities affecting PSC patients, we have reviewed the current literature on epidemiology, pathogenesis, treatment and the possible influence of rejection on the risk of recurrent disease in the allograft. PMID:22228965

  20. Prospects and limitations of antibody-mediated clearing of lipoproteins from blood plasma prior to nanoparticle tracking analysis of extracellular vesicles.

    Science.gov (United States)

    Mørk, Morten; Handberg, Aase; Pedersen, Shona; Jørgensen, Malene M; Bæk, Rikke; Nielsen, Morten K; Kristensen, Søren R

    2017-01-01

    Introduction: Nanoparticle tracking analysis (NTA) enables measurement of extracellular vesicles (EVs) but lacks the ability to distinct between EVs and lipoproteins which are abundantly present in blood plasma. Limitations in ultracentrifugation and size exclusion chromatography applied for EV isolation may result in inadequate EV purification and preservation. In this proof of concept study, we aimed to evaluate the potential of antibody-mediated removal of lipoproteins from plasma prior to extracellular vesicle (EV) analysis by nanoparticle tracking analysis (NTA). Methods: Ten platelet-free plasma (PFP) samples from healthy fasting subjects were incubated with magnetic beads coated with antibodies against apolipoprotein B-48 and B-100 (ApoB). Plasma samples were analysed with NTA before and after application of the bead procedure. Four fasting PFP samples were analysed with an ELISA specific for human ApoB to estimate the degree of removal of lipoproteins and EV array analysis was used for identification of possible EV loss. Results: The magnetic bead separation procedure resulted in a median reduction of the particle concentration in plasma by 62% (interquartile range 32-72%). The mean size of the remaining particles generally increased. ApoB concentration was reduced to a level close to the background signal, whereas a median reduction of the EV content by 21% (range 8-43%) was observed. Conclusion: Anti-ApoB antibody coated magnetic beads may hold potential for removal of lipoproteins from human PFP prior to EV measurement by NTA but some artefactual effect and EV loss may have to be endured.

  1. The effect of daily co-trimoxazole prophylaxis on natural development of antibody-mediated immunity against P. falciparum malaria infection in HIV-exposed uninfected Malawian children.

    Science.gov (United States)

    Longwe, Herbert; Jambo, Kondwani C; Phiri, Kamija S; Mbeye, Nyanyiwe; Gondwe, Thandile; Hall, Tom; Tetteh, Kevin K A; Drakeley, Chris; Mandala, Wilson L

    2015-01-01

    Co-trimoxazole prophylaxis, currently recommended in HIV-exposed, uninfected (HEU) children as protection against opportunistic infections, also has some anti-malarial efficacy. We determined whether daily co-trimoxazole prophylaxis affects the natural development of antibody-mediated immunity to blood-stage Plasmodium falciparum malaria infection. Using an enzyme-linked immunosorbent assay, we measured antibodies to 8 Plasmodium falciparum antigens (AMA-1, MSP-119, MSP-3, PfSE, EBA-175RII, GLURP R0, GLURP R2 and CSP) in serum samples from 33 HEU children and 31 HIV-unexposed, uninfected (HUU) children, collected at 6, 12 and 18 months of age. Compared to HIV-uninfected children, HEU children had significantly lower levels of specific IgG against AMA-1 at 6 months (p = 0.001), MSP-119 at 12 months (p = 0.041) and PfSE at 6 months (p = 0.038), 12 months (p = 0.0012) and 18 months (p = 0.0097). No differences in the IgG antibody responses against the rest of the antigens were observed between the two groups at all time points. The breadth of specificity of IgG response was reduced in HEU children compared to HUU children during the follow up period. Co-trimoxazole prophylaxis seems to reduce IgG antibody responses to P. falciparum blood stage antigens, which could be as a result of a reduction in exposure of those children under this regime. Although antibody responses were regarded as markers of exposure in this study, further studies are required to establish whether these responses are correlated in any way to clinical immunity to malaria.

  2. 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.

  3. Indicators of rejection in groups of children

    Directory of Open Access Journals (Sweden)

    Vera Regina Miranda Gomes da Silva

    2001-12-01

    Full Text Available The issue of rejection is motivating countless researchers due to the close relationship between peer rejection and difficulties in future adjustment. The study of this issue can contribute towards the detection of factors that trigger rejection, consequently making possible preventive interventions. This text is intended to provide a summary of the research undertaken by the author as part of her Master's Degree, the aim of which was to detect indicators of rejection in the final year of a private primary school in Curitiba (n=52. In this study, “indicators of rejection” are understood to be criteria that lead children to exclude each other from their recreation and working activities, within the context of the school. The study used one instrument designed to collect data from the children (“voting for the least popular” and “tag” and another aimed at obtaining data from the teachers (“teacher's card”. The analysis and cross-referencing of the data obtained indicated that children tend to reject their peers based on their inadequate behaviour (bossiness, disruptive behaviour, and this perception was reinforced by the data obtained from the teachers. On the other hand, children tend to chose other children who frequently demonstrate sociable behaviour to be their peers. Keywords: Rejection, rejected children, peer rejection, recognition of rejection.

  4. Perturbations in the Urinary Exosome in Transplant Rejection

    Directory of Open Access Journals (Sweden)

    Tara eSigdel

    2015-01-01

    Full Text Available Urine exosomes are small vesicles exocytosed into the urine by all renal epithelial cell types under normal physiologic and disease states. Urine exosomal proteins may mirror disease specific proteome perturbations in kidney injury. Analysis methodologies for the exosomal fraction of the urinary proteome were developed for comparing the urinary exosomal fraction versus unfractionated proteome for biomarker discovery. Urine exosomes were isolated by centrifugal filtration of urine samples collected from kidney transplant patients with and without acute rejection, which were biopsy matched. The proteomes of unfractionated whole urine (Uw and urine exosomes (Ue underwent mass spectroscopy-based quantitative proteonomics analysis. The proteome data were analyzed for significant differential protein abundances in acute rejection (AR. A total of 1018 proteins were identified in Uw and 349 proteins in Ue. 279 overlapped between the two urinary compartments and 70 proteins were unique to the Ue compartment. Of 349 exosomal proteins identified from transplant patients,220 had not been previously identified in the normal Ue fraction. 11 Ue proteins, functionally involved in an inflammatory and stress response, were more abundant in urine samples from patients with acute rejection, 3 of which are exclusive to the Ue fraction. Ue AR-specific biomarkers(8 were also detected in Uw, but since they were observed at significantly lower abundances in Uw, they were not significant for AR in Uw. A rapid urinary exosome isolation method and quantitative measurement of enriched Ue proteins was applied. Perturbed proteins in the exosomal compartment of urine collected from kidney transplant patients were specific to inflammatory responses, and were not observed in the Ue fraction from normal healthy subjects. Ue specific protein alterations in renal disease provide potential mechanistic insights and offer a unique panel of sensitive biomarkers for monitoring AR.

  5. Not all rejections are alike : Competence and warmth as a fundamental distinction in social rejection

    NARCIS (Netherlands)

    Celik, P.; Lammers, J.; van Beest, I.; Bekker, M.H.J.; Vonk, R.

    2013-01-01

    Social rejection can lead to a variety of emotions. Two studies show that specific emotional reactions to social rejection can be understood by relying on the fundamental distinction between competence and warmth. Rejection that is perceived to be due to incompetence leads to anger, whereas

  6. 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...

  7. Fractional active disturbance rejection control.

    Science.gov (United States)

    Li, Dazi; Ding, Pan; Gao, Zhiqiang

    2016-05-01

    A fractional active disturbance rejection control (FADRC) scheme is proposed to improve the performance of commensurate linear fractional order systems (FOS) and the robust analysis shows that the controller is also applicable to incommensurate linear FOS control. In FADRC, the traditional extended states observer (ESO) is generalized to a fractional order extended states observer (FESO) by using the fractional calculus, and the tracking differentiator plus nonlinear state error feedback are replaced by a fractional proportional-derivative controller. To simplify controller tuning, the linear bandwidth-parameterization method has been adopted. The impacts of the observer bandwidth ωo and controller bandwidth ωc on system performance are then analyzed. Finally, the FADRC stability and frequency-domain characteristics for linear single-input single-output FOS are analyzed. Simulation results by FADRC and ADRC on typical FOS are compared to demonstrate the superiority and effectiveness of the proposed scheme. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

  8. An Evolutionary Perspective on Mate Rejection.

    Science.gov (United States)

    Kelly, Ashleigh J; Dubbs, Shelli L; Barlow, Fiona Kate

    2016-01-01

    We argue that mate rejection and ex-partner relationships are important, multifaceted topics that have been underresearched in social and evolutionary psychology. Mate rejection and relationship dissolution are ubiquitous and form integral parts of the human experience. Both also carry with them potential risks and benefits to our fitness and survival. Hence, we expect that mate rejection would have given rise to evolved behavioral and psychological adaptations. Herein, we outline some of the many unanswered questions in evolutionary psychology on these topics, at each step presenting novel hypotheses about how men and women should behave when rejecting a mate or potential mate or in response to rejection. We intend these hypotheses and suggestions for future research to be used as a basis for enriching our understanding of human mating from an evolutionary perspective.

  9. Intrathymic immune modulation prevents acute rejection but not the development of graft arteriosclerosis (chronic rejection)

    NARCIS (Netherlands)

    Hillebrands, JL; Raue, HP; Klatter, FA; Hylkema, MN; Platteel, [No Value; Hardonk-Wubbena, A; Nieuwenhuis, P; Rozing, J

    2001-01-01

    Background. We showed previously that our intrathymic immune modulation protocol induces virtually permanent graft survival of simultaneously transplanted cardiac allografts in MHC-incompatible rat strain combinations. It is, however, unknown whether this procedure prevents the development of graft

  10. Explaining the paradoxical rejection-aggression link: the mediating effects of hostile intent attributions, anger, and decreases in state self-esteem on peer rejection-induced aggression in youth.

    Science.gov (United States)

    Reijntjes, Albert; Thomaes, Sander; Kamphuis, Jan H; Bushman, Brad J; de Castro, Bram Orobio; Telch, Michael J

    2011-07-01

    People are strongly motivated to feel accepted by others. Yet when faced with acute peer rejection they often aggress against the very peers they desire acceptance from, which may lead to further rejection. The present experiment tests three potential mediators of aggressive responses to acute peer rejection in the critical developmental stage of early adolescence. Participants (N=185, M(age)=11.5 years) completed personal profiles that were allegedly evaluated online by peers. After receiving negative or neutral peer feedback, participants could aggress against the same peers who had evaluated them. Rejected participants attributed more hostile intent to the peers, were angrier, showed a greater reduction in state self-esteem, and were more aggressive. Mediational analyses showed that hostile intent attributions mediated the acute peer rejection-aggression relationship, whereas increases in anger and decreases in state self-esteem did not. Thus, acute peer rejection evokes hostile intent attributions that, in turn, lead to aggressive reactions. © 2011 by the Society for Personality and Social Psychology, Inc

  11. Expression of class II major histocompatibility complex antigens (HLA-DR) and lymphocyte subset immunotyping in chronic pulmonary transplant rejection.

    Science.gov (United States)

    Hasegawa, S; Ockner, D M; Ritter, J H; Patterson, G A; Trulock, E P; Cooper, J D; Wick, M R

    1995-05-01

    Currently, the bronchiolitis obliterans syndrome (BOS) of chronic airway rejection represents the most significant obstacle to the long-term function of isolated pulmonary allografts in humans. Between 20% and 30% of recipients are affected by this condition. To define the possible pathogenetic role of altered expression of class II major histocompatibility complex antigens (ie, HLA-DR) in BOS, the authors studied well-characterized examples of this process immunohistologically. Eleven BOS specimens were compared with seven controls, represented by allografts with no pathologic abnormalities taken from patients with normal posttransplant respiratory function, as well as 14 biopsies showing acute rejection. In addition, immunophenotypic subtyping of lymphocytes in all specimens was undertaken. Control tissues exhibited variable but weak expression of HLA-DR in bronchiolar epithelium and alveolar pneumocytes. In comparison, immunostaining for class II major histocompatibility complex antigens in BOS showed no statistically significant differences, whereas the 14 examples of acute rejection manifested intense HLA-DR expression in epithelia and endothelial cells. The numbers of intrabronchiolar and peribronchiolar lymphocytes were clearly higher in both acute rejection and BOS than in controls, but these cells differed in lineage in the two rejection states. Acute rejection showed an obvious preponderance of CD43-positive T lymphocytes, whereas lymphoid cells in BOS were a relatively equal mixture of CD20-positive B cells and CD43-positive T cells. Moreover, incipient peribronchiolar B-cell follicles were observed in BOS. Natural killer (CD57-positive) lymphocytes were rare in all specimens. These data suggest that alterations in HLA-DR expression probably do not play a central role in the genesis of BOS, as they do in acute rejection. In contrast, the results of lymphocyte immunophenotyping and correlative histologic findings in BOS suggest that both T cells and B

  12. 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

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

    Science.gov (United States)

    Aparici, C M; Narula, J; Puig, M; Camprecios, M; Martín, J C; Tembl, A; Flotats, A; Estorch, M; Catafau, A M; Bernà, L; Ballester, M; Carrió, I

    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 12-4,745 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. 111In-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

  14. 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

  15. Predicting cellular rejection with a cell-based assay: Pre-clinical evaluation in children

    Science.gov (United States)

    Ashokkumar, Chethan; Soltys, Kyle; Mazariegos, George; Bond, Geoffrey; Higgs, Brandon W.; Ningappa, Mylarappa; Sun, Qing; Brown, Amanda; White, Jaimie; Levy, Samantha; Fazzolare, Tamara; Remaley, Lisa; Dirling, Katie; Harris, Patti; Hartle, Tara; Kachmar, Pam; Nicely, Megan; O'Toole, Lindsay; Boehm, Brittany; Jativa, Nicole; Stanley, Paula; Jaffe, Ronald; Ranganathan, Sarangarajan; Zeevi, Adriana; Sindhi, Rakesh

    2015-01-01

    Background Allospecific CD154+T-cytotoxic memory cells (CD154+TcM) predict acute cellular rejection (ACR) after liver or intestine transplantation (LTx, ITx) in small cohorts of children and can enhance immunosuppression management, but await validation and clinical implementation. Methods To establish safety and probable benefit, CD154+TcM were measured in cryopreserved samples from 214 children 1 implies increased rejection-risk. Results Training and validation set subjects were demographically similar. Mean coefficient of test variation was <10% under several conditions. Logistic regression incorporating several confounding variables identified separate pre-transplant and post-transplant IR thresholds for prediction of rejection in respective training set samples. An IR ≥ 1.1 in post-transplant training samples, and IR ≥1.23 in pre-transplant training samples predicted LTx or ITx rejection in corresponding validation set samples in the 60-day post-sampling period with sensitivity, specificity, positive and negative predictive values of 84%, 80%, 64%, and 92%, respectively (AUC 0.792), and 57%, 89%, 78%, and 74%, respectively (AUC 0.848). No adverse events were encountered due to phlebotomy. Conclusions Allospecific CD154+T-cytotoxic memory cells predict acute cellular rejection after liver or intestine transplantation in children. Adjunctive use can enhance clinical outcomes. PMID:26950712

  16. 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....

  17. Comparing reports of peer rejection: associations with rejection sensitivity, victimization, aggression, and friendship.

    Science.gov (United States)

    Zimmer-Gembeck, Melanie J; Nesdale, Drew; McGregor, Leanne; Mastro, Shawna; Goodwin, Belinda; Downey, Geraldine

    2013-12-01

    Perceiving that one is rejected is an important correlate of emotional maladjustment. Yet, self-perceptions can substantially differ from classmate-reports of who is rejected. In this study, discrepancies between self- and classmate-reports of rejection were identified in 359 Australian adolescents (age 10-12 years). As expected, adolescents who overestimated rejection reported more rejection sensitivity and felt more victimized by their peers, but were not seen by peers as more victimized. Adolescents who underestimated rejection identified themselves as high in overt aggression, and their peers identified them as high in overt and relational aggression and low in prosocial behavior. Yet, underestimators' feelings of friendship satisfaction did not seem to suffer and they reported low rejection sensitivity. Results suggest that interventions to promote adolescent health should explicitly recognize the different needs of those who do and do not seem to perceive their high rejection, as well as adolescents who overestimate their rejection. Copyright © 2013 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  18. Corneal Graft Rejection: Incidence and Risk Factors

    Directory of Open Access Journals (Sweden)

    Alireza Baradaran-Rafii

    2008-12-01

    Full Text Available

    PURPOSE: To determine the incidence and risk factors of late corneal graft rejection after penetrating keratoplasty (PKP. METHODS: Records of all patients who had undergone PKP from 2002 to 2004 without immunosuppressive therapy other than systemic steroids and with at least one year of follow up were reviewed. The role of possible risk factors such as demographic factors, other host factors, donor factors, indications for PKP as well as type of rejection were evaluated. RESULTS: During the study period, 295 PKPs were performed on 286 patients (176 male, 110 female. Mean age at the time of keratoplasty was 38±20 (range, 40 days to 90 years and mean follow up period was 20±10 (range 12-43 months. Graft rejection occurred in 94 eyes (31.8% at an average of 7.3±6 months (range, 20 days to 39 months after PKP. The most common type of rejection was endothelial (20.7%. Corneal vascularization, regrafting, anterior synechiae, irritating sutures, active inflammation, additional anterior segment procedures, history of trauma, uncontrolled glaucoma, prior graft rejection, recurrence of herpetic infection and eccentric grafting increased the rate of rejection. Patient age, donor size and bilateral transplantation had no significant influence on graft rejection. CONCLUSION: Significant risk factors for corneal graft rejection include

  19. The fate of triaged and rejected manuscripts.

    Science.gov (United States)

    Zoccali, Carmine; Amodeo, Daniela; Argiles, Angel; Arici, Mustafa; D'arrigo, Graziella; Evenepoel, Pieter; Fliser, Danilo; Fox, Jonathan; Gesualdo, Loreto; Jadoul, Michel; Ketteler, Markus; Malyszko, Jolanta; Massy, Ziad; Mayer, Gert; Ortiz, Alberto; Sever, Mehmet; Vanholder, Raymond; Vinck, Caroline; Wanner, Christopher; Więcek, Andrzej

    2015-12-01

    In 2011, Nephrology Dialysis and Transplantation (NDT) established a more restrictive selection process for manuscripts submitted to the journal, reducing the acceptance rate from 25% (2008-2009) to currently about 12-15%. To achieve this goal, we decided to score the priority of manuscripts submitted to NDT and to reject more papers at triage than in the past. This new scoring system allows a rapid decision for the authors without external review. However, the risk of such a restrictive policy may be that the journal might fail to capture important studies that are eventually published in higher-ranked journals. To look into this problem, we analysed random samples of papers (∼10%) rejected by NDT in 2012. Of the papers rejected at triage and those rejected after regular peer review, 59 and 61%, respectively, were accepted in other journals. A detailed analysis of these papers showed that only 4 out of 104 and 7 out of 93 of the triaged and rejected papers, respectively, were published in journals with an impact factor higher than that of NDT. Furthermore, for all these papers, independent assessors confirmed the evaluation made by the original reviewers. The number of citations of these papers was similar to that typically obtained by publications in the corresponding journals. Even though the analyses seem reassuring, previous observations made by leading journals warn that the risk of 'big misses', resulting from selective editorial policies, remains a real possibility. We will therefore continue to maintain a high degree of alertness and will periodically track the history of manuscripts rejected by NDT, particularly papers that are rejected at triage by our journal. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  20. Image rejects in general direct digital radiography

    Science.gov (United States)

    Rosanowsky, Tine Blomberg; Jensen, Camilla; Wah, Kenneth Hong Ching

    2015-01-01

    Background 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. Purpose 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. Material and Methods 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. Results 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. Conclusion 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. PMID:26500784

  1. Human polyclonal anti-hepatitis B surface antigen immunoglobulin reduces the frequency of acute rejection after liver transplantation for chronic hepatitis B A imunoglobulina policlonal humana anti-antígeno de superfície da hepatite B reduz a freqüência da rejeição aguda após transplante de fígado

    Directory of Open Access Journals (Sweden)

    Claudia Alves COUTO

    2001-12-01

    Full Text Available BACKGROUND: Use of polyclonal anti-hepatitis B surface antigen immunoglobulin (HBIg has been shown to reduce hepatitis B virus (HBV recurrence after liver transplantation (LT and to decrease the frequency of acute cellular rejection (ACR. However, the protective role of HBIg against ACR remains controversial, since HBV infection has been also associated with a lower incidence of ACR. AIM: To assess the relationship between HBIg immunoprophylaxis and the incidence of rejection after LT. METHODS: 260 patients (158 males, 43 ± 14 years old submitted to LT were retrospectively evaluated and divided into three groups, according to the presence of HBsAg and the use of HBIg. Group I was comprised of HBsAg-positive patients (n = 12 that received HBIg for more than 6 months. Group II was comprised of HBsAg-positive patients that historically have not received HBIg or have been treated irregularly for less than 3 months (n = 10. Group III was composed of 238 HBsAg-negative subjects that have not received HBIg. RESULTS: HBIg-treated patients (group I had significantly less ACR episodes, when compared to group II and III. No differences between groups II and III were observed. CONCLUSIONS: Long-term HBIg administration contributes independently to reduce the number of ACR episodes after LT.INTRODUÇÃO: O emprego da imunoglobulina policlonal anti-antígeno de superfície da hepatite B (HBIg tem reduzido a recorrência da hepatite B após transplante hepático (TH, assim como também a freqüência de rejeição celular aguda (RCA. No entanto, o papel protetor da HBIg contra a RCA permanece controverso, pois a própria infecção por vírus B foi também associada a menor incidência de RCA. OBJETIVOS: Verificar a relação entre HBIg e a freqüência de RCA após TH. MÉTODOS: 260 pacientes (158 do sexo masculino, com 43 ± 14 anos submetidos a TH foram avaliados, retrospectivamente, e divididos em três grupos de acordo com a presença de AgHBs e uso de

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

    Science.gov (United States)

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

    2017-01-01

    Objective: The aim of this research was to obtain the views of young children regarding their reasons for rejecting a peer. Method: To achieve this goal, we conducted a qualitative study in the context of theory building research using an analysis methodology based on Grounded Theory. The collected information was extracted through semi-structured individual interviews from a sample of 853 children aged 6 from 13 urban public schools in Spain. Results: The children provided 3,009 rejection nominations and 2,934 reasons for disliking the rejected peers. Seven reason categories emerged from the analysis. Four categories refer to behaviors of the rejected children that have a cost for individual peers or peer group such as: direct aggression, disturbance of wellbeing, problematic social and school behaviors and dominance behaviors. A further two categories refer to the identities arising from the preferences and choices of rejected and rejecter children and their peers: personal identity expressed through preferences and disliking, and social identity expressed through outgroup prejudices. The “no-behavior or no-choice” reasons were covered by one category, unfamiliarity. In addition, three context categories were found indicating the participants (interpersonal–group), the impact (low–high), and the subjectivity (subjective–objective) of the reason. Conclusion: This study provides researchers and practitioners with a comprehensive taxonomy of reasons for rejection that contributes to enrich the theoretical knowledge and improve interventions for preventing and reducing peer rejection. PMID:28421008

  3. Peer Rejection as a Social Antecedent to Rejection Sensitivity in Youth: The Role of Relational Valuation.

    Science.gov (United States)

    Wang, Jennifer; McDonald, Kristina L; Rubin, Kenneth H; Laursen, Brett

    2012-11-01

    Although much is known about the consequences of rejection sensitivity (RS), less is known about its social antecedents, particularly during development. Despite research demonstrating the role of peer rejection in the development and maintenance of problematic social schema like RS, little is known about why some youth are more susceptible to these negative consequences than others. We examined how relational valuation might moderate the effects of peer rejection on RS in a sample of 294 youth (138 boys) who made the transition from middle to high school. Results from path analysis revealed that 8th grade peer rejection was most highly associated with 9th grade RS for youth who held high regard for social relationships. Findings demonstrate the importance of examining cognitive moderators in the links between negative social experiences and problematic social schema, and highlight the need to move beyond simple main effects models for understanding the heterogeneity of rejection.

  4. Large Solar-Rejection Filter

    Science.gov (United States)

    Roberts, William; Sheikh, David; Patrick, Brian

    2007-01-01

    times solar, and sulfur is 20 times solar. From its previously observed optical emission lines, P831-57 (WD 0334 6400 or Ret 1 in A Catalog and Atlas of Cataclysmic Variables: Living Edition) has been suspected to contain an accretion disk associated with a companion star in orbit around a subdwarf star with a temperature T is greater than 21,000K. P831-57 has therefore been classified as a nova-like. However, our present observations show it to be a DA + dMe binary. The analysis of its Far Ultraviolet Spectroscopic Explorer (FUSE) spectrum (continuum and lines) reveal an average mass white dwarf (Log(g) approximately equals 7.8 plus or minus 0.1)with a temperature T approximately equals 37,000 plus or minus 500K, an extremely low projected rotational velocity, and a distance of about 115 plus or minus 5pc. The photosphere contains C, N, Si, and S (at about 1% of solar abundances). The dMe star is seen as a flux excess in near-infrared photometry and appears to show occasional flaring of about one magnitude as seen in the Harvard plates. There is no evidence of periodic variability in the spectroscopic or photometric data. We find no evidence of a an accretion disk, instead we find evidence of wind accretion as the stellar carbon abundance (N(C)/N(H) = 2.5 x 10 (exp -6) is about ten times larger than predicted by radiative levitation for such a gravity and temperature. The power needs and solutions for the space exploration and lunar mobility program are discussed. Long term missions in space and on the lunar surface require high energy batteries. Rechargeable batteries for mobility systems and portable utility pallet are needed for successful exploration missions. Nanomaterial usage increases the energy density of the cells apart from increasing the power density. The symptoms and threats from acute mountain sickness (AMS) are discussed. The underlying assumptions concerning spacecraft atmosphere mean there is a potential risk to astronauts. The baseline worst case

  5. Successful management of immunological rejection following allogeneic simple limbal epithelial transplantation (SLET) for bilateral ocular burns.

    Science.gov (United States)

    Bhalekar, Swapnil; Basu, Sayan; Sangwan, Virender S

    2013-03-14

    A 41-year-old woman presented with bilateral total limbal stem cell deficiency, one year after chemical injury. She underwent allogeneic simple limbal epithelial transplantation (SLET) from a cadaveric donor in her right eye. One month later her unaided visual acuity (VA) improved to 20/100 from hand-motions. The corneal surface was avascular and epithelialised. Three months later, she presented with acute pain in right eye with peripheral corneal neovascularisation encircling the transplants, engorged and tortuous perilimbal vessels and diffuse epithelial haze. For a diagnosis of allograft rejection, pulse doses of intravenous methyl prednisolone with intensive topical steroids were administered. Her symptoms resolved in a week, confirming the diagnosis. She recovered her pre-rejection VA. She was maintained on systemic immunosuppressive agents. Her ocular surface continues to be stable. This case describes hitherto unknown clinical features of allograft rejection following SLET and emphasises the importance of continued immunosuppression in allogeneic limbal transplantation.

  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. Ferrite grade iron oxides from ore rejects

    Indian Academy of Sciences (India)

    Unknown

    Abstract. 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 ...

  8. 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 ...

  9. 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.

  10. 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

  11. Rejection Pathways in Heart Transplant Recipients

    NARCIS (Netherlands)

    N.M. van Besouw (Nicole)

    1999-01-01

    textabstractSince the beginning of this century experimental heart transplantations in animal studies were performed.' These studies were started in Rotterdam in the seventies to compare heterotopic and orthotopic heart transplantations, and to study the process of chronic rejection. The history of

  12. 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...

  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. The outcast-lash-out effect in youth: alienation increases aggression following peer rejection.

    Science.gov (United States)

    Reijntjes, Albert; Thomaes, Sander; Bushman, Brad J; Boelen, Paul A; de Castro, Bram Orobio; Telch, Michael J

    2010-10-01

    Although there are good theoretical reasons to believe that youth who are high in alienation (i.e., estranged from society, significant others, and themselves) are prone to behave aggressively, empirical evidence is lacking. The present experiment tested whether alienation moderates the effects of acute peer rejection on aggression in youth. Participants (N = 121; mean age = 11.5 years) completed a personal profile (e.g., "How do you describe yourself?") that was allegedly evaluated online by a panel of peer judges. After randomly receiving negative or positive feedback from peer judges, participants were given the opportunity to aggress against them (i.e., by reducing their monetary reward and by posting negative comments about them online). As predicted, alienation increased participants' aggression against peers who had rejected them, but not against peers who had praised them, even after controlling for peer-nominated chronic rejection and peer-nominated aggression. Thus, alienated youth are more aggressive than others when they experience acute peer rejection.

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

    Directory of Open Access Journals (Sweden)

    Lumbini Devi

    2017-01-01

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

  16. Ciclosporin metabolite pattern in blood and urine of liver graft recipients. II. Influence of cholestasis and rejection.

    Science.gov (United States)

    Christians, U; Kohlhaw, K; Budniak, J; Bleck, J S; Schottmann, R; Schlitt, H J; Almeida, V M; Deters, M; Wonigeit, K; Pichlmayr, R

    1991-01-01

    The pattern of metabolites of ciclosporin in blood and 24 h-urine of 58 liver graft recipients was routinely monitored by HPLC from transplantation until discharge from hospital. Liver function and ciclosporin metabolite pattern in patients with an uncomplicated clinical course and in those with cholestasis or acute rejection were compared. During cholestasis M19 and M1A, and during acute rejection M19, in blood were significantly elevated compared to the control group. Blood M19 was significantly correlated with bilirubin concentration and gamma-glutamyl transferase activity in serum, and M1A with the serum bilirubin concentration. Analysis of the metabolite pattern over the observation period showed higher concentrations of M19 and M1A in blood from patients with cholestasis and acute rejection than in the control group; concentrations were lower in the rejection group than in the cholestasis group. The metabolite pattern in 24 h-urine showed similar alterations in ciclosporin metabolite pattern to those in blood. Cholestasis and rejection shift the ciclosporin metabolite pattern in blood and urine to higher concentrations of M19 and M1A, whereas the concentrations of other metabolites and ciclosporin were not significantly affected.

  17. Batting 300 is good: perspectives of faculty researchers and their mentors on rejection, resilience, and persistence in academic medical careers.

    Science.gov (United States)

    DeCastro, Rochelle; Sambuco, Dana; Ubel, Peter A; Stewart, Abigail; Jagsi, Reshma

    2013-04-01

    Professional rejection is a frequent experience in an academic medical career. The authors sought to understand how rejection affects those pursuing such careers and why some individuals may be more resilient than others in a population of individuals with demonstrated ability and interest in research careers. Between February 2010 and August 2011, the authors conducted semistructured, in-depth telephone interviews with 100 former recipients of National Institutes of Health mentored career development awards and 28 of their mentors. Purposive sampling ensured a diverse range of viewpoints. Multiple analysts thematically coded verbatim transcripts using qualitative data analysis software. Participants described a variety of experiences with criticism and rejection in their careers, as well as an acute need for persistence and resilience in the face of such challenges. Through their narratives, participants also vividly described a range of emotional and behavioral responses to their experiences of professional rejection. Their responses illuminated the important roles that various factors, including mentoring and gender, have played in shaping the ultimate influence of rejection on their own careers and on the careers of those they have mentored. Responses to rejection vary considerably, and negative responses can lead promising individuals to abandon careers in academic medicine. Resilience does not, however, seem to be immutable-It can be learned. Given the frequency of experiences with rejection in academic medicine, strategies such as training mentors to foster resilience may be particularly helpful in improving faculty retention in academic medicine.

  18. History of abuse and risky sex among substance users: The role of rejection sensitivity and the need to belong.

    Science.gov (United States)

    Woerner, Jacqueline; Kopetz, Catalina; Lechner, William V; Lejuez, Carl

    2016-11-01

    This study investigates abuse and rejection sensitivity as important correlates of risky sexual behavior in the context of substance use. Victims of abuse may experience heightened sensitivity to acute social rejection and consequently engage in risky sexual behavior in an attempt to restore belonging. Data were collected from 258 patients at a substance use treatment facility in Washington, D.C. Participants' history of abuse and risky sexual behavior were assessed via self-report. To test the mediating role of rejection sensitivity, participants completed a social rejection task (Cyberball) and responded to a questionnaire assessing their reaction to the rejection experience. General risk-taking propensity was assessed using a computerized lab measure. Abuse was associated with increased rejection sensitivity (B=0.124, SE=0.040, p=0.002), which was in turn associated with increased risky sex (B=0.06, SE=0.028, p=0.03) (indirect effect=0.0075, SE=0.0043; 95% CI [0.0006, 0.0178]), but not with other indices of risk-taking. These findings suggest that rejection sensitivity may be an important mechanism underlying the relationship between abuse and risky sexual behavior among substance users. These effects do not extend to other risk behaviors, supporting the notion that risky sex associated with abuse represents a means to interpersonal connection rather than a general tendency toward self-defeating behavior. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. 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.

    2013-01-01

    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. PMID:24729668

  20. Modeling the rejection probability in plant imports.

    Science.gov (United States)

    Surkov, I V; van der Werf, W; van Kooten, O; Lansink, A G J M Oude

    2008-06-01

    Phytosanitary inspection of imported plants and flowers is a major means for preventing pest invasions through international trade, but in a majority of countries availability of resources prevents inspection of all imports. Prediction of the likelihood of pest infestation in imported shipments could help maximize the efficiency of inspection by targeting inspection on shipments with the highest likelihood of infestation. This paper applies a multinomial logistic (MNL) regression model to data on import inspections of ornamental plant commodities in the Netherlands from 1998 to 2001 to investigate whether it is possible to predict the probability that a shipment will be (i) accepted for import, (ii) rejected for import because of detected pests, or (iii) rejected due to other reasons. Four models were estimated: (i) an all-species model, including all plant imports (136,251 shipments) in the data set, (ii) a four-species model, including records on the four ornamental commodities that accounted for 28.9% of inspected and 49.5% of rejected shipments, and two models for single commodities with large import volumes and percentages of rejections, (iii) Dianthus (16.9% of inspected and 46.3% of rejected shipments), and (iv) Chrysanthemum (6.9 and 8.6%, respectively). All models were highly significant (P < 0.001). The models for Dianthus and Chrysanthemum and for the set of four ornamental commodities showed a better fit to data than the model for all ornamental commodities. Variables that characterized the imported shipment's region of origin, the shipment's size, the company that imported the shipment, and season and year of import, were significant in most of the estimated models. The combined results of this study suggest that the MNL model can be a useful tool for modeling the probability of rejecting imported commodities even with a small set of explanatory variables. The MNL model can be helpful in better targeting of resources for import inspection. The

  1. Pharmacodynamics of cyclosporine in heart and heart-lung transplant recipients. I: Blood cyclosporine concentrations and other risk factors for cardiac allograft rejection.

    Science.gov (United States)

    Best, N G; Trull, A K; Tan, K K; Spiegelhalter, D J; Cary, N; Wallwork, J

    1996-11-27

    We have attempted to determine the optimal clinical use of cyclosporine during the first 3 months after heart transplantation. We used multiple logistic regression to quantify how blood cyclosporine concentrations and other potential risk factors influence the risk of histologically confirmed acute rejection in 111 heart transplant recipients. A 50% increase in cyclosporine concentration was associated with a 15% reduction in risk of rejection in the subsequent 5 days (P=0.002). Increasing oral corticosteroid dose also protected against rejection (P=0.01). Rejection was over 2.5 times more likely during the first 20 postoperative days, and patients with 2 HLA-DR mismatches who were transplanted for cardiomyopathy or who had multiple previous rejection episodes were predisposed to further rejection (Pcyclosporine concentrations was weakly associated with risk of rejection (P=0.1). Investigation of threshold levels for the cyclosporine concentration-effect relationship suggested that concentrations above 375 microgram L(-1) provide optimal protection against acute cardiac allograft rejection. This result yields an objectively defined therapeutic threshold for targeting early cyclosporine concentrations following heart transplantation, although the upper end of the range will depend on the individual's susceptibility to nephrotoxicity and infection.

  2. Background Rejection in the ARA Experiment

    Directory of Open Access Journals (Sweden)

    Pfendner Carl

    2017-01-01

    Full Text Available The Askaryan Radio Array (ARA is a radio frequency observatory under construction at the South Pole that is searching for ultrahigh energy neutrinos via the Askaryan effect. Thermal fluctuations currently dominate the trigger-level background for the observatory and anthropogenic sources also introduce a significant source of noise. By taking advantage of the observatory’s regular geometry and the expected coincident nature of the RF signals arriving from neutrino-induced events, this background can be filtered efficiently. This contribution will discuss techniques developed for the ARA analyses to reject these thermal signals, to reject anthropogenic backgrounds, and to search for neutrino-induced particle showers in the Antarctic ice. The results of a search for neutrinos from GRBs using the prototype station using some of these techniques will be presented.

  3. Differential intragraft cytokine messenger RNA profiles during rejection and repair of clinical heart transplants. A longitudinal study

    NARCIS (Netherlands)

    de Groot-Kruseman, Hester A; Mol, Wendy M; Niesters, Hubert G M; Maat, Alex P W; van Gelder, Teun; Balk, Aggie H M M; Weimar, Willem; Baan, Carla C

    After clinical heart transplantation, ischemia, acute rejection, and repair mechanisms can trigger the up-regulation of cytokines. To investigate the cytokine profile early after transplantation, we monitored messenger RNA (mRNA) expression levels of tumor necrosis factor-alpha (TNF-alpha), monocyte

  4. Effect of dietary fish oil on renal function and rejection in cyclosporine-treated recipients of renal transplants

    NARCIS (Netherlands)

    van der Heide, J. J.; Bilo, H. J.; Donker, J. M.; Wilmink, J. M.; Tegzess, A. M.

    1993-01-01

    Dietary fish oil exerts effects on renal hemodynamics and the immune response that may benefit renal-transplant recipients treated with cyclosporine. To evaluate this possibility, we studied the effect of fish oil on renal function, blood pressure, and the incidence of acute rejection episodes in

  5. Peer acceptance/rejection and academic achievement

    Directory of Open Access Journals (Sweden)

    Spasenović Vera Z.

    2003-01-01

    Full Text Available Considerations of the nature and role of peer relations in child development indicate that peer interaction is an important factor in developing social and cognitive competences. Peer relations not only influence current but also subsequent academic, behavioral and emotional development. Accepted students more often display better academic achievement, whereas the status of rejection is coupled with academic difficulties and lower academic achievement. Peer rejection is a relatively stable characteristic that can be used to predict difficulties in the years to come, such as repeat of a grade, early drop out, unjustified absences, adaptability problems etc. It is considered that correlation between academic achievement and peer group status is mediated by student social behavior at school. The quality of peer relations and academic achievement are mutually influential i.e. peer acceptance serves as a social resource that facilitates academic achievement, but academic achievement has effects on student acceptance. To help students who display difficulties in social relations, various intervention programs have been well thought of so as to contribute to interpersonal efficiency promotion. Concerning interdependence of social behavior, peer status and academic achievement, it is reasonable to expect that positive changes in behavior, frequently leading to the change of rejection status, will produce, directly or indirectly, positive effects on academic achievement too.

  6. 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.

  7. Active disturbance rejection controller for chemical reactor

    Energy Technology Data Exchange (ETDEWEB)

    Both, Roxana; Dulf, Eva H.; Muresan, Cristina I., E-mail: roxana.both@aut.utcluj.ro [Technical University of Cluj-Napoca, 400114 Cluj-Napoca (Romania)

    2015-03-10

    In the petrochemical industry, the synthesis of 2 ethyl-hexanol-oxo-alcohols (plasticizers alcohol) is of high importance, being achieved through hydrogenation of 2 ethyl-hexenal inside catalytic trickle bed three-phase reactors. For this type of processes the use of advanced control strategies is suitable due to their nonlinear behavior and extreme sensitivity to load changes and other disturbances. Due to the complexity of the mathematical model an approach was to use a simple linear model of the process in combination with an advanced control algorithm which takes into account the model uncertainties, the disturbances and command signal limitations like robust control. However the resulting controller is complex, involving cost effective hardware. This paper proposes a simple integer-order control scheme using a linear model of the process, based on active disturbance rejection method. By treating the model dynamics as a common disturbance and actively rejecting it, active disturbance rejection control (ADRC) can achieve the desired response. Simulation results are provided to demonstrate the effectiveness of the proposed method.

  8. When is peer rejection justifiable?: Children's understanding across two cultures.

    Science.gov (United States)

    Park, Yoonjung; Killen, Melanie

    2010-07-01

    This study investigated how Korean (N = 397) and U.S. (N = 333) children and adolescents (10 and 13 years of age) evaluated personality (aggression, shyness) and group (gender, nationality) characteristics as a basis for peer rejection in three contexts (friendship rejection, group exclusion, victimization). Overall, peer rejection based on group membership was viewed as more unfair than peer rejection based on personality traits. Children viewed friendship rejection as more legitimate than group exclusion or victimization and used more personal choice reasoning for friendship rejection than for rejection in any other context. Although there were a few cultural differences, overall, the findings provided support for the cultural generalizability of social reasoning about peer rejection.

  9. Heterosexual Rejection and Mate Choice: A Sociometer Perspective.

    Science.gov (United States)

    Zhang, Lin; Liu, Shen; Li, Yue; Ruan, Lu-Jun

    2015-01-01

    Previous studies about the effects of social rejection on individuals' social behaviors have produced mixed results and tend to study mating behaviors from a static point of view. However, mate selection in essence is a dynamic process, and therefore sociometer theory opens up a new perspective for studying mating and its underlying practices. Based on this theory and using self-perceived mate value in the relationship between heterosexual rejection and mate choice as a mediating role, this current study examined the effects of heterosexual rejection on mate choice in two experiments. Results showed that heterosexual rejection significantly reduced self-perceived mate value, expectation, and behavioral tendencies, while heterosexual acceptance indistinctively increased these measures. Self-perceived mate value did not serve as a mediator in the relationship between heterosexual rejection and mate expectation, but it mediated the relationship between heterosexual rejection and mating behavior tendencies toward potential objects. Moreover, individuals evaded both rejection and irrelevant people when suffering from rejection.

  10. Graft rejection in pediatric penetrating keratoplasty: Clinical features and outcomes

    Directory of Open Access Journals (Sweden)

    Rakhi Kusumesh

    2015-01-01

    Conclusion: This study showed irreversible graft rejection was the leading cause of graft failure of pediatric PK. Though, the incidence (12.1% of graft rejection in current study was not high, but the percentage of reversal (25% was one of the lowest in literature because of delayed presentation and longer interval between corneal graft rejection and treatment. In addition, categorization of the type of graft rejection was very difficult and cumbersome in pediatric patients.

  11. Rejection Sensitivity in Late Adolescence: Social and Emotional Sequelae

    OpenAIRE

    Marston, Emily G.; Hare, Amanda; Allen, Joseph P.

    2010-01-01

    This study used longitudinal, multi-reporter data, in a community sample, to examine the role of rejection sensitivity in late adolescents’ social and emotional development. Rejection sensitivity was linked to a relative increase in adolescent depressive and anxiety symptoms over a three-year period, even after accounting for teens’ baseline level of social competence. Additionally, reciprocal relationships emerged between rejection sensitivity and internalizing symptoms. Rejection sensitivit...

  12. B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction

    Science.gov (United States)

    Zouggari, Yasmine; Ait-Oufella, Hafid; Bonnin, Philippe; Simon, Tabassome; Sage, Andrew P; Guérin, Coralie; Vilar, José; Caligiuri, Giuseppina; Tsiantoulas, Dimitrios; Laurans, Ludivine; Dumeau, Edouard; Kotti, Salma; Bruneval, Patrick; Charo, Israel F; Binder, Christoph J; Danchin, Nicolas; Tedgui, Alain; Tedder, Thomas F; Silvestre, Jean-Sébastien; Mallat, Ziad

    2014-01-01

    Acute myocardial infarction is a severe ischemic disease responsible for heart failure and sudden death. Here, we show that after acute myocardial infarction in mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6Chi monocyte mobilization and recruitment to the heart, leading to enhanced tissue injury and deterioration of myocardial function. Genetic (Baff receptor deficiency) or antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B lymphocytes impeded Ccl7 production and monocyte mobilization, limited myocardial injury and improved heart function. These effects were recapitulated in mice with B cell–selective Ccl7 deficiency. We also show that high circulating concentrations of CCL7 and BAFF in patients with acute myocardial infarction predict increased risk of death or recurrent myocardial infarction. This work identifies a crucial interaction between mature B lymphocytes and monocytes after acute myocardial ischemia and identifies new therapeutic targets for acute myocardial infarction. PMID:24037091

  13. Prevention of chronic renal allograft rejection by soluble CD83.

    Science.gov (United States)

    Lan, Zhu; Lian, Dameng; Liu, Weihua; Arp, Jacqueline; Charlton, Brayden; Ge, Wei; Brand, Stephen; Healey, Don; DeBenedette, Mark; Nicolette, Charles; Garcia, Bertha; Wang, Hao

    2010-12-27

    Recombinant human soluble CD83 had previously exhibited significant immunosuppressive properties that involved interference with dendritic cell maturation in both mouse and humans, inhibition of autoimmunity in mice, and induction of antigen-specific mouse cardiac allograft tolerance when used in combination with other immunosuppressive drugs. Our current research focus turned to examining the effects of peritransplant soluble CD83 (sCD83) administration on prevention of chronic renal allograft rejection. Fisher344-to-Lewis orthotopic rat renal transplants were performed with sequential recipient killing on postoperative days (PODs) 2, 14, and 140 to examine both the acute and chronic effects of peritransplant sCD83 treatment in rat recipients. Recipients treated with sCD83 exhibited a marked decrease in IgM and IgG deposition in the graft and antidonor antibody levels in the circulation, as early as POD14 and persisting until POD140. sCD83 treatment also reduced the infiltration of T cells and monocytes into the graft tissue and inhibited intragraft expression of MyD88 and inflammatory cytokine levels during the observation period. sCD83-treated grafts demonstrated normal histology beyond POD140, including dramatic reductions in tubular atrophy and interstitial fibrosis compared with untreated recipients. We have demonstrated that peritransplant treatment with recombinant sCD83 attenuates both innate and adaptive immune responses and leads to prevention of chronic rejection in a rat renal transplant model. Because sCD83 is of human origin, the therapeutic approach used in our rodent transplant model holds significant promise for clinical transplantation.

  14. When Is Peer Rejection Justifiable? Children's Understanding across Two Cultures

    Science.gov (United States)

    Park, Yoonjung; Killen, Melanie

    2010-01-01

    This study investigated how Korean (N = 397) and U.S. (N = 333) children and adolescents (10 and 13 years of age) evaluated personality (aggression, shyness) and group (gender, nationality) characteristics as a basis for peer rejection in three contexts (friendship rejection, group exclusion, victimization). Overall, peer rejection based on…

  15. Children's Coping with "In Vivo" Peer Rejection: An Experimental Investigation

    Science.gov (United States)

    Reijntjes, Albert; Stegge, Hedy; Terwogt, Mark Meerum; Kamphuis, Jan Henk; Telch, Michael J.

    2006-01-01

    We examined children's behavioral coping in response to an "in vivo" peer rejection manipulation. Participants (N = 186) ranging between 10 and 13 years of age, played a computer game based on the television show "Survivor" and were randomized to either peer rejection (i.e., being voted out of the game) or non-rejection control. During a five-min.…

  16. Paying to belong: when does rejection trigger ingratiation?

    Science.gov (United States)

    Romero-Canyas, Rainer; Downey, Geraldine; Reddy, Kavita S; Rodriguez, Sylvia; Cavanaugh, Timothy J; Pelayo, Rosemary

    2010-11-01

    Societies and social scientists have long held the belief that exclusion induces ingratiation and conformity, an idea in contradiction to robust empirical evidence linking rejection with hostility and aggression. The classic literatures on ingratiation and conformity help resolve this contradiction by identifying circumstances under which rejection may trigger efforts to ingratiate. Jointly, findings from these literatures suggest that when people are given an opportunity to impress their rejecters, ingratiation is likely after rejection experiences that are harsh and that occur in important situations that threaten the individual's self-definition. Four studies tested the hypothesis that people high in rejection sensitivity and therefore dispositionally concerned about rejection will utilize opportunities to ingratiate after harsh rejection in situations that are self-defining. In 3 studies of situations that are particularly self-defining for men, rejection predicted ingratiation among men (but not women) who were high in rejection sensitivity. In a 4th study, harsh rejection in a situation particularly self-defining for women predicted ingratiation among highly rejection-sensitive women (but not men). These findings help identify the specific circumstances under which people are willing to act in socially desirable ways toward those who have rejected them harshly.

  17. Cultural Rejection and Re-identification in Minority Group Members.

    Science.gov (United States)

    Diller, Jerry V.

    There is little consistent research available on cultural rejection and re-identification in minority group members, but this report uses case study material to extrapolate three general factors precipitating rejection: self-hatred and negative chauvinism, quality of ethnic experience and rejection of religious experience. A four-step model for…

  18. The heartbrake of social rejection: heart rate deceleration in response to unexpected peer rejection.

    Science.gov (United States)

    Gunther Moor, Bregtje; Crone, Eveline A; van der Molen, Maurits W

    2010-09-01

    Social relationships are vitally important in human life. Social rejection in particular has been conceptualized as a potent social cue resulting in feelings of hurt. Our study investigated the psychophysiological manifestation of hurt feelings by examining the beat-by-beat heart rate response associated with the processing of social rejection. Study participants were presented with a series of unfamiliar faces and were asked to predict whether they would be liked by the other person. Following each judgment, participants were provided with feedback indicating that the person they had viewed had either accepted or rejected them. Feedback was associated with transient heart rate slowing and a return to baseline that was considerably delayed in response to unexpected social rejection. Our results reveal that the processing of unexpected social rejection is associated with a sizable response of the parasympathetic nervous system. These findings are interpreted in terms of a cardiovagal manifestation of a neural mechanism implicated in the central control of autonomic function during cognitive processes and affective regulation.

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

    Science.gov (United States)

    Arjona, Alvaro

    2009-09-01

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

  20. Partial interference subspace rejection in CDMA systems

    DEFF Research Database (Denmark)

    Hansen, Henrik; Affes, Sofiene; Mewelstein, Paul

    2001-01-01

    Previously presented interference subspace rejection (ISR) proposed a family of new efficient multiuser detectors for CDMA. We reconsider in this paper the modes of ISR using decision feedback (DF). DF modes share similarities with parallel interference cancellation (PIC) but attempt to cancel...... interference by nulling rather than subtraction. However like the PIC they are prone to wrong tentative decisions. We propose a modification to DF modes that performs partial ISR instead of complete interference cancellation. When tentative decisions are correct, interference is therefore not perfectly...

  1. Solar Rejection Filter for Large Telescopes

    Science.gov (United States)

    Hemmati, Hamid; Lesh, James

    2009-01-01

    To reject solar radiation photons at the front aperture for large telescopes, a mosaic of large transmission mode filters is placed in front of the telescope or at the aperture of the dome. Filtering options for effective rejection of sunlight include a smaller filter down-path near the focus of the telescope, and a large-diameter filter located in the front of the main aperture. Two types of large filters are viable: reflectance mode and transmittance mode. In the case of reflectance mode, a dielectric coating on a suitable substrate (e.g. a low-thermal-expansion glass) is arranged to reflect only a single, narrow wavelength and to efficiently transmit all other wavelengths. These coatings are commonly referred to as notch filter. In this case, the large mirror located in front of the telescope aperture reflects the received (signal and background) light into the telescope. In the case of transmittance mode, a dielectric coating on a suitable substrate (glass, sapphire, clear plastic, membrane, and the like) is arranged to transmit only a single wavelength and to reject all other wavelengths (visible and near IR) of light. The substrate of the large filter will determine its mass. At first glance, a large optical filter with a diameter of up to 10 m, located in front of the main aperture, would require a significant thickness to avoid sagging. However, a segmented filter supported by a structurally rugged grid can support smaller filters. The obscuration introduced by the grid is minimal because the total area can be made insignificant. This configuration can be detrimental to a diffraction- limited telescope due to diffraction effects at the edges of each sub-panel. However, no discernable degradation would result for a 20 diffraction-limit telescope (a photon bucket). Even the small amount of sagging in each subpanel should have minimal effect in the performance of a non-diffraction limited telescope because the part has no appreciable optical power. If the

  2. Legal nature of acceptance and rejection wand

    OpenAIRE

    DEHGHANI, Asieh; KHOEINI, Ghafoor

    2015-01-01

    Abstract. We must conclude from existing legal articles and research that bequest ownership is not resulting of inherit will (or determination) and ownership does not take place by his satisfaction. The ownership of bequest is enforcement and that is, take place by the law verdict, and inherit determination don’t have interference in it and death die is initialized of it. The major effect of bequest accepts and reject is, in charge of that debts are on the hereditary obligation and remained f...

  3. Social Rejection and Alcohol Use in Daily Life.

    Science.gov (United States)

    Laws, Holly B; Ellerbeck, Nicole E; Rodrigues, Alyne S; Simmons, Jessica A; Ansell, Emily B

    2017-04-01

    Prior studies have found that social rejection is associated with increases in negative affect, distress, and hostility. Fewer studies, however, have examined the impact of social rejection on alcohol use, and no known studies have tested whether the impact of social rejection by close others differs from social rejection by acquaintances in its association with subsequent drinking. Participants completed event-contingent reports of their social interactions and alcohol use for 14 consecutive days on smartphones. Multilevel negative binomial regression models tested whether experiencing more social rejection than usual was associated with increased drinking, and whether this association was stronger when participants were rejected by close others (e.g., friends, spouses, family members) versus strangers or acquaintances. Results showed a significant interaction between social rejection and relationship closeness. On days characterized by rejection by close others, the likelihood of drinking significantly increased. On days characterized by rejection by acquaintances, by contrast, there was no increase in the likelihood of drinking. There was no main effect of rejection on likelihood of drinking. These results suggest that relationship type is a key factor in whether social rejection translates to potentially harmful behaviors, such as increased alcohol use. This finding is in contrast to many laboratory paradigms of rejection, which emphasize rejection and ostracism by strangers rather than known others. In the more naturalistic setting of measuring social interactions on smartphone in daily life, our findings suggest that only social rejection delivered by close others, and not strangers, led to subsequent drinking. Copyright © 2017 by the Research Society on Alcoholism.

  4. 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

  5. The heartbrake of social rejection: heart rate deceleration in response to unexpected peer rejection

    NARCIS (Netherlands)

    Gunther Moor, B.; Crone, E.A.; van der Molen, M.W.

    2010-01-01

    Social relationships are vitally important in human life. Social rejection in particular has been conceptualized as a potent social cue resulting in feelings of hurt. Our study investigated the psychophysiological manifestation of hurt feelings by examining the beat-by-beat heart rate response

  6. The relations between secrecy, rejection sensitivity and autonomy-connectedness.

    Science.gov (United States)

    Wismeijer, Andreas A J; Van Assen, Marcel A L M; Bekker, Marrie H J

    2014-01-01

    The aim of this study was to examine the effects of two attachment-related variables on secrecy: rejection sensitivity and autonomy-connectedness. We hypothesized that rejection sensitivity is positively associated with secrecy, and autonomy-connectedness negatively with rejection sensitivity and secrecy. These hypotheses were generally corroborated in a sample of 303 university students. Moreover, we found that autonomy-connectedness at least partly explained the association between rejection sensitivity and secrecy. Self-awareness was negatively related to secrecy, suggesting that being aware of what one needs and thinks and being able to realize one's needs in social interactions reduce the tendency to keep secrets. In addition, interesting gender effects were found suggesting that men have a higher tendency to have secrets than women after controlling for the effects of autonomy-connectedness and rejection sensitivity. Our findings deepen the insight into possible reasons behind established associations between rejection sensitivity and secrecy, and may have clinical implications.

  7. The rejection-rage contingency in borderline personality disorder.

    Science.gov (United States)

    Berenson, Kathy R; Downey, Geraldine; Rafaeli, Eshkol; Coifman, Karin G; Paquin, Nina Leventhal

    2011-08-01

    Though long-standing clinical observation reflected in the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) suggests that the rage characteristic of borderline personality disorder (BPD) often appears in response to perceived rejection, the role of perceived rejection in triggering rage in BPD has never been empirically tested. Extending basic personality research on rejection sensitivity to a clinical sample, a priming-pronunciation experiment and a 21-day experience-sampling diary examined the contingent relationship between perceived rejection and rage in participants diagnosed with BPD compared with healthy controls. Despite the differences in these 2 assessment methods, the indices of rejection-contingent rage that they both produced were elevated in the BPD group and were strongly interrelated. They provide corroborating evidence that reactions to perceived rejection significantly explain the rage seen in BPD. © 2011 American Psychological Association

  8. Rejection Sensitivity in Late Adolescence: Social and Emotional Sequelae

    Science.gov (United States)

    Marston, Emily G.; Hare, Amanda; Allen, Joseph P.

    2010-01-01

    This study used longitudinal, multi-reporter data, in a community sample, to examine the role of rejection sensitivity in late adolescents’ social and emotional development. Rejection sensitivity was linked to a relative increase in adolescent depressive and anxiety symptoms over a three-year period, even after accounting for teens’ baseline level of social competence. Additionally, reciprocal relationships emerged between rejection sensitivity and internalizing symptoms. Rejection sensitivity was also linked to relative decreases in peer-reports of teens’ social competence over a three-year period. Consistent with research on gendered socialization, males reported higher levels of rejection sensitivity than females at age 16 and 17. Results are interpreted as highlighting the importance of rejection sensitivity in understanding late adolescent social and emotional development. PMID:21113326

  9. Graft rejection after hematopoietic cell transplantation with nonmyeloablative conditioning

    DEFF Research Database (Denmark)

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

    2008-01-01

    Graft rejection after hematopoietic cell transplantation (HCT) with nonmyeloablative conditioning is a rare but serious clinical problem. Graft rejection and salvage therapy in eight patients in a retrospective analysis of 124 consecutive patients is reported. The patients were conditioned with low......-dose fludarabine and total body irradiation (TBI). The association of pretransplantation risk factors with rejection and the effect of chimerism and graft-versus-host disease on rejection were analyzed. Overall survival (OS) and progression free survival (PFS) were compared between patients with and without...... rejection. Retransplantation was performed with increased TBI conditioning for all patients, and with increased mycophenolate mofetil doses for recipients with HLA-identical sibling donors. No known pretransplantation risk factors were confirmed in this study. Rejection episodes were unevenly distributed...

  10. Challenging men to reject gender stereotypes.

    Science.gov (United States)

    Gokova, J K

    1998-01-01

    Creation of a society based on gender justice requires the involvement of men as well as women. Padare, an anti-sexist organization for men in Zimbabwe, encourages men to reject gender-based stereotypes and work to recognize women as equal partners. Patriarchy forces men to be collaborators in a system that oppresses women. Men's insistence on a doctrine of male superiority undermines their own psychological growth and forces them to deny their own humanity. The challenge is for men to devise new role models that complement those of women who are demanding respect and recognition as individuals. Padare encourages men to discuss the assumptions they have internalized that make them oppressive and prevent them from establishing equal relationships with women. It serves as a support group for men who are committed to social change. From these discussions, a new definition of African manhood is emerging.

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

    Science.gov (United States)

    Murphy, Anna M; Russell, Gemma

    2016-01-21

    The development and maintenance of interpersonal relationships lead individuals to risk rejection in the pursuit of acceptance. Some individuals are predisposed to experience a hypersensitivity to rejection that is hypothesized to be related to jealous and aggressive reactions within interpersonal relationships. The current study used convenience sampling to recruit 247 young adults to evaluate the relationship between rejection sensitivity, jealousy, and aggression. A mediation model was used to test three hypotheses: Higher scores of rejection sensitivity would be positively correlated to higher scores of aggression (Hypothesis 1); higher scores of rejection sensitivity would be positively correlated to higher scores of jealousy (Hypothesis 2); jealousy would mediate the relationship between rejection sensitivity and aggression (Hypothesis 3). Study results suggest a tendency for individuals with high rejection sensitivity to experience higher levels of jealousy, and subsequently have a greater propensity for aggression, than individuals with low rejection sensitivity. Future research that substantiates a link between hypersensitivity to rejection, jealousy, and aggression may provide an avenue for prevention, education, or intervention in reducing aggression within interpersonal relationships. © The Author(s) 2016.

  12. Value of endothelin in cellular rejection after liver transplantation.

    Science.gov (United States)

    Fábrega, E; Figols, J; Dueñas, C; Crespo, J; Casafont, F; Sanchez-Antolín, G; de las Heras, G; Amado, J A; Pons-Romero, F

    1997-02-01

    Endothelin-1 is a vasoconstrictor peptide released by the vascular endothelium by various chemical and mechanical factors. Cellular rejection is one of the most common complications following orthotopic liver transplantation, endotheliitis being its most specific and consistent histological feature. To assess the role of endothelin in cellular hepatic rejection, we studied 21 cirrhotic patients undergoing elective liver transplantation. These patients were divided in two groups: Group I comprised 10 patients without cellular rejection, and Group II comprised 11 patients with cellular rejection. Endothelin was measured on day 7 after transplantation, on the day of liver biopsy, and after treatment for rejection. We found a significant increase in the plasma endothelin levels in the early postoperative period in the patients with moderate or severe cellular rejection compared with the non-rejection group. It remained significantly elevated until the clinical diagnosis of rejection was made. This value returned to baseline with successful treatment. So, the monitorization of this peptide may be of help in the diagnosis of rejection, its severity, and the evaluation of its resolution.

  13. 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

  14. 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.

  15. Composite filter steepens rejection slopes in microwave application

    Science.gov (United States)

    1966-01-01

    Composite filter is used to obtain sharp rejection slopes in microwave transmission by filtering techniques. It consists of a bandpass filter to shape the passband and a bandreject filter on each edge of the bandpass filter to steepen the rejection slopes.

  16. Cytokine mRNA expression during experimental corneal allograft rejection

    NARCIS (Netherlands)

    Torres, P. F.; de Vos, A. F.; van der Gaag, R.; Martins, B.; Kijlstra, A.

    1996-01-01

    Allograft rejection is the main cause of corneal graft failure. T lymphocytes and macrophages have been implied to be involved in corneal rejection, but little is known about the molecular mechanism in this process. In this study, cytokine mRNA expression in the cornea was analysed during

  17. Peer victimization and peer rejection during early childhood

    Science.gov (United States)

    Godleski, Stephanie A.; Kamper, Kimberly E.; Ostrov, Jamie M.; Hart, Emily J.; Blakely-McClure, Sarah J.

    2014-01-01

    Objective The development and course of the subtypes of peer victimization is a relatively understudied topic despite the association of victimization with important developmental and clinical outcomes. Moreover, understanding potential predictors, such as peer rejection and emotion regulation, in early childhood may be especially important to elucidate possible bi-directional pathways between relational and physical victimization and rejection. The current study (N = 97) was designed to explore several gaps and limitations in the peer victimization and peer rejection literature. In particular, the prospective associations between relational and physical victimization and peer rejection over the course of 3.5 months during early childhood (i.e., 3- to 5- years-old) were investigated in an integrated model. Method The study consisted of 97 (42 girls) preschool children recruited from four early childhood schools in the northeast of the US. Using observations, research assistant report and teacher report, relational and physical aggression, relational and physical victimization, peer rejection, and emotion regulation were measured in a short-term longitudinal study. Path analyses were conducted to test the overall hypothesized model. Results Peer rejection was found to predict increases in relational victimization. In addition, emotion regulation was found to predict decreases in peer rejection and physical victimization. Conclusions Implications for research and practice are discussed, including teaching coping strategies for peer rejection and emotional distress. PMID:25133659

  18. Rejection Sensitivity in Late Adolescence: Social and Emotional Sequelae

    Science.gov (United States)

    Marston, Emily G.; Hare, Amanda; Allen, Joseph P.

    2010-01-01

    This study used longitudinal, multireporter data, in a community sample, to examine the role of rejection sensitivity in late adolescents' social and emotional development. Rejection sensitivity was linked to a relative increase in adolescent depressive and anxiety symptoms over a 3-year period, even after accounting for teens' baseline level of…

  19. Peer victimization and peer rejection during early childhood.

    Science.gov (United States)

    Godleski, Stephanie A; Kamper, Kimberly E; Ostrov, Jamie M; Hart, Emily J; Blakely-McClure, Sarah J

    2015-01-01

    The development and course of the subtypes of peer victimization is a relatively understudied topic despite the association of victimization with important developmental and clinical outcomes. Moreover, understanding potential predictors, such as peer rejection and emotion regulation, in early childhood may be especially important to elucidate possible bidirectional pathways between relational and physical victimization and rejection. The current study (N = 97) was designed to explore several gaps and limitations in the peer victimization and peer rejection literature. In particular, the prospective associations between relational and physical victimization and peer rejection over the course of 3.5 months during early childhood (i.e., 3 to 5 years old) were investigated in an integrated model. The study consisted of 97 (42 girls) preschool children recruited from four early childhood schools in the northeast of the United States. Using observations, research assistant report, and teacher report, relational and physical aggression, relational and physical victimization, peer rejection, and emotion regulation were measured in a short-term longitudinal study. Path analyses were conducted to test the overall hypothesized model. Peer rejection was found to predict increases in relational victimization. In addition, emotion regulation was found to predict decreases in peer rejection and physical victimization. Implications for research and practice are discussed, including teaching coping strategies for peer rejection and emotional distress.

  20. Developmental Pathways from Child Maltreatment to Peer Rejection.

    Science.gov (United States)

    Bolger, Kerry E.; Patterson, Charlotte J.

    2001-01-01

    Used prospective longitudinal design to examine peer rejection, aggressive behavior, and social withdrawal among 107 maltreated and 107 nonmaltreated children. Found that chronic maltreatment was associated with heightened risk of peer rejection from childhood to early adolescence. Aggression accounted largely for the association between chronic…

  1. Peer Rejection in Preschool: Foregrounding Children’s Voices

    Science.gov (United States)

    Tay-Lim, Joanna; Gan, Linda

    2013-01-01

    Existing studies on peer rejection are predominantly quantitative in nature and do not adequately engage children’s voices and provide a comprehensive view of the peer rejection phenomenon. There are also limited studies at the preschool level, especially in the Singapore context. This study addresses these limitations by presenting insights into…

  2. Social Rejection and ADHD in Young Adults: An Analogue Experiment

    Science.gov (United States)

    Paulson, James F.; Buermeyer, Curt; Nelson-Gray, Rosemery O.

    2005-01-01

    Poor outcomes in ADHD may be related to problematic social functioning and consequences of social rejection. This study examines how ADHD symptom expression affects mood and social rejection. Working from findings in depression that describe maintenance through negative interpersonal interactions, the authors seek to examine this theory's…

  3. 32 CFR 274.8 - Bids-revocations-rejections-postponements.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Bids-revocations-rejections-postponements. 274.8... EXPORT LOAN AGREEMENTS § 274.8 Bids-revocations-rejections-postponements. The Secretary of Defense or his... these respects shall be final. In the event of a postponement, known bidders will be advised thereof and...

  4. Effects of composite mango ( Mangifera indica ) fruit reject meal on ...

    African Journals Online (AJOL)

    The experiment was conducted to determine the effect of mango fruit reject meal on growth performance, digestibility and economics of production of growing rabbits. Mango fruit rejects were sliced such that the peel and pulp were together and the seed discarded, sun dried until it attained about 10% moisture and milled to ...

  5. Heterosexual Rejection and Mate Choice: A Sociometer Perspective

    Directory of Open Access Journals (Sweden)

    Lin eZHANG

    2015-12-01

    Full Text Available Previous studies about the effects of social rejection on individuals’ social behaviors have produced mixed results and tend to study mating behaviors from a static point of view. However, mate selection in essence is a dynamic process, and therefore sociometer theory opens up a new perspective for studying mating and its underlying practices. Based on this theory and using self-perceived mate value in the relationship between heterosexual rejection and mate choice as a mediating role, this current study examined the effects of heterosexual rejection on mate choice in two experiments. Results showed that heterosexual rejection significantly reduced self-perceived mate value, expectation, and behavioral tendencies, while heterosexual acceptance indistinctively increased these measures. Self-perceived mate value did not serve as a mediator in the relationship between heterosexual rejection and mate expectation, but it mediated the relationship between heterosexual rejection and mating behavior tendencies towards potential objects. Moreover, individuals evaded both rejection and irrelevant people when suffering from rejection.

  6. Apoptosis of acinar cells in pancreas allograft rejection

    NARCIS (Netherlands)

    Boonstra, J. G.; Wever, P. C.; Laterveer, J. C.; Bruijn, J. A.; van der Woude, F. J.; ten Berge, I. J.; Daha, M. R.

    1997-01-01

    BACKGROUND: Recently it has been recognized that apoptosis of target cells may occur during liver and kidney allograft rejection and is probably induced by infiltrating cells. Pancreas rejection is also characterized by a cellular infiltrate, however, the occurrence of apoptosis has not been

  7. Quantum Communication Using Coherent Rejection Sampling

    Science.gov (United States)

    Anshu, Anurag; Devabathini, Vamsi Krishna; Jain, Rahul

    2017-09-01

    Compression of a message up to the information it carries is key to many tasks involved in classical and quantum information theory. Schumacher [B. Schumacher, Phys. Rev. A 51, 2738 (1995), 10.1103/PhysRevA.51.2738] provided one of the first quantum compression schemes and several more general schemes have been developed ever since [M. Horodecki, J. Oppenheim, and A. Winter, Commun. Math. Phys. 269, 107 (2007); , 10.1007/s00220-006-0118-xI. Devetak and J. Yard, Phys. Rev. Lett. 100, 230501 (2008); , 10.1103/PhysRevLett.100.230501A. Abeyesinghe, I. Devetak, P. Hayden, and A. Winter, Proc. R. Soc. A 465, 2537 (2009), 10.1098/rspa.2009.0202]. However, the one-shot characterization of these quantum tasks is still under development, and often lacks a direct connection with analogous classical tasks. Here we show a new technique for the compression of quantum messages with the aid of entanglement. We devise a new tool that we call the convex split lemma, which is a coherent quantum analogue of the widely used rejection sampling procedure in classical communication protocols. As a consequence, we exhibit new explicit protocols with tight communication cost for quantum state merging, quantum state splitting, and quantum state redistribution (up to a certain optimization in the latter case). We also present a port-based teleportation scheme which uses a fewer number of ports in the presence of information about input.

  8. Luminex-based virtual crossmatching for renal transplantation in ...

    African Journals Online (AJOL)

    antibodies (PRAs, an estimate of the percentage of HLA types in ... needle biopsy of the renal allograft.12 Acute antibody-mediated rejection is a sequential process; initial endothelial damage by donor-specific anti-HLA antibodies is followed much later by histological alterations (such as C4d deposition and significant.

  9. Evaluation of sustainable concrete produced with desalinated reject brine

    Directory of Open Access Journals (Sweden)

    Kazi P. Fattah

    2017-06-01

    With the intent of reducing the carbon footprint of concrete production, a study was carried out to determine the effect of using reject brine as the source of water and the use of ground granulated blast furnace slag (GGBS as a replacement for cement. Concrete samples having three different cement contents were prepared with normal tap water and reject brine. Results showed that the use of GGBS and reject brine improved the strength of concrete produced by 16.5%. Replacing 50% of the cement with GGBS and using reject brine as the source of water has a potential for reducing 176 kg CO2 and 1.7–3.4 kg of CO2 equivalents per one cubic meter of concrete, respectively. The use of the waste reject brine can potentially save USD 170–340 per cubic meter of concrete produced.

  10. Group marginalization: extending research on interpersonal rejection to small groups.

    Science.gov (United States)

    Betts, Kevin R; Hinsz, Verlin B

    2013-11-01

    An extensive research literature has examined the reactions of individuals facing interpersonal rejection. Small groups can also be rejected, but current research tells us little about the experiences of groups and their members directly. We integrate findings from various literatures to gain insight into shared rejection experiences and their outcomes. Of most practical importance, we argue that groups can be expected to react with more hostility than individuals when rejected. Four existing models that account for how group processes might alter such reactions are examined: a need-threat model, a rejection-identification model, a multimotive model, and a dual attitudes model. Aspects of these models are then integrated into a unifying framework that is useful for understanding hostile reactions to group marginalization. Implications for natural groups such as terrorist cells, school cliques, racial and ethnic minorities, and gangs are discussed.

  11. Antibody-Mediated Pathogen Resistance in Plants.

    Science.gov (United States)

    Peschen, Dieter; Schillberg, Stefan; Fischer, Rainer

    2016-01-01

    The methods described in this chapter were developed in order to produce transgenic plants expressing pathogen-specific single-chain variable fragment (scFv) antibodies fused to antifungal peptides (AFPs), conferring resistance against fungal pathogens. We describe the selection from a phage display library of avian scFv antibodies that recognize cell surface proteins on fungi from the genus Fusarium, and the construction of scFv-AFP fusion protein constructs followed by their transient expression in tobacco (Nicotiana spp.) plants and stable expression in Arabidopsis thaliana plants. Using these techniques, the antibody fusion with the most promising in vitro activity can be used to generate transgenic plants that are resistant to pathogens such as Fusarium oxysporum f. sp. matthiolae.

  12. Immunologic basis of graft rejection and tolerance following transplantation of liver or other solid organs.

    Science.gov (United States)

    Sánchez-Fueyo, Alberto; Strom, Terry B

    2011-01-01

    Transplantation of organs between genetically different individuals of the same species causes a T cell-mediated immune response that, if left unchecked, results in rejection and graft destruction. The potency of the alloimmune response is determined by the antigenic disparity that usually exists between donors and recipients and by intragraft expression of proinflammatory cytokines in the early period after transplantation. Studies in animal models have identified many molecules that, when targeted, inhibit T-cell activation. In addition, some of these studies have shown that certain immunologic interventions induce transplantation tolerance, a state in which the allograft is specifically accepted without the need for chronic immunosuppression. Tolerance is an important aspect of liver transplantation, because livers have a unique microenvironment that promotes tolerance rather than immunity. In contrast to the progress achieved in inducing tolerance in animal models, patients who receive transplanted organs still require nonspecific immunosuppressant drugs. The development of calcineurin inhibitors has reduced the acute rejection rate and improved short-term, but not long-term, graft survival. However, long-term use of immunosuppressive drugs leads to nephrotoxicity and metabolic disorders, as well as manifestations of overimmunosuppression such as opportunistic infections and cancers. The status of pharmacologic immunosuppression in the clinic is therefore not ideal. We review recently developed therapeutic strategies to promote tolerance to transplanted livers and other organs and diagnostic tools that might be used to identify patients most likely to accept or reject allografts. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  13. Rejection of micropollutants by clean and fouled forward osmosis membrane

    KAUST Repository

    Valladares Linares, Rodrigo

    2011-12-01

    As forward osmosis (FO) gains attention as an efficient technology to improve wastewater reclamation processes, it is fundamental to determine the influence of fouling in the rejection of emerging contaminants (micropollutants). This study focuses on the rejection of 13 selected micropollutants, spiked in a secondary wastewater effluent, by a FO membrane, using Red Sea water as draw solution (DS), differentiating the effects on the rejection caused by a clean and fouled membrane. The resulting effluent was then desalinated at low pressure with a reverse osmosis (RO) membrane, to produce a high quality permeate and determine the rejection with a coupled forward osmosis - low pressure reverse osmosis (FO-LPRO) system. When considering only FO with a clean membrane, the rejection of the hydrophilic neutral compounds was between 48.6% and 84.7%, for the hydrophobic neutrals the rejection ranged from 40.0% to 87.5%, and for the ionic compounds the rejections were between 92.9% and 96.5%. With a fouled membrane, the rejections were between 44.6% and 95.2%, 48.7%-91.5% and 96.9%-98.6%, respectively. These results suggest that, except for the hydrophilic neutral compounds, the rejection of the micropollutants is increased by the presence of a fouling layer, possibly due to the higher hydrophilicity of the FO fouled membrane compared to the clean one, the increased adsorption capacity of hydrophilic compounds and reduced mass transport capacity, membrane swelling, and the higher negative charge of the membrane surface, related to the foulants composition, mainly NOM acids (carboxylic radicals) and polysaccharides or polysaccharide-like substances. However, when coupled with RO, the rejections in both cases increased above 96%. The coupled FO-LPRO system was an effective double barrier against the selected micropollutants. © 2011 Elsevier Ltd.

  14. Trait rejection sensitivity is associated with vigilance and defensive response rather than detection of social rejection cues

    Directory of Open Access Journals (Sweden)

    Taishi eKawamoto

    2015-10-01

    Full Text Available Prior studies suggest that psychological difficulties arise from higher trait rejection sensitivity (RS—heightened vigilance and differential detection of social rejection cues and defensive response to. On the other hand, from an evolutionary perspective, rapid and efficient detection of social rejection cues can be considered beneficial. We conducted a survey and an electrophysiological experiment to reconcile this seeming contradiction. We compared the effects of RS and rejection detection capability (RDC on perceived interpersonal experiences (Study 1 and on neurocognitive processes in response to cues of social rejection (disgusted faces; Study 2. We found that RS and RDC were not significantly related, although RS was positively related to perceived social rejection experiences and RDC was positively related to perceived social inclusion experiences. Event-related brain potentials (ERPs revealed that higher RS was related to cognitive avoidance (i.e., P1 and heightened motivated attention (i.e., late positive potential: LPP, but not to facial expression encoding (i.e., N170 toward disgusted faces. On the other hand, higher RDC was related to heightened N170 amplitude, but not to P1 and LPP amplitudes. These findings imply that sensitivity to rejection is apparently distinct from the ability to detect social rejection cues and instead reflects intense vigilance and defensive response to those cues. We discussed an alternative explanation of the relationship between RS and RDC from a signal detection perspective.

  15. Rejected by Peers--Attracted to Antisocial Media Content: Rejection-Based Anger Impairs Moral Judgment among Adolescents

    Science.gov (United States)

    Plaisier, Xanthe S.; Konijn, Elly A.

    2013-01-01

    Adolescence is an important developmental stage during which both peers and the media have a strong influence. Both peer rejection and the use of morally adverse media are associated with negative developmental outcomes. This study examines processes by which peer rejection might drive adolescents to select antisocial media content by tying…

  16. Rejected by peers – Attracted to antisocial media content: Rejection-based anger impairs moral judgment among adolescents

    NARCIS (Netherlands)

    Plaisier, X.S.; Konijn, E.A.

    2013-01-01

    Adolescence is an important developmental stage during which both peers and the media have a strong influence. Both peer rejection and the use of morally adverse media are associated with negative developmental outcomes. This study examines processes by which peer rejection might drive adolescents

  17. Rejected by peers-attracted to antisocial media content: rejection-based anger impairs moral judgment among adolescents.

    Science.gov (United States)

    Plaisier, Xanthe S; Konijn, Elly A

    2013-06-01

    Adolescence is an important developmental stage during which both peers and the media have a strong influence. Both peer rejection and the use of morally adverse media are associated with negative developmental outcomes. This study examines processes by which peer rejection might drive adolescents to select antisocial media content by tying together developmental research on peer rejection and research on media effects. Assumed underlying mechanisms are rejection-based anger and frustration and the adolescent's moral judgment. A between-participants experimental design manipulated peer rejection versus acceptance in adolescents (Mage = 13.88 years; N = 74) and young adults (Mage = 21.37 years; N = 75), applying the Cyberball paradigm. Measures included the State Anger Inventory (STAXI) to assess feelings of rejection and the newly devised Media, Morals, and Youth Questionnaire (MMaYQue) to assess media preferences and moral judgment of media content. Using bootstrapping analyses, a double mediation was established: Higher levels of state anger in peer-rejected adolescents induced more tolerable moral judgments of antisocial media content, subsequently instigating a preference for antisocial media content. In contrast, the young adult sample showed no relations between peer rejection and antisocial media preference. Results are discussed within a downward spiral framework of combined peer and media influences. PsycINFO Database Record (c) 2013 APA, all rights reserved

  18. Immunosuppressive effects of ginsenoside-Rd on skin allograft rejection in rats.

    Science.gov (United States)

    Wang, Li; Zhang, Yunxin; Chen, Jiajia; Li, Sijia; Wang, Yanhong; Hu, Lamei; Wang, Lihua; Wu, Yongjie

    2012-07-01

    Organ transplantation is a life-saving procedure for patients with organ failure. However, the side effects of long-term application of classic immunosuppressant remain major obstacles for successful transplantation. Therefore, new and safe immunosuppressive drugs against acute and chronic rejection are eagerly awaited. In the present study, we detected the effect of ginsenoside-Rd on mitogen-induced mouse spleen lymphocytes proliferation in vitro and observed the effect of ginsenoside-Rd on allograft rejection in a rat skin transplantation model. Th1/Th2 type cytokines secretion and T-cell subsets were also detected. The results showed that ginsenoside-Rd could markedly inhibit Concanavalin A (ConA)-induced mouse spleen T lymphocytes proliferation. Also, ginsenoside-Rd could significantly prolong the mean survival time of skin allograft and improve the skin allograft pathological damage. Furthermore, ginsenoside-Rd could markedly suppress alloantigen-specific production of Th1 cytokines IL-2 and IFN-γ as well as proinflammatory cytokines TNFα and IL-12. In parallel, Th2 cytokine IL-10 production in serum of rat recipients was markedly up-regulated. Ginsenoside-Rd at a dose of 25 mg/kg could significantly reduce the percentages of CD4(+) T cells and CD8(+) T cells in peripheral blood of rat recipients. Our results suggest that ginsenoside-Rd can effectively antagonize transplant rejection, which might qualify ginsenoside-Rd as a putative, therapeutic drug for the treatment of Th1-driven diseases, including transplant rejection. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Quantum Communication Using Coherent Rejection Sampling.

    Science.gov (United States)

    Anshu, Anurag; Devabathini, Vamsi Krishna; Jain, Rahul

    2017-09-22

    Compression of a message up to the information it carries is key to many tasks involved in classical and quantum information theory. Schumacher [B. Schumacher, Phys. Rev. A 51, 2738 (1995)PLRAAN1050-294710.1103/PhysRevA.51.2738] provided one of the first quantum compression schemes and several more general schemes have been developed ever since [M. Horodecki, J. Oppenheim, and A. Winter, Commun. Math. Phys. 269, 107 (2007); CMPHAY0010-361610.1007/s00220-006-0118-xI. Devetak and J. Yard, Phys. Rev. Lett. 100, 230501 (2008); PRLTAO0031-900710.1103/PhysRevLett.100.230501A. Abeyesinghe, I. Devetak, P. Hayden, and A. Winter, Proc. R. Soc. A 465, 2537 (2009)PRLAAZ1364-502110.1098/rspa.2009.0202]. However, the one-shot characterization of these quantum tasks is still under development, and often lacks a direct connection with analogous classical tasks. Here we show a new technique for the compression of quantum messages with the aid of entanglement. We devise a new tool that we call the convex split lemma, which is a coherent quantum analogue of the widely used rejection sampling procedure in classical communication protocols. As a consequence, we exhibit new explicit protocols with tight communication cost for quantum state merging, quantum state splitting, and quantum state redistribution (up to a certain optimization in the latter case). We also present a port-based teleportation scheme which uses a fewer number of ports in the presence of information about input.

  20. Hyperexpression of the granzyme B inhibitor PI-9 in human renal allografts: A potential mechanism for stable renal function in patients with subclinical rejection

    NARCIS (Netherlands)

    Rowshani, Ajda T.; Florquin, Sandrine; Bemelman, Frederike; Kummer, J. Alain; Hack, C. Erik; ten Berge, Ineke J. M.

    2004-01-01

    Background. Granzyme B-positive T lymphocytes infiltrate renal allografts during acute cellular rejection and cause graft injury by inducing apoptosis of tubular cells. Protease inhibitor 9 (PI-9), an intracellular serpin that inhibits granzyme B, is known to protect cells from the action of

  1. Effect of dietary fish-oil on renal-function and rejection in cyclosporine-treated recipients of renal-transplants

    NARCIS (Netherlands)

    van der Heide, Jaap J. Homan; Bilo, Henk J. G.; Donker, J. M.; Wilmink, J. M.; Tegzess, Adam M.

    1993-01-01

    Background. Dietary fish oil exerts effects on renal hemodynamics and the immune response that may benefit renal-transplant recipients treated with cyclosporine. To evaluate this possibility, we studied the effect of fish oil on renal function, blood pressure, and the incidence of acute rejection

  2. Reject mechanisms for massively parallel neural network character recognition systems

    Science.gov (United States)

    Garris, Michael D.; Wilson, Charles L.

    1992-12-01

    Two reject mechanisms are compared using a massively parallel character recognition system implemented at NIST. The recognition system was designed to study the feasibility of automatically recognizing hand-printed text in a loosely constrained environment. The first method is a simple scalar threshold on the output activation of the winning neurode from the character classifier network. The second method uses an additional neural network trained on all outputs from the character classifier network to accept or reject assigned classifications. The neural network rejection method was expected to perform with greater accuracy than the scalar threshold method, but this was not supported by the test results presented. The scalar threshold method, even though arbitrary, is shown to be a viable reject mechanism for use with neural network character classifiers. Upon studying the performance of the neural network rejection method, analyses show that the two neural networks, the character classifier network and the rejection network, perform very similarly. This can be explained by the strong non-linear function of the character classifier network which effectively removes most of the correlation between character accuracy and all activations other than the winning activation. This suggests that any effective rejection network must receive information from the system which has not been filtered through the non-linear classifier.

  3. Lunar Dust on Heat Rejection System Surfaces: Problems and Prospects

    Science.gov (United States)

    Gaier, James R.; Jaworske, Donald A.

    2007-01-01

    Heat rejection from power systems will be necessary for human and robotic activity on the lunar surface. Functional operation of such heat rejection systems is at risk of degradation as a consequence of dust accumulation. The Apollo astronauts encountered marked degradation of performance in heat rejection systems for the lunar roving vehicle, science packages, and other components. Although ground testing of dust mitigation concepts in support of the Apollo mission identified mitigation tools, the brush concept adopted by the Apollo astronauts proved essentially ineffective. A better understanding of the issues associated with the impact of lunar dust on the functional performance of heat rejection systems and its removal is needed as planning gets underway for human and robotic missions to the Moon. Renewed emphasis must also be placed on ground testing of pristine and dust-covered heat rejection system surfaces to quantify degradation and address mitigation concepts. This paper presents a review of the degradation in performance of heat rejection systems encountered on the lunar surface to-date, and will discuss current activities underway to evaluate the durability of candidate heat rejection system surfaces and current dust mitigation concepts.

  4. Rejection of Organic Micropollutants by Clean and Fouled Nanofiltration Membranes

    Directory of Open Access Journals (Sweden)

    Lifang Zhu

    2015-01-01

    Full Text Available The rejection of organic micropollutants, including three polycyclic aromatic hydrocarbons (PAHs and three phthalic acid esters (PAEs, by clean and fouled nanofiltration membranes was investigated in the present study. The rejection of organic micropollutants by clean NF90 membranes varied from 87.9 to more than 99.9%, while that of NF270 membranes ranged from 32.1 to 92.3%. Clear time-dependence was observed for the rejection of hydrophobic micropollutants, which was attributed to the adsorption of micropollutants on the membrane. Fouling with humic acid had a negligible influence on the rejection of organic micropollutants by NF90 membranes, while considerable effects were observed with NF270 membranes, which are significantly looser than NF90 membranes. The observed enhancement in the rejection of organic micropollutants by fouled NF270 membranes was attributed to pore blocking, which was a dominating fouling mechanism for loose NF membranes. Changes in the ionic strength (from 10 to 20 mM reduced micropollutant rejection by both fouled NF membranes, especially for the rejection of dimethyl phthalate and diethyl phthalate by NF270 membranes (from 65.8 to 25.0% for dimethyl phthalate and 75.6 to 33.3% for diethyl phthalate.

  5. Effect of Donor and Recipient Factors on Corneal Graft Rejection

    Science.gov (United States)

    Stulting, R. Doyle; Sugar, Alan; Beck, Roy; Belin, Michael; Dontchev, Mariya; Feder, Robert S.; Gal, Robin L.; Holland, Edward J.; Kollman, Craig; Mannis, Mark J.; Price, Francis; Stark, Walter; Verdier, David D.

    2014-01-01

    Purpose To assess the relationship between donor and recipient factors and corneal allograft rejection in eyes that underwent penetrating keratoplasty (PK) in the Cornea Donor Study. Methods 1090 subjects undergoing corneal transplantation for a moderate risk condition (principally Fuchs’ dystrophy or pseudophakic corneal edema) were followed for up to 5 years. Associations of baseline recipient and donor factors with the occurrence of a probable or definite rejection event were assessed in univariate and multivariate proportional hazards models. Results Eyes with pseudophakic or aphakic corneal edema (N=369) were more likely to experience a rejection event than eyes with Fuchs’ dystrophy (N=676) (34% ± 6% versus 22% ± 4%; hazard ratio = 1.56; 95% confidence interval 1.21 to 2.03). Among eyes with Fuchs’dystrophy, a higher probability of a rejection event was observed in phakic post-transplant eyes compared with eyes that underwent cataract extraction with or without intraocular lens implantation during PK (29% vs. 19%; hazard ratio = 0.54; 95% confidence interval 0.36 to 0.82). Female recipients had a higher probability of a rejection event than males (29% vs. 21%; hazard ratio=1.42; 95% confidence interval 1.08 to 1.87), after controlling for the effect of preoperative diagnosis and lens status. Donor age and donor recipient ABO compatibility were not associated with rejection. Conclusions There was a substantially higher graft rejection rate in eyes with pseudophakic or aphakic corneal edema compared with eyes with Fuchs’ dystrophy. Female recipients were more likely to have a rejection event than males. Graft rejection was not associated with donor age. PMID:22488114

  6. Ozone Therapy Protects Against Rejection in a Lung Transplantation Model: A New Treatment?

    Science.gov (United States)

    Santana-Rodríguez, Norberto; Llontop, Pedro; Clavo, Bernardino; Fiuza-Pérez, María D; Zerecero, Keila; Ayub, Adil; Alshehri, Khalid; Yordi, Nagib A; Re, Lamberto; Raad, Wissam; Fernández-Pérez, Leandro; García-Herrera, Ricardo; Huang, Chyun-Yin J; Bhora, Faiz Y

    2017-08-01

    No satisfactory treatment exists for chronic rejection (CR) after lung transplantation (LT). Our objective was to assess whether ozone (O3) treatment could ameliorate CR. Male Sprague-Dawley inbred rats (n = 36) were randomly assigned into four groups: (1) control (n = 6), (2) sham (n = 6), (3) LT (n = 12), and (4) O3-LT (n = 12). Animals underwent left LT. O3 was rectally administered daily for 2 weeks before LT (from 20 to 50 μg) and 3 times/wk (50 μg/dose) up to 3 months. CR; acute rejection; and Hspb27, Prdx, Epas1, Gpx3, Vegfa, Sftpa1, Sftpb, Plvap, Klf2, Cldn5, Thbd, Dsip, Fmo2, and Sepp1 mRNA gene expression were determined. Severe CR was observed in all animals of LT group, but none of the O3-LT animals showed signs of CR, just a mild acute rejection was observed in 1 animal. A significant decrease of Hspb27, Prdx, Epas1, Gpx3, Vegfa, Sftpa1, Sftpb, Plvap, Klf2, Cldn5, Thbd, Dsip, and Fmo2 gene expression in the O3-LT group was observed CONCLUSIONS: O3 therapy significantly delayed the onset of CR regulating the expression of genes involved in its pathogenesis. No known immunosuppressive therapy has been capable of achieving similar results. From a translational point of view, O3 therapy could become a new adjuvant treatment for CR in patients undergoing LT. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  7. Effect of CD4+ memory T cells on rejection response of ectopic heart transplantation in mice.

    Science.gov (United States)

    Zhao, Y; Shan, Z; Li, Q; Zhou, Y; Zeng, X; Fan, Q; Liao, C; Zhu, Y; Zhao, Y; Lu, X; Liu, J

    2011-06-01

    CD4(+) memory T cells mediate resistance of the body to infection by exotic pathogens. This study investigated the effects of alloreactive CD4(+) memory T cells on acute graft rejection responses toward ectopic hearts in the abdominal cavities of mice. BALB/C mice were used as recipients and C57BL/6 mice as donors. The animals in the CD4(+) memory T-cell group were infused with CD4(+) memory T cells, those in the other group were infused with nonsensitized CD4(+) T cells, and those in the control group received no CD4(+) T cells. Heart transplantation was performed at 3 weeks after the cell infusion with cyclosporine administered beginning 1 day before transplantation via intraperitoneal injection. The survival among the CD4(+) memory T-cell group was significantly shorter than that of the nonsensitized CD4(+) T-cell group or the control group (P .05; n = 10). On the 5th day after the transplantation of heart, the histologic grades of the nonsensitized CD4(+) T-cell and the blank control group were lower than those of the CD4(+) memory T-cell group. There was no significant difference in the histologic grades between the nonsensitized CD4(+) T-cell and control groups. The CD4(+) memory T cells that mediate acute rejection of allografted hearts are insensitive to cyclosporine. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Suicide Screening for Prisoners: An Ethical Critique of Research Rejection.

    Science.gov (United States)

    Guinn, David; Burgermeister, Diane M

    2016-01-01

    A retrospective review of medical records was proposed to examine mental health staff compliance with documentation of a suicide assessment tool according to institutional policy on suicide screening within a U.S. correctional facility. A shift in focus was necessary when the proposed study was rejected by the institutional review board. Reasons for the rejection included low perceived benefit versus greater risk to the correctional facility and the need for prisoner informed consent, albeit the design was a retrospective medical record review. Because of this rejection, ethical issues in the prevention of suicide in prisons were examined with implications for the forensic nurse leading quality improvement initiatives.

  9. Associations between rejection sensitivity and mental health outcomes : A meta-analytic review

    NARCIS (Netherlands)

    Gao, S.; Assink, M.; Cipriani, A.; Lin, K.

    2017-01-01

    Rejection sensitivity is a personality disposition characterized by oversensitivity to social rejection. Using a three-level meta-analytic model, 75 studies were reviewed that examined associations between rejection sensitivity and five mental health outcomes: depression, anxiety, loneliness,

  10. Children's coping with in vivo peer rejection: an experimental investigation.

    Science.gov (United States)

    Reijntjes, Albert; Stegge, Hedy; Terwogt, Mark Meerum; Kamphuis, Jan Henk; Telch, Michael J

    2006-12-01

    We examined children's behavioral coping in response to an in vivo peer rejection manipulation. Participants (N=186) ranging between 10 and 13 years of age, played a computer game based on the television show Survivor and were randomized to either peer rejection (i.e., being voted out of the game) or non-rejection control. During a five-min. post-feedback waiting period children's use of several behavioral coping strategies was assessed. Rejection elicited a marked shift toward more negative affect, but higher levels of perceived social competence attenuated the negative mood shift. Children higher in depressive symptoms were more likely to engage in passive and avoidant coping behavior. Types of coping were largely unaffected by gender and perceived social competence. Implications are discussed.

  11. Paying To Belong: When Does Rejection Trigger Ingratiation?

    OpenAIRE

    Romero-Canyas, Rainer; Downey, Geraldine; Reddy, Kavita S; Rodriguez, Sylvia; Cavanaugh, Timothy J.; Pelayo, Rosemary

    2010-01-01

    Societies and social scientists have long held the belief that exclusion induces ingratiation and conformity, an idea in contradiction with robust empirical evidence linking rejection with hostility and aggression. The classic literatures on ingratiation and conformity help resolve this contradiction by identifying circumstances under which rejection may trigger efforts to ingratiate. Jointly, findings from these literatures suggest that when people are given an opportunity to impress their r...

  12. Rejection or selection: influence of framing in investment decisions.

    Science.gov (United States)

    Cheng, Pi-Yueh; Chiou, Wen-Bin

    2010-02-01

    According to prospect theory, reflection effects result in preferences for risk-averse choices in gain situations and risk-seeking choices in loss situations. However, relevant literature in regard to decision making has suggested that positive information receives more weight in a selection task, whereas negative information receives more weight in a rejection task. The present study examined whether the nature of a decision task (selection vs rejection) would moderate the reflection effects. Undergraduates (47 men, 49 women; M age = 20.5 yr., SD = 1.1), selected according to specific screening criteria, participated in an experimental study. Typical reflection effects were observed in both selection and rejection task conditions. More importantly, negative information (i.e., the information about probable loss in risky choice of gain situations and the information about certain loss in cautious choice of loss situations) provided in the context of a rejection task received more weight and resulted in more frequent endorsements of the cautious choice in gain situations and of the risky choice in loss situations. Hence, the findings suggest that a decision context characterized by rejection may expand the reflection effects and thereby provide important information about situations in which investment decisions occur in a context characterized by rejection.

  13. Higher boron rejection with a new TFC forward osmosis membrane

    KAUST Repository

    Valladares Linares, Rodrigo

    2014-07-17

    Due to the stringent limits for boron in drinking and irrigation water, water treatment facilities have to incur additional treatment to remove boron down to a safe concentration. Forward osmosis (FO) is a membrane technology that may reduce the energy required to remove boron present in seawater. In direct FO desalination hybrid systems, fresh water is recovered from seawater using a recoverable draw solution, FO membranes are expected to show high boron rejection. This study focuses on determining the boron rejection capabilities of a new generation thin-film composite (TFC) FO membrane compared to a first generation cellulose triacetate (CTA) FO membrane. The effects of water permeate flux, membrane structure, draw solute charge, and reverse solute flux on boron rejection were determined. For TFC and CTA FO membranes, experiments showed that when similar operating conditions are applied (e.g. membrane type and draw solute type) boron rejection decreases with increase in permeate flux. Reverse draw solute flux and membrane fouling have no significant impact on boron rejection. Compared to the first generation CTA FO membrane operated at the same conditions, the TFC FO membrane showed a 40% higher boron rejection capability and a 20% higher water flux. This demonstrates the potential for boron removal for new generation TFC FO membranes. © 2014 © 2014 Balaban Desalination Publications. All rights reserved.

  14. The role of indium-111 antimyosin (Fab) imaging as a noninvasive surveillance method of human heart transplant rejection

    Energy Technology Data Exchange (ETDEWEB)

    De Nardo, D.; Scibilia, G.; Macchiarelli, A.G.; Cassisi, A.; Tonelli, E.; Papalia, U.; Gallo, P.; Antolini, M.; Pitucco, G.; Reale, A. (Universita degli Studi di Roma I La Sapienza Policlinico Umberto I (Italy))

    1989-09-01

    The identification of rejection after heart transplantation in patients receiving cyclosporine immunosuppressive therapy requires the endomyocardial biopsy, an invasive method associated with a finite morbidity. To evaluate the role of indium-111 antimyosin (Fab) scintigraphy as a noninvasive surveillance method of heart transplant rejection, the Fab fragment of murine monoclonal antimyosin antibodies labeled with indium-111 was administered intravenously in 30 scintigraphic studies to 10 consecutive heart transplant recipients. Endomyocardial biopsy specimens were obtained 72 hours after each scintigraphic study. Nineteen scintigraphic studies had negative findings; no false negative finding was obtained. Eleven antimyosin scintigraphic studies had positive findings, and in these studies endomyocardial biopsy revealed mild rejection in two cases, moderate acute rejection with myocyte necrosis in two cases, myocyte necrosis as a consequence of ischemic injury in six cases, and possibly cytotoxic damage in one case. Antimyosin scintigraphy may represent a reliable screening method for the surveillance of heart transplant patients. In the presence of a negative finding from antimyosin scintigraphy, it may be possible to avoid endomyocardial biopsy. Conversely, in patients who have a positive finding from antimyosin scintigraphy, the endomyocardial biopsy is mandatory to establish the definitive diagnosis by histologic examination of the myocardium.

  15. Rejection mechanisms for contaminants in polymeric reverse osmosis membranes

    CERN Document Server

    Shen, Meng; Lueptow, Richard M

    2016-01-01

    Despite the success of reverse osmosis (RO) for water purification, the molecular-level physico-chemical processes of contaminant rejection are not well understood. Here we carry out NEMD simulations on a model polyamide RO membrane to understand the mechanisms of transport and rejection of both ionic and neutral contaminants in water. We observe that the rejection changes non-monotonously with ion sizes. In particular, the rejection of urea, 2.4 A radius, is higher than ethanol, 2.6 A radius, and the rejections for organic solutes, 2.2-2.8 A radius, are lower than Na+, 1.4 A radius, or Cl-, 2.3 A radius. We show that this can be explained in terms of the solute accessible intermolecular volume in the membrane and the solute-water pair interaction energy. If the smallest open spaces in the membrane's molecular structure are all larger than the hydrated solute, then the solute-water pair interaction energy does not matter. However, when the open spaces in the polymeric structure are such that solutes have to s...

  16. The composition of the microbiota modulates allograft rejection.

    Science.gov (United States)

    Lei, Yuk Man; Chen, Luqiu; Wang, Ying; Stefka, Andrew T; Molinero, Luciana L; Theriault, Betty; Aquino-Michaels, Keston; Sivan, Ayelet S; Nagler, Cathryn R; Gajewski, Thomas F; Chong, Anita S; Bartman, Caroline; Alegre, Maria-Luisa

    2016-07-01

    Transplantation is the only cure for end-stage organ failure, but without immunosuppression, T cells rapidly reject allografts. While genetic disparities between donor and recipient are major determinants of the kinetics of transplant rejection, little is known about the contribution of environmental factors. Because colonized organs have worse transplant outcome than sterile organs, we tested the influence of host and donor microbiota on skin transplant rejection. Compared with untreated conventional mice, pretreatment of donors and recipients with broad-spectrum antibiotics (Abx) or use of germ-free (GF) donors and recipients resulted in prolonged survival of minor antigen-mismatched skin grafts. Increased graft survival correlated with reduced type I IFN signaling in antigen-presenting cells (APCs) and decreased priming of alloreactive T cells. Colonization of GF mice with fecal material from untreated conventional mice, but not from Abx-pretreated mice, enhanced the ability of APCs to prime alloreactive T cells and accelerated graft rejection, suggesting that alloimmunity is modulated by the composition of microbiota rather than the quantity of bacteria. Abx pretreatment of conventional mice also delayed rejection of major antigen-mismatched skin and MHC class II-mismatched cardiac allografts. This study demonstrates that Abx pretreatment prolongs graft survival, suggesting that targeting microbial constituents is a potential therapeutic strategy for enhancing graft acceptance.

  17. The role of peer rejection in adolescent depression.

    Science.gov (United States)

    Platt, Belinda; Cohen Kadosh, Kathrin; Lau, Jennifer Y F

    2013-09-01

    Adolescence is a period of major risk for depression, which is associated with negative personal, social, and educational outcomes. Yet, in comparison to adult models of depression, very little is known about the specific psychosocial stressors that contribute to adolescent depression, and whether these can be targeted by interventions. In this review, we consider the role of peer rejection. First, we present a comprehensive review of studies using innovative experimental paradigms to understand the role of peer rejection in adolescent depression. We show how reciprocal relationships between peer rejection and depressive symptoms across adolescence powerfully shape and maintain maladaptive trajectories. Second, we consider how cognitive biases and their neurobiological substrates may explain why some adolescents are more vulnerable to the effects of, and perhaps exposure to, peer rejection compared to others. Finally, we draw attention to emerging cognitive and functional magnetic resonance imaging-based neurofeedback training, which by modifying aspects of information processing may promote more adaptive responses to peer rejection. A better understanding of the mechanisms underlying adolescent depression may not only alleviate symptoms during a period of substantial developmental challenges, but may also reduce the burden of the disorder across the lifespan. © 2013 Wiley Periodicals, Inc.

  18. Self-contained heat rejection module for future spacecraft

    Science.gov (United States)

    Fleming, M. L.; Williams, J. L.; Baskett, J. D.; Leach, J. W.

    1975-01-01

    This paper discusses development of a Self-Contained Heat Rejection Module (SHRM) which can be used on a wide variety of future spacecraft launched by the space shuttle orbiter. The SHRM contains radiators which are deployed by a scissor-mechanism and the flow equipment including pumps, accumulator, by-pass valves, and controllers necessary to reject heat from those radiators. Heat transfer between SHRM and the parent vehicle is effected by a contact heat exchanger. This device provides heat transfer between two separate flow loops through a mechanical connection. This approach reduces the time required to attach the SHRM to the payload, and increases the reliability of the SHRM flow loop since breaking into the fluid system in the field is not required. The SHRM concept also includes a refrigeration system to increase heat rejection capacity in adverse environments, or to provide for a lower return temperature, down to -23 C.

  19. Active disturbance rejection control for fractional-order system.

    Science.gov (United States)

    Li, Mingda; Li, Donghai; Wang, Jing; Zhao, Chunzhe

    2013-05-01

    Fractional-order proportional-integral (PI) and proportional-integral-derivative (PID) controllers are the most commonly used controllers in fractional-order systems. However, this paper proposes a simple integer-order control scheme for fractional-order system based on active disturbance rejection method. By treating the fractional-order dynamics as a common disturbance and actively rejecting it, active disturbance rejection control (ADRC) can achieve the desired response. External disturbance, sensor noise, and parameter disturbance are also estimated using extended state observer. The ADRC stability of rational-order model is analyzed. Simulation results on three typical fractional-order systems are provided to demonstrate the effectiveness of the proposed method. Copyright © 2013 ISA. Published by Elsevier Ltd. All rights reserved.

  20. Rejected! Cognitions of rejection and intergroup anxiety as mediators of the impact of cross-group friendships on prejudice.

    Science.gov (United States)

    Barlow, Fiona Kate; Louis, Winnifred R; Hewstone, Miles

    2009-09-01

    In a sample of White Australians (N=273), cross-group friendship with Aboriginal Australians was associated with reduced cognitions of rejection and intergroup anxiety, and these variables fully mediated the effect of cross-group friendship on conversational avoidance of sensitive intergroup topics, active avoidance of the outgroup, and old-fashioned prejudice. The novel mediator proposed here, cognitions of rejection, predicted intergroup anxiety, and also predicted the three outcome variables via intergroup anxiety. Over and above its indirect effects via anxiety, cognitions of rejection directly predicted both conversational and active avoidance, suggesting that whilst the cognitive and affective mediators are linked, they predict intergroup outcomes in different ways. The results demonstrate the beneficial impact of cross group friendship in reducing prejudice and avoidance by diminishing cognitions of rejection and intergroup anxiety. We also highlight that individuals without cross-group friends may perceive the outgroup as rejecting, feel anxious about cross-group interaction, and desire both conversational and physical avoidance of the outgroup.

  1. Learning biases underlying individual differences in sensitivity to social rejection.

    Science.gov (United States)

    Olsson, Andreas; Carmona, Susanna; Downey, Geraldine; Bolger, Niall; Ochsner, Kevin N

    2013-08-01

    People vary greatly in their dispositions to anxiously expect, readily perceive, and strongly react to social rejection (rejection sensitivity [RS]) with implications for social functioning and health. Here, we examined how RS influences learning about social threat. Using a classical fear conditioning task, we established that high compared to low individuals displayed a resistance to extinction of the conditioned response to angry faces, but not to neutral faces or nonsocial stimuli. Our findings suggest that RS biases the flexible updating of acquired expectations for threat, which helps to explain how RS operates as a self-fulfilling prophecy. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  2. Inspection of lead aprons: a practical rejection model.

    Science.gov (United States)

    Stam, W; Pillay, M

    2008-08-01

    As a sequel to the article by Ken Lambert and Tara McKeon, we propose a model by which defects in lead aprons may easily be evaluated on a routine basis. The model is applicable to lead aprons of various lead equivalent thicknesses. As recommended rejection criteria, we have used the concept of additional dose that an individual might receive due to defects in the lead (Pb) apron. The model has been implemented as an annual quality check in a large medical facility. In this article we consider only dose-related rejection criteria, since financial aspects related to ALARA have already been addressed in the abovementioned article.

  3. Albedo particle rejection with the RICH study prototype of AMS

    CERN Document Server

    Thuillier, T; Buénerd, M; Gallin-Martel, L; Ohlsson-Malek, F

    2001-01-01

    An experimental test has been performed on the Ring Imaging Cherenkov (RICH) study prototype of AMS, with cosmic ray particles on the ground, to evaluate the counter performance for Albedo particle rejection. The test was made with two radiators : Sodium Fluoride crystal (NaF, n approx 1.33) and Silica Aerogel (n=1.035). The experimental results are shown and can be consistently accounted for on the basis of random events generated from PMT background counting by means of a simple model, used to estimate the Albedo rejection performance of the future AMS RICH.

  4. Improved pyrite rejection by chemically-modified fine coal flotation

    Energy Technology Data Exchange (ETDEWEB)

    Miller, J.D.; Ye, Y.; Jin, R.

    1989-01-01

    Improved pyrite rejection during fine coal flotation can be achieved by chemical pretreatment of the coal prior to flotation. The process involves conditioning the suspension with potassium monopersulfate or other peroxy compounds followed by conventional flotation. The ambient-temperature treatment seems to improve the hydrophobic character of certain low-rank coals as is evident from induction time measurements and bench-scale flotation experiments. In addition, the chemical pretreatment leads to an improvement in ash rejection and to enhanced depression of pyrite. 23 refs., 9 figs., 2 tabs.

  5. Method and apparatus for analog pulse pile-up rejection

    Science.gov (United States)

    De Geronimo, Gianluigi

    2013-12-31

    A method and apparatus for pulse pile-up rejection are disclosed. The apparatus comprises a delay value application constituent configured to receive a threshold-crossing time value, and provide an adjustable value according to a delay value and the threshold-crossing time value; and a comparison constituent configured to receive a peak-occurrence time value and the adjustable value, compare the peak-occurrence time value with the adjustable value, indicate pulse acceptance if the peak-occurrence time value is less than or equal to the adjustable value, and indicate pulse rejection if the peak-occurrence time value is greater than the adjustable value.

  6. When is peer rejection justifiable?: Children’s understanding across two cultures

    OpenAIRE

    Park, Yoonjung; Killen, Melanie

    2010-01-01

    This study investigated how Korean (N = 397) and U.S. (N = 333) children and adolescents (10 and 13 years of age) evaluated personality (aggression, shyness) and group (gender, nationality) characteristics as a basis for peer rejection in three contexts (friendship rejection, group exclusion, victimization). Overall, peer rejection based on group membership was viewed as more unfair than peer rejection based on personality traits. Children viewed friendship rejection as more legitimate than g...

  7. Adeno-associated viral vector 2.9 thymosin ß4 application attenuates rejection after heart transplantation: results of a preclinical study in the pig.

    Science.gov (United States)

    Postrach, Johannes; Schmidt, Maximilian; Thormann, Michael; Thein, Eckart; Burdorf, Lars; Reichart, Bruno; Sotlar, Karl; Walz, Christoph; Faber, Claudius; Bauer, Andreas; Schmoeckel, Michael; Kupatt, Christian; Hinkel, Rabea

    2014-10-27

    Graft survival is the most important factor for morbidity and mortality in cardiac transplantation. Improved immunosuppression significantly reduced early graft rejection. However, acute rejection may predispose to chronic rejection. Targeting both phases of the recipient's immune-reactivity by means of long-acting recombinant adeno-associated viral vectors (AAVs) encoding anti-inflammatory and cardioprotective factors appears to be a promising therapeutic approach. We investigate thymosin ß4 (Tß4) possessing anti-inflammatory and prosurvival abilities, as a means for pretransplant gene therapy. Heterotopic, abdominal transplantation of cardiac allografts into landrace or into Munich mini pigs (n=5 per group) was performed. Transplants were transduced with AAV2.9 before transplantation by means of in situ perfusion of the donor organ. Vascuar endothelial growth factor and AAV2.9.Tß4 or AAV2.9.LacZ were added to the autologous blood used for perfusing the grafts for a period of 45 min. Immunosuppression was applied for 10 days after the operation. Transgene expression, capillary density, graft function, survival, and rejection were assessed. The AAV2.9 transduction induced robust overexpression of the transgene. In addition, Tß4 ameliorated inflammation, necrosis, vascular reaction (acute rejection) and in parallel improved capillary density. In addition, graft survival was significantly prolonged (10±3 days AAV2.9.LacZ vs. 31±4 days AAV2.9.Tß4). In the mini pig model, regional myocardial function of the grafts was improved by Tß4 transduction compared to LacZ (9.1%±0.9% subendocardial segment shortening in AAV2.9.LacZ vs. 15.8%±2.3% in AAV2.9.Tß4). In situ AAV2.9-mediated gene transfer of thymosin β4 attenuated graft rejection in a heterotopic heart transplantation model. Perioperative cardioprotection by means of gene therapy might improve graft survival in cardiac allotransplantation.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  9. 9 CFR 354.35 - Rejection of application.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Rejection of application. 354.35 Section 354.35 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... holding office or a responsible position with or having a substantial financial interest or share in the...

  10. 7 CFR 56.24 - Rejection of application

    Science.gov (United States)

    2010-01-01

    ... AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) VOLUNTARY GRADING OF SHELL EGGS Grading of Shell Eggs Application for Grading Service § 56.24 Rejection of application (a) An... benefits of the Act; (3) Where any individual holding office or a responsible position with or having a...

  11. Perceived parental rejection mediates the effects of previous ...

    African Journals Online (AJOL)

    However, mental illness had no moderating effect on these relationships. Conclusion: These results are consistent with the literature on maltreatment and parent-child relationships and provide empirical support for the view that emotional and behavioural problems related to perceived parental rejection underlie the ...

  12. Examining Appearance-Based Rejection Sensitivity during Early Adolescence

    Science.gov (United States)

    Bowker, Julie C.; Thomas, Katelyn K.; Spencer, Sarah V.; Park, Lora E.

    2013-01-01

    The present study of 150 adolescents ("M" age = 13.05 years) examined the associations between appearance-based rejection sensitivity (Appearance-RS) and psychological adjustment during early adolescence, and evaluated three types of other-gender peer experiences (other-gender friendship, peer acceptance, and romantic relationships) as…

  13. Developmental Differences in the Use of Recognition Memory Rejection Mechanisms

    Science.gov (United States)

    Odegard, Timothy N.; Jenkins, Kara M.; Koen, Joshua D.

    2010-01-01

    The current experiment examined the use of plausibility judgments by children to reject distractors presented on "yes/no" recognition memory tests. Participants studied two lists of word pairs that shared either a categorical or rhyme association, which constituted the global nature of the two study conditions. During the recognition memory tests,…

  14. Maternal Acceptance/Rejection of Mexican Migrant Mothers.

    Science.gov (United States)

    Siantz, Mary Lou de Leon

    1990-01-01

    Examines correlates of maternal acceptance of preschool children by their Mexican-American migrant farmworker mothers, including problems in life conditions and social support. Findings indicate social support accounts for more variation in maternal acceptance/rejection than problems in life conditions alone. Suggests the importance of identifying…

  15. Geo-engineering Characteristics and Behaviour of Coal-reject ...

    African Journals Online (AJOL)

    The influence of raw-meal on the geotechnical properties of Nigerian coal-reject was studied and the behavior of the improved material evaluated based on Atterberg limits, linear shrinkage, compaction, California bearing ratio and strength tests. The results of the tests indicate that the liquid limit, plastic limit and plasticity ...

  16. Dimensions of self-appraisal and perceived peer rejection among ...

    African Journals Online (AJOL)

    Accordingly, the main aim of this study is to explore influence of skin colour satisfaction, self-esteem and self-attractiveness on perceived peer rejection among entry level tertiary students. A cross-sectional research design was adopted for the study. Data was collected from a sample of 341 entry level students. Stratified ...

  17. From Acceptance to Rejection: Food Contamination in the Classroom.

    Science.gov (United States)

    Rajecki, D. W.

    1989-01-01

    Describes a classroom exercise to explain design and measurement principles in methodology and statistics courses. This demonstration which involves measurement of a shift from food acceptance to food rejection produces meaningful data sets. The realism of the exercise gives students a view of problems that emerge in research. (KO)

  18. Solar collector apparatus having increased energy rejection during stagnation

    Science.gov (United States)

    Moore, Stanley W.

    1983-07-12

    The disclosure relates to an active solar collector having increased energy rejection during stagnation. The collector's glazing is brought into substantial contact with absorber during stagnation to increase re-emittance and thereby to maintain lower temperatures when the collector is not in operation.

  19. Peer rejection cues induce cardiac slowing after transition into adolescence

    NARCIS (Netherlands)

    Gunther Moor, B.; Bos, M.G.N.; Crone, E.A.; van der Molen, M.W.

    2014-01-01

    The present study examined developmental and gender differences in sensitivity to peer rejection across the transition into adolescence by examining beat-by-beat heart rate responses. Children between the ages of 8 and 14 years were presented with unfamiliar faces of age-matched peers and were asked

  20. Biased Self-Perceptions, Peer Rejection, and Aggression in Children

    Science.gov (United States)

    White, Bradley A.; Kistner, Janet A.

    2011-01-01

    This study examined whether children's biased self-perceptions of peer acceptance are associated in a linear or curvilinear fashion with aggression, whether associations are moderated by peer rejection status, and whether associations apply uniquely to reactive aggression. Children in the 4th through 7th grades completed a self-report measure on…

  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. Diffusion-based outlier rejection for underwater navigation

    DEFF Research Database (Denmark)

    Vike, Steinar; Jouffroy, Jerome

    This paper addresses the issue of rejecting spurious acoustic position measurements for the estimation of trajectories in underwater vehicle navigation. The method relies on the diffusion-based observer approach (Jouffroy and Opderbecke, 2004; 2005), which allows one to consider and process entire...

  3. Rejected Ballots and Democratic Consolidation in Ghana's Fourth ...

    African Journals Online (AJOL)

    The nation has received several commendations for the giant strides made towards democratic consolidation. Given the high incidence of rejected ballot papers that however characterizes the conduct of elections in Ghana, it is feared that the giant strides being made towards democratic consolidation may suffer severe set ...

  4. Rejected Ballots and Democratic Consolidation in Ghana's Fourth ...

    African Journals Online (AJOL)

    Nekky Umera

    Ransford Edward Van Gyampo - Department of Political Science,. University of Ghana, P. O. Box LG ... commendations for the giant strides made towards democratic consolidation. Given the high incidence of rejected .... posed to democratic consolidation and the conduct of free and fair elections by incidence such as the.

  5. Rejected Manuscripts in Publishers' Archives: Legal Rights and Access

    Science.gov (United States)

    Hamburger, Susan

    2011-01-01

    This article focuses on an analysis of how various archival repositories deal with rejected manuscripts in publishers' archives as part of existing collections and as potential donations, and includes suggestions for ways to provide access while maintaining the author's legal rights. Viewpoints from the journal editor, author, archivist, and…

  6. Improving harmonic rejection for spectrum sensing using crosscorrelation

    NARCIS (Netherlands)

    Oude Alink, M.S.; Kokkeler, Andre B.J.; Klumperink, Eric A.M.; Ru, Z.; Cheng, W.; Nauta, Bram

    2012-01-01

    Harmonic downmixing may cause a spectrum sensing device to erroneously flag parts of the spectrum as occupied. Receivers employing harmonic rejection (HR) rarely obtain more than 60 dB of HR, which may not be enough for spectrum sensing for dynamic spectrum access. We improve HR by employing two

  7. Peer Rejection Cues Induce Cardiac Slowing after Transition into Adolescence

    Science.gov (United States)

    Gunther Moor, Bregtje; Bos, Marieke G. N.; Crone, Eveline A.; van der Molen, Maurits W.

    2014-01-01

    The present study examined developmental and gender differences in sensitivity to peer rejection across the transition into adolescence by examining beat-by-beat heart rate responses. Children between the ages of 8 and 14 years were presented with unfamiliar faces of age-matched peers and were asked to predict whether they would be liked by the…

  8. Fate of Manuscripts Rejected From the Red Journal

    Energy Technology Data Exchange (ETDEWEB)

    Holliday, Emma B., E-mail: emmaholliday@gmail.com [Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Yang, George [The University of South Florida Morsani College of Medicine, Tampa, Florida (United States); Jagsi, Reshma [Department of Radiation Oncology, The University of Michigan, Ann Arbor, Michigan (United States); Hoffman, Karen E. [Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Bennett, Katherine Egan; Grace, Calley [Scientific Publications, American Society for Radiation Oncology, Fairfax, Virginia (United States); Zietman, Anthony L. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2015-01-01

    Purpose: To evaluate characteristics associated with higher rates of acceptance for original manuscripts submitted for publication to the International Journal of Radiation Oncology • Biology • Physics (IJROBP) and describe the fate of rejected manuscripts. Methods and Materials: Manuscripts submitted to the IJROBP from May 1, 2010, to August 31, 2010, and May 1, 2012, to August 31, 2012, were evaluated for author demographics and acceptance status. A PubMed search was performed for each IJROBP-rejected manuscript to ascertain whether the manuscript was ultimately published elsewhere. The Impact Factor of the accepting journal and the number of citations of the published manuscript were also collected. Results: Of the 500 included manuscripts, 172 (34.4%) were accepted and 328 (65.6%) were rejected. There was no significant difference in acceptance rates according to gender or degree of the submitting author, but there were significant differences seen based on the submitting author's country, rank, and h-index. On multivariate analysis, earlier year submitted (P<.0001) and higher author h-index (P=.006) remained significantly associated with acceptance into the IJROBP. Two hundred thirty-five IJROBP-rejected manuscripts (71.7%) were ultimately published in a PubMed-listed journal as of July 2014. There were no significant differences in any submitting author characteristics. Journals accepting IJROBP-rejected manuscripts had a lower median [interquartile range] 2013 impact factor compared with the IJROBP (2.45 [1.53-3.71] vs 4.176). The IJROBP-rejected manuscripts ultimately published elsewhere had a lower median [interquartile range] number of citations (1 [0-4] vs 6 [2-11]; P<.001), which persisted on multivariate analysis. Conclusions: The acceptance rate for manuscripts submitted to the IJROBP is approximately one-third, and approximately 70% of rejected manuscripts are ultimately published in other PubMed-listed journals, but these ultimate

  9. Involvement of the Fas system in liver allograft rejection.

    Science.gov (United States)

    Rivero, M; Crespo, J; Mayorga, M; Fábrega, E; Casafont, F; Pons-Romero, F

    2002-06-01

    Recent studies suggest that apoptosis is an important mechanism of cell death in the rejection of liver allografts and that this process is mediated via Fas. The aim of this study was to analyze the expression of the Fas system during the liver allograft rejection and its evolution after treatment. We evaluated 14 patients with liver allograft rejection before and after treatment. Fas immunostaining was performed by the labeled streptavidin-biotin peroxidase method using a 200-fold dilution of a monoclonal antibody. Assessment of apoptosis was determined by the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) technique on deparaffined liver samples. Serum levels of soluble Fas antigen (sFas) were detected by an enzyme immunoassay procedure. Twelve liver transplant patients without allograft rejection were analyzed as a control group. The number of hepatocytes expressing Fas antigen, the percentage of apoptotic hepatocytes, and the sFas levels were higher in patients with liver allograft rejection than in controls (27.9+/-23.1% vs 1.4+/-1.2%, p < 0.001; 2.2+/-0.9% vs 1.0+/-0.1%, p = 0.02; 24.2+/-39.6 vs 2.8+/-4.0 IU/ml, p = 0.03, respectively). There was a correlation between the levels of sFas, AST (r = 0.86, p < 0.001), ALT (r = 0.78, p = 0.02), and gamma-globulin levels (r = 0.86, p < 0.001). After the rejection treatment we found a significant decrease in the Fas antigen expression (18.6+/-13.3%, p < 0.05), TUNEL index (0.2+/-0.4, p < 0.05), and levels of sFas (9.9+/-30.25 IU/ml, p = 0.005). 1) The demonstration of hepatocytes with Fas antigen expression and the labeling of the nuclei by the TUNEL assay suggest that apoptosis mediated by the Fas system plays a role in the pathogenesis of liver allograft rejection. 2) The Fas expression and the sFas levels decreased in patients with treatment response.

  10. Peer rejection and physical health problems in early adolescence.

    Science.gov (United States)

    Brendgen, Mara; Vitaro, Frank

    2008-06-01

    Rejection from the peer group may constitute an important source of stress that may weaken children's immune system and leave them vulnerable to infection and physical illness. Controlling for family adversity and depressed mood, this study examined the predictive link between peer rejection and physical health problems, as well as the putative moderating effect of adolescents' reactivity/emotional negativity in this context. A total of 122 high school students (50% girls) were assessed over two consecutive years in grades 7 (time [T] 1) and 8 (time [T] 2). More than 90% of the participants were white and French speaking and were from average socioeconomic backgrounds. Physical health problems at T1 and T2 as well as depression symptoms at T1 were assessed using adolescent self-reports. Peer rejection at T1 was assessed through peer nominations. Reactivity/negative emotionality at T1 was assessed via teacher ratings. Family adversity at T1 was assessed via mother reports. Peer rejection at T1 predicted an increase in physical health problems from T1 to T2, even when controlling for physical health problems and depression symptoms at T1. This result, however, was only true for girls with moderate or high levels of reactivity/negative emotionality. For boys, peer rejection was unrelated to change in physical health problems. The present findings are in line with the diathesis stress model of disease and emphasize the need for health education programs that specifically target girls and that foster problem-solving skills to help vulnerable adolescents cope more effectively with peer conflict.

  11. Acute Bronchitis

    Science.gov (United States)

    ... of bronchitis: acute and chronic. Most cases of acute bronchitis get better within several days. But your cough ... that cause colds and the flu often cause acute bronchitis. These viruses spread through the air when people ...

  12. Development of CD3 cell quantitation algorithms for renal allograft biopsy rejection assessment utilizing open source image analysis software.

    Science.gov (United States)

    Moon, Andres; Smith, Geoffrey H; Kong, Jun; Rogers, Thomas E; Ellis, Carla L; Farris, Alton B Brad

    2017-11-08

    Renal allograft rejection diagnosis depends on assessment of parameters such as interstitial inflammation; however, studies have shown interobserver variability regarding interstitial inflammation assessment. Since automated image analysis quantitation can be reproducible, we devised customized analysis methods for CD3+ T-cell staining density as a measure of rejection severity and compared them with established commercial methods along with visual assessment. Renal biopsy CD3 immunohistochemistry slides (n = 45), including renal allografts with various degrees of acute cellular rejection (ACR) were scanned for whole slide images (WSIs). Inflammation was quantitated in the WSIs using pathologist visual assessment, commercial algorithms (Aperio nuclear algorithm for CD3+ cells/mm(2) and Aperio positive pixel count algorithm), and customized open source algorithms developed in ImageJ with thresholding/positive pixel counting (custom CD3+%) and identification of pixels fulfilling "maxima" criteria for CD3 expression (custom CD3+ cells/mm(2)). Based on visual inspections of "markup" images, CD3 quantitation algorithms produced adequate accuracy. Additionally, CD3 quantitation algorithms correlated between each other and also with visual assessment in a statistically significant manner (r = 0.44 to 0.94, p = 0.003 to CD3-stained slides using various open source image analysis algorithms presents salient correlations with established methods of CD3 quantitation. These analysis techniques are promising and highly customizable, providing a form of on-slide "flow cytometry" that can facilitate additional diagnostic accuracy in tissue-based assessments.

  13. Tunable rejection filters with ultra-wideband using zeroth shear mode plate wave resonators

    Science.gov (United States)

    Kadota, Michio; Sannomiya, Toshio; Tanaka, Shuji

    2017-07-01

    This paper reports wide band rejection filters and tunable rejection filters using ultra-wideband zeroth shear mode (SH0) plate wave resonators. The frequency range covers the digital TV band in Japan that runs from 470 to 710 MHz. This range has been chosen to meet the TV white space cognitive radio requirements of rejection filters. Wide rejection bands were obtained using several resonators with different frequencies. Tunable rejection filters were demonstrated using Si diodes connected to the band rejection filters. Wide tunable ranges as high as 31% were measured by applying a DC voltage to the Si diodes.

  14. Quantification of C4d deposition and hepatitis C virus RNA in tissue in cases of graft rejection and hepatitis C recurrence after liver transplantation

    Directory of Open Access Journals (Sweden)

    Alice Tung Wan Song

    2015-02-01

    Full Text Available Histology is the gold standard for diagnosing acute rejection and hepatitis C recurrence after liver transplantation. However, differential diagnosis between the two can be difficult. We evaluated the role of C4d staining and quantification of hepatitis C virus (HCV RNA levels in liver tissue. This was a retrospective study of 98 liver biopsy samples divided into four groups by histological diagnosis: acute rejection in patients undergoing liver transplant for hepatitis C (RejHCV+, HCV recurrence in patients undergoing liver transplant for hepatitis C (HCVTx+, acute rejection in patients undergoing liver transplant for reasons other than hepatitis C and chronic hepatitis C not transplanted (HCVTx-. All samples were submitted for immunohistochemical staining for C4d and HCV RNA quantification. Immunoexpression of C4d was observed in the portal vessels and was highest in the HCVTx- group. There was no difference in C4d expression between the RejHCV+ and HCVTx+ groups. However, tissue HCV RNA levels were higher in the HCVTx+ group samples than in the RejHCV+ group samples. Additionally, there was a significant correlation between tissue and serum levels of HCV RNA. The quantification of HCV RNA in liver tissue might prove to be an efficient diagnostic test for the recurrence of HCV infection.

  15. Culture-Based Rejection of Taboo-Infringing Imports

    Directory of Open Access Journals (Sweden)

    Brice William D.

    2017-09-01

    Full Text Available This empirical study analyzes the cultural basis of the United States market response to imported Spanish products that seem to violate strongly-held cultural taboos. Survey responses were obtained from students in two contrasting majors, Art and Business, in two distinct cities and universities, i.e. Little Rock at the University of Arkansas, and Dominguez Hills at California State University. The study focused on a baby doll marketed to piggy-back on the new movement towards breastfeeding babies. Although accepted in its original European market, the United States media reports strong moral objections to this product among U. S. citizens. The toy was overwhelmingly rejected in some, but not all, population sub-groups. This study attempts to discern the cultural basis for product rejection by comparing responses between regions, college majors, genders and gender/major combinations. Differences in acceptance between groups are correlated with specific cultural constructs.

  16. Heat pipe radiator. [for spacecraft waste heat rejection

    Science.gov (United States)

    Swerdling, B.; Alario, J.

    1973-01-01

    A 15,000 watt spacecraft waste heat rejection system utilizing heat pipe radiator panels was investigated. Of the several concepts initially identified, a series system was selected for more in-depth analysis. As a demonstration of system feasibility, a nominal 500 watt radiator panel was designed, built and tested. The panel, which is a module of the 15,000 watt system, consists of a variable conductance heat pipe (VCHP) header, and six isothermalizer heat pipes attached to a radiating fin. The thermal load to the VCHP is supplied by a Freon-21 liquid loop via an integral heat exchanger. Descriptions of the results of the system studies and details of the radiator design are included along with the test results for both the heat pipe components and the assembled radiator panel. These results support the feasibility of using heat pipes in a spacecraft waste heat rejection system.

  17. Performance Evaluation of Air-Based Heat Rejection Systems

    Directory of Open Access Journals (Sweden)

    Hannes Fugmann

    2015-01-01

    Full Text Available On the basis of the Number of Transfer Units (NTU method a functional relation between electric power for fans/pumps and effectiveness in dry coolers and wet cooling towers is developed. Based on this relation, a graphical presentation method of monitoring and simulation data of heat rejection units is introduced. The functional relation allows evaluating the thermodynamic performance of differently sized heat rejection units and comparing performance among them. The method is used to evaluate monitoring data of dry coolers of different solar cooling field projects. The novelty of this approach is that performance rating is not limited by a design point or standardized operating conditions of the heat exchanger, but is realizable under flexible conditions.

  18. Practical Active Disturbance Rejection Solution for Furnace Temperature Control System

    Directory of Open Access Journals (Sweden)

    Jian Huan Su

    2014-08-01

    Full Text Available A practical active disturbance rejection control (ADRC solution is proposed for the furnace temperature system. Employing a linear reduced-order model with optimized parameters, the practical ADRC is simple to use, easy to tune and energy-efficient in dealing with the uncertainties and disturbances in plant dynamics. Through the order reduction in both the plant model and the state observer, we develop a first order extended state observer for estimating in real-time the total value of the external and internal disturbances. The practical and standard ADRCs outperform the Smith Predictor and the PID controller in disturbance-rejection and robustness; however, the practical ADRC has fewer adjustable parameters and significantly smaller energy consumption than the standard ADRC, making it a viable candidate for industrial applications.

  19. On the centrality of disturbance rejection in automatic control.

    Science.gov (United States)

    Gao, Zhiqiang

    2014-07-01

    In this paper, it is shown that the problem of automatic control is, in essence, that of disturbance rejection, with the notion of disturbance generalized to symbolize the uncertainties, both internal and external to the plant. A novel, unifying concept of disturbance rejector is proposed to compliment the traditional notion of controller. The new controller-rejector pair is shown to be a powerful organizing principle in the realm of automatic control, leading to a Copernican moment where the model-centric design philosophy is replaced by the one that is control-centric in the following sense: the controller is designed for a canonical model and is fixed; the difference between the plant and the canonical model is deemed as disturbance and rejected. © 2013 ISA. Published by Elsevier Ltd. All rights reserved.

  20. Active disturbance rejection in large flexible space structures

    Science.gov (United States)

    Parlos, Alexander G.; Sunkel, John W.

    1990-01-01

    The design of an active control law for the rejection of persistent disturbances, in large space structures is presented. The control system design approach is based on a deterministic model of the disturbances and it optimizes the magnitude of the disturbance that the structure can tolerate without violating certain predetermined constraints. In addition to closed-loop stability, the explicit treatment of state, control, and control rate constraints, such as structural displacement and control actuator effort, guarantees that the final design will exhibit desired performance characteristics. The technique is applied to a simple two-bay truss structure, and its response is compared with that obtained using a linear-quadratic-Gaussian/loop-transfer-recovery (LQG/LTR) compensator. Preliminary results indicate that the proposed control system can reject persistent disturbances of greater magnitude by utilizing most of the available control, while limiting the structural displacements to within desired tolerances.

  1. Modified active disturbance rejection control for time-delay systems.

    Science.gov (United States)

    Zhao, Shen; Gao, Zhiqiang

    2014-07-01

    Industrial processes are typically nonlinear, time-varying and uncertain, to which active disturbance rejection control (ADRC) has been shown to be an effective solution. The control design becomes even more challenging in the presence of time delay. In this paper, a novel modification of ADRC is proposed so that good disturbance rejection is achieved while maintaining system stability. The proposed design is shown to be more effective than the standard ADRC design for time-delay systems and is also a unified solution for stable, critical stable and unstable systems with time delay. Simulation and test results show the effectiveness and practicality of the proposed design. Linear matrix inequality (LMI) based stability analysis is provided as well. © 2013 ISA Published by ISA All rights reserved.

  2. ST2 IN REJECTION OF THE TRANSPLANTED HEART

    Directory of Open Access Journals (Sweden)

    O. P. Shevchenko

    2015-01-01

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

  3. Rejection sensitivity and disruption of attention by social threat cues.

    Science.gov (United States)

    Berenson, Kathy R; Gyurak, Anett; Ayduk, Ozlem; Downey, Geraldine; Garner, Matthew J; Mogg, Karin; Bradley, Brendan P; Pine, Daniel S

    2009-12-01

    Two studies tested the hypothesis that Rejection Sensitivity (RS) increases vulnerability to disruption of attention by social threat cues, as would be consistent with prior evidence that it motivates individuals to prioritize detecting and managing potential rejection at a cost to other personal and interpersonal goals. In Study 1, RS predicted disruption of ongoing goal-directed attention by social threat but not negative words in an Emotional Stroop task. In Study 2, RS predicted attentional avoidance of threatening but not pleasant faces in a Visual Probe task. Threat-avoidant attention was also associated with features of borderline personality disorder. This research extends understanding of processes by which RS contributes to a self-perpetuating cycle of interpersonal problems and distress.

  4. Background rejection in NEXT using deep neural networks

    CERN Document Server

    Renner, J.

    2017-01-01

    We investigate the potential of using deep learning techniques to reject background events in searches for neutrinoless double beta decay with high pressure xenon time projection chambers capable of detailed track reconstruction. The differences in the topological signatures of background and signal events can be learned by deep neural networks via training over many thousands of events. These networks can then be used to classify further events as signal or background, providing an additional background rejection factor at an acceptable loss of efficiency. The networks trained in this study performed better than previous methods developed based on the use of the same topological signatures by a factor of 1.2 to 1.6, and there is potential for further improvement.

  5. Microtab dynamic modelling for wind turbine blade load rejection

    OpenAIRE

    MacQuart, Terence; Maheri, Alireza; Busawon, Krishna

    2014-01-01

    A dynamic model characterising the effect of microtab deployment on the aerodynamics of its base aerofoil is presented. The developed model predicts the transient aerodynamic coefficients consistent with the experimental and computational data reported in the literature. The proposed model is then used to carry out investigation on the effectiveness of microtabs in load alleviation and lifespan increase of wind turbine blades. Simulating a bang–bang controller, different load rejection scenar...

  6. Vibroacoustic Analysis of Large Heat Rejection Radiators for Future Spacecraft

    Science.gov (United States)

    Larko, Jeffrey M.; McNelis, Mark E.; Hughes, William O.

    2006-01-01

    Spacecraft structures such as antennas, solar arrays and radiator panels significantly respond to high acoustic levels seen at lift-off. Some future spacecraft may utilize nuclear electric propulsion that require large radiator panels to reject waste heat. A vibroacoustic assessment was performed for two different radiator panel designs. Results from the analysis of the two designs using different analytical approaches are presented and discussed.

  7. Breast Rejection: A Little-Appreciated Cause of Lactation Failure

    OpenAIRE

    Newman, Jack; Wilmott, Beth

    1990-01-01

    Breast rejection is a common cause of breast-feeding failure. We describe 51 mother-infant pairs who visited the Hospital for Sick Children breast-feeding clinic because the baby refused to take the breast. Management was successful in 21 (40%), partially successful in 11 cases (22%), and unsuccessful in 16 (31%). (Three mothers were lost to follow up.) We believe that the early introduction of bottles results in the baby's developing an ineffective suckle, which then causes frustration when ...

  8. Reverse osmosis membrane of high urea rejection properties. [water purification

    Science.gov (United States)

    Johnson, C. C.; Wydeven, T. J. (Inventor)

    1980-01-01

    Polymeric membranes suitable for use in reverse osmosis water purification because of their high urea and salt rejection properties are prepared by generating a plasma of an unsaturated hydrocarbon monomer and nitrogen gas from an electrical source. A polymeric membrane is formed by depositing a polymer of the unsaturated monomer from the plasma onto a substrate, so that nitrogen from the nitrogen gas is incorporated within the polymer in a chemically combined form.

  9. Domestic violence and rejection of LGBT children in Serbia

    OpenAIRE

    Mršević, Zorica

    2015-01-01

    The paper provides analysis of different forms of violence against LGBT children within the regime of so-called forced normalization (Butler) committed by their parents and other close relatives. These regimes are often rigid normative type, much less of the flexible type of normalizing. The term 'production of the body' in the case of domestic violence against LGBT chil­dren comprises rejection, threats, forced medical treatment, various forms of physical and psychological violence and eject...

  10. Exploiting Reject Option in Classification for Social Discrimination Control

    KAUST Repository

    Kamiran, Faisal

    2017-09-29

    Social discrimination is said to occur when an unfavorable decision for an individual is influenced by her membership to certain protected groups such as females and minority ethnic groups. Such discriminatory decisions often exist in historical data. Despite recent works in discrimination-aware data mining, there remains the need for robust, yet easily usable, methods for discrimination control. In this paper, we utilize reject option in classification, a general decision theoretic framework for handling instances whose labels are uncertain, for modeling and controlling discriminatory decisions. Specifically, this framework permits a formal treatment of the intuition that instances close to the decision boundary are more likely to be discriminated in a dataset. Based on this framework, we present three different solutions for discrimination-aware classification. The first solution invokes probabilistic rejection in single or multiple probabilistic classifiers while the second solution relies upon ensemble rejection in classifier ensembles. The third solution integrates one of the first two solutions with situation testing which is a procedure commonly used in the court of law. All solutions are easy to use and provide strong justifications for the decisions. We evaluate our solutions extensively on four real-world datasets and compare their performances with previously proposed discrimination-aware classifiers. The results demonstrate the superiority of our solutions in terms of both performance and flexibility of applicability. In particular, our solutions are effective at removing illegal discrimination from the predictions.

  11. Dynamic positioning system based on active disturbance rejection technology

    Science.gov (United States)

    Lei, Zhengling; Guo, Chen; Fan, Yunsheng

    2015-08-01

    A dynamically positioned vessel, by the International Maritime Organization (IMO) and the certifying class societies (DNV, ABS, LR, etc.), is defined as a vessel that maintains its position and heading (fixed location or pre-determined track) exclusively by means of active thrusters. The development of control technology promotes the upgrading of dynamic positioning (DP) systems. Today there are two different DP systems solutions available on the market: DP system based on PID regulator and that based on model-based control. Both systems have limited disturbance rejection capability due to their design principle. In this paper, a new DP system solution is proposed based on Active Disturbance Rejection Control (ADRC) technology. This technology is composed of Tracking-Differentiator (TD), Extended State Observer (ESO) and Nonlinear Feedback Combination. On one hand, both TD and ESO can act as filters and can be used in place of conventional filters; on the other hand, the total disturbance of the system can be estimated and compensated by ESO, which therefore enhances the system's disturbance rejection capability. This technology's advantages over other methods lie in two aspects: 1) This method itself can not only achieve control objectives but also filter noisy measurements without other specialized filters; 2) This method offers a new useful approach to suppress the ocean disturbance. The simulation results demonstrate the effectiveness of the proposed method.

  12. 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.

  13. An author’s guide to submission, revision and rejection

    Science.gov (United States)

    Smart, Pippa

    2015-01-01

    ‘Continuous effort, not strength or intelligence, is the key to understanding our potential.’ Winston Churchill The sting of rejection is nasty. However, when you get that letter (which you will), remember you will be in esteemed company. Many of us would like to publish in Science or Nature but what better revenge when they reject you than a Nobel Prize! This is exactly what happened to Hans Krebs, the biochemist who won the Nobel Prize in 1953 for discovering the citric acid cycle, commonly known as the Krebs cycle. Krebs submitted his findings to Nature but was faced with rejection. Never has Frank Sinatra’s famous quote been truer: ‘The best revenge is massive success.’ Nature has admitted to many other such faux pas in its publishing history and it is not unique in its misjudgements. Publishing is a game of risk-taking behaviour and strategy. Authors must convince editors and referees that their work is worthy of publishing. When journals do not publish this work, authors must remember the value of their manuscript and persist in finding it another home. JYOTI SHAH Commissioning Editor PMID:26492899

  14. Enhanced water transport and salt rejection through hydrophobic zeolite pores

    Science.gov (United States)

    Humplik, Thomas; Lee, Jongho; O’Hern, Sean; Laoui, Tahar; Karnik, Rohit; Wang, Evelyn N.

    2017-12-01

    The potential of improvements to reverse osmosis (RO) desalination by incorporating porous nanostructured materials such as zeolites into the selective layer in the membrane has spurred substantial research efforts over the past decade. However, because of the lack of methods to probe transport across these materials, it is still unclear which pore size or internal surface chemistry is optimal for maximizing permeability and salt rejection. We developed a platform to measure the transport of water and salt across a single layer of zeolite crystals, elucidating the effects of internal wettability on water and salt transport through the ≈5.5 Å pores of MFI zeolites. MFI zeolites with a more hydrophobic (i.e., less attractive) internal surface chemistry facilitated an approximately order of magnitude increase in water permeability compared to more hydrophilic MFI zeolites, while simultaneously fully rejecting both potassium and chlorine ions. However, our results also demonstrated approximately two orders of magnitude lower permeability compared to molecular simulations. This decreased performance suggests that additional transport resistances (such as surface barriers, pore collapse or blockages due to contamination) may be limiting the performance of experimental nanostructured membranes. Nevertheless, the inclusion of hydrophobic sub-nanometer pores into the active layer of RO membranes should improve both the water permeability and salt rejection of future RO membranes (Fasano et al 2016 Nat. Commun. 7 12762).

  15. Loss of Myeloid Related Protein-8/14 Exacerbates Cardiac Allograft Rejection

    Science.gov (United States)

    Shimizu, Koichi; Libby, Peter; Rocha, Viviane Z.; Folco, Eduardo J.; Shubiki, Rica; Grabie, Nir; Jang, Sunyoung; Lichtman, Andrew H.; Shimizu, Ayako; Hogg, Nancy; Simon, Daniel I.; Mitchell, Richard N.; Croce, Kevin

    2011-01-01

    Background The calcium-binding proteins myeloid-related protein (MRP)-8 (S100A8) and MRP-14 (S100A9) form MRP-8/14 heterodimers (S100A8/A9, calprotectin) that regulate myeloid cell function and inflammatory responses, and serve as early serum markers for monitoring acute allograft rejection. Despite functioning as a pro-inflammatory mediator, the pathophysiological role of MRP-8/14 complexes in cardiovascular disease is incompletely defined. This study investigated the role of MRP-8/14 in cardiac allograft rejection using MRP-14-deficient mice (MRP14-/-) that lack MRP-8/14 complexes. Methods and Results We examined parenchymal rejection (PR) after major histocompatibility complex (MHC) class II allomismatched cardiac transplantation (bm12 donor heart and B6 recipients) in wild-type (WT) and MRP14-/- recipients. Allograft survival averaged 5.9 ± 2.9 weeks (n=10) in MRP14-/- recipients, compared to > 12 weeks (n = 15, p MRP14-/- recipients had significantly higher PR scores (2.8 ± 0.8, n=8) than did WT recipients (0.8 ± 0.8, n=12, pMRP14-/- recipients had significantly increased T-cell and macrophage infiltration, as well as increased mRNA levels of IFN-γ and IFN-γ–associated chemokines (CXCL9, CXCL10, and CXCL11), IL-6, and IL-17, with significantly higher levels of Th17 cells. MRP14-/- recipients also had significantly more lymphocytes in the adjacent paraaortic lymph nodes than did WT recipients (cell number per lymph node: 23.7 ± 0.7 × 105 for MRP14-/- vs. 6.0 ± 0.2 × 105 for WT, p MRP14-/- recipients of bm12 hearts expressed significantly higher levels of the co-stimulatory molecules CD80 and CD86 than did those of WT recipients 2 weeks after transplantation. Mixed leukocyte reactions using allo-EC-primed MRP14-/- DCs resulted in significantly higher antigen-presenting function than reactions using WT DCs. Ovalbumin-primed MRP14-/- DCs augmented proliferation of OT-II CD4+ T cells with increased IL-2 and IFN-γ production. Cardiac allografts of B6 MHC

  16. Comparison of the Image Rejection between the Passive and the Gilbert Mixer

    DEFF Research Database (Denmark)

    Wang, Xiaoyan; Andreani, Pietro

    2004-01-01

    This paper presents a comparison of the image rejection between Gilbert mixer and the passive mixer. A simple model for mixers is set up, and the image rejection performance of passive and Gilbert mixer is analyzed based on it. Simulations and calculations were done to compare the image rejection...... of the two mixers. The results show that the Gilbert mixer, comparing with the passive one, shows a stronger rejection to the amplitude error of the quadrature signals at its input....

  17. X-ray film reject rate analysis at eight selected government hospitals ...

    African Journals Online (AJOL)

    The collected data were then entered into a database for analysis using descriptive statistics. Results: Reject rate was calculated in eight governmental hospitals across all plain film examinations. The overall reject rate was 374 (3.1 %) in 12,165 x-ray exposures. Total reject rate by hospital showed 10.5% for Zewditu and ...

  18. Personal and Appearance-Based Rejection Sensitivity in Body Dysmorphic Disorder

    Science.gov (United States)

    Kelly, Megan M.; Didie, Elizabeth R.; Phillips, Katharine A.

    2014-01-01

    Although rejection sensitivity may be an important feature of body dysmorphic disorder (BDD), no studies have examined rejection sensitivity in a clinical sample and compared types of rejection sensitivity in individuals with BDD. Personal and appearance-based rejection sensitivity scores in forty-six patients diagnosed with BDD were compared with published norms. Associations between rejection sensitivity, BDD severity, and other clinical variables were examined. Personal and appearance-based rejection sensitivity scores were 0.6 and 1.1 standard deviation units above published norms, respectively. Greater personal rejection sensitivity was associated with more severe BDD and depressive symptoms, poorer mental health, general health, and physical and social functioning. Greater appearance-based rejection sensitivity was associated with more severe BDD and depressive symptoms, and poorer general health. Appearance-based rejection sensitivity contributed more unique variance to BDD severity than personal rejection sensitivity did; however, personal rejection sensitivity contributed more unique variance to general health than appearance-based rejection sensitivity did. PMID:24958661

  19. Rejection Sensitivity and College Student Depression: Findings and Implications for Counseling

    Science.gov (United States)

    Mellin, Elizabeth A.

    2008-01-01

    This study examined whether rejection sensitivity, or the fear of interpersonal rejection, was related to depression among college students. The regression model that resulted from the study indicated that level of rejection sensitivity accounted for approximately 11% of variance in depression among students in the research. Implications for…

  20. Personal and appearance-based rejection sensitivity in body dysmorphic disorder.

    Science.gov (United States)

    Kelly, Megan M; Didie, Elizabeth R; Phillips, Katharine A

    2014-06-01

    Although rejection sensitivity may be an important feature of body dysmorphic disorder (BDD), no studies have examined rejection sensitivity in a clinical sample and compared types of rejection sensitivity in individuals with BDD. Personal and appearance-based rejection sensitivity scores in forty-six patients diagnosed with BDD were compared with published norms. Associations between rejection sensitivity, BDD severity, and other clinical variables were examined. Personal and appearance-based rejection sensitivity scores were 0.6 and 1.1 standard deviation units above published norms, respectively. Greater personal rejection sensitivity was associated with more severe BDD and depressive symptoms, poorer mental health, general health, and physical and social functioning. Greater appearance-based rejection sensitivity was associated with more severe BDD and depressive symptoms, and poorer general health. Appearance-based rejection sensitivity contributed more unique variance to BDD severity than personal rejection sensitivity did; however, personal rejection sensitivity contributed more unique variance to general health than appearance-based rejection sensitivity did. Published by Elsevier Ltd.

  1. Effects of Peer Group Rejection and a New Group's Norms on Children's Intergroup Attitudes

    Science.gov (United States)

    Nesdale, Drew; Maass, Anne; Kiesner, Jeff; Durkin, Kevin; Griffiths, Judith; James, Bre

    2009-01-01

    This study examined the effects of peer group rejection and a new group's norms on 7- and 9-year old children's intergroup attitudes. Children (N = 82) were rejected or accepted by an initial group, then accepted by a new group that had a norm of inclusion versus exclusion towards others. Results showed that rejected compared with accepted…

  2. The Regulating Role of Negative Emotions in Children's Coping with Peer Rejection

    Science.gov (United States)

    Goodman, Kimberly L.; Southam-Gerow, Michael A.

    2010-01-01

    This study examined the role of emotions as predictors of children's coping responses to peer rejection experiences. Children ages 7-12 (N = 79) completed questionnaires to assess emotional and coping responses to peer rejection scenarios. This study examined three coping factors specific to peer rejection (positive reappraisal, ruminative coping,…

  3. Language Skills, Peer Rejection, and the Development of Externalizing Behavior from Kindergarten to Fourth Grade

    Science.gov (United States)

    Menting, Barbara; Van Lier, Pol A. C.; Koot, Hans M.

    2011-01-01

    Background: Children with poorer language skills are more likely to show externalizing behavior problems, as well as to become rejected by their peers. Peer rejection has also been found to affect the development of externalizing behavior. This study explored the role of peer rejection in the link between language skills and the development of…

  4. Language skills, peer rejection, and the development of externalizing behavior from kindergarten to fourth grade

    NARCIS (Netherlands)

    Menting, B.; van Lier, P.A.C.; Koot, H.M.

    2011-01-01

    Background: Children with poorer language skills are more likely to show externalizing behavior problems, as well as to become rejected by their peers. Peer rejection has also been found to affect the development of externalizing behavior. This study explored the role of peer rejection in the link

  5. Vicarious Group-Based Rejection : Creating a Potentially Dangerous Mix of Humiliation, Powerlessness, and Anger

    NARCIS (Netherlands)

    Veldhuis, Tinka M.; Gordijn, Ernestine H.; Veenstra, Rene; Lindenberg, Siegwart

    2014-01-01

    Rejection can convey that one is seen as inferior and not worth bothering with. Is it possible for people to feel vicariously rejected in this sense and have reactions that are similar to those following personal rejection, such as feeling humiliated, powerless, and angry? A study on personal

  6. Extension of the Rejection Sensitivity Construct to the Interpersonal Functioning of Gay Men

    Science.gov (United States)

    Pachankis, John E.; Goldfried, Marvin R.; Ramrattan, Melissa E.

    2008-01-01

    On the basis of recent evidence suggesting that gay men are particularly likely to fear interpersonal rejection, the authors set out to extend the "rejection sensitivity" construct to the mental health concerns of gay men. After establishing a reliable and valid measure of the gay-related rejection sensitivity construct, the authors use this to…

  7. Acute rejection before cytomegalovirus infection enhances von Willebrand factor and soluble VCAM-1 in blood

    NARCIS (Netherlands)

    Kas-Deelen, AM; Harmsen, MC; de Maar, EF; Oost-Kort, WW; Tervaert, JWC; van der Meer, J; van Son, WJ; The, TH

    2000-01-01

    Background. Human cytomegalovirus (HCMV) infections in transplantation patients are associated with vascular endothelial damage. This is reflected by the appearance of cytomegalic endothelial cells (CECs) and noninfected endothelial cells (ECs) in blood. To get more insight in the extent of vascular

  8. Expression of granzyme A and B proteins by cytotoxic lymphocytes involved in acute renal allograft rejection

    NARCIS (Netherlands)

    Kummer, J. A.; Wever, P. C.; Kamp, A. M.; ten Berge, I. J.; Hack, C. E.; Weening, J. J.

    1995-01-01

    Granzymes A and B are serine-proteinases stored in the granules of activated cytotoxic T-lymphocytes and natural killer (NK) cells. Expression of granzymes in tissues can be used as an activation marker for cytotoxic cells. Using mAbs specific for human granzyme A or B in immunohistochemical

  9. Thrombalexins: Cell-Localized Inhibition of Thrombin and Its Effects in a Model of High-Risk Renal Transplantation.

    Science.gov (United States)

    Karegli, J; Melchionna, T; Farrar, C A; Greenlaw, R; Smolarek, D; Horsfield, C; Charif, R; McVey, J H; Dorling, A; Sacks, S H; Smith, R A G

    2017-01-01

    Allograft transplantation into sensitized recipients with antidonor antibodies results in accelerated antibody-mediated rejection (AMR), complement activation, and graft thrombosis. We have developed a membrane-localizing technology of wide applicability that enables therapeutic agents, including anticoagulants, to bind to cell surfaces and protect the donor endothelium. We describe here how this technology has been applied to thrombin inhibitors to generate a novel class of drugs termed thrombalexins (TLNs). Using a rat model of hyperacute rejection, we investigated the potential of one such inhibitor (thrombalexin-1 [TLN-1]) to prevent acute antibody-mediated thrombosis in the donor organ. TLN-1 alone was able to reduce intragraft thrombosis and significantly delay rejection. The results confirm a pivotal role for thrombin in AMR in vivo. This approach targets donor organs rather than the recipient and is intended to be directly translatable to clinical use. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  10. Active rejection of persistent disturbances in flexible space structures

    Science.gov (United States)

    Hwang, Cheng-Neng; Jayasuriya, Suhada; Parlos, Alexander G.; Sunkel, John W.

    1990-01-01

    A dynamic compensator for active rejection of persistent disturbances in flexible space structures is designed on the principle of the H(infinity)-optimization of the sensitivity transfer function matrix. A general state space solution is formulated to the multiinput multioutput H(infinity)-optimal control problem, allowing the use of the H(infinity)-optimal synthesis algorithm for the state-space models of space structures that result from model order reduction. Disturbances encountered in flexible space structures, such as shuttle docking, are investigated using the high-mode and the reduced-order models of a cantilevered two-bay truss, demonstrating the applicability of the H(infinity)-optimal approach.

  11. An observer with controller to detect and reject disturbances

    Science.gov (United States)

    de Jesús Rubio, José; Meléndez, Fidel; Figueroa, Maricela

    2014-03-01

    In this paper, a novel states observer is designed. This observer not only estimates the states, but also detects the disturbances by creating estimated signals. Then, both the observed states and detected disturbances are used in a control law to reject the disturbances, avoiding the requirement to know the states and disturbances. The observer is designed by the combination of the poles assignation and geometric techniques. Both the observer and controller work simultaneously. The proposed method is applied in an active suspension system and a liquid-level hydraulic system.

  12. Active disturbance rejection control of temperature for ultrastable optical cavities.

    Science.gov (United States)

    Pizzocaro, Marco; Calonico, Davide; Calosso, Claudio; Clivati, Cecilia; Costanzo, Giovanni A; Levi, Filippo; Mura, Alberto

    2013-02-01

    This paper describes the application of a novel active disturbance rejection control (ADRC) to the stabilization of the temperature of two ultra-stable Fabry-Perot cavities. The cavities are 10 cm long and entirely made of ultralow- expansion glass. The control is based on a linear extended state observer that estimates and compensates the disturbance in the system in real time. The resulting control is inherently robust and easy to tune. A digital implementation of ADRC gives a temperature instability of 200 μK at one day of integration time.

  13. Disturbance rejection in space applications: Problems and solutions

    Science.gov (United States)

    Canuto, Enrico; Molano-Jimenez, Andrés; Perez-Montenegro, Carlos

    2012-03-01

    Navigation, control and guidance of the propulsive phase of planetary landing, e.g. on Mars (or the Moon), with a soft landing being the only target, are driven by Inertial Measurement Units and a radar altimeter/velocimeter. Their measurements are affected by bias and scale errors. The latter ones are aggravated by the attitude navigation error as it accumulates during the ballistic (and aerodynamic) flight after orbiter separation and couples for most of the descent trajectory with the vehicle axis inclination from the local vertical direction. By complementing the center-of-mass dynamics with appropriate disturbance state equations driven by noise vectors and estimating the noise from the model error (plant measurements minus model output), scale errors and bias can be retrieved in real time in the form of disturbance state variables. Although a similar complement is adopted in the standard navigation algorithms, it takes the form of an output disturbance, which may lead to unobservability. In this paper instead, the disturbance complement is designed to be fully observable, which may require that the derivatives of smooth systematic errors be pushed up to the command channel (a form of back-stepping). It is then viable, unlike standard navigation, to eliminate them from position and velocity tracking errors through disturbance rejection, under appropriate convergence conditions and sensor layout. It will, however, be demonstrated in this paper that the same result cannot be achieved under pure feedback control. Since constant errors (bias) become zero through back-stepping, a well known fact derives: bias can only be eliminated by disposing of supplementary sensors. To further enlighten and solve the question of bias rejection, a further case study is treated. The attitude control of drag-free satellites is considered, where fine accelerometers allow for the rejection of wide-band aerodynamic torques (think of low-Earth orbit spacecrafts) at the price of

  14. The experimental treatment of corneal graft rejection with the interleukin-1 receptor antagonist (IL-1ra gene.

    Directory of Open Access Journals (Sweden)

    Jin Yuan

    Full Text Available PURPOSE: To investigate the protective effects of interleukin-1 receptor antagonist (IL-1ra gene transfer in a rat model of corneal graft rejection. METHODS: We constructed a recombinant plasmid (pcDNA3.1-hIL-1ra with high IL-1ra expression in eukaryotic cells. Using a Wistar-SD rat model of corneal graft rejection, we examined the effects of IL-1ra in vivo after cationic polymer jetPEI-mediated nonviral gene delivery. Four groups were included: negative controls (group I, n = 20, pcDNA3.1-hIL-1ra corneal stromal injection (group II, n = 34, pcDNA3.1-hIL-1ra anterior chamber injection (group III, n = 34, and 500 µg/ml IL-1ra protein subconjunctiva injection (group IV, n = 20. IL-1ra expression after transfection was evaluated by real-time polymerase chain reaction (RT-PCR and western blotting. The rejection indices of corneal grafts were analysed in the different groups. The expression levels of transforming growth factor β1 (TGF-β1, inflammatory chemokines including RANTES, interleukin-1 (IL-1 and the numbers of CD4+ and CD8+ T cells in the grafts were determined by biochemical assays at different time points after corneal transplantation. RESULTS: Various degrees of inflammatory cell infiltration and graft neovascularisation were observed by histopathology. After injecting the pcDNA3.1-hIL-1ra plasmid into the cornea, IL-1ra mRNA and protein expression was detected in the corneal stroma and reached a peak on day 3. The graft survival curves indicated that the corneal transparency rates of grafts in the IL-1ra gene-treated group and the IL-1ra protein-treated group were higher compared with the untreated group (P<0.05. During the period of acute rejection, TGF-β1, RANTES, IL-1α and IL-1β levels in the grafts in the IL-1ra treatment groups were lower than the control group (P<0.05. CD4+ and CD8+ T cell counts were reduced significantly in the corneal grafts of groups II, III and IV compared with group I (P<0.05. CONCLUSION

  15. Emergency surgical treatment of complicated acute pancreatitis after kidney transplantation with acute rejection: Case report and literature review

    Directory of Open Access Journals (Sweden)

    Dušan Klos

    2016-06-01

    Conclusions: With regard to the patient's comorbidities, early surgical therapy was indicated – drainage and closed lavage and immunosuppressive medication as a suspected tobe ethiological factor was discontinued. This course of treatment led to a complete recovery with preservation of good function of the cadaverous kidney.

  16. The identification of novel potential injury mechanisms and candidate biomarkers in renal allograft rejection by quantitative proteomics.

    Science.gov (United States)

    Sigdel, Tara K; Salomonis, Nathan; Nicora, Carrie D; Ryu, Soyoung; He, Jintang; Dinh, Van; Orton, Daniel J; Moore, Ronald J; Hsieh, Szu-Chuan; Dai, Hong; Thien-Vu, Minh; Xiao, Wenzhong; Smith, Richard D; Qian, Wei-Jun; Camp, David G; Sarwal, Minnie M

    2014-02-01

    Early transplant dysfunction and failure because of immunological and nonimmunological factors still presents a significant clinical problem for transplant recipients. A critical unmet need is the noninvasive detection and prediction of immune injury such that acute injury can be reversed by proactive immunosuppression titration. In this study, we used iTRAQ -based proteomic discovery and targeted ELISA validation to discover and validate candidate urine protein biomarkers from 262 renal allograft recipients with biopsy-confirmed allograft injury. Urine samples were randomly split into a training set of 108 patients and an independent validation set of 154 patients, which comprised the clinical biopsy-confirmed phenotypes of acute rejection (AR) (n = 74), stable graft (STA) (n = 74), chronic allograft injury (CAI) (n = 58), BK virus nephritis (BKVN) (n = 38), nephrotic syndrome (NS) (n = 8), and healthy, normal control (HC) (n = 10). A total of 389 proteins were measured that displayed differential abundances across urine specimens of the injury types (p 1.5) from all other transplant categories (HLA class II protein HLA-DRB1, KRT14, HIST1H4B, FGG, ACTB, FGB, FGA, KRT7, DPP4). Increased levels of three of these proteins, fibrinogen beta (FGB; p = 0.04), fibrinogen gamma (FGG; p = 0.03), and HLA DRB1 (p = 0.003) were validated by ELISA in AR using an independent sample set. The fibrinogen proteins further segregated AR from BK virus nephritis (FGB p = 0.03, FGG p = 0.02), a finding that supports the utility of monitoring these urinary proteins for the specific and sensitive noninvasive diagnosis of acute renal allograft rejection.

  17. The Identification of Novel Potential Injury Mechanisms and Candidate Biomarkers in Renal Allograft Rejection by Quantitative Proteomics*

    Science.gov (United States)

    Sigdel, Tara K.; Salomonis, Nathan; Nicora, Carrie D.; Ryu, Soyoung; He, Jintang; Dinh, Van; Orton, Daniel J.; Moore, Ronald J.; Hsieh, Szu-Chuan; Dai, Hong; Thien-Vu, Minh; Xiao, Wenzhong; Smith, Richard D.; Qian, Wei-Jun; Camp, David G.; Sarwal, Minnie M.

    2014-01-01

    Early transplant dysfunction and failure because of immunological and nonimmunological factors still presents a significant clinical problem for transplant recipients. A critical unmet need is the noninvasive detection and prediction of immune injury such that acute injury can be reversed by proactive immunosuppression titration. In this study, we used iTRAQ -based proteomic discovery and targeted ELISA validation to discover and validate candidate urine protein biomarkers from 262 renal allograft recipients with biopsy-confirmed allograft injury. Urine samples were randomly split into a training set of 108 patients and an independent validation set of 154 patients, which comprised the clinical biopsy-confirmed phenotypes of acute rejection (AR) (n = 74), stable graft (STA) (n = 74), chronic allograft injury (CAI) (n = 58), BK virus nephritis (BKVN) (n = 38), nephrotic syndrome (NS) (n = 8), and healthy, normal control (HC) (n = 10). A total of 389 proteins were measured that displayed differential abundances across urine specimens of the injury types (p 1.5) from all other transplant categories (HLA class II protein HLA-DRB1, KRT14, HIST1H4B, FGG, ACTB, FGB, FGA, KRT7, DPP4). Increased levels of three of these proteins, fibrinogen beta (FGB; p = 0.04), fibrinogen gamma (FGG; p = 0.03), and HLA DRB1 (p = 0.003) were validated by ELISA in AR using an independent sample set. The fibrinogen proteins further segregated AR from BK virus nephritis (FGB p = 0.03, FGG p = 0.02), a finding that supports the utility of monitoring these urinary proteins for the specific and sensitive noninvasive diagnosis of acute renal allograft rejection. PMID:24335474

  18. Bronchitis - acute

    Science.gov (United States)

    ... sharing features on this page, please enable JavaScript. Acute bronchitis is swelling and inflamed tissue in the main ... present only for a short time. Causes When acute bronchitis occurs, it almost always comes after having a ...

  19. Acute cholecystitis

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000264.htm Acute cholecystitis To use the sharing features on this page, please enable JavaScript. Acute cholecystitis is sudden swelling and irritation of the gallbladder. ...

  20. Sugar or spice: Using I3 metatheory to understand how and why glucose reduces rejection-related aggression.

    Science.gov (United States)

    Pfundmair, Michaela; DeWall, C Nathan; Fries, Veronika; Geiger, Babette; Krämer, Tanya; Krug, Sebastian; Frey, Dieter; Aydin, Nilüfer

    2015-01-01

    Social rejection can increase aggression, especially among people high in rejection sensitivity. Rejection impairs self-control, and deficits in self-control often result in aggression. A dose of glucose can counteract the effect of situational factors that undermine self-control. But no research has integrated these literatures to understand why rejection increases aggression, and how to reduce it. Using the I(3) model of aggression, we proposed that aggression would be highest under conditions of high instigation (rejection), high impellance (high rejection sensitivity), and low inhibition (drinking a beverage sweetened with a sugar substitute instead of glucose). As predicted, aggression was highest among participants who experienced social rejection, were high in rejection sensitivity, and drank a placebo beverage. A dose of glucose reduced aggression, especially among rejected people high in rejection sensitivity. These findings point to the importance of self-control in understanding why social rejection increases aggression, and how to prevent it. © 2015 Wiley Periodicals, Inc.

  1. Parametric Adaptive Radar Detector with Enhanced Mismatched Signals Rejection Capabilities

    Directory of Open Access Journals (Sweden)

    Liu Bin

    2010-01-01

    Full Text Available We consider the problem of adaptive signal detection in the presence of Gaussian noise with unknown covariance matrix. We propose a parametric radar detector by introducing a design parameter to trade off the target sensitivity with sidelobes energy rejection. The resulting detector merges the statistics of Kelly's GLRT and of the Rao test and so covers Kelly's GLRT and the Rao test as special cases. Both invariance properties and constant false alarm rate (CFAR behavior for this detector are studied. At the analysis stage, the performance of the new receiver is assessed and compared with several traditional adaptive detectors. The results highlight better rejection capabilities of this proposed detector for mismatched signals. Further, we develop two two-stage detectors, one of which consists of an adaptive matched filter (AMF followed by the aforementioned detector, and the other is obtained by cascading a GLRT-based Subspace Detector (SD and the proposed adaptive detector. We show that the former two-stage detector outperforms traditional two-stage detectors in terms of selectivity, and the latter yields more robustness.

  2. Aire deficiency promotes TRP-1 specific immune rejection of melanoma

    Science.gov (United States)

    Zhu, Meng-Lei; Nagavalli, Anil; Su, Maureen A.

    2013-01-01

    The thymic transcription factor AIRE prevents autoimmunity in part by promoting expression of tissue-specific self-antigens, which include many cancer antigens. For example, AIRE-deficient patients are predisposed to vitiligo, an autoimmune disease of melanocytes that is often triggered by efficacious immunotherapies against melanoma. Therefore, we hypothesized that Aire deficiency in mice may elevate immune responses to cancer and provide insights into how such responses might be triggered. In this study, we show that Aire deficiency decreases thymic expression of TRP-1 (TYRP1), which is a self-antigen in melanocytes and a cancer antigen in melanomas. Aire deficiency resulted in defective negative selection of TRP-1 specific T cells without affecting thymic numbers of regulatory T cells. Aire deficient mice displayed elevated T cell immune responses that were associated with suppression of melanoma outgrowth. Further, transplantation of Aire-deficient thymic stroma was sufficient to confer more effective immune rejection of melanoma in an otherwise Aire wildtype host. Together, our work showed how Aire deficiency can enhance immune responses against melanoma, and how manipulating TRP-1 specific T cell negative selection may offer a logical strategy to enhance immune rejection of melanoma. PMID:23370329

  3. Aire deficiency promotes TRP-1-specific immune rejection of melanoma.

    Science.gov (United States)

    Zhu, Meng-Lei; Nagavalli, Anil; Su, Maureen A

    2013-04-01

    The thymic transcription factor autoimmune regulator (Aire) prevents autoimmunity in part by promoting expression of tissue-specific self-antigens, which include many cancer antigens. For example, AIRE-deficient patients are predisposed to vitiligo, an autoimmune disease of melanocytes that is often triggered by efficacious immunotherapies against melanoma. Therefore, we hypothesized that Aire deficiency in mice may elevate immune responses to cancer and provide insights into how such responses might be triggered. In this study, we show that Aire deficiency decreases thymic expression of TRP-1 (TYRP1), which is a self-antigen in melanocytes and a cancer antigen in melanomas. Aire deficiency resulted in defective negative selection of TRP-1-specific T cells without affecting thymic numbers of regulatory T cells. Aire-deficient mice displayed elevated T-cell immune responses that were associated with suppression of melanoma outgrowth. Furthermore, transplantation of Aire-deficient thymic stroma was sufficient to confer more effective immune rejection of melanoma in an otherwise Aire wild-type host. Together, our work showed how Aire deficiency can enhance immune responses against melanoma and how manipulating TRP-1-specific T-cell negative selection may offer a logical strategy to enhance immune rejection of melanoma. ©2013 AACR.

  4. Implementation and Rejection of Industrial Steam System Energy Efficiency Measures

    Energy Technology Data Exchange (ETDEWEB)

    Therkelesen, Peter [Environmental Energy Technologies Division Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); McKane, Aimee [Environmental Energy Technologies Division Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

    2013-05-01

    Steam systems consume approximately one third of energy applied at U.S. industrial facilities. To reduce energy consumption, steam system energy assessments have been conducted on a wide range of industry types over the course of five years through the Energy Savings Assessment (ESA) program administered by the U.S. Department of Energy (U.S. DOE). ESA energy assessments result in energy efficiency measure recommendations that are given potential energy and energy cost savings and potential implementation cost values. Saving and cost metrics that measure the impact recommended measures will have at facilities, described as percentages of facility baseline energy and energy cost, are developed from ESA data and used in analyses. Developed savings and cost metrics are examined along with implementation and rejection rates of recommended steam system energy efficiency measures. Based on analyses, implementation of steam system energy efficiency measures is driven primarily by cost metrics: payback period and measure implementation cost as a percentage of facility baseline energy cost (implementation cost percentage). Stated reasons for rejecting recommended measures are primarily based upon economic concerns. Additionally, implementation rates of measures are not only functions of savings and cost metrics, but time as well.

  5. Enhancing boron rejection in FO using alkaline draw solutions.

    Science.gov (United States)

    Wang, Yi-Ning; Li, Weiyi; Wang, Rong; Tang, Chuyang Y

    2017-07-01

    This study provides a novel method to enhance boron removal in a forward osmosis (FO) process. It utilizes the reverse solute diffusion (RSD) of ions from alkaline draw solutions (DSs) and the concentration polarization of the hydroxyl ions to create a highly alkaline environment near the membrane active surface. The results show that boron rejection can be significantly enhanced by increasing the pH of NaCl DS to 12.5 in the active-layer-facing-feed-solution (AL-FS) orientation. The effect of RSD enhanced boron rejection was further promoted in the presence of concentration polarization (e.g., in the active-layer-facing-draw-solution (AL-DS) orientation). The current study opens a new dimension for controlling contaminant removal by FO using tailored DS chemistry, where the RSD-induced localized water chemistry change is taken advantage in contrast to the conventional method of chemical dosing to the bulk feed water. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Rejection Sensitivity and Depression: Indirect Effects Through Problem Solving.

    Science.gov (United States)

    Kraines, Morganne A; Wells, Tony T

    2017-01-01

    Rejection sensitivity (RS) and deficits in social problem solving are risk factors for depression. Despite their relationship to depression and the potential connection between them, no studies have examined RS and social problem solving together in the context of depression. As such, we examined RS, five facets of social problem solving, and symptoms of depression in a young adult sample. A total of 180 participants completed measures of RS, social problem solving, and depressive symptoms. We used bootstrapping to examine the indirect effect of RS on depressive symptoms through problem solving. RS was positively associated with depressive symptoms. A negative problem orientation, impulsive/careless style, and avoidance style of social problem solving were positively associated with depressive symptoms, and a positive problem orientation was negatively associated with depressive symptoms. RS demonstrated an indirect effect on depressive symptoms through two social problem-solving facets: the tendency to view problems as threats to one's well-being and an avoidance problem-solving style characterized by procrastination, passivity, or overdependence on others. These results are consistent with prior research that found a positive association between RS and depression symptoms, but this is the first study to implicate specific problem-solving deficits in the relationship between RS and depression. Our results suggest that depressive symptoms in high RS individuals may result from viewing problems as threats and taking an avoidant, rather than proactive, approach to dealing with problems. These findings may have implications for problem-solving interventions for rejection sensitive individuals.

  7. Heat Rejection Concepts for Brayton Power Conversion Systems

    Science.gov (United States)

    Siamidis, John; Mason, Lee; Beach, Duane; Yuko, James

    2005-01-01

    This paper describes potential heat rejection design concepts for closed Brayton cycle (CBC) power conversion systems. Brayton conversion systems are currently under study by NASA for Nuclear Electric Propulsion (NEP) applications. The Heat Rejection Subsystem (HRS) must dissipate waste heat generated by the power conversion system due to inefficiencies in the thermal-to-electric conversion process. Space Brayton conversion system designs tend to optimize at efficiencies of about 20 to 25 percent with radiator temperatures in the 400 to 600 K range. A notional HRS was developed for a 100 kWe-class Brayton power system that uses a pumped sodium-potassium (NaK) heat transport loop coupled to a water heat pipe radiator. The radiator panels employ a sandwich construction consisting of regularly-spaced circular heat pipes contained within two composite facesheets. Heat transfer from the NaK fluid to the heat pipes is accomplished by inserting the evaporator sections into the NaK duct channel. The paper evaluates various design parameters including heat pipe diameter, heat pipe spacing, and facesheet thickness. Parameters were varied to compare design options on the basis of NaK pump pressure rise and required power, heat pipe unit power and radial flux, radiator panel areal mass, and overall HRS mass.

  8. Identification and rejection of scattered neutrons in AGATA

    CERN Document Server

    Şenyiğit, M; Akkoyun, S; Kaşkaş, A; Bazzacco, D; Nyberg, J; Recchia, F; Brambilla, S; Camera, F; Crespi, F C L; Farnea, E; Giaz, A; Gottardo, A; Kempley, R; Ljungvall, J; Mengoni, D; Michelagnoli, C; Million, B; Palacz, M; Pellegri, L; Riboldi, S; Şahin, E; Söderström, P A; Dobon, J J Valiente

    2013-01-01

    Gamma rays and neutrons, emitted following spontaneous fission of 252Cf, were measured in an AGATA experiment performed at INFN Laboratori Nazionali di Legnaro in Italy. The setup consisted of four AGATA triple cluster detectors (12 36-fold segmented high-purity germanium crystals), placed at a distance of 50 cm from the source, and 16 HELENA BaF2 detectors. The aim of the experiment was to study the interaction of neutrons in the segmented high-purity germanium detectors of AGATA and to investigate the possibility to discriminate neutrons and gamma rays with the gamma-ray tracking technique. The BaF2 detectors were used for a time-of-flight measurement, which gave an independent discrimination of neutrons and gamma rays and which was used to optimise the gamma-ray tracking-based neutron rejection methods. It was found that standard gamma-ray tracking, without any additional neutron rejection features, eliminates effectively most of the interaction points due to recoiling Ge nuclei after elastic scattering of...

  9. fMRI Artefact Rejection and Sleep Scoring Toolbox

    Directory of Open Access Journals (Sweden)

    Yves Leclercq

    2011-01-01

    Full Text Available We started writing the “fMRI artefact rejection and sleep scoring toolbox”, or “FAST”, to process our sleep EEG-fMRI data, that is, the simultaneous recording of electroencephalographic and functional magnetic resonance imaging data acquired while a subject is asleep. FAST tackles three crucial issues typical of this kind of data: (1 data manipulation (viewing, comparing, chunking, etc. of long continuous M/EEG recordings, (2 rejection of the fMRI-induced artefact in the EEG signal, and (3 manual sleep-scoring of the M/EEG recording. Currently, the toolbox can efficiently deal with these issues via a GUI, SPM8 batching system or hand-written script. The tools developed are, of course, also useful for other EEG applications, for example, involving simultaneous EEG-fMRI acquisition, continuous EEG eye-balling, and manipulation. Even though the toolbox was originally devised for EEG data, it will also gracefully handle MEG data without any problem. “FAST” is developed in Matlab as an add-on toolbox for SPM8 and, therefore, internally uses its SPM8-meeg data format. “FAST” is available for free, under the GNU-GPL.

  10. Heat Rejection Concepts for Lunar Fission Surface Power Applications

    Science.gov (United States)

    Siamidis, John

    2006-01-01

    This paper describes potential heat rejection design concepts for lunar surface Brayton power conversion systems. Brayton conversion systems are currently under study by NASA for surface power applications. Surface reactors may be used for the moon to power human outposts enabling extended stays and closed loop life support. The Brayton Heat Rejection System (HRS) must dissipate waste heat generated by the power conversion system due to inefficiencies in the thermal-to-electric conversion process. Space Brayton conversion system designs tend to optimize at efficiencies of about 20 to 25 percent with radiator temperatures in the 400 K to 600 K range. A notional HRS was developed for a 100 kWe-class Brayton power system that uses a pumped water heat transport loop coupled to a water heat pipe radiator. The radiator panels employ a tube and fin construction consisting of regularly-spaced circular heat pipes contained within two composite facesheets. The water heat pipes interface to the coolant through curved sections partially contained within the cooling loop. The paper evaluates various design parameters including radiator panel orientation, coolant flow path, and facesheet thickness. Parameters were varied to compare design options on the basis of H2O pump pressure rise and required power, heat pipe unit power and radial flux, radiator area, radiator panel areal mass, and overall HRS mass.

  11. Heat pipe heat rejection system. [for electrical batteries

    Science.gov (United States)

    Kroliczek, E. J.

    1976-01-01

    A prototype of a battery heat rejection system was developed which uses heat pipes for more efficient heat removal and for temperature control of the cells. The package consists of five thermal mock-ups of 100 amp-hr prismatic cells. Highly conductive spacers fabricated from honeycomb panels into which heat pipes are embedded transport the heat generated by the cells to the edge of the battery. From there it can be either rejected directly to a cold plate or the heat flow can be controlled by means of two variable conductance heat pipes. The thermal resistance between the interior of the cells and the directly attached cold plate was measured to be 0.08 F/Watt for the 5-cell battery. Compared to a conductive aluminum spacer of equal weight the honeycomb/heat pipe spacer has approximately one-fifth of the thermal resistance. In addition, the honeycomb/heat pipe spacer virtually eliminates temperature gradients along the cells.

  12. Potential use of power plant reject heat in commercial aquaculture

    Energy Technology Data Exchange (ETDEWEB)

    Olszewski, M.

    1977-01-01

    Current research and commercial activities in aquaculture operations have been reviewed. An aquaculture system using mostly herbivorous species in pond culture is proposed as a means of using waste heat to produce reasonably priced protein. The system uses waste water streams, such as secondary sewage effluent, animal wastes, or some industrial waste streams as a primary nutrient source to grow algae, which is fed to fish and clams. Crayfish feed on the clam wastes thereby providing a clean effluent from the aquaculture system. Alternate fish associations are presented and it appears that a carp or tilapia association is desirable. An aquaculture system capable of rejecting all the waste heat from a 1000-MW(e) power station in winter can accommodate about half the summer heat rejection load. The aquaculture facility would require approximately 133 ha and would produce 4.1 x 10/sup 5/ kg/year of fish, 1.5 x 10/sup 6/ kg/year of clam meat, and 1.5 x 10/sup 4/ kg/year of live crayfish. The estimated annual pretax profit from this operation is one million dollars. Several possible problem areas have been identified. However, technical solutions appear to be readily available to solve these problems. The proposed system shows considerable economic promise. Small scale experiments have demonstrated the technical feasibility of various components of the system. It therefore appears that a pilot scale experimental facility should be operated.

  13. Gender nonconformity, childhood rejection, and adult attachment: a study of gay men.

    Science.gov (United States)

    Landolt, Monica A; Bartholomew, Kim; Saffrey, Colleen; Oram, Doug; Perlman, Daniel

    2004-04-01

    Several childhood factors are reported to be associated with a homosexual orientation in men, including gender nonconformity and rejection by parents and peers. The purpose of this study was to explore the associations between these childhood factors and attachment anxiety (the tendency to experience anxiety regarding potential loss and rejection in close relationships) and attachment avoidance (the tendency to avoid versus seek out closeness in relationships) in gay and bisexual men. A community sample of 191 gay and bisexual men completed questionnaires and an attachment interview. Gender nonconformity was significantly associated with paternal, maternal, and peer rejection in childhood. In addition, paternal and peer rejection, but not maternal rejection, independently predicted attachment anxiety. Peer rejection and, to a lesser extent, paternal rejection mediated the association between gender nonconformity and attachment anxiety. Finally, peer rejection mediated the association between paternal rejection and attachment avoidance. Findings highlight the role of gender nonconformity in contributing to childhood rejection and the importance of peer relationships in the socialization of gay men.

  14. Relational victimization, loneliness and depressive symptoms: indirect associations via self and peer reports of rejection sensitivity.

    Science.gov (United States)

    Zimmer-Gembeck, Melanie J; Trevaskis, Sarah; Nesdale, Drew; Downey, Geraldine A

    2014-04-01

    Theory suggests that aversive social experiences generate emotional maladjustment because they prompt the development of a hypersensitivity to perceiving and overreacting to rejection. The primary aim of this study was to test hypothesized direct and indirect (via rejection sensitivity) links of overt/relational victimization and friendship conflict with early adolescents' loneliness and depressive symptoms. Participants were 366 Australian early adolescents age 10-14 years (50.5 % girls). Using both a self-report and peer-report measure of rejection sensitivity, no difference was found when comparing the significant correlations of each measure with loneliness and depressive symptoms. Tests of direct and indirect associations with structural equation modeling showed that adolescents higher in relational victimization reported more loneliness and depressive symptoms and part of this association was by way of their greater self-reports of rejection sensitivity and their peers' identification that they were higher in rejection sensitivity. Additionally, relational victimization was the only unique correlate of emotional maladjustment, and adolescents who reported more overt victimization were identified by their peers as higher in rejection sensitivity. Finally, gender and rejection sensitivity were tested as moderators. No gender moderation was found, but friendship conflict was associated more strongly with emotional maladjustment for adolescents low, rather than high, in rejection sensitivity. These findings identify relational victimization as particularly salient for emotional maladjustment both directly and indirectly via links with elevated rejection sensitivity. They show how rejection sensitivity and aversive experiences may contribute independently and jointly to emotional maladjustment for both boys and girls.

  15. When Saying Sorry May Not Help: The Impact of Apologies on Social Rejections

    Directory of Open Access Journals (Sweden)

    Gili Freedman

    2017-08-01

    Full Text Available If you have to socially reject someone, will it help to apologize? Social rejection is a painful emotional experience for targets, yet research has been silent on recommendations for rejectors. Across three sets of studies, apologies increased hurt feelings and the need to express forgiveness but did not increase feelings of forgiveness. The investigation of hurt feelings arising from a social rejection is challenging because previous research has shown that participants are reluctant to admit they felt hurt by the rejection. The present research addressed the self-report issue in two ways. First, participants rated how much social rejections would hurt someone’s feelings as a function of whether an apology was included across various social rejection scenarios (Studies 1a–e. Second, aggressive behavior was measured in response to face-to-face social rejections that were manipulated to include or exclude apologies (Studies 2a–c. More specifically, Studies 1a–e (N = 1096 found that although individuals sometimes use apologies in social rejections, social rejections with apologies are associated with higher levels of explicit hurt feelings. Studies 2a–c (N = 355 manipulated the presence of an apology in face-to-face social rejections and found that social rejections with apologies cause more aggressive behavior. As in previous research, participants are reluctant to admit to feeling hurt. Finally, Study 3 (N = 426 found that in response to social rejections with apologies, individuals feel more compelled to express forgiveness despite not actually feeling more forgiveness. Implications for the role of language in social rejections are discussed.

  16. CNS immunological modulation of neural graft rejection and survival.

    Science.gov (United States)

    Borlongan, C V; Stahl, C E; Cameron, D F; Saporta, S; Freeman, T B; Cahill, D W; Sanberg, P R

    1996-08-01

    Neural transplantation therapy as a possible alternative treatment for neurological movement disorders, such as in Parkinson's disease (PD), has accentuated research interest on the immune status of the central nervous system (CNS). Most animal studies concerned with neural transplantation for the treatment of PD have utilized dopamine (DA) neurons from tissues of the embryonic ventral mesencephalon. Rat embryonic DA neurons, grafted either as solid blocks or dissociated into a cell suspension and stereotaxically injected intraparenchymally into a rat lesion model of PD, have been shown to survive and form connections with the host brain, and ameliorate the behavioral deficits of PD. Similarly, studies on nonhuman primate models of PD provide considerable support for neural transplantation of DA neurons as an experimental clinical procedure for the treatment of PD. To this end, experimental clinical trials have been centered upon transplantation of the embryonic ventral mesencephalic cells for PD patients. Although not conclusive, the findings from clinical studies have provided some evidence that most patients with marked increases in fluorodopa uptake (indicating graft survival) have been immunosuppressed. Furthermore, immune reactions have been observed in rats xenografted with human embryonic tissue. Of note, embryonic ventral mesencephalic tissues compared to adult tissues produce better morphological and long-lasting behavioral amelioration of the neurobehavioral deficits of PD, thus advocating the use of grafts from young donors (embryo) to circumvent the CNS immune rejection. The possible graft rejection due to CNS immune reactions, coupled with the social and ethical problems surrounding the use of embryonic neural tissue, and the logistical problems concerning tissue availability have prompted the development of alternative sources of DA-secreting cells. To circumvent these obstacles, several methods have been suggested including the use of

  17. What Protects Rejected Adolescents from Also Being Bullied by Their Peers? The Moderating Role of Peer-Valued Characteristics

    Science.gov (United States)

    Knack, Jennifer M.; Tsar, Vasilinka; Vaillancourt, Tracy; Hymel, Shelley; McDougall, Patricia

    2012-01-01

    Adolescents rejected by peers are often targets of bullying. However, peer rejection is not a sure path to victimization. We examined whether characteristics valued by peers (i.e., attractiveness, wealth, academic, and athletic ability) moderated the relationship between peer rejection and victimization. We predicted rejected adolescents high on…

  18. The extent of HLA-DR expression on HLA-DR(+) Tregs allows the identification of patients with clinically relevant borderline rejection.

    Science.gov (United States)

    Schaier, Matthias; Seissler, Nicole; Becker, Luis Eduardo; Schaefer, Sebastian Markus; Schmitt, Edgar; Meuer, Stefan; Hug, Friederike; Sommerer, Claudia; Waldherr, Rüdiger; Zeier, Martin; Steinborn, Andrea

    2013-03-01

    Regulatory T cells (Tregs) were shown to be involved into the pathogenesis of acute rejection after transplantation. The suppressive activity of the total regulatory T cell pool depends on its percentage of highly suppressive HLA-DR(+) -Treg cells. Therefore, both the suppressive activity of the total Treg pool and the extent of HLA-DR expression of HLA-DR(+) -Tregs (MFI HLA-DR) were estimated in non transplanted volunteers, patients with end-stage renal failure (ESRF), healthy renal transplant patients with suspicion on rejection, due to sole histological Bord-R or sole acute renal failure (ARF), and patients with clinically relevant borderline rejection (Bord-R and ARF). Compared to patients with only Bord-R or only ARF, the suppressive activity of the total Treg cell pool was exclusively reduced in patients with clinically relevant Bord-R. In parallel, the HLA-DR MFI of the DR(+) -Treg subset was significantly decreased in these patients, due to a significantly lower proportion of DR(high+) -Tregs, which were shown to have the highest suppressive capacity within the total Treg pool. Our findings clearly demonstrate that the determination of the HLA-DR MFI of the HLA-DR(+) -Treg subset allows a highly sensitive, specific and non-invasive discrimination between patients with clinically relevant Bord-R (Bord and ARF) and patients with subclinical rejection or other causes of transplant failure. © 2013 The Authors Transplant International © 2013 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.

  19. Stomaching rejection: Self-compassion and self-esteem moderate the impact of daily social rejection on restrictive eating behaviours among college women.

    Science.gov (United States)

    Beekman, Janine B; Stock, Michelle L; Howe, George W

    2017-11-01

    The present study examined whether having high self-esteem or a self-compassionate perspective help mitigate the impact of daily social rejection on negative affect and restrictive eating behaviours. Following a baseline survey assessing self-esteem and self-compassion, 121 college women completed online daily diaries for one week. Negative affect and restrictive eating behaviours. On days when women reported more rejection, they also reported higher restrictive eating behaviours and greater negative affect. Effects were moderated by self-esteem and self-compassion, such that the lower participants were in self-esteem or self-compassion, the stronger the positive relation between rejection and negative affect and restrictive eating. However, only the common humanity/isolation dimension of self-compassion significantly moderated daily effects of rejection when controlling for self-esteem. Mediated moderation results reveal different mechanisms by which self-esteem and self-compassion buffer against rejections' effects on affect and restrictive eating. Self-compassion and self-esteem influence the complex impact that social rejection has on affect and restrictive eating. More than other dimensions of self-compassion or self-esteem, remembering one's common humanity can result in a healthier response to social rejection.

  20. System for the Reduction of Substances in Reject Water from Reed-Bed Sludge Mineralization Plants

    DEFF Research Database (Denmark)

    2004-01-01

    The invention is a system for the reduction of substances in reject water from reed-bed sludge mineralization plants (also referred to as sludge dewatering reed-beds). The systems utilizes the composition of substances in reject water from reed-beds and that of sludge to reduce substance mass from...... the reject water via recirculation into a mixed reactor and back onto the reed-beds. The mixed rector consists of a container in which sludge (that is typically loaded directly on to reed-beds) is mixed with recirculated reject water from reed-beds. The sludge mixture has a definable hydraulic retention time...... within the container. The solution is then applied to the reed-beds, which dewaters, converts, and partially mineralize the sludge mixture. The reject water from the reed-beds is split where up to100% of the reject water is recirculated back to the mixed reactor and the remaining usually disposed...

  1. Rejected by Family for Being Gay or Lesbian: Portrayals, Perceptions, and Resilience.

    Science.gov (United States)

    Carastathis, Geoffrey S; Cohen, Lynne; Kaczmarek, Elizabeth; Chang, Paul

    2017-01-01

    A myriad of negative psychosocial outcomes face gay men and lesbians who experience rejection by their family for not being heterosexual. However, what constitutes rejection is not clear, and, more importantly, it is not known how resilience is fostered within such a context. This qualitative study sought to examine these issues by exploring the lived experiences of Australian gay men and lesbians who were previously or were currently experiencing family rejection because of their sexuality. A total of 21 in-depth, semistructured interviews were individually conducted and analyzed. Thematic analysis of the interviews revealed several themes that provided greater understanding of the portrayals and perceptions of family rejection; the impact of family rejection on mental health; and, importantly, how these individuals came to establish resilience in the face of experiencing family rejection. Limitations, directions for future research, and clinical implications of the findings are also discussed.

  2. Peer Rejection and Attention Deficit Hyperactivity Disorder Symptoms: Reciprocal Relations Through Ages 4, 6, and 8.

    Science.gov (United States)

    Stenseng, Frode; Belsky, Jay; Skalicka, Vera; Wichstrøm, Lars

    2016-01-01

    Attention deficit hyperactivity disorder (ADHD) predicts poor peer relationships. What remains unclear is whether poor peer relationships affect ADHD symptomatology. Hence, reciprocal effects of peer rejection and ADHD symptoms were examined in a community sample of 962 Norwegian children at ages 4, 6, and 8. Results showed that ADHD symptoms at age 4 predicted more peer rejection at age 6, and that peer rejection at age 4 predicted more symptoms at age 6. However, when conducting analyses on ADHD subtypes, hyperactivity-impulsivity and inattentiveness symptoms were adversely affected by peer rejection at ages 6 and 8, whereas peer rejection was unaffected by such symptoms, indicating that the effect of peer rejection on ADHD symptoms was most robust. Mediational relation were also identified. © 2015 The Authors. Child Development © 2015 Society for Research in Child Development, Inc.

  3. "I'm worth more than that": trait positivity predicts increased rejection of unfair financial offers.

    Directory of Open Access Journals (Sweden)

    Barnaby D Dunn

    Full Text Available Humans react strongly to unfairness, sometimes rejecting inequitable proposals even if this sacrifices personal financial gain. Here we explored whether emotional dispositions--trait tendencies to experience positive or negative feelings--shape the rejection of unfair financial offers. Participants played an Ultimatum Game, where the division of a sum of money is proposed and the player can accept or reject this offer. Individuals high in trait positivity and low in trait negativity rejected more unfair offers. These relationships could not be explained by existing accounts which argue that rejection behaviour results from a failure to regulate negative emotions, or serves to arbitrate social relationships and identity. Instead, the relationship between dispositional affect and rejection behaviour may be underpinned by perceived self worth, with those of a positive disposition believing that they are "worth more than that" and those of a negative disposition resigning themselves to "taking the crumbs from under the table".

  4. Long-Term Associations of Justice Sensitivity, Rejection Sensitivity, and Depressive Symptoms in Children and Adolescents

    Science.gov (United States)

    Bondü, Rebecca; Sahyazici-Knaak, Fidan; Esser, Günter

    2017-01-01

    Depressive symptoms have been related to anxious rejection sensitivity, but little is known about relations with angry rejection sensitivity and justice sensitivity. We measured rejection sensitivity, justice sensitivity, and depressive symptoms in 1,665 9-to-21-year olds at two points of measurement. Participants with high T1 levels of depressive symptoms reported higher anxious and angry rejection sensitivity and higher justice sensitivity than controls at T1 and T2. T1 rejection, but not justice sensitivity predicted T2 depressive symptoms; high victim justice sensitivity, however, added to the stabilization of depressive symptoms. T1 depressive symptoms positively predicted T2 anxious and angry rejection and victim justice sensitivity. Hence, sensitivity toward negative social cues may be cause and consequence of depressive symptoms and requires consideration in cognitive-behavioral treatment of depression. PMID:28955257

  5. Mouse model of alloimmune-induced vascular rejection and transplant arteriosclerosis.

    Science.gov (United States)

    Enns, Winnie; von Rossum, Anna; Choy, Jonathan

    2015-05-17

    Vascular rejection that leads to transplant arteriosclerosis (TA) is the leading representation of chronic heart transplant failure. In TA, the immune system of the recipient causes damage of the arterial wall and dysfunction of endothelial cells and smooth muscle cells. This triggers a pathological repair response that is characterized by intimal thickening and luminal occlusion. Understanding the mechanisms by which the immune system causes vasculature rejection and TA may inform the development of novel ways to manage graft failure. Here, we describe a mouse aortic interposition model that can be used to study the pathogenic mechanisms of vascular rejection and TA. The model involves grafting of an aortic segment from a donor animal into an allogeneic recipient. Rejection of the artery segment involves alloimmune reactions and results in arterial changes that resemble vascular rejection. The basic technical approach we describe can be used with different mouse strains and targeted interventions to answer specific questions related to vascular rejection and TA.

  6. Non-clairvoyant weighted flow time scheduling with rejection penalty

    DEFF Research Database (Denmark)

    Chan, Ho-Leung; Chan, Sze-Hang; Lam, Tak-Wah

    2012-01-01

    is defined as the weighted flow time of the job plus the penalty if it is rejected before completion. Previous work on minimizing the total user cost focused on the clairvoyant single-processor setting [BBC+03,CLL11] and has produced O(1)-competitive online algorithm for jobs with arbitrary weights...... and penalties. This paper gives the first non-clairvoyant algorithms that are O(1)-competitive for minimizing the total user cost on a single processor and multi-processors, when using slightly faster (i.e., (1+ε)-speed for any ε > 0) processors. Note that if no extra speed is allowed, no online algorithm can...... be O(1)-competitive even for minimizing (unweighted) flow time alone. The new user cost results can also be regarded as a generalization of previous non-clairvoyant results on minimizing weighted flow time alone (WSETF [BaD07] for a single processor; WLAPS [ZCL11] for multi-processors). The above...

  7. Biopsychosocial responses to social rejection in targets of relational aggression.

    Science.gov (United States)

    Zwolinski, Jennifer

    2008-10-01

    A total of 28 college students participated in a live interpersonal challenge to assess psychosocial and neuroendocrine stress responses to social exclusion in females. Using the tend-and-befriend theory as a model for interpersonal stress response, this study examined how social exclusion is related to social information processing, willingness to affiliate, psychological state affect, and cortisol reactivity in women with a history of relational victimization. Results revealed that cortisol reactivity was associated with better social information processing among women who reported the least relational victimization. Most women, regardless of relational victimization history, were willing to pursue relationships with rejecting female peers. Following the social exclusion stressor, women who reported the most state anxiety were women with the lowest reported levels of relational victimization. Cortisol reactivity was the highest during the luteal phase among females with the most relational victimization. These results offer some support for the tend-and-befriend theory in terms of neuroendocrine and psychosocial responses to interpersonal distress.

  8. Active disturbance rejection control in steering by wire haptic systems.

    Science.gov (United States)

    Rodriguez-Angeles, A; Garcia-Antonio, J A

    2014-07-01

    This paper introduces a steering by wired haptic system based on disturbance rejection control techniques. High gain Generalized Proportional Integral (GPI) observers are considered for the estimation of tire and steering wheel dynamic disturbances. These disturbances are on line canceled to ensure tracking between the commanded steering wheel angle and the tire orientation angle. The estimated disturbances at the steering rack are feedback to the steering wheel to provide a haptic interface with the driver. The overall system behaves as a bilateral master-slave system. Very few sensors and minimum knowledge of the dynamic model are required. Experimental results are presented on a prototype platform that consists on: (1) half of the steering rack of a beetle VW vehicle, (2) a steering wheel. © 2013 ISA. Published by Elsevier Ltd. All rights reserved.

  9. Lewy and his inclusion bodies: Discovery and rejection

    Directory of Open Access Journals (Sweden)

    Eliasz Engelhardt

    Full Text Available ABSTRACT Fritz Jacob Heinrich Lewy described the pathology of Paralysis agitans [Parkinson disease] and was the first to identify eosinophilic inclusion bodies in neurons of certain brain nuclei, later known as Lewy bodies, the pathological signature of the Lewy body diseases. In 1912, he published his seminal study, followed soon after by an update paper, and 10 years later, in 1923, by his voluminous book, where he exhaustively described the subject. The publication provided extensive information on the pathology of Paralysis agitans, and the entirely novel finding of eosinophilic inclusion bodies, which would become widely recognized and debated in the future. His discovery was acknowledged by important researchers who even named the structure after him. However, after his last publication on the issue, inexplicably, he never mentioned his histopathological discovery again. Despite several hypotheses, the reasons that led him to neglect (reject the structure which he so preeminently described have remained elusive.

  10. The School Violence Between Peers in Popular and Rejected Students

    Directory of Open Access Journals (Sweden)

    Teresa I. Jiménez Gutiérrez

    2011-12-01

    Full Text Available Psychosocial models of adolescent development have pointed to the importance of considering the interrelationship between relevant contexts (family, school and community in understanding psychosocial adjustment. However, few studies have examined the combined influence of these contexts in the development of specific behavioral problems such as violent behavior in schools. The present study aims to explore the links between the perception of the family, school and community climate on school violence considering the role of subjective well-being and adolescent distress. To test these multiple relationships a sample of 1795 adolescents of both sexes aged between 11 and 18 has been used. Data were analyzed using a structural equation model, including a multi-group analysis for popular and rejected students in the classroom. The results support the expected relationships and the resulting model is equivalent for both sociometric status. The discussion considers the implications of these findings for intervention with adolescents from an individual and contextual perspective.

  11. How to Manage Rejected Scientific Papers? UNAIS as Final Solution

    Directory of Open Access Journals (Sweden)

    Alessandro Diana

    2012-07-01

    Full Text Available Before publication, biomedical papers might undergo a very complex process, from journal selection, authors’ motivations for submissions, modifications, and final publication or refusal. UNAIS (Unpublished Articles In Science is an online repository in which authors can publish previously rejected scientific articles or articles that have never been submitted for publication. At UNAIS, authors can also publish the reasons behind the refusals to publication. UNAIS is more than an e-journal: it is a scientific drop box in which scientists can find indicative and negative results, as well as ideas that can inspire others. UNAIS’s goal is also to help students and scientists who want to learn how to write scientific articles. UNAIS’ aim is to exchange and promote knowledge. Have a look on www.unais.net.

  12. Enhancing interference rejection of preamplified electrodes by automated gain adaption.

    Science.gov (United States)

    Degen, Thomas; Jäckel, Heinz

    2004-11-01

    The use of preamplified electrodes in electrocardiography (ECG) or electroencephalography (EEG) has a numbe of benefits, most importantly, the noise reduction through preamplification and the interference reduction through buffering (Fernandez and Pallas-Areny, 1997). Normally, preamplified electrodes are not used because the mismatch in amplification due to component tolerances leads to a reduced common mode rejection ration (CMRR) (Pallas-Areny and Webster, 1991). In this paper, we introduce a new technique to restore the CMRR. We do this by adapting the gain of the differential amplifier (DA) following the preamplified electrodes. The technique is based on measuring the transfer function of a chosen common mode signal. The gain of the DA is adjusted by a closed loop controller to maximize the CMRR. With this technique, there is no adverse effect on the ECG or EEG. In this way, the control loop can be operated continuously if needed.

  13. Allogeneic H-2 antigen expression is insufficient for tumor rejection.

    Science.gov (United States)

    Cole, G A; Cole, G A; Clements, V K; Garcia, E P; Ostrand-Rosenberg, S

    1987-12-01

    Murine A strain (KkDdLd) sarcoma I (SaI) tumor cells have been transfected with a cloned H-2Kb gene. The resulting clones (SKB clones) stably express high levels of a molecule that is serologically and biochemically indistinguishable from the H-2Kb antigen. SKB clones are not susceptible to cytotoxic T lymphocyte-mediated lysis by H-2Kb-specific bulk, cloned, or H-2Kb-restricted lymphocytic choriomeningitis virus-specific effectors. Survival times of A/J and B10.A mice challenged i.p. with the H-2Kb-expressing transfectants and the parental SaI cells are similar, suggesting that the presence of an allogeneic major histocompatibility complex class I antigen on the surface of this tumor line is insufficient for tumor rejection.

  14. De novo production of K-alpha1 tubulin-specific antibodies: role in chronic lung allograft rejection.

    Science.gov (United States)

    Goers, Trudie A; Ramachandran, Sabarinathan; Aloush, Aviva; Trulock, Elbert; Patterson, G Alexander; Mohanakumar, Thalachallour

    2008-04-01

    Lung transplantation is the treatment option for a variety of end-stage pulmonary diseases. Posttransplant development of Abs against donor HLA and non-HLA Ags have been associated with acute and chronic rejection of transplanted organs. Development of bronchiolitis obliterans syndrome (BOS) following lung transplantation has been correlated with de novo production of anti-donor-HLA Abs. However, only a portion of the patients with BOS demonstrate detectable anti-donor-HLA Abs. Airway epithelium is considered as a major target for lung allograft rejection. In this study we demonstrate that many BOS(+) patients (12 of 36) develop Abs reactive to epithelial cell Ag that are distinct from HLA. Furthermore, de novo production of antiepithelial cell Ab precedes clinical onset of BOS. N-terminal sequencing and blastx analysis as well as blocking with K-alpha1 tubulin-specific Ab identified the epithelial Ag as K-alpha1 tubulin. Binding of the de novo-produced anti-K-alpha1 tubulin Abs to the airway epithelial cells resulted in the increased expression of transcription factors (TCF5 and c-Myc), leading to increased expression of fibrogenic growth factors, activation of cell cycle signaling, and fibroproliferation, the central events in immunopathogenesis of BOS following human lung transplantation.

  15. Anti-LFA-1 Therapy in a Nonhuman Primate Renal Transplant Model of Costimulation Blockade Resistant Rejection

    Science.gov (United States)

    Anderson, Douglas J.; Lo, Denise J.; Leopardi, F.; Song, Mingqing; Turgeon, Nicole A.; Strobert, Elizabeth A.; Jenkins, Joe B.; Wang, Rijian; Reimann, Keith A.; Larsen, Christian P.; Kirk, Allan D.

    2016-01-01

    Costimulation blockade with the fusion protein belatacept provides a desirable side-effect profile and improvement in renal function compared to calcineurin inhibition in renal transplantation. This comes at the cost of increased rates of early acute rejection. Blockade of the integrin molecule LFA-1 has been shown to be an effective adjuvant to costimulation blockade in a rigorous non-human primate (NHP) model of islet transplantation. We therefore sought to test this combination in an NHP renal transplant model. Rhesus macaques received belatacept maintenance therapy with or without the addition of LFA-1 blockade, achieved using a murine derived LFA-1 specific antibody, TS1/22. Additional experiments were performed using chimeric, rhesus IgG1 (TS1/22R1) or IgG4 (TS1/22R4) variants, each engineered to limit antibody clearance. Despite evidence of proper binding to the target molecule and impaired cellular egress from the intravascular space indicative of a therapeutic effect similar to prior islet studies, LFA-1 blockade failed to significantly prolong graft survival. Furthermore, evidence of impaired protective immunity against CMV was observed. These data highlight the difficulties in translating treatment regimens between organ models, and suggest that the primarily vascularized renal model is more robust with regard to belatacept resistant rejection than the islet model. PMID:26602755

  16. Late cytomegalovirus infection in children: High incidence of allograft rejection and hepatitis in donor negative and seropositive liver transplant recipients.

    Science.gov (United States)

    Verma, A; Palaniswamy, K; Cremonini, G; Heaton, N; Dhawan, A

    2017-05-01

    The complications and outcome associated with late CMV infection and disease on the graft are poorly characterized in PLT recipients. We studied the overall incidence, risk factors, and outcome of late CMV infection and disease (infection 6 months after transplant) in 180 PLT recipients admitted between 2008 and 2011 at the King's College Hospital. Antiviral prophylaxis of intravenous ganciclovir was given only to the D+R- group starting at day 7 post-transplant. The remaining groups (D-R+, D+R+, and D-R-) received pre-emptive therapy when they have CMV viremia above cut-off value and treatment for symptomatic CMV infection. The overall incidence of late CMV infection and disease was 9.4% (19/180) and 14.5% (19/130) in D+R-, D-R+, D+R- groups. The D-R+ group had the highest incidence of hepatitis (37.5%) and significantly increased incidence of CMV disease, and single and multiple acute rejection episodes when compared to the D+R- group, which received prophylaxis. The late CMV infection and disease in pediatric LT recipients was comparable to adult LT recipients despite variable duration of antiviral prophylaxis. Our results show that D-R+ group had highest rate of hepatitis and rejection episodes, associated with high morbidity, and should be considered for antiviral prophylaxis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Frontal-Brainstem Pathways Mediating Placebo Effects on Social Rejection.

    Science.gov (United States)

    Koban, Leonie; Kross, Ethan; Woo, Choong-Wan; Ruzic, Luka; Wager, Tor D

    2017-03-29

    Placebo treatments can strongly affect clinical outcomes, but research on how they shape other life experiences and emotional well-being is in its infancy. We used fMRI in humans to examine placebo effects on a particularly impactful life experience, social pain elicited by a recent romantic rejection. We compared these effects with placebo effects on physical (heat) pain, which are thought to depend on pathways connecting prefrontal cortex and periaqueductal gray (PAG). Placebo treatment, compared with control, reduced both social and physical pain, and increased activity in the dorsolateral prefrontal cortex (dlPFC) in both modalities. Placebo further altered the relationship between affect and both dlPFC and PAG activity during social pain, and effects on behavior were mediated by a pathway connecting dlPFC to the PAG, building on recent work implicating opioidergic PAG activity in the regulation of social pain. These findings suggest that placebo treatments reduce emotional distress by altering affective representations in frontal-brainstem systems. SIGNIFICANCE STATEMENT Placebo effects are improvements due to expectations and the socio-medical context in which treatment takes place. Whereas they have been extensively studied in the context of somatic conditions such as pain, much less is known of how treatment expectations shape the emotional experience of other important stressors and life events. Here, we use brain imaging to show that placebo treatment reduces the painful feelings associated with a recent romantic rejection by recruiting a prefrontal-brainstem network and by shifting the relationship between brain activity and affect. Our findings suggest that this brain network may be important for nonspecific treatment effects across a wide range of therapeutic approaches and mental health conditions. Copyright © 2017 the authors 0270-6474/17/373621-11$15.00/0.

  18. Acute Porphyrias.

    Science.gov (United States)

    Besur, Siddesh; Schmeltzer, Paul; Bonkovsky, Herbert L

    2015-09-01

    Porphyrias are a group of eight metabolic disorders characterized by defects in heme biosynthesis. Porphyrias are classified into two major categories: 1) the acute or inducible porphyrias and 2) the chronic cutaneous porphyrias. The acute hepatic porphyrias are further classified into acute intermittent porphyria (AIP), hereditary coproporphyria, variegate porphyria, and porphyria due to severe deficiency of delta-aminolevulinic acid (ALA) dehydratase (ALADP). AIP is the most common, and ALADP is the least common acute porphyria. The clinical presentations of acute porphyrias are nonspecific. There are no pathognomonic signs or symptoms. The most frequent presenting symptom is abdominal pain, but pain in the chest, back, or lower extremities may also occur. Hyponatremia is the most common electrolyte abnormality during acute attacks, and hypomagnesemia is also common. Both are risk factors for development of seizures, which occur in ∼ 20-30% of acute attacks. Once suspected, the diagnosis of porphyria can be rapidly established by checking random urinary porphobilinogen. Initial management of acute porphyria includes discontinuation of all potentially harmful drugs and management of symptoms. Acute attacks should be treated emergently with intravenous heme and glucose to avoid considerable morbidity and mortality. Acute attacks last a few days, and the majority of patients are asymptomatic between attacks. Prognosis is good if the condition is recognized early and treated aggressively. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Family and community rejection and a Congolese led mediation intervention to reintegrate rejected survivors of sexual violence in Eastern Democratic Republic of Congo.

    Science.gov (United States)

    Kohli, Anjalee; Tosha, Maphie; Ramazani, Paul; Safari, Octave; Bachunguye, Richard; Zahiga, Isaya; Iragi, Aline; Glass, Nancy

    2013-01-01

    Our purpose in this study is to describe the multiple and inter-related health, economic, and social reasons for rejection and to provide an example of a Congolese-led family mediation program to reintegrate survivors into their families. We conducted this study in Eastern Democratic Republic of Congo (DRC) and included two focus group discussions and twenty-seven interviews. Rejection extends beyond physical dislocation to include economic and social aspects. Family mediation is a process requiring knowledge of traditions and norms. Understanding the context of rejection and supporting promising local reintegration efforts will likely improve health, economic, and social outcomes for the survivor, her family, and her community.

  20. Rapid Heartbeat, But Dry Palms: Reactions of Heart Rate and Skin Conductance Levels to Social Rejection

    OpenAIRE

    Benjamin eIffland; Lisa Margareta Sansen; Claudia eCatani; Frank eNeuner

    2014-01-01

    Background: Social rejection elicits negative mood, emotional distress and neural activity in networks that are associated with physical pain. However, studies assessing physiological reactions to social rejection are rare and results of these studies were found to be ambiguous. Therefore, the present study aimed to examine and specify physiological effects of social rejection.Methods: Participants (N = 50) were assigned to either a social exclusion or inclusion condition of a virtual ball-to...

  1. The Daily Relation between Parental Rejection and Emotional Eating in Youngsters: A Diary Study.

    Science.gov (United States)

    Vandewalle, Julie; Mabbe, Elien; Debeuf, Taaike; Braet, Caroline; Moens, Ellen

    2017-01-01

    KEY POINTS  Cross-sectional survey studies have demonstrated significant associations between parental rejection and peer rejection on the one hand and disturbed eating in youngsters, like emotional eating, on the other hand. In this study, we wanted to expand our knowledge on these relationships by investigating the daily fluctuations in these variables. Youngsters completed a 7-day diary to assess daily parental rejection, peer rejection and emotional eating. Using multilevel analyses, our results showed that daily variations in parental rejection were related to daily variations in emotional eating of the youngsters. This highlights the importance of addressing the parent-child relationship in interventions for emotional eating in youngsters. Background: This study investigated the daily relation between parental rejection and peer rejection on the one hand and emotional eating in youngsters on the other hand. Methods: Participants (N = 55) between the ages of 11 and 15 years completed a 7-day diary. A multilevel design was used to examine day-to-day within-person relationships between parental and peer rejection (measured by CHS) and emotional eating (measured by DEBQ-C) of youngsters. Results: The results showed that daily variations in parental rejection were related to daily variations in emotional eating of the youngsters. Daily peer rejection was only marginally significantly related to the emotional eating of the youngsters. Conclusions: These results indicate that especially parental rejection, and to a lesser extent peer rejection, are associated with the emotional eating of youngsters. The findings highlight the importance of addressing the parent-child relationship in interventions for emotional eating in youngsters.

  2. The Daily Relation between Parental Rejection and Emotional Eating in Youngsters: A Diary Study

    Directory of Open Access Journals (Sweden)

    Julie Vandewalle

    2017-05-01

    Full Text Available KEY POINTS Cross-sectional survey studies have demonstrated significant associations between parental rejection and peer rejection on the one hand and disturbed eating in youngsters, like emotional eating, on the other hand. In this study, we wanted to expand our knowledge on these relationships by investigating the daily fluctuations in these variables. Youngsters completed a 7-day diary to assess daily parental rejection, peer rejection and emotional eating. Using multilevel analyses, our results showed that daily variations in parental rejection were related to daily variations in emotional eating of the youngsters. This highlights the importance of addressing the parent-child relationship in interventions for emotional eating in youngsters.Background: This study investigated the daily relation between parental rejection and peer rejection on the one hand and emotional eating in youngsters on the other hand.Methods: Participants (N = 55 between the ages of 11 and 15 years completed a 7-day diary. A multilevel design was used to examine day-to-day within-person relationships between parental and peer rejection (measured by CHS and emotional eating (measured by DEBQ-C of youngsters.Results: The results showed that daily variations in parental rejection were related to daily variations in emotional eating of the youngsters. Daily peer rejection was only marginally significantly related to the emotional eating of the youngsters.Conclusions: These results indicate that especially parental rejection, and to a lesser extent peer rejection, are associated with the emotional eating of youngsters. The findings highlight the importance of addressing the parent-child relationship in interventions for emotional eating in youngsters.

  3. Linear Active Disturbance Rejection Control for LCL Type Grid-connected Converter

    DEFF Research Database (Denmark)

    Lu, Jinghang; Savaghebi, Mehdi; Guerrero, Josep M.

    2016-01-01

    This paper presents a linear active disturbance rejection control (LADRC) for grid-connected converter with LCL filter. The high rejection performance for external disturbance, internal decoupling, parameter variation is achieved by adopting extended state observer(ESO) and designing controller...... with direct pole placement. Robustness of parameter uncertainty and sensitivity of input disturbance are analyzed in frequency domain to demonstrate the superior characteristic in disturbance rejection. The theoretical analysis is verified in Matlab/Simulink. The simulation results show the excellent...... capability of rejection in grid voltage disturbance....

  4. Parental alignments and rejection: an empirical study of alienation in children of divorce.

    Science.gov (United States)

    Johnston, Janet R

    2003-01-01

    This study of family relationships after divorce examined the frequency and extent of child-parent alignments and correlates of children's rejection of a parent, these being basic components of the controversial idea of "parental alienation syndrome." The sample consisted of 215 children from the family courts and general community two to three years after parental separation. The findings indicate that children's attitudes toward their parents range from positive to negative, with relatively few being extremely aligned or rejecting. Rejection of a parent has multiple determinants, with both the aligned and rejected parents contributing to the problem, in addition to vulnerabilities within children themselves.

  5. Improved High-Rejection Filters and MEMS-Enabled Smart Reconfigurable Antennas Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Proposed work envisions development of high-rejection filters and smart reconfigurable antennas using MEMS switches. Adaptive feature of the proposed antenna...

  6. Film reject analysis and image quality in diagnostic Radiology Department of a Teaching hospital in Ghana

    Directory of Open Access Journals (Sweden)

    J. Owusu-Banahene

    2014-10-01

    Full Text Available Patients usually undergo repeated X-ray examinations after their initial X-ray radiographs are rejected due to poor image quality. This subjects the patients to an excess radiation exposure and extra cost and necessitates the need to investigate the causes of reject. The use of reject analysis as part of the overall quality assurance programs in clinical radiography and radiology services is vital in the evaluation of image quality of a well-established practice. It is shown that, in spite of good quality control maintained by the Radiology Department of a Teaching hospital in Ghana, reject analysis performed on a number of radiographic films developed indicated 14.1% reject rate against 85.9% accepted films. The highest reject rate was 57.1 ± 0.7% which occurs in cervical spine and the lowest was7.7 ± 0.5% for lumbar spine. The major factors contributing to film rejection were found to be over exposure and patient positioning in cervical spine examinations. The most frequent examination was chest X-ray which accounts for about 42.2% of the total examinations. The results show low reject rates by considering the factors for radiographic rejection analysis in relation to both equipment functionality and film development in the facility.

  7. Remembering rejection: specificity and linguistic styles of autobiographical memories in borderline personality disorder and depression.

    Science.gov (United States)

    Rosenbach, Charlotte; Renneberg, Babette

    2015-03-01

    High levels of rejection sensitivity are assumed to be the result of early and prolonged experiences of rejection. Aim of this study was to investigate autobiographical memories of rejection in clinical samples high in rejection sensitivity (Borderline Personality Disorder, BPD, and Major Depressive Disorder, MDD) and to identify group differences in the quality of the memories. Memories of rejection were retrieved using an adapted version of the Autobiographical Memory Test (AMT; five positive cue words, five cue words referring to rejection). Specificity of memories and linguistic word usage was analyzed in 30 patients with BPD, 27 patients with MDD and 30 healthy controls. Patients with BPD retrieved less specific memories compared to the healthy control group, whereas patients with MDD did not differ from controls in this regard. The group difference was no longer significant when controlling for rejection sensitivity. Linguistic analysis indicated that compared to both other groups, patients with BPD showed a higher self-focus, used more anger-related words, referred more frequently to social environments, and rated memories of rejection as more relevant for today's life. Clinical symptoms were not assessed in the control group. Moreover, the written form of the AMT might reduce the total number of specific memories. The level of rejection sensitivity influenced the specificity of the retrieved memories. Analysis of linguistic styles revealed specific linguistic patterns in BPD compared to non-clinical as well as depressed participants. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Simulation of disturbance rejection control of half-car active suspension system using active disturbance rejection control with decoupling transformation

    Science.gov (United States)

    Hasbullah, Faried; Faris, Waleed F.

    2017-12-01

    In recent years, Active Disturbance Rejection Control (ADRC) has become a popular control alternative due to its easy applicability and robustness to varying processes. In this article, ADRC with input decoupling transformation (ADRC-IDT) is proposed to improve ride comfort of a vehicle with an active suspension system using half-car model. The ride performance of the ADRC-IDT is evaluated and compared with decentralized ADRC control as well as the passive system. Simulation results show that both ADRC and ADRC-IDT manage to appreciably reduce body accelerations and able to cope well with varying conditions typically encountered in an active suspension system. Also, it is sufficient to control only the body motions with both active controllers to improve ride comfort while maintaining good road holding and small suspension working space.

  9. Acute cholecystitis

    OpenAIRE

    Fialkowski, Elizabeth; Halpin, Valerie; Whinney, Robb R

    2008-01-01

    Acute cholecystitis causes unremitting right upper quadrant pain, anorexia, nausea, vomiting, and fever, and if untreated can lead to perforations, abscess formation, or fistulae. About 95% of people with acute cholecystitis have gallstones.It is thought that blockage of the bile duct by a gallstone or local inflammation can lead to acute cholecystitis, but we don't know whether bacterial infection is also necessary.

  10. Acute cholecystitis

    OpenAIRE

    Halpin, Valerie

    2014-01-01

    Acute cholecystitis causes unremitting right upper quadrant pain, anorexia, nausea, vomiting, and fever, and if untreated can lead to perforations, abscess formation, or fistulae. About 95% of people with acute cholecystitis have gallstones.It is thought that blockage of the cystic duct by a gallstone or local inflammation can lead to acute cholecystitis, but we don't know whether bacterial infection is also necessary.

  11. Acute cholecystitis

    OpenAIRE

    Halpin, Valerie; Gupta, Aditya

    2011-01-01

    Acute cholecystitis causes unremitting right upper quadrant pain, anorexia, nausea, vomiting, and fever, and if untreated can lead to perforations, abscess formation, or fistulae. About 95% of people with acute cholecystitis have gallstones.It is thought that blockage of the bile duct by a gallstone or local inflammation can lead to acute cholecystitis, but we don't know whether bacterial infection is also necessary.

  12. Parental control in interpersonal acceptance-rejection theory: a study with a Spanish sample using Parents’ Version of Parental Acceptation-Rejection/Control Questionnaire

    National Research Council Canada - National Science Library

    Carmen-María Fernández-García; Carmen Rodríguez-Menéndez

    2017-01-01

    .... In the context of this theory, our study was conducted with a sample of Spanish parents to (a) examine whether parental perceived acceptance-rejection was related to parental behavioral control; (2...

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

    Directory of Open Access Journals (Sweden)

    Khurram Shahzad

    2010-01-01

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

  14. Influence of evoked contexts on consumers' rejection of two products: Implications for shelf life estimation.

    Science.gov (United States)

    Giménez, Ana; Gagliardi, Andrés; Ares, Gastón

    2015-10-01

    Consumers' increasing demand for fresh, safe and high quality products requires food companies to accurately estimate sensory shelf life and tolerance limits for sensory defects. Sensory shelf-life and acceptance limits for sensory defects have been estimated with consumers' rejection data using survival analysis without considering contextual variables, which could have a major influence on consumers' perception. The aim of the present study was to study how consumers' rejection is affected by different evoked contexts in a laboratory setting. Two studies were carried out to study the influence of evoked contexts on consumers' rejection. In the first study consumers' rejection for consumption at home and purchase at a supermarket was compared using orange juice samples with different storage times. In the second study, consumers' rejection for consumption at home and purchase at a supermarket for brands of different familiarities was compared using dulce de leche with different plastic flavour intensities as samples. Consumers' rejection data were analysed using survival analysis. The use of written scenarios to evoke different contexts affected consumers' rejection of products with different storage times and intensities of a sensory defect. Shelf lives that were estimated based on consumers' rejection to purchase were shorter than those estimated considering consumers' rejection to consume. In the second study, consumers' rejection under the consumption at home evoked context was similar to rejection to repeat purchase of a usual brand. However, a large difference existed between the evoked contexts that involved a usual and a new brand. Consumers were harsher when considering to repeat purchase of a new brand compared to their usual brand. These results suggest that the consideration of evoked contexts could contribute to increase the accuracy of sensory shelf life estimation and acceptance limits of sensory defects, leading to more informed business decisions

  15. Kinetics of indium-111-labeled leukemic cells in patients with acute nonlymphocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Yamauchi, K.; Suzuki, Y.; Sugihara, M.; Nagao, T.; Arimori, S.

    1984-08-01

    The distribution within the body of autologous leukemic cells labeled with indium-111 oxine was studied in seven patients with acute nonlymphocytic leukemia. The leukemic blood cells initially entered the spleen and liver, and the major site of localization was the former rather than the latter. The majority of the leukemic cells had not left the spleen and liver within 48 hr. Liver radioactivity fell transitorily up to the third hr after the initial rise. The clearance curve of radioactivity from the blood showed a plateau or the appearance of a ''hump'' from 1 to 5 hr after injection of labeled leukemic cells. These results might reflect recirculation of a portion of the leukemic cells between these organs and the bloodstream. In a patient with acute monoblastic leukemia. OKM1 monoclonal-antibody-treated monoblasts showed the lowest recovery into the blood and a greater increase of liver than splenic radioactivity at 30 min after injection. These results suggest the removal of damaged cells by the cytotoxic effects of antibody mediated by reticuloendothelial clearance mainly of the liver and others. In one patient with acute promyelocytic leukemia, leukemic cells accumulated in both kidneys, indicating the possible infiltration of these cells. Since indium-111 oxine stays firmly attached to the cells in spite of the possibility of radiation damaged in a long-term survey, it seems an ideal label for studying leukemic cell kinetics.

  16. Bronchitis (acute)

    OpenAIRE

    Wark, Peter

    2015-01-01

    Acute bronchitis affects more than 40 in 1000 adults per year in the UK. The causes are usually considered to be infective, but only around half of people have identifiable pathogens.The role of smoking or environmental tobacco smoke inhalation in predisposing to acute bronchitis is unclear.One third of people may have longer-term symptoms or recurrence.

  17. Acute nierschade

    NARCIS (Netherlands)

    Hageman, D.; Kooman, J.P.; Lance, M.D.; van Heurn, L.W.E.; Snoeijs, M.G.

    2012-01-01

    - 'Acute kidney injury' is modern terminology for a sudden decline in kidney function, and is defined by the RIFLE classification (RIFLE is an acronym for Risk, Injury, Failure, Loss and End-stage kidney disease).- Acute kidney injury occurs as a result of the combination of reduced perfusion in the

  18. Analysis and Economic Implication of X-Ray Film Reject in ...

    African Journals Online (AJOL)

    BACKGROUND: Patients usually undergo repeated X-ray examinations after their initial X-ray radiographs are rejected due to poor image quality. This subjects the patients to excess radiation exposure and extra cost.It is therefore investigating the magnitude and causes of reject is mandatory. This study aimed to assess the ...

  19. 40 CFR 204.57-7 - Acceptance and rejection of batch sequence.

    Science.gov (United States)

    2010-07-01

    ... sequence. 204.57-7 Section 204.57-7 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... § 204.57-7 Acceptance and rejection of batch sequence. (a) The manufacturer will continue to inspect consecutive batches until the batch sequence is accepted or rejected. The batch sequence will be accepted or...

  20. An Audit Of Rejected Repeated X-ray Films As A Quality Assurance ...

    African Journals Online (AJOL)

    To find out the causes, number, percentage and sizes of rejected radiographic filmswith a view of adopting measures that will reduce the rate and number of rejected films. Radiology Department of a University Teaching Hospital. Over a two-year period (1 April 2002 to 31 March 2004), the total number of x-ray films utilized ...

  1. Mental Health in Marriage: The Roles of Need for Affiliation, Sensitivity to Rejection, and Other Factors.

    Science.gov (United States)

    Moffitt, Paul F.; And Others

    1986-01-01

    Reports on the associations between personality factors and spouse mental health, happiness, and communication. Lower Affiliative Drive and higher Sensitivity to Rejection emerge as being associated in wives with increased psychological morbidity. Wives had higher levels of both Need for Affiliation and Sensitivity to Rejection than husbands,…

  2. 75 FR 35019 - Hampshire Paper Company; Notice Rejecting Application, Waiving Regulations, and Soliciting...

    Science.gov (United States)

    2010-06-21

    ... Energy Regulatory Commission Hampshire Paper Company; Notice Rejecting Application, Waiving Regulations, and Soliciting Applications June 15, 2010. On June 2, 2010, Hampshire Paper Company (Hampshire Paper... filed and is hereby rejected.\\1\\ \\1\\ Hampshire Paper was issued a major license for the project on June...

  3. On the Distribution of Norm of Vector Projection and Rejection of Two Complex Normal Random Vectors

    Directory of Open Access Journals (Sweden)

    Mehdi Maleki

    2015-01-01

    Full Text Available Vector projection and vector rejection are highly common and useful operations in mathematics, information theory, and signal processing. In this paper, we find the distribution of the norm of projection and rejection vectors when the original vectors are standard complex normally distributed.

  4. Constructing a minority group identity out of shared rejection : The case of international students

    NARCIS (Netherlands)

    Schmitt, MT; Spears, R; Branscombe, NR

    2003-01-01

    With a sample of international students, we investigated how perceptions of rejection by the host community are related to a sense of identification with other international students. Based on the rejection-identification model (Branscombe, Schmitt, & Harvey, 1999) we predicted that perceiving

  5. Sociocultural Influence and Appearance-Based Rejection Sensitivity among College Students

    Science.gov (United States)

    Park, Lora E.; DiRaddo, Ann Marie; Calogero, Rachel M.

    2009-01-01

    The present research examined the influence of parents, peers, and the media in predicting college students' Appearance-based Rejection Sensitivity (Appearance-RS)--the degree to which individuals anxiously expect to be rejected based on their physical appearance. Given that women are socialized to be more appearance-focused than men, women were…

  6. X-ray film reject rate analysis at eight selected government hospitals ...

    African Journals Online (AJOL)

    admin

    Objective: The purpose of this research was to identify the main causes of film faults as well as the pattern and magnitude of film rejection. Methods: Using a prospective cross-sectional hospital based approach; eight public hospitals were selected in Addis. Ababa through .... clinical radiology service. In this respect, reject ...

  7. X-ray film reject rate analysis at eight selected government hospitals ...

    African Journals Online (AJOL)

    admin

    The collected data were then entered into a database for analysis using descriptive ... dealing with this situation would thus be analysis of the reasons for reject or repeat films. Repeat analysis is a helpful element to determine how big the waste of films is and where the ... Secondly, reject analysis will enable one to note any.

  8. Foreign egg retention by avian hosts in repeated brood parasitism : Why do rejecters accept?

    NARCIS (Netherlands)

    Moskat, Csaba; Hauber, Mark E.; Elek, Zoltan; Gommers, Moniek; Ban, Miklos; Groenewoud, Frank; Versluijs, Tom S. L.; Hoetz, Christiaan W. A.; Komdeur, Jan

    Great reed warblers (Acrocephalus arundinaceus) are frequently parasitized by egg-mimetic common cuckoos (Cuculus canorus) in Hungary, and these hosts reject about a third of parasitic eggs. The timing of parasitism is important, in that the probability of rejection decreases with advancing breeding

  9. Effects of age and MAOA genotype on the neural processing of social rejection.

    Science.gov (United States)

    Sebastian, C L; Roiser, J P; Tan, G C Y; Viding, E; Wood, N W; Blakemore, S-J

    2010-08-01

    Adolescents are often sensitive to peer rejection, a factor that might contribute to the risk of affective disorder in this age group. Previous studies suggest a significant overlap among socioaffective brain regions involved in the response to social rejection, regions continuing to develop functionally during adolescence and regions influenced by monoamine oxidase A (MAOA) polymorphism. The current study investigated whether the neural response to social rejection is functionally immature in adolescents compared with adults, and whether these responses are modulated by MAOA genotype. Blood-oxygen-level-dependent response was measured with functional magnetic resonance imaging during a rejection-themed emotional Stroop task in 19 adolescents (aged 14-16) and 16 adults (aged 23-28) genotyped for MAOA polymorphism. Similar numbers of MAOA-L and MAOA-H carriers were recruited to maximize power to detect genotype effects. Main effects of rejection stimuli (relative to neutral and acceptance control stimuli) were seen in predicted socioaffective brain regions. Adolescents did not show the adult pattern of modulation by rejection stimuli in the right ventrolateral prefrontal cortex, suggesting continued functional maturation of this regulatory region during adolescence. Age and genotype interacted in the left amygdala, in which the predicted effect of genotype on responses to rejection stimuli was seen in the adults, but not in the adolescents. The data suggest continued functional development of the circuitry underlying the processing of social rejection between adolescence and adulthood, and show that the effects of MAOA genotype on neural responses may vary with age.

  10. Social Prominence and the Heterogeneity of Rejected Status in Late Elementary School

    Science.gov (United States)

    Farmer, Thomas W.; Hall, Cristin M.; Leung, Man-Chi; Estell, David B.; Brooks, Debra

    2011-01-01

    The heterogeneity of peer rejection was examined as a function of social prominence in fifth grade classrooms. From an overall sample of 3,891 (1,931 girls) students, 721 youth (424 boys) were identified with rejected status. Social prominence was determined from the aggregation of peer nominations for "leader", "athletic", "cool", and "popular".…

  11. Resilient Adolescent Adjustment among Girls: Buffers of Childhood Peer Rejection and Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Mikami, Amori Yee; Hinshaw, Stephen P.

    2006-01-01

    Examined a risk-resilience model of peer rejection and attention-deficit/hyperactivity disorder (ADHD) in a 5-year longitudinal study of 209 ethnically and socioeconomically diverse girls aged 6-13 at baseline and 11-18 at follow-up. Risk factors were childhood ADHD diagnosis and peer rejection; hypothesized protective factors were childhood…

  12. Prevention of peer rejection through a classroom-level intervention in middle school.

    Science.gov (United States)

    Mikami, Amori Yee; Boucher, Margaret A; Humphreys, Keith

    2005-01-01

    This project evaluated an intervention for preventing peer rejection in middle school that promoted social acceptance in the classroom environment. The systems-level and preventive focus of this intervention differed markedly from traditional interventions that target putative deficits within individual rejected children. In collaboration with 24 teachers and their classrooms, the intervention team led mixed groups of accepted and rejected children in cooperative games that required teamwork and mutual respect among all members in order to succeed. To reinforce these alliances between children, as well as to prevent future peer rejection, teachers were encouraged to use cooperative, teamwork-based group activities for academic instruction. The intervention was evaluated using a randomized control (waitlist) design. Results suggested that the intervention reduced the amount of self-reported peer rejection in classrooms. Implications for the further development and evaluation of systems-level interventions to prevent peer rejection are discussed. EDITORS' STRATEGIC IMPLICATIONS: The use of a systems-based prevention program shows promise for the prevention of children's perceived peer rejection. The authors demonstrate a model of university-community collaboration with a plan for sustainability and a focus on low-income and minority populations. Educators, school administrators, and researchers will be intrigued by the positive experiences of non-rejected peers and teachers in promoting a socially accepting school climate.

  13. Rapid Heartbeat, But Dry Palms: Reactions of Heart Rate and Skin Conductance Levels to Social Rejection

    Directory of Open Access Journals (Sweden)

    Benjamin eIffland

    2014-08-01

    Full Text Available Background: Social rejection elicits negative mood, emotional distress and neural activity in networks that are associated with physical pain. However, studies assessing physiological reactions to social rejection are rare and results of these studies were found to be ambiguous. Therefore, the present study aimed to examine and specify physiological effects of social rejection.Methods: Participants (N = 50 were assigned to either a social exclusion or inclusion condition of a virtual ball-tossing game (Cyberball. Immediate and delayed physiological (skin conductance level and heart rate reactions were recorded. In addition, subjects reported levels of affect, emotional states and fundamental needs.Results: Subjects who were socially rejected showed increased heart rates. However, social rejection had no effect on subjects’ skin conductance levels. Both conditions showed heightened arousal on this measurement. Furthermore, psychological consequences of social rejection indicated the validity of the paradigm.Conclusions: Our results reveal that social rejection evokes an immediate physiological reaction. Accelerated heart rates indicate that behavior activation rather than inhibition is associated with socially threatening events. In addition, results revealed gender-specific response patterns suggesting that sample characteristics such as differences in gender may account for ambiguous findings of physiological reactions to social rejection.

  14. Trajectories of Italian Children's Peer Rejection: Associations with Aggression, Prosocial Behavior, Physical Attractiveness, and Adolescent Adjustment.

    Science.gov (United States)

    Di Giunta, Laura; Pastorelli, Concetta; Thartori, Eriona; Bombi, Anna Silvia; Baumgartner, Emma; Fabes, Richard A; Martin, Carol Lynn; Enders, Craig K

    2017-12-08

    In the present study, the predictors and outcomes associated with the trajectories of peer rejection were examined in a longitudinal sample of Italian children (338 boys, 269 girls) ages 10 to 14 years. Follow-up assessments included 60% of the original sample at age 16-17. Low, medium, and high rejection trajectory groups were identified using growth mixture models. Consistent with previous studies, we found that (a) being less prosocial and more physically aggressive at age 10 was characteristic of those children with the high rejection trajectory; (b) being less attractive was related to higher peer rejection from age 10 to 14; and (c) boys with a high rejection trajectory showed high levels of delinquency and anxiety-depression and low levels of academic aspiration at age 16-17, whereas girls with a high rejection trajectory showed low levels of academic aspiration and social competence at age 16-17. Our findings indicate the detrimental consequences of peer rejection on children's development and adjustment and shed light on the mechanisms that contribute to maintaining or worsening (e.g., being attractive, prosocial, and aggressive) a child's negative status (e.g., being rejected) within his or her peer group over time.

  15. On Understanding the Processes of Peer Rejection: The Potential Contributions of Labelling Theory.

    Science.gov (United States)

    Thomas, Sydney Carroll

    1997-01-01

    Peer rejection often goes ignored or undetected by teachers and counselors. Labeling theory underscores the seriousness of this problem by illustrating interactional sequences that lead to self-fulfilling prophecy effects. Grouping potential labelers and peer-rejected children together to discuss common problems, creating positive labels for…

  16. MORPHOLOGICAL ACTIVATION OF LYMPHOCYTES IN BLOOD DURING REJECTION OF HEART AND LUNG GRAFTS IN RATS

    NARCIS (Netherlands)

    WESTRA, AL; HEIJN, AA; UYAMA, T; PROP, J; WILDEVUUR, CRH

    We investigated morphologic activation of lymphocytes in blood in a standardized, infection-free rat model and compared lymphocyte activation during rejection of heart grafts and that of lung grafts with other parameters of rejection. For heart grafts the other parameters were histology and

  17. Popular and rejected children's reasoning about negative emotions in social situation: The role of gender

    NARCIS (Netherlands)

    Banerjee, R.; Rieffe, C.J.; Meerum Terwogt, M.; Gerlein, A.M.; Voutsina, M.

    2006-01-01

    Two studies compared popular and rejected children's reasoning regarding social interactions involving negative emotions. The first study, with 23 rejected and 23 popular 10- to 11-year-olds, involved hypothetical social scenarios where a classmate 'victim' was likely to experience a negative

  18. Utilization Of Diets Containing Cashew-Nut Reject Meal By Weaner ...

    African Journals Online (AJOL)

    A trial was conducted to assess the performance and digestibility of weaner pigs fed diets containing cashew nut reject meal (CNM). A control diet was formulated without cashew nut reject meal while two other diets were also formulated to contain either 50g or 100g/kg diet. The CNM replaced soybean meal in the control ...

  19. X-ray film reject rate analysis at eight selected government hospitals ...

    African Journals Online (AJOL)

    admin

    The collected data were then entered into a database for analysis using descriptive statistics. Results: Reject rate ... dealing with this situation would thus be analysis of the reasons for reject or repeat films. Repeat analysis is a helpful element to determine how big the waste of films is and where the sources of the error are.

  20. Rapid heartbeat, but dry palms: reactions of heart rate and skin conductance levels to social rejection.

    Science.gov (United States)

    Iffland, Benjamin; Sansen, Lisa M; Catani, Claudia; Neuner, Frank

    2014-01-01

    Social rejection elicits negative mood, emotional distress, and neural activity in networks that are associated with physical pain. However, studies assessing physiological reactions to social rejection are rare and results of these studies were found to be ambiguous. Therefore, the present study aimed to examine and specify physiological effects of social rejection. Participants (n = 50) were assigned to either a social exclusion or inclusion condition of a virtual ball-tossing game (Cyberball). Immediate and delayed physiological [skin conductance level (SCL) and heart rate] reactions were recorded. In addition, subjects reported levels of affect, emotional states, and fundamental needs. Subjects who were socially rejected showed increased heart rates. However, social rejection had no effect on subjects' SCLs. Both conditions showed heightened arousal on this measurement. Furthermore, psychological consequences of social rejection indicated the validity of the paradigm. Our results reveal that social rejection evokes an immediate physiological reaction. Accelerated heart rates indicate that behavior activation rather than inhibition is associated with socially threatening events. In addition, results revealed gender-specific response patterns suggesting that sample characteristics such as differences in gender may account for ambiguous findings of physiological reactions to social rejection.