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Sample records for acute rejection bpar

  1. Role of the Fyn -93A>G polymorphism (rs706895) in acute rejection after liver transplantation.

    PubMed

    Thude, Hansjörg; Kramer, Kathrin; Peine, Sven; Sterneck, Martina; Nashan, Björn; Koch, Martina

    2015-09-01

    The tyrosine kinase Fyn phosphorylates tyrosine residues on key targets involved in early T-cell signal transduction. T-cell signal transduction is one essential step for acute transplant rejection. The aim of this study was to evaluate the association of Fyn -93A>G single nucleotide polymorphism (SNP) (rs706895) with the susceptibility to acute rejection episodes in liver transplantation. In total, 72 liver transplant recipients with one biopsy proven acute rejection (S-BPAR), 56 with multiple BPAR (M-BPAR), 105 without BPAR (No-BPAR), and 145 healthy controls were enrolled in this case-control study. The SNP was genotyped by polymerase chain reaction-allele specific restriction enzyme analysis (PCR-ASRA) and was analyzed for a recessive and a dominant model. The Fyn -93G allele exhibits in healthy controls a statistically significant lower frequency than in liver recipients (18% vs. 24%; p=0.046) or in liver recipients with BPAR (18% vs. 27%; p=0.017). However, the genotype and allele frequencies of the Fyn -93A>G SNP demonstrate no significant differences between recipients with acute rejection episodes (S-BPAR and M-BPAR) and No-BPAR recipients. Thus our results provide no evidence that the Fyn -93A>G SNP contributes to the susceptibility to acute liver transplant rejection in a Caucasian population. PMID:26407913

  2. Immunosuppression status of liver transplant recipients with hepatitis C affects biopsy-proven acute rejection

    PubMed Central

    Kim, Jong Man; Lee, Kwang-Woong; Song, Gi-Won; Jung, Bo-Hyun; Lee, Hae Won; Yi, Nam-Joon; Kwon, ChoonHyuck David; Hwang, Shin; Suh, Kyung-Suk; Joh, Jae-Won; Lee, Suk-Koo; Lee, Sung-Gyu

    2016-01-01

    Background/Aims The relationship between patient survival and biopsy-proven acute rejection (BPAR) in liver transplant recipients with hepatitis C remains unclear. The aims of this study were to compare the characteristics of patients with and without BPAR and to identify risk factors for BPAR. Methods We retrospectively reviewed the records of 169 HCV-RNA-positive patients who underwent LT at three centers. Results BPAR occurred in 39 (23.1%) of the HCV-RNA-positive recipients after LT. The 1-, 3-, and 5-year survival rates were 92.1%, 90.3%, and 88.5%, respectively, in patients without BPAR, and 75.7%, 63.4%, and 58.9% in patients with BPAR (P<0.001). Multivariate analyses showed that BPAR was associated with the non-use of basiliximab and tacrolimus and the use of cyclosporin in LT recipients with HCV RNA-positive. Conclusion The results of the present study suggest that the immunosuppression status of HCV-RNA-positive LT recipients should be carefully determined in order to prevent BPAR and to improve patient survival. PMID:27729628

  3. Imaging-based diagnosis of acute renal allograft rejection

    PubMed Central

    Thölking, Gerold; Schuette-Nuetgen, Katharina; Kentrup, Dominik; Pawelski, Helga; Reuter, Stefan

    2016-01-01

    Kidney transplantation is the best available treatment for patients with end stage renal disease. Despite the introduction of effective immunosuppressant drugs, episodes of acute allograft rejection still endanger graft survival. Since efficient treatment of acute rejection is available, rapid diagnosis of this reversible graft injury is essential. For diagnosis of rejection, invasive core needle biopsy of the graft is the “gold-standard”. However, biopsy carries the risk of significant graft injury and is not immediately feasible in patients taking anticoagulants. Therefore, a non-invasive tool assessing the whole organ for specific and fast detection of acute allograft rejection is desirable. We herein review current imaging-based state of the art approaches for non-invasive diagnostics of acute renal transplant rejection. We especially focus on new positron emission tomography-based as well as targeted ultrasound-based methods. PMID:27011915

  4. Apoptotic tubular cell death during acute renal allograft rejection.

    PubMed

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

    1998-01-01

    Tubular cells are important targets during acute renal allograft rejection and induction of apoptosis might be a mechanism of tubular cell destruction. Susceptibility to induction of apoptosis is regulated by the homologous Bcl-2 and Bax proteins. Expression of Bcl-2 and Bax is regulated by p53, which down-regulates expression of Bcl-2, while simultaneously up-regulating expression of Bax. We studied apoptotic tubular cell death in 10 renal allograft biopsies from transplant recipients with acute rejection by in situ end-labelling and the DNA-binding fluorochrome propidium iodide. Tubular expression of p53, Bcl-2 and Bax was studies by immunohistochemistry. Five renal allograft biopsies from transplant recipients with uncomplicated clinical course and histologically normal renal tissue present in nephrectomy specimens from 4 patients with renal adenocarcinoma served as control specimens. Apoptotic cells and apoptotic bodies were detected in tubular epithelia and tubular lumina in 9 out of 10 acute rejection biopsies. In control renal tissue, apoptotic cells were detected in 1 biopsy only. Compared to control renal tissue, acute renal allograft rejection was, furthermore, associated with a shift in the ratio of Bcl-2 to Bax in favour of Bax in tubular epithelia and increased expression of p53 in tubular nuclei. These observations demonstrate that apoptosis contributes in part to tubular cell destruction during acute renal allograft rejection. In accordance, the shift in the ratio of Bcl-2 to Bax in favour of Bax indicates increased susceptibility of tubular epithelia to induction of apoptosis. The expression of p53 in tubular nuclei during acute renal allograft rejection indicates the presence of damaged DNA, which can be important in initiation of part of the observed apoptosis. These findings elucidate part of the mechanisms controlling apoptotic tubular cell death during acute renal allograft rejection.

  5. Spontaneous restoration of transplantation tolerance after acute rejection.

    PubMed

    Miller, Michelle L; Daniels, Melvin D; Wang, Tongmin; Chen, Jianjun; Young, James; Xu, Jing; Wang, Ying; Yin, Dengping; Vu, Vinh; Husain, Aliya N; Alegre, Maria-Luisa; Chong, Anita S

    2015-01-01

    Transplantation is a cure for end-stage organ failure but, in the absence of pharmacological immunosuppression, allogeneic organs are acutely rejected. Such rejection invariably results in allosensitization and accelerated rejection of secondary donor-matched grafts. Transplantation tolerance can be induced in animals and a subset of humans, and enables long-term acceptance of allografts without maintenance immunosuppression. However, graft rejection can occur long after a state of transplantation tolerance has been acquired. When such an allograft is rejected, it has been assumed that the same rules of allosensitization apply as to non-tolerant hosts and that immunological tolerance is permanently lost. Using a mouse model of cardiac transplantation, we show that when Listeria monocytogenes infection precipitates acute rejection, thus abrogating transplantation tolerance, the donor-specific tolerant state re-emerges, allowing spontaneous acceptance of a donor-matched second transplant. These data demonstrate a setting in which the memory of allograft tolerance dominates over the memory of transplant rejection.

  6. BATF inhibition prevent acute allograft rejection after cardiac transplantation

    PubMed Central

    Yang, Bo; He, Fan; Dai, Chen; Tan, Rumeng; Ma, Dongxia; Wang, Zhimin; Zhang, Bo; Feng, Jincheng; Wei, Lai; Zhu, Hua; Chen, Zhishui

    2016-01-01

    Acute allograft rejection is a serious and life-threatening complication of organ transplantation. Th17 cells induced inflammation has been described to play an important role in allograft rejection. Since there is a plenty of evidence indicating that transcriptional factor BATF regulates the differentiation of Th17 and follicular T helper cells both in vitro and in vivo, we investigated whether is BATF involved in acute rejection and allograft survival by injecting lentivirus containing BATF shRNA through tail vein before the cardiac transplantation operation. We found that the allograft survival time of the mice treated with BATF shRNA was significantly prolonged compared with that of negative shRNA treated group and the control group. Further pathological analysis revealed that the BATF shRNA treatment group had significantly lower rejection degree than the negative shRNA group, while there was no significant difference between the negative shRNA group and the control group. Furthermore, flow cytometry analysis and quantitative polymerase chain reaction and enzyme-linked immuno sorbent assay were used to determine the proportion of T helper cells, the expression of specific transcription factor and the inflammatory cytokines respectively. Data showed that BATF regulated Th17 and Treg responses during allograft rejection. And BATF inhibition led to reduction of the expression level of Rorγ-t and enhancement of the Foxp-3. In addition, cytokines IL-17A and IL-4 were found decreased. This may indicate BATF as a novel therapy target for treatment of acute allograft rejection. PMID:27648151

  7. BATF inhibition prevent acute allograft rejection after cardiac transplantation.

    PubMed

    Yang, Bo; He, Fan; Dai, Chen; Tan, Rumeng; Ma, Dongxia; Wang, Zhimin; Zhang, Bo; Feng, Jincheng; Wei, Lai; Zhu, Hua; Chen, Zhishui

    2016-01-01

    Acute allograft rejection is a serious and life-threatening complication of organ transplantation. Th17 cells induced inflammation has been described to play an important role in allograft rejection. Since there is a plenty of evidence indicating that transcriptional factor BATF regulates the differentiation of Th17 and follicular T helper cells both in vitro and in vivo, we investigated whether is BATF involved in acute rejection and allograft survival by injecting lentivirus containing BATF shRNA through tail vein before the cardiac transplantation operation. We found that the allograft survival time of the mice treated with BATF shRNA was significantly prolonged compared with that of negative shRNA treated group and the control group. Further pathological analysis revealed that the BATF shRNA treatment group had significantly lower rejection degree than the negative shRNA group, while there was no significant difference between the negative shRNA group and the control group. Furthermore, flow cytometry analysis and quantitative polymerase chain reaction and enzyme-linked immuno sorbent assay were used to determine the proportion of T helper cells, the expression of specific transcription factor and the inflammatory cytokines respectively. Data showed that BATF regulated Th17 and Treg responses during allograft rejection. And BATF inhibition led to reduction of the expression level of Rorγ-t and enhancement of the Foxp-3. In addition, cytokines IL-17A and IL-4 were found decreased. This may indicate BATF as a novel therapy target for treatment of acute allograft rejection. PMID:27648151

  8. BATF inhibition prevent acute allograft rejection after cardiac transplantation

    PubMed Central

    Yang, Bo; He, Fan; Dai, Chen; Tan, Rumeng; Ma, Dongxia; Wang, Zhimin; Zhang, Bo; Feng, Jincheng; Wei, Lai; Zhu, Hua; Chen, Zhishui

    2016-01-01

    Acute allograft rejection is a serious and life-threatening complication of organ transplantation. Th17 cells induced inflammation has been described to play an important role in allograft rejection. Since there is a plenty of evidence indicating that transcriptional factor BATF regulates the differentiation of Th17 and follicular T helper cells both in vitro and in vivo, we investigated whether is BATF involved in acute rejection and allograft survival by injecting lentivirus containing BATF shRNA through tail vein before the cardiac transplantation operation. We found that the allograft survival time of the mice treated with BATF shRNA was significantly prolonged compared with that of negative shRNA treated group and the control group. Further pathological analysis revealed that the BATF shRNA treatment group had significantly lower rejection degree than the negative shRNA group, while there was no significant difference between the negative shRNA group and the control group. Furthermore, flow cytometry analysis and quantitative polymerase chain reaction and enzyme-linked immuno sorbent assay were used to determine the proportion of T helper cells, the expression of specific transcription factor and the inflammatory cytokines respectively. Data showed that BATF regulated Th17 and Treg responses during allograft rejection. And BATF inhibition led to reduction of the expression level of Rorγ-t and enhancement of the Foxp-3. In addition, cytokines IL-17A and IL-4 were found decreased. This may indicate BATF as a novel therapy target for treatment of acute allograft rejection.

  9. Biliary epithelial senescence and plasticity in acute cellular rejection.

    PubMed

    Brain, J G; Robertson, H; Thompson, E; Humphreys, E H; Gardner, A; Booth, T A; Jones, D E J; Afford, S C; von Zglinicki, T; Burt, A D; Kirby, J A

    2013-07-01

    Biliary epithelial cells (BEC) are important targets in some liver diseases, including acute allograft rejection. Although some injured BEC die, many can survive in function compromised states of senescence or phenotypic de-differentiation. This study was performed to examine changes in the phenotype of BEC during acute liver allograft rejection and the mechanism driving these changes. Liver allograft sections showed a positive correlation (p < 0.0013) between increasing T cell mediated acute rejection and the number of BEC expressing the senescence marker p21(WAF1/Cip) or the mesenchymal marker S100A4. This was modeled in vitro by examination of primary or immortalized BEC after acute oxidative stress. During the first 48 h, the expression of p21(WAF1/Cip) was increased transiently before returning to baseline. After this time BEC showed increased expression of mesenchymal proteins with a decrease in epithelial markers. Analysis of TGF-β expression at mRNA and protein levels also showed a rapid increase in TGF-β2 (p < 0.006) following oxidative stress. The epithelial de-differentiation observed in vitro was abrogated by pharmacological blockade of the ALK-5 component of the TGF-β receptor. These data suggest that stress induced production of TGF-β2 by BEC can modify liver allograft function by enhancing the de-differentiation of local epithelial cells.

  10. Plasma cell-rich acute rejection of the renal allograft: A distinctive morphologic form of acute rejection?

    PubMed

    Gupta, R; Sharma, A; Mahanta, P J; Agarwal, S K; Dinda, A K

    2012-05-01

    This study was aimed at evaluating the clinicopathologic features of plasma cell-rich acute rejection (PCAR) of renal allograft and comparing them with acute cellular rejection (ACR), non-plasma cell-rich type. During a 2-year period, eight renal allograft biopsies were diagnosed as PCAR (plasma cells >10% of interstitial infiltrate). For comparison, 14 biopsies with ACR were included in the study. Detailed pretransplant data, serum creatinine at presentation, and other clinical features of all these cases were noted. Renal biopsy slides were reviewed and relevant immunohistochemistry performed for characterization of plasma cell infiltrate. The age range and duration of transplantation to diagnosis of acute rejection were comparable in both the groups. Histologically, the proportion of interstitial plasma cells, mean interstitial inflammation, and tubulitis score were higher in the PCAR group compared with cases with ACR. A significant difference was found in the outcome at last follow-up, being worse in patients with PCAR. This study shows that PCAR portends a poor outcome compared with ACR, with comparable Banff grade of rejection. Due to its rarity and recent description, nephrologists and renal pathologists need to be aware of this entity.

  11. Blocking MHC class II on human endothelium mitigates acute rejection

    PubMed Central

    Abrahimi, Parwiz; Qin, Lingfeng; Chang, William G.; Bothwell, Alfred L.M.; Tellides, George; Saltzman, W. Mark; Pober, Jordan S.

    2016-01-01

    Acute allograft rejection is mediated by host CD8+ cytotoxic T lymphocytes (CTL) targeting graft class I major histocompatibility complex (MHC) molecules. In experimental rodent models, rejection requires differentiation of naive CD8+ T cells into alloreactive CTL within secondary lymphoid organs, whereas in humans, CTL may alternatively develop within the graft from circulating CD8+ effector memory T cells (TEM) that recognize class I MHC molecules on graft endothelial cells (EC). This latter pathway is poorly understood. Here, we show that host CD4+ TEM, activated by EC class II MHC molecules, provide critical help for this process. First, blocking HLA-DR on EC lining human artery grafts in immunodeficient mice reduces CD8+ CTL development within and acute rejection of the artery by adoptively transferred allogeneic human lymphocytes. Second, siRNA knockdown or CRISPR/Cas9 ablation of class II MHC molecules on EC prevents CD4+ TEM from helping CD8+ TEM to develop into CTL in vitro. Finally, implanted synthetic microvessels, formed from CRISPR/Cas9-modified EC lacking class II MHC molecules, are significantly protected from CD8+ T cell–mediated destruction in vivo. We conclude that human CD8+ TEM–mediated rejection targeting graft EC class I MHC molecules requires help from CD4+ TEM cells activated by recognition of class II MHC molecules. PMID:26900601

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

    SciTech Connect

    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

  13. Acute rejection in low-toxicity regimens: clinical impact and risk factors in the Symphony study.

    PubMed

    Frei, Ulrich; Daloze, Pierre; Vítko, Stefan; Klempnauer, Jürgen; Reyes-Acevedo, Rafael; Titiz, Izzet; Fricke, Lutz; Bernasconi, Corrado; Ekberg, Henrik

    2010-01-01

    The Symphony study assessed whether mycophenolate mofetil (MMF)-based regimens containing reduced doses of adjunct immunosuppressants could reduce toxicity while maintaining efficacy. Here, we examined the impact of acute rejection and associated risk factors. The incidence of biopsy-proven acute rejection in the low-dose tacrolimus group was approximately half that of the standard-dose cyclosporine and low-dose cyclosporine groups, and a third of that in the low-dose sirolimus group. The low-dose cyclosporine group had more severe rejection episodes (≥grade II) compared with other groups. Acute rejection was associated with a 10 mL/min glomerular filtration rate (GFR) reduction and a 5.3% absolute increase in graft loss at 12 months. Overall, the highest GFR was found in both rejecters and non-rejecters receiving low-dose tacrolimus, both in an intent-to-treat analysis and in patients successfully treated according to the protocol. In Cox regression models, human leukocyte antigen (HLA) mismatches and expanded criteria donors increased the acute rejection risk, while recipient age, living related donor, and MMF dose were associated with a reduced risk. Acute rejection was associated with worse outcome but did not entirely explain the differences among the treatment groups. The 2 g MMF plus low-dose tacrolimus combination appears to be the most efficient of all regimens examined regardless of acute rejection.

  14. Longitudinal analysis of whole blood transcriptomes to explore molecular signatures associated with acute renal allograft rejection.

    PubMed

    Shin, Heesun; Günther, Oliver; Hollander, Zsuzsanna; Wilson-McManus, Janet E; Ng, Raymond T; Balshaw, Robert; Keown, Paul A; McMaster, Robert; McManus, Bruce M; Isbel, Nicole M; Knoll, Greg; Tebbutt, Scott J

    2014-01-01

    In this study, we explored a time course of peripheral whole blood transcriptomes from kidney transplantation patients who either experienced an acute rejection episode or did not in order to better delineate the immunological and biological processes measureable in blood leukocytes that are associated with acute renal allograft rejection. Using microarrays, we generated gene expression data from 24 acute rejectors and 24 nonrejectors. We filtered the data to obtain the most unambiguous and robustly expressing probe sets and selected a subset of patients with the clearest phenotype. We then performed a data-driven exploratory analysis using data reduction and differential gene expression analysis tools in order to reveal gene expression signatures associated with acute allograft rejection. Using a template-matching algorithm, we then expanded our analysis to include time course data, identifying genes whose expression is modulated leading up to acute rejection. We have identified molecular phenotypes associated with acute renal allograft rejection, including a significantly upregulated signature of neutrophil activation and accumulation following transplant surgery that is common to both acute rejectors and nonrejectors. Our analysis shows that this expression signature appears to stabilize over time in nonrejectors but persists in patients who go on to reject the transplanted organ. In addition, we describe an expression signature characteristic of lymphocyte activity and proliferation. This lymphocyte signature is significantly downregulated in both acute rejectors and nonrejectors following surgery; however, patients who go on to reject the organ show a persistent downregulation of this signature relative to the neutrophil signature.

  15. Acute Antibody-Mediated Rejection in Renal Transplantation: Current Clinical Management

    PubMed Central

    Schinstock, Carrie; Stegall, Mark D.

    2014-01-01

    Acute antibody mediated rejection (AMR) is recognized as a major cause of graft loss in renal transplant recipients. Early acute AMR in the first few days after transplantation occurs primarily in sensitized renal transplant recipients with donor-specific alloantibody at the time of transplant and is a relatively “pure” form of acute AMR. Late acute AMR occurs months to years after transplantation and is commonly a mixed cellular and humoral rejection. While there is no consensus regarding optimum treatment, we contend that rational therapeutic approaches are emerging and the acute episode can be managed in most instances. However, new therapies are needed to prevent ongoing chronic injury in these patients.

  16. Nerve Regeneration in Rat Limb Allografts: Evaluation of Acute Rejection Rescue

    PubMed Central

    Yan, Ying; MacEwan, Matthew R.; Hunter, Daniel A.; Farber, Scott; Newton, Piyaraj; Tung, Thomas H.; Mackinnon, Susan E.; Johnson, Philip J.

    2013-01-01

    Background Successful nerve regeneration is critical to the functional success of composite tissue allografts (CTA). The present study was designed to characterize the effect of acute rejection on nerve regeneration and functional recovery in the setting of orthotopic limb transplantation. Methods A rat orthotopic limb transplantation model was used to evaluate the effects of acute rejection on nerve regeneration and motor recovery. Continuous administration of FK506 (Full suppression), administration of FK506 for the first 8 of 12 weeks (Late rejection), or delayed administration of FK506 / dexamethasone following noticeable rejection (Early rejection) was used to preclude or induce rejection following limb transplantation. Twelve weeks postoperatively, nerve regeneration was assessed via histomorphometric analysis of explanted sciatic nerve, and motor recovery was assessed via evoked muscle force measurement in extensor digitorum longus (EDL) muscle. Results A single episode of acute rejection that occurs immediately or late after reconstruction does not significantly alter the number of regenerating axonal fibers. Acute rejection occurring late after reconstruction adversely affects EDL muscle function in CTA. Conclusion Collected data reinforces that adequate immunosuppressant administration in cases of allogeneic limb transplantation ensures levels of nerve regeneration and motor functional recovery equivalent to that of syngeneic transplants. Prompt rescue following acute rejection was further demonstrated not to significantly affect nerve regeneration and functional recovery post-operatively. However, instances of acute rejection that occur late after reconstruction affect graft function. In total, the present study begins to characterize the effect of immunosuppression regimens on nerve regeneration and motor recovery in the setting of CTA. PMID:23542267

  17. Aggressive treatment of the first acute rejection episode using first-line anti-lymphocytic preparation reduces further acute rejection episodes after human kidney transplantation.

    PubMed

    Theodorakis, J; Schneeberger, H; Illner, W D; Stangl, M; Zanker, B; Land, W

    1998-01-01

    The detrimental effect of acute rejection episodes on long-term outcome of renal allografts in cyclosporin-treated patients is well established, although has not been seen by all investigators. To analyse the possibility that aggressive treatment of the first episode may ameliorate this detrimental effect, we performed an open label, randomised prospective trial in cyclosporin-based, immunosuppressed recipients of postmortem renal allografts in order to compare two different treatment protocols during primary acute rejection episodes: (1) group 1 of 25 patients received 3 x 250 mg methylprednisolone (MP) i.v.; (2) group 2 of 25 patients received 7 x anti-thymocyte globulin (ATG)-Fresenius i.v. (4 mg/kg body weight). During a period of 4 years, the following clinical observations were made: (1) The incidence of an acute re-rejection episode was significantly reduced in the ATG-treated study group (16%) compared to the MP-treated study group (72%); (2) The severity of the first acute rejection episode (intensity of renal dysfunction measured in terms of 10-day creatinine area under curve) showed no significant difference between the groups (37 mg x 10-d/dl to 58 mg x 10-d/dl); and (3) The half-lives of allografts in both groups have not shown any significant differences so far. In conclusion, aggressive treatment of the first rejection episode of renal allografts with the use of ATG reduced the incidence of re-rejection episodes which, however, are not reflected so far by improvement of the 4-year survival rate of these allografts. Since it could be observed that re-rejection is an even worse predictor for chronic transplant failure, a better long-term outcome of renal allografts in ATG-treated patients may be expected during a longer observation period. The incidence of a third episode was also reduced in the ATG-treated group (0%) compared to the MP-treated group (12%).

  18. Granzyme expression in fine-needle aspirates from liver allografts is increased during acute rejection.

    PubMed

    Kuijf, M L; Kwekkeboom, Jaap; Kuijpers, Marianne A; Willems, Marc; Zondervan, Pieter E; Niesters, Hubert G M; Hop, Wim C J; Hack, C Erik; Paavonen, Timo; Höckerstedt, Krister; Tilanus, Hugo W; Lautenschlager, Irmeli; Metselaar, Herold J; Kuijf, Mark M L

    2002-10-01

    We investigated whether determination in fine-needle aspiration biopsy (FNAB) specimens of cells expressing granzymes (Grs) and Fas ligand would provide a reliable, easy, and quantitative measure of rejection activity in the transplanted liver. Retrospectively, 13 FNAB specimens obtained during clinical acute rejection, 10 FNAB specimens obtained during subclinical rejection, 12 FNAB specimens obtained during cytomegalovirus (CMV) infection, and 26 FNAB specimens obtained in the absence of rejection or infection were included on the study. Cytospin preparations of FNAB and peripheral-blood specimens were immunocytochemically stained for Fas-ligand and Gr, and increments in the liver were calculated by subtracting frequencies of positive cells in blood from those in FNAB specimens. Only sporadically Fas ligand-expressing, but many Gr-expressing, cells were detected in FNAB specimens. Increments in Gr-positive (Gr(+)) cells were significantly greater in FNAB specimens obtained during clinical rejection (median, 70 Gr(+) cells; range, 0 to 312 Gr(+) cells; P = .006) and tended to be greater in FNAB specimens obtained during subclinical rejection (median, 62 Gr(+) cells; range, 5 to 113 Gr(+) cells; P = .09) compared with those obtained in the absence of rejection (median, 16 Gr(+) cells; range, 0 to 103 Gr(+) cells). Increments obtained during clinical or subclinical rejection did not differ from those obtained during CMV infection (median, 27 Gr(+) cells; range, 6 to 212 Gr(+) cells). With the exclusion of specimens obtained during CMV infection, the sensitivity of Gr determination in FNAB specimens for the diagnosis of acute rejection (either clinical or subclinical) was 70%, and specificity, 69%. In FNAB specimens obtained during clinical and subclinical acute rejection episodes after liver transplantation, increased numbers of Gr-expressing cells were present; in the absence of CMV infection, their quantification provides a measure for rejection activity with

  19. The Complex Role of iNOS in Acutely-Rejecting Cardiac Transplants

    PubMed Central

    Pieper, Galen M.; Roza, Allan M.

    2008-01-01

    This review summarizes the evidence for a detrimental role of nitric oxide (NO) derived from inducible NO synthase (iNOS) and/or reactive nitrogen species such as peroxynitrite in acutely-rejecting cardiac transplants. In chronic cardiac transplant rejection, iNOS may have an opposing beneficial component. The purpose of this review is primarily to address issues related to acute rejection which is a recognized risk factor for chronic rejection. The evidence for a detrimental role is based upon strategies involving non-selective NOS inhibitors, NO neutralizers, selective iNOS inhibitors and iNOS gene deletion in rodent models of cardiac rejection. The review is discussed in the context of the impact on various components including graft survival, histological rejection and cardiac function which may contribute in toto to the process of graft rejection. Possible limitations of each strategy are discussed in order to understand better the variance in published findings including issues related to the potential importance of cell localization of iNOS expression. Finally, the concept of a dual role of NO and its down-stream product, peroxynitrite, in rejection vs. immune regulation is discussed. PMID:18291116

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

    PubMed Central

    de Camargo, Priscila Cilene León Bueno; Afonso, José Eduardo; Samano, Marcos Naoyuki; Acencio, Milena Marques Pagliarelli; Antonangelo, Leila; Teixeira, Ricardo Henrique de Oliveira Braga

    2014-01-01

    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. PMID:25210966

  1. The effect of cytomegalovirus infection on acute rejection in kidney transplanted patients

    PubMed Central

    Hasanzamani, Boshra; Hami, Maryam; Zolfaghari, Vajihe; Torkamani, Mahtab; Ghorban Sabagh, Mahin; Ahmadi Simab, Saiideh

    2016-01-01

    Introduction: It is known that cytomegalovirus (CMV) infection is a common problem among kidney transplant patients. This infection can be increased morbidity and decreased graft survival. This problem has been associated with acute rejection too. Patients and Methods: One hundred and thirty renal transplant patients were included in a prospective, case-control study. The renal transplant patients were divided into two groups; patients group with CMV infection and control group without CMV infection. Serum CMV-IgG in all patients was positive (donor and recipients). None of patients had received anti-thymocyte-globulin and thymoglobulin. CMV infection was diagnosed by quantitative CMV-PCR (polymerase chain reaction) test (more than 500 copies/μg). Rejection episode was defined by kidney isotope scan or biopsy. Results: In the group of 66 CMV infection patients (41 male [62.1%] and 25 female [37.9%]) the incidence of graft rejection was 36%, however in the group of 64 control patients the incidence of graft rejection was 9.4 % (P < 0.005). Conclusion: CMV infection is important predisposing factor for acute allograft rejection after kidney transplantation. The results of this study suggests that the control of CMV infection could decrease episodes of acute kidney rejection. PMID:27471740

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

    PubMed

    Wolfram, Dolores; Starzl, Ravi; Hackl, Hubert; Barclay, Derek; Hautz, Theresa; Zelger, Bettina; Brandacher, Gerald; Lee, W P Andrew; Eberhart, Nadine; Vodovotz, Yoram; Pratschke, Johann; Pierer, Gerhard; Schneeberger, Stefan

    2014-01-01

    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.

  3. Requirement of the Chemokine Receptor CXCR3 for Acute Allograft Rejection

    PubMed Central

    Hancock, Wayne W.; Lu, Bao; Gao, Wei; Csizmadia, Vilmos; Faia, Kerrie; King, Jennifer A.; Smiley, Stephen T.; Ling, Mai; Gerard, Norma P.; Gerard, Craig

    2000-01-01

    Chemokines provide signals for activation and recruitment of effector cells into sites of inflammation, acting via specific G protein–coupled receptors. However, in vitro data demonstrating the presence of multiple ligands for a given chemokine receptor, and often multiple receptors for a given chemokine, have led to concerns of biologic redundancy. Here we show that acute cardiac allograft rejection is accompanied by progressive intragraft production of the chemokines interferon (IFN)-γ–inducible protein of 10 kD (IP-10), monokine induced by IFN-γ (Mig), and IFN-inducible T cell α chemoattractant (I-TAC), and by infiltration of activated T cells bearing the corresponding chemokine receptor, CXCR3. We used three in vivo models to demonstrate a role for CXCR3 in the development of transplant rejection. First, CXCR3-deficient (CXCR3−/−) mice showed profound resistance to development of acute allograft rejection. Second, CXCR3−/− allograft recipients treated with a brief, subtherapeutic course of cyclosporin A maintained their allografts permanently and without evidence of chronic rejection. Third, CXCR+/+ mice treated with an anti-CXCR3 monoclonal antibody showed prolongation of allograft survival, even if begun after the onset of rejection. Taken in conjunction with our findings of CXCR3 expression in rejecting human cardiac allografts, we conclude that CXCR3 plays a key role in T cell activation, recruitment, and allograft destruction. PMID:11085753

  4. Usefulness of liver stiffness measurement during acute cellular rejection in liver transplantation.

    PubMed

    Crespo, Gonzalo; Castro-Narro, Graciela; García-Juárez, Ignacio; Benítez, Carlos; Ruiz, Pablo; Sastre, Lydia; Colmenero, Jordi; Miquel, Rosa; Sánchez-Fueyo, Alberto; Forns, Xavier; Navasa, Miquel

    2016-03-01

    Liver stiffness measurement (LSM) is a useful method to estimate liver fibrosis and portal hypertension. The inflammatory process that takes place in post-liver transplant acute cellular rejection (ACR) may also increase liver stiffness. We aimed to explore the association between liver stiffness and the severity of ACR, as well as to assess the relationship between liver stiffness and response to rejection treatment in a prospective study that included 27 liver recipients with biopsy-proven ACR, 30 stable recipients with normal liver tests, and 30 hepatitis C virus (HCV)-infected LT recipients with histologically diagnosed HCV recurrence. Patients with rejection were stratified into 2 groups (mild and moderate/severe) according to the severity of rejection evaluated with the Banff score. Routine biomarkers and LSM with FibroScan were performed at the time of liver biopsy (baseline) and at 7, 30, and 90 days in patients with rejection and at baseline in control patients. Median baseline liver stiffness was 5.9 kPa in the mild rejection group, 11 kPa in the moderate/severe group (P = 0.001), 4.2 kPa in stable recipients (P = 0.02 versus mild rejection), and 13.6 kPa in patients with recurrent HCV (P = 0.17 versus moderate/severe rejection). The area under the receiver operator characteristic curve of LSM to discriminate mild versus moderate/severe ACR was 0.924, and a LSM value of 8.5 kPa yielded a positive predictive value of 100% to diagnose moderate/severe rejection. Liver stiffness improved in 7%, 21%, and 64% of patients with moderate/severe rejection at 7, 30, and 90 days. In conclusion, according to the results of this exploratory study, LSM is associated with the severity of ACR in liver transplantation and thus may be of help in its assessment. PMID:26609794

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

    PubMed

    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.

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

    PubMed Central

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

    2016-01-01

    Background 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. Results 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. Conclusions 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. PMID:27631127

  7. Spleen tyrosine kinase contributes to acute renal allograft rejection in the rat.

    PubMed

    Ramessur Chandran, Sharmila; Tesch, Greg H; Han, Yingjie; Woodman, Naomi; Mulley, William R; Kanellis, John; Blease, Kate; Ma, Frank Y; Nikolic-Paterson, David J

    2015-02-01

    Kidney allografts induce strong T-cell and antibody responses which mediate acute rejection. Spleen tyrosine kinase (Syk) is expressed by most leucocytes, except mature T cells, and is involved in intracellular signalling following activation of the Fcγ-receptor, B-cell receptor and some integrins. A role for Syk signalling has been established in antibody-dependent native kidney disease, but little is known of Syk in acute renal allograft rejection. Sprague-Dawley rats underwent bilateral nephrectomy and received an orthotopic Wistar renal allograft. Recipient rats were treated with a Syk inhibitor (CC0482417, 30 mg/kg/bid), or vehicle, from 1 h before surgery until being killed 5 days later. Vehicle-treated recipients developed severe allograft failure with marked histologic damage in association with dense leucocyte infiltration (T cells, macrophages, neutrophils and NK cells) and deposition of IgM, IgG and C3. Immunostaining identified Syk expression by many infiltrating leucocytes. CC0482417 treatment significantly improved allograft function and reduced histologic damage, although allograft injury was still clearly evident. CC0482417 failed to prevent T-cell infiltration and activation within the allograft. However, CC0482417 significantly attenuated acute tubular necrosis, infiltration of macrophages and neutrophils and thrombosis of peritubular capillaries. In conclusion, this study identifies a role for Syk in acute renal allograft rejection. Syk inhibition may be a useful addition to T-cell-based immunotherapy in renal transplantation.

  8. Expression of granzyme A and B proteins by cytotoxic lymphocytes involved in acute renal allograft rejection.

    PubMed

    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 staining techniques we investigated expression of granzyme A and B by lymphocytes infiltrating acutely rejected renal allografts. Twelve core needle biopsies were taken from ten different patients during an episode of acute rejection. Eleven biopsies contained high numbers of granzyme A and B positive lymphocytes infiltrating tubular epithelium, and vascular and glomerular structures. In one patient infiltrating lymphocytes did not express granzyme A and only low amounts of granzyme B. No correlation was found between the number of granzyme positive cells and the severity of the rejection as classified by conventional histological criteria. In one tissue specimen from a patient with a renal allograft without signs of rejection, the number of granzyme positive cells was much lower compared to that of the transplant group. In spite of the presence of a marked inflammatory infiltrate, no granzyme positive cells were detected in renal biopsies from patients with various inflammatory, not transplant-related, renal diseases. Phenotypic analysis showed that granzymes A and B were expressed by CD56+ NK cells and CD3+ cells, representing cytotoxic T-lymphocytes. Thus, this study demonstrates that granzyme A and B protein-expressing lymphocytes infiltrate the kidney allografts during an acute cellular rejection but not in several other inflammatory renal diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Tumor Necrosis Factor Receptor 2: Its Contribution to Acute Cellular Rejection and Clear Cell Renal Carcinoma

    PubMed Central

    Wang, Jun; Al-Lamki, Rafia S.

    2013-01-01

    Tumor necrosis factor receptor 2 (TNFR2) is a type I transmembrane glycoprotein and one of the two receptors that orchestrate the complex biological functions of tumor necrosis factor (TNF, also designed TNF-α). Accumulating experimental evidence suggests that TNFR2 plays an important role in renal disorders associated with acute cellular rejection and clear cell renal carcinoma but its exact role in these settings is still not completely understood. This papers reviews the factors that may mediate TNFR2 induction in acute cellular rejection and clear cell renal carcinoma and its contribution to these conditions and discusses its therapeutic implications. A greater understanding of the function of TNFR2 may lead to the development of new anti-TNF drugs. PMID:24350291

  10. Combined Detection of Serum IL-10, IL-17, and CXCL10 Predicts Acute Rejection Following Adult Liver Transplantation

    PubMed Central

    Kim, Nayoung; Yoon, Young-In; Yoo, Hyun Ju; Tak, Eunyoung; Ahn, Chul-Soo; Song, Gi-Won; Lee, Sung-Gyu; Hwang, Shin

    2016-01-01

    Discovery of non-invasive diagnostic and predictive biomarkers for acute rejection in liver transplant patients would help to ensure the preservation of liver function in the graft, eventually contributing to improved graft and patient survival. We evaluated selected cytokines and chemokines in the sera from liver transplant patients as potential biomarkers for acute rejection, and found that the combined detection of IL-10, IL-17, and CXCL10 at 1-2 weeks post-operation could predict acute rejection following adult liver transplantation with 97% specificity and 94% sensitivity. PMID:27498551

  11. Myoglobinuria masquerading as acute rejection in a renal allograft recipient with recurrent post transplant diabetic nephropathy.

    PubMed

    Gupta, Pallav; Sharma, Amit; Khullar, Dinesh

    2014-08-01

    Rhabdomyolysis contributes to 7-10% of total AKI cases. Myoglobinuria as a cause of acute renal allograft dysfunction is extremely uncommon. Renal allograft recipient on cyclosporine or tacrolimus can develop myoglobinuria in presence of other precipitating factors. Present case describes an interesting report of myoglobinuria in a patient with post transplant diabetic nephropathy mimicking acute graft rejection. Clinically myoglobinuria presenting as renal allograft dysfunction is diagnosis of exclusion and renal biopsy is extremely important in making a correct diagnosis and planning optimal management in such cases.

  12. The effect of pravastatin on acute rejection after kidney transplantation--a pilot study.

    PubMed

    Katznelson, S; Wilkinson, A H; Kobashigawa, J A; Wang, X M; Chia, D; Ozawa, M; Zhong, H P; Hirata, M; Cohen, A H; Teraski, P I

    1996-05-27

    Hyperlipidemia is an important complication of kidney transplantation affecting up to 74% of recipients. HMG-CoA reductase inhibitors are reported to provide safe and effective treatment for this problem. A recent study suggests that pravastatin, an HMG-CoA reductase inhibitor, also decreases the incidence of both clinically severe acute rejection episodes and natural killer cell cytotoxicity after orthotopic heart transplantation. We have performed a prospective randomized pilot study of the effect of pravastatin on these same parameters after cadaveric kidney transplantation. Graft recipients were randomized to receive pravastatin after transplantation or no pravastatin (24 patients in each group) in addition to routine cyclosporine and prednisone immunosuppression. Lipid levels, acute rejection episodes and serial natural killer cell cytotoxicities were followed for 4 months after the transplant. At the end of the study period, pravastatin had successfully controlled mean total cholesterol levels (202.6 +/- 9.3 vs. 236.5 +/- 11.9 mg/dl, P < 0.02), LDL levels (107.9 +/- 6.6 vs.149.6 +/- 10.7 mg/dl, P < 0.002), and triglyceride levels (118.8 +/- 14.2 vs. 157.2 +/- 13.8 mg/dl, P < 0.05). In addition, the pravastatin-treated group experienced a reduction in the incidence of biopsy-proven acute rejection episodes (25% vs. 58%, P = 0.01), the incidence of multiple rejections episodes (P < 0.05), and the use of both pulse methylprednisolone (P = 0.01) and OKT3 (P = 0.02). Mean natural killer cell cytotoxicity was similarly reduced (11.3 +/- 1.6 vs. 20.0 +/- 2.0% lysis of K562 target cells, P < 0.002). These data suggest that pravastatin exerts an additional immunosuppressive effect in kidney transplant recipients treated with cyclosporine-based immunosuppression. PMID:8633373

  13. Characterization of acute renal allograft rejection by proteomic analysis of renal tissue in rat.

    PubMed

    Chen, Gang; Huang, Jing-Bin; Mi, Jie; He, Yun-Feng; Wu, Xiao-Hou; Luo, Chun-Li; Liang, Si-Min; Li, Jia-Bing; Tang, Ya-Xiong; Li, Jie

    2012-02-01

    Rapid and reliable biomarkers of renal allograft rejection have not been available. This study aimed to investigate biomarkers in renal allograft tissue using proteomic analysis. Orthotopic kidney transplantations were performed using Fisher (F344) or Lewis rats as donors and Lewis rats as recipients. Syngenic control group (Group I) constituted F344-to-F344 orthotopic kidney allo-transplantations (n = 8); and allogenic group (Group II) consisted of F344-to-Lewis orthotopic kidney allo-transplantations (n = 8). Renal tissues were harvested 7 days after transplantation. Samples were analyzed using 2-D electrophoresis and matrix assisted laser desorption ionization-time of flight mass spectrometry. 6 differentially expressed proteins were identified between allogenic group and syngenic control group. A rat model of acute renal allograft rejection was successfully set up. Differentially expressed proteins in renal allograft tissue of rat were detected using proteomic analysis and might serve as novel diagnostic and therapeutic targets in human. Quantitative proteomics, using MALDL-TOF-MS methodology has the potential to provide a profiling and a deeper understanding of acute renal rejection.

  14. Effect of adopting a new histological grading system of acute rejection after heart transplantation

    PubMed Central

    Balk, A.; Zondervan, P.; van der Meer, P.; van Gelder, T.; Mochtar, B.; Simoons, M.; Weimar, W.

    1997-01-01

    Background—Treatment policy of acute rejection after heart transplantation has been changed after adopting the ISHLT endomyocardial biopsy grading system in 1991.
Objective—To determine the effect of this policy change on clinical outcome after transplantation.
Methods—The outcome of 147 patients who had a transplant before (early group, median follow up 96 months) and 114 patients who had a transplant after (late group, median follow up 41 months) the introduction of the ISHLT biopsy grading system was studied retrospectively. Initially "moderate rejection" according to Billingham's conventional criteria was treated. From January 1991 grade 3A and higher was considered to require intensification of immunosuppression.
Results—There were some differences between the two groups: recipients (50 v 44 years) as well as donors (28 v 24 years) were older in the "late group" and more patients of this group received early anti-T cell prophylaxis (92% v 56%). Despite more extensive use of early prophylaxis more rejection episodes were diagnosed (2.4 v 1.4) and considerably more courses of rejection treatment were instituted in the late compared with the early group (3.2 v 1.5). There were no deaths because of rejection in the late group, however, more infections occurred within the first year (mean 1.8 v 1.4) and more non-skin malignancies within the first 41 months were diagnosed (8 of 57 v 6 of 147, 95% CIs of difference includes 0). The incidence of graft vascular disease in the late group has been comparable to the early group until now. 
Conclusion—The interpretation of the ISHLT grading system resulted in lowering of the threshold for the diagnosis of rejection thereby increasing the number of rejections and subsequently the immunosuppressive load and its complications.

 Keywords: transplantation;  biopsy grading system;  rejection PMID:9470880

  15. Participation of functionally active plasma cells in acute rejection and response to therapy in renal allografts.

    PubMed

    Bhat, Zeenat Yousuf; Bostwick, David G; Hossain, Deloar; Zeng, Xu

    2014-07-01

    Acute rejection (AR) includes T-cell-mediated and antibody-mediated rejection. The inflammatory infiltrate comprised not only T cells but also varying amounts of B cells (CD20(+)) and plasma cells (CD138(+)). The latter are associated with poor clinical outcomes, but their functional status is not clear. The phosphorylation of the S6 ribosomal protein (p-S6RP) is present in cells that are metabolically active, thus identifying functionally active antibody-secreting plasma cells. This study was designed to evaluate the clinical significance of functionally active p-S6RP plasma cells in AR in renal allografts. Renal allografts with biopsy evidence of AR during 2006-2009 were included. Immunohistochemistry staining for CD20, CD138, and p-S6RP was performed on paraffin-embedded slides and scaled as 0-6. The response to antirejection treatment was assessed by the serum creatinine ratio (CrR) at rejection episode (time 0) and following treatment (4 and 12 weeks). Patients with lower scores (0-2) were compared with a higher scored group (3-6). The T-test was conducted using statistical significance of p<0.05. A total of 28 patients (40.7 ± 14.3 year; M:F=15:13) were diagnosed with acute T-cell-mediated rejection (I and II). The p-S6RP staining in the high-score group had a significantly higher CrR (p<0.05) than the low-score group at the time of biopsy, 4 and 12 weeks following treatment. There was no significant difference in the CrR between groups for CD20 or CD138 staining. Functional antibody-secreting p-S6RP plasma cells are actively participating in AR and associated with poor response to treatment in renal allografts. PMID:24684655

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

    SciTech Connect

    Liu, Xiaoyou; Dong, Changgui; Jiang, Zhengyao; Wu, William K.K.; Chan, Matthew T.V.; Zhang, Jie; Li, Haibin; Qin, Ke; Sun, Xuyong

    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.

  17. Difficulties, guidelines and review of developing an acute rejection model after rat intestinal transplantation.

    PubMed

    Andres, Ane Miren; Santamaria, Monica; Hernandez-Oliveros, Francisco; Guerra, Laura; Lopez, Sergio; Stringa, Pablo; Vallejo, Maria Teresa; Largo, Carlota; Encinas, Jose Luis; Garcia de Las Heras, Maria Soledad; Lopez-Santamaria, Manuel; Tovar, Juan Antonio

    2016-05-01

    Experimental small bowel transplantation (SBT) in rats has been proven to be a useful tool for the study of ischemia-reperfusion and immunological aspects related to solid organ transplantation. However, the model is not completely refined, specialized literature is scarce and complex technical details are typically omitted or confusing. Most studies related to acute rejection (AR) use the orthotopic standard, with small sample sizes due to its high mortality, whereas those studying chronic rejection (CR) use the heterotopic standard, which allows longer term survival but does not exactly reflect the human clinical scenario. Various animal strains have been used, and the type of rejection and the timing of its analysis differ among authors. The double purpose of this study was to develop an improved unusual AR model of SBT using the heterotopic technique, and to elaborate a guide useful to implement experimental models for studying AR. We analyzed the model's technical details and expected difficulties in overcoming the learning curve for such a complex microsurgical model, identifying the potential problem areas and providing a step-by-step protocol and reference guide for future surgeons interested in the topic. We also discuss the historic and more recent options in the literature. PMID:27102447

  18. Bacterial translocation in acute rejection after small bowel transplantation in rats.

    PubMed

    Zou, Y; Hernandez, F; Burgos, E; Martinez, L; Gonzalez-Reyes, S; Fernandez-Dumont, V; Lopez, G; Romero, M; Lopez-Santamaria, M; Tovar, J A

    2005-03-01

    Acute rejection after small bowel transplantation (SBTx) may facilitate bacterial translocation (BT) and subsequent changes in the liver, spleen, and lungs. This study investigated whether BT occurs after acute rejection and whether this is followed by changes in the structure of the intestine and the phagocytic organs interposed between the gut and the general circulation. Orthotopic SBTx was performed in allogeneic (ALLO) rat-strain combinations (BN-Wistar, n=5). For comparison we used syngeneic SBTx (SYN) (BN-BN, n=6) controls. Animals were sacrificed on postoperative day 7. Mesenteric lymph nodes and portal and caval blood were cultured for aerobes and anaerobes. Escherichia coli beta-galactosidase DNA was assessed by polymerase chain reaction in the blood samples. Intestine, liver, spleen, and lung protein and DNA contents were measured. Histologic changes were graded according to standard criteria of acute rejection. For comparisons we used chi(2) and nonparametric Mann-Whitney test with a threshold of significance of p<0.05. ALLO rats lost more weight after SBTx than SYN rats (-13.02+/-4.39% vs. -8.04+/-5.08% of preoperative weight), although the difference was not significant (ns). A variable degree of graft rejection was histologically demonstrated in all ALLO rats, and DNA/protein content in the graft was significantly higher in this group (0.245+/-0.85 vs. 0.134+/-0.21, p<0.05). Gram-negative enteric bacteria were found in 4/5 ALLO and 4/6 SYN rats (ns), and aerobic Gram-positive bacteria in 2/5 and 3/6 (ns), respectively. Anaerobic growth occurred in mesenteric lymph nodes in one ALLO rat and in the bloodstream in another one. E. coli DNA was isolated in none of the ALLO but in two SYN rats (ns). BT was frequent after SBTx in both syngeneic and allogeneic strain combinations. Contrary to our expectations, BT after SBTx was not higher in ALLO group rats. However, anaerobic germs were isolated only in this group.

  19. Doppler spectrum analysis to diagnose rejection during posttransplant acute renal failure.

    PubMed

    Merkus, J W; Hoitsma, A J; van Asten, W N; Koene, R A; Skotnicki, S H

    1994-09-15

    During posttransplant acute renal failure (ARF), the diagnosis of allograft rejection constitutes a major problem. We evaluated the value of Doppler ultrasonography in identifying grafts at risk of rejection during ARF. In 184 recipients of a renal allograft, Doppler examinations were performed on the first and fifth postoperative day. Doppler spectra were quantitatively analyzed with a user-written computer program. Doppler findings were not used in clinical decision making. ARF was defined as a diuresis < 400 ml/24 hr and/or the necessity for dialysis. Doppler spectra obtained on the first day after transplantation showed a resistance index (RI) of 0.59 +/- 0.09 in recipients with immediately functioning cadaveric grafts (n = 123), while living related donor grafts (n = 20) showed a lower RI (0.55 +/- 0.07; P < 0.05). Grafts with ARF (n = 41) showed a considerably higher RI (0.67 +/- 0.13; P < 0.05). When grafts with a duration of ARF < or = 4 days (n = 17) were compared with ARF > 4 days (n = 24), RI was not significantly different (0.63 +/- 0.07 vs. 0.68 +/- 0.15; NS). However, the acceleration time of the systolic deflection of the spectrum waveform (Tmax) was shorter in grafts with ARF > 4 days (86 +/- 47 msec vs. 128 +/- 39 msec; P < 0.05). On the fifth day after transplantation, Doppler spectra in grafts with ARF > 4 days (n = 24) showed a Tmax < 90 msec in 9 patients, 8 of whom experienced rejection during ARF (positive predictive value, 8/9 = 89%). In the 15 patients with Tmax > or = 90 msec, only 2 rejections occurred (negative predictive value, 13/15 = 87%). For the RI (> 0.85), positive predictive value was 4/5 = 80% and negative predictive value (RI < or = 0.85) was 13/19 = 68%. In conclusion, a short acceleration time of the Doppler waveform on the first day after transplantation is associated with a longer duration of ARF. Quantitative analysis of Doppler spectra can be helpful in the identification of patients at risk for rejection and in the

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

    PubMed Central

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

    2016-01-01

    Background: 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. Objective: To determine the incidence and features of acute cellular rejection (ACR) episodes confirmed by biopsy. Methods: 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. Results: 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. Conclusion: 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. PMID:27721962

  1. Decreased humoral antibody episodes of acute renal allograft rejection in recipients expressing the HLA-DQβ1*0202 allele.

    PubMed

    Mannam, Venkat K R; Santos, Mark; Lewis, Robert E; Cruse, Julius M

    2012-10-01

    The present investigation was designed to show the effect of human leukocyte antigen (HLA) class II molecular allelic specificities in the recipient on the induction of humoral antibody rejection, identified by C4d peritubular capillary staining, as well as specific antibody identified by Luminex technology. Major histocompatibility complex (MHC) class II molecules are expressed on dendritic cells, macrophages, and B lymphocytes and they present antigenic peptides to CD4 positive T lymphocytes. Human renal peritubular and glomerular capillaries express class II MHC molecules upon activation. Expression of class II molecules on renal microvascular endothelial cells exposes them to possible interaction with specific circulating antibodies. We hypothesize that HLA-DQβ1*0202 expression in recipients decreases the likelihood of antibody-mediated renal allograft rejection. We found that 80% (=25) of DQ2 positive haplotype recipients failed to induce humoral antibody renal allograft rejection and 20% (n=25) of DQ2 positive haplotype recipients induced humoral antibody renal allograft rejection (p=0.008). By contrast, 48% (n=46) of DQ2 negative haplotype recipients failed to induce a humoral antibody component of renal allograft rejection and 52% (n=46) of DQ2 negative haplotype recipients induced humoral antibody-mediated renal allograft rejection. Our results suggest that recipients who express the DQβ1*0202 allele are less likely to induce a humoral antibody component of acute renal allograft rejection than are those expressing DQ1, DQ3, or DQ4 alleles. DQβ1*0202 allele expression in recipients could possibly be protective against acute humoral allograft rejection and might serve as a future criterion in recipient selection and in appropriate therapy for acute renal rejection episodes.

  2. Acute Cardiac Rejection Requires Directly Cytotoxic CD4 T cells: A Parallel Pathway between Fas and Perforin1

    PubMed Central

    Grazia, Todd J.; Plenter, Robert J.; Weber, Sarah M.; Lepper, Helen M.; Victorino, Francisco; Zamora, Martin R.; Pietra, Biagio A.; Gill, Ronald G.

    2009-01-01

    Background CD4 T cells can suffice as effector cells to mediate primary acute cardiac allograft rejection. While CD4 T cells can readily kill appropriate target cells in vitro, the corresponding role of such cytolytic activity for mediating allograft rejection in vivo is unknown. Therefore, we determined whether the cytolytic effector molecules perforin and/or FasL (CD95L) were necessary for CD4 T cell-mediated rejection in vivo. Methods Wild type C3H(H-2k) or Fas (CD95)-deficient C3Hlpr (H-2k) hearts were transplanted into immune-deficient C57B6rag−/− (H-2b) mice. Recipients then were reconstituted with naïve purified CD4 T cells from either wild-type, perforin (pfp)-deficient, or FasL (gld)-deficient T cell donors. Results In vitro, alloreactive CD4 T cells were competent to lyse donor MHC class II+ target cells, largely by a Fas-dependent mechanism. In vivo, the individual disruption of either donor Fas expression (lpr) or CD4 T cell-derived perforin had no signifcant impact on acute rejection. However, FasL-deficient (gld) CD4 T cells demonstrated delayed allograft rejection. Importantly, the simultaneous removal of both donor Fas expression and CD4 T cell perforin completely abrograted acute rejection, despite the persistence of CD4 T cells within the graft. Conclusions Results demonstrate that the direct rejection of cardiac allografts by CD4 effector T cells requires the alternative contribution of graft Fas expression and T cell perforin expression. To our knowledge, this is the first demonstration that cytolytic activity by CD4 T cells can play an obligate role for primary acute allograft rejection in vivo. PMID:20061916

  3. Efficacy of Anti-Interleukin-2 Receptor Antibody (Daclizumab) in Reducing the Incidence of Acute Rejection After Renal Transplantation

    PubMed Central

    Saghafi, Hossein; Rahbar, Khosrow; Nobakht Haghighi, Ali; Qoreishi, Mohammad; Safdari, Farshad

    2012-01-01

    Background Acute rejection remains a major problem in renal transplantation and represents one of the most important causes of chronic allograft dysfunction and late graft loss. Daclizumab is a genetically engineered human IgG1 monoclonal antibody that binds specifically to the α chain of the interleukin-2 receptor, and may thus reduce the risk of rejection after renal transplantation. Objectives The aim of this study was to examine the effect of daclizumab induction therapy combined with a triple immunosuppressive protocol including prednisolone,cyclosporine microemulsion (CsA), and mycophenolate mofetil (MMF), in reducing the incidence of acute rejection in recipients of living unrelated donor kidneys. Patients and Methods In this historical cohort study, 43 adult recipients of their first kidney allograft received daclizumab (three 1 mg/kg doses administered every 2 weeks) with triple immunosuppressive therapy (steroids, CsA, and MMF). This group was compared to 43 first-time graft recipients who received maintenance triple immunosuppressive therapy comprising steroids, CsA, and MMF. The end point was the incidence of biopsy confirmed acute rejection within 6 months after transplantation. Results At 6 months, 5 (11.6%) of the patients in the daclizumab group had biopsy-proven rejections, as compared to 14 (32.5%) in the control group (P = 0.017). The sex and the age of recipients had no impact on the incidence of acute rejection episodes in the two groups. Conclusions Adding interleukin-2 receptor antibody (daclizumab) to maintenance triple immunosuppressive therapy (prednisolone, CsA, and MMF) reduces the incidence of acute rejection episodes at 6 months in first-time transplant recipients of living unrelated donor. PMID:23573470

  4. Non-viral human IL-10 gene expression reduces acute rejection in heterotopic auxiliary liver transplantation in rats.

    PubMed

    Hong, In Chul; Mullen, Patricia M; Precht, Andrew F; Khanna, Ajai; Li, Melissa; Behling, Cynthia; Lopez, Valerie F; Chiou, Henry C; Moss, Ronald B; Hart, Marquis E

    2003-01-01

    We studied nonviral delivery, expression, and the effect of the human interleukin-10 (Hu IL-10) gene on the rat model of heterotopic auxiliary liver transplantation (HALT). Two previous pilot studies showed remarkable expression of the Hu IL-10 gene in donor and recipient rats, and a decreasing effect of acute rejection in certain cases. In this study, we focused on the efficacy of Hu IL-10 gene expression to decrease acute rejection compared with cyclosporine A (CyA) in a HALT model. Three study groups and one control group were designed. Each group consisted of 6 DA donor and 6 Lewis recipient rats, which underwent HALT. In the control group, donors and recipients were not treated at all. In group II, recipients were treated with one dose of CyA. In group III, donors were treated with Hu IL-10 plasmid. In group IV, donors were treated with Hu IL-10 plasmid, and recipients were treated with one dose of CyA. Rejection was established by histopathology: it revealed 100% rejection in control and 33.3% rejection in study groups II, III, and IV. Human IL-10 gene expression prevented acute rejection with the same efficacy as CyA in the HALT model in rats.

  5. Dose-related reversal of acute lung rejection by aerosolized cyclosporine.

    PubMed

    Iacono, A T; Smaldone, G C; Keenan, R J; Diot, P; Dauber, J H; Zeevi, A; Burckart, G J; Griffith, B P

    1997-05-01

    This study evaluated the effectiveness of aerosolized cyclosporine as rescue therapy for refractory acute rejection in lung-transplant patients that is unresponsive to conventional therapy. Over 2 yr, nine allograft recipients with histologic evidence of persistent acute rejection and worsening pulmonary function were enrolled. Twenty-two patients with similar degrees of unremitting rejection served as historical controls. Aerosolization of cyclosporin A (300 mg in 4.8 ml propylene glycol) using an AeroTech II jet nebulizer was instituted daily for 12 consecutive days followed by a maintenance regimen of 3 d/wk. Cyclosporine and tacrolimus blood and plasma levels were maintained within therapeutic ranges throughout this trial. Efficacy was assessed by histologic grade of rejection, interleukin-6 (IL-6) mRNA expression by graft bronchoalveolar lavage cells, and pulmonary function testing before and during cyclosporine therapy. In seven patients, results were correlated to deposition of cyclosporine aerosol in the allograft(s) as measured by radioisotopic techniques. At a mean of 37 d after initiation of aerosolized cyclosporine, graft histology improved in eight of the nine patients. Cellular IL-6 mRNA expression decreased significantly in seven patients (mean IL-6/actin +/- SD, 40.96 +/- 118 versus 0.33 +/- 0.57 [p = 0.038]). Pulmonary function (FEV1), which had decreased posttransplant (over a mean of 347 d of observation) from a best value of 1.98 +/- 0.8 L to 1.59 +/- 0.6 L (p = 0.0077), improved over time (152 d) to a posttransplant value of 1.90 +/- 0.8 (p = 0.025). In the control subjects, FEV1 inexorably declined over a comparable period of observation (best posttransplant value 2.36 +/- 0.86 to 1.32 +/- 0.53, p < 0.0001). There was a strong correlation between cyclosporine deposition in the allograft and improvement in FEV1 (r = 0.900, p < 0.01). Fewer cycles of pulsed corticosteroids (1.4 +/- 0.9 versus 0.2 +/- 0.4, p = 0.011) and anti-thymocyte globulin 0

  6. Differences in reporting of acute rejections between American and European publications of large immunosuppressive trials impair comparability of study results.

    PubMed

    Fleiner, F; Budde, K; Dragun, D; Hartmann, M; Neumayer, H H; Fritsche, L

    2005-06-01

    This study examined the use of different definitions for acute rejection in recent large multicenter trials performed in America and Europe in order to assess whether systematic differences exist between both scientific cultures. We systematically selected recent publications on multicenter randomized controlled trials, investigating immunosuppressive regimens in de novo kidney transplant recipients. Publications included were classified according to the type of acute rejection reported: group 1 reported no or only one type of rejection rate (biopsy-proven or treated); group 2 reported information on both treated and biopsy-proven rates. Other potential factors (journal's impact-factor, study size) were compared within the subgroups. To determine the rates of treated but not biopsy-proven acute rejections, additional analyses were performed within subgroup 2. The reviewed publications were 24/44 (54.5%) European (E) and 20/44 (45.5%) American (A) origin. Eighteen of 44 publications reported no or only one type of rejection rate (group 1); 26 publications reported treated as well as biopsy-proven rates (group 2). Significantly more European publications reported both treated and biopsy-proven rates (E: 18/24 [75.0%] vs A: 8/20 [40.0%]; P = .019). Group 1 American papers were published in higher-ranked journals than European ones. The rate of blindly treated rejections did not differ significantly (A: 6.13% [range 0% to 12.8%] vs E: 8.43% [range 0% to 16.9%]) and the proportion of blindly treated rejections was slightly lower in American studies (A: 18.5% vs E: 26.5%). Our systematic review showed large discrepancies with a trend to report biopsy-proven rejection rates only in recent years.

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

    PubMed Central

    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

  8. Successful Salvage Treatment of Resistant Acute Antibody-Mediated Kidney Transplant Rejection with Eculizumab.

    PubMed

    Khan, Saif A; Al-Riyami, Dawood; Al-Mula Abed, Yasser W; Mohammed, Saja; Al-Riyami, Marwa; Al-Lawati, Nabil M

    2016-08-01

    Antibody-mediated rejection (ABMR) jeopardises short- and long-term transplant survival and remains a challenge in the field of organ transplantation. We report the first use of the anticomplement agent eculizumab in Oman in the treatment of a 61-year-old female patient with ABMR following a living unrelated kidney transplant. The patient was admitted to the Sultan Qaboos University Hospital in Muscat, Oman, in 2013 on the eighth day post-transplantation with serum creatinine (Cr) levels of 400 µmol/L which continued to rise, necessitating haemodialysis. A biopsy indicated ABMR with acute cellular rejection. No improvement was observed following standard ABMR treatment and she continued to require dialysis. Five doses of eculizumab were administered over six weeks with a subsequent dramatic improvement in renal function. The patient became dialysis-free with serum Cr levels of 119 µmol/L within four months. This case report indicates that eculizumab is a promising agent in the treatment of ABMR. PMID:27606122

  9. Successful Salvage Treatment of Resistant Acute Antibody-Mediated Kidney Transplant Rejection with Eculizumab

    PubMed Central

    Khan, Saif A.; Al-Riyami, Dawood; Al-Mula Abed, Yasser W.; Mohammed, Saja; Al-Riyami, Marwa; Al-Lawati, Nabil M.

    2016-01-01

    Antibody-mediated rejection (ABMR) jeopardises short- and long-term transplant survival and remains a challenge in the field of organ transplantation. We report the first use of the anticomplement agent eculizumab in Oman in the treatment of a 61-year-old female patient with ABMR following a living unrelated kidney transplant. The patient was admitted to the Sultan Qaboos University Hospital in Muscat, Oman, in 2013 on the eighth day post-transplantation with serum creatinine (Cr) levels of 400 µmol/L which continued to rise, necessitating haemodialysis. A biopsy indicated ABMR with acute cellular rejection. No improvement was observed following standard ABMR treatment and she continued to require dialysis. Five doses of eculizumab were administered over six weeks with a subsequent dramatic improvement in renal function. The patient became dialysis-free with serum Cr levels of 119 µmol/L within four months. This case report indicates that eculizumab is a promising agent in the treatment of ABMR.

  10. Successful Salvage Treatment of Resistant Acute Antibody-Mediated Kidney Transplant Rejection with Eculizumab

    PubMed Central

    Khan, Saif A.; Al-Riyami, Dawood; Al-Mula Abed, Yasser W.; Mohammed, Saja; Al-Riyami, Marwa; Al-Lawati, Nabil M.

    2016-01-01

    Antibody-mediated rejection (ABMR) jeopardises short- and long-term transplant survival and remains a challenge in the field of organ transplantation. We report the first use of the anticomplement agent eculizumab in Oman in the treatment of a 61-year-old female patient with ABMR following a living unrelated kidney transplant. The patient was admitted to the Sultan Qaboos University Hospital in Muscat, Oman, in 2013 on the eighth day post-transplantation with serum creatinine (Cr) levels of 400 µmol/L which continued to rise, necessitating haemodialysis. A biopsy indicated ABMR with acute cellular rejection. No improvement was observed following standard ABMR treatment and she continued to require dialysis. Five doses of eculizumab were administered over six weeks with a subsequent dramatic improvement in renal function. The patient became dialysis-free with serum Cr levels of 119 µmol/L within four months. This case report indicates that eculizumab is a promising agent in the treatment of ABMR. PMID:27606122

  11. Alloreactive T Cells to Identify Risk HLA Alleles for Retransplantation After Acute Accelerated Steroid-Resistant Rejection.

    PubMed

    Leyking, S; Wolf, M; Mihm, J; Schaefer, M; Bohle, R M; Fliser, D; Sester, M; Sester, U

    2015-10-01

    The risk of rejection by cellular alloreactivity to the transplant donor is not routinely assessed. Here we analyzed alloreactive T cells in kidney transplant recipients and report how their detection may have helped to prevent rejection of a second kidney graft in a patient with a history of acute accelerated steroid-resistant nonhumoral rejection. Alloreactive CD4 and CD8 T cells were quantified using a flow-cytometric mixed lymphocyte reaction assay based on interferon-γ induction. A group of 16 nonrejecting transplant recipients did not show any alloreactive T-cell immunity to their respective donors, whereas alloreactivity to third-party controls was detectable. In the patient with rejection, HLA-specific antibodies were not detectable before and shortly after rejection, but after transplantation the patient showed exceptionally high frequencies of alloreactive T cells against 2 of 11 HLA-typed controls (0.604% and 0.791% alloreactive CD4 T cells and 0.792% and 0.978% alloreactive CD8 T cells) who shared HLA alleles (HLA-A*24, -B*44, -C*02, -DQB1*5) with the kidney donor. These HLA alleles were subsequently excluded for allocation of a second graft. No alloreactive T cells were observed toward the second kidney donor, and this transplantation was performed successfully. Thus, shared HLA alleles between the donor and third-party controls may suggest that alloreactive T cells had contributed to rejection of the first graft. The rejecting patient highlights that determination of cellular alloreactivity before transplantation may be applied to identify unacceptable mismatches and to reduce the risk for acute cellular rejection episodes. PMID:26518945

  12. Late acute antibody mediated rejection after nine years of renal transplantation.

    PubMed

    Halim, Medhat Abdel; Al-Otaibi, Torki; Al-Waheeb, Salah; Tawab, Khaled Abdel; El Kholy, Osama; Nair, Prasad; Said, Tarek; Narayanan Nampoory, M R

    2010-11-01

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

  13. A systematic review of the role of C4d in the diagnosis of acute antibody-mediated rejection.

    PubMed

    Sapir-Pichhadze, Ruth; Curran, Simon P; John, Rohan; Tricco, Andrea C; Uleryk, Elizabeth; Laupacis, Andreas; Tinckam, Kathryn; Sis, Banu; Beyene, Joseph; Logan, Alexander G; Kim, S Joseph

    2015-01-01

    In this study, we conducted a systematic review of the literature to re-evaluate the role of C4d in the diagnosis of acute antibody-mediated rejection of kidney allografts. Electronic databases were searched until September 2013. Eligible studies allowed derivation of diagnostic tables for the performance of C4d by immunofluorescence or immunohistochemistry with comparison to histopathological features of acute antibody-mediated rejection and/or donor-specific antibody (DSA) assays. Of 3492 unique abstracts, 29 studies encompassing 3485 indication and 868 surveillance biopsies were identified. Assessment of C4d by immunofluorescence and immunohistochemistry exhibited slight to moderate agreement with glomerulitis, peritubular capillaritis, solid-phase DSA assays, DSA with glomerulitis, and DSA with peritubular capillaritis. The sensitivity and specificity of C4d varied as a function of C4d and comparator test thresholds. Prognostically, the presence of C4d was associated with inferior allograft survival compared with DSA or histopathology alone. Thus, our findings support the presence of complement-dependent and -independent phenotypes of acute antibody-mediated rejection. Whether the presence of C4d in combination with histopathology or DSA should be considered for the diagnosis of acute antibody-mediated rejection warrants further study. PMID:24827778

  14. Acute rejection in the elderly recipient: influence of age in the outcome of kidney transplantation.

    PubMed

    Palomar, Rosa; Ruiz, Juan C; Zubimendi, José A; Cotorruelo, Julio G; de Francisco, Angel L M; Rodrigo, Emilio; Sanz, Saturnino; Fernández-Fresnedo, Gema; Arias, Manuel

    2002-01-01

    Since the immune response in older recipients is weaker they should be less likely to reject a transplanted organ and should need less aggressive immunosuppressive treatment. Our aim was to record the incidence and severity of episodes of acute rejection (AR), estimate the influence of these events on graft survival of elderly recipients (> or = 60) and to compare these with that in younger ones. We performed 363 kidney transplants between 1/94 and 12/98, and recorded clinical and immunological data, incidence-severity of AR and cause of graft loss. Patients were divided into two groups, according to the age at transplantation: A (<60, n = 281/77.4%) and B (> 60, n = 82/22.6%). The percentage of aging recipients and mean age of donors and recipients increased throughout the period. Although the incidence of ATN was higher in the older group (29% vs.19%, p < 0.0001) the number of graft biopsies was equal in both groups. The incidence of AR was similar, 33.4% vs. 26.8%, pNS. The number of AR episodes per patient was 0.44 and 0.41 respectively. The severity of AR was: Banff grade I: A (40.3%)/B (45.7%) pNS; grade II: A (44.1%)/B (48.57) pNS; grade III: A (15.5%)/B (5.7%) pNS. Younger recipients presented a higher level of panel-reactive antibodies (PRA) (4.3% vs. 2.07%, p = 0.01). One-yearpatient survival was 96%/91% (p < 0.05) and graft survival was 81%/78% (pNS) respectively. The age of recipient does not seem to have influenced the incidence-severity of AR or the graft survival. Thus immunosuppression should be individualized for each patient and should not depend on the age at transplantation.

  15. Molecular dysfunctions in acute rejection after renal transplantation revealed by integrated analysis of transcription factor, microRNA and long noncoding RNA.

    PubMed

    Sui, Weiguo; Lin, Hua; Peng, Wujian; Huang, Yuanshuai; Chen, Jiejing; Zhang, Yue; Dai, Yong

    2013-10-01

    Acute rejection remains a problem in renal transplantation. To further illustrate the mechanism of rejection, we integrated protein array-based proteomics and RNA microarray-based genomics to investigate the transcription factor, microRNA and long noncoding RNA of biopsies of three patients with acute rejections and a control group. 99 transcription factors were identified in acute rejection biopsies compared to normal renal tissue. We correlated transcription factor data with microRNA and long noncoding RNA data sets and reported the expression of 5 transcription factors (AP-1, AP-4, STATx, c-Myc and p53), 12 miRNAs and 32 lncRNAs in acute rejection biopsies. Pathway analysis demonstrated that over-presentation of transcription factor pathway plays a critical role in acute rejection. This is the first study to comprehensively report the acute rejection transcription factor pathway. Integrative analysis of the transcription factor, microRNA and long noncoding RNA provided an expansive view of molecular signaling pathways in acute rejection after renal transplantation.

  16. A Case Report of Acute Cellular Rejection Following Intestinal Transplantation Managed With Adalimumab.

    PubMed

    Rao, B; Jafri, S-M; Kazimi, M; Mullins, K; Raoufi, M; Segovia, M C

    2016-03-01

    There is a higher incidence of acute cellular rejection (ACR) in small bowel transplantation (SBT) compared with transplantation of other solid organs. Although there are reports on the use of infliximab to successfully treat ACR refractory to other treatments, there are no reports, to our knowledge, regarding the use of adalimumab. We present a case of a female patient with a history of Crohn's disease who underwent an isolated SBT and developed an episode of severe ACR. She was initially treated with methylprednisolone, thymoglobulin, basiliximab, and a dosage adjustment of tacrolimus. Results of repeat endoscopies and biopsies revealed no significant improvement. The patient initiated treatment with adalimumab every 2 weeks for a total of 6 months, in addition to maintenance treatment with prednisone and tacrolimus. Subsequent evaluations showed gradual improvement to normal mucosa and villi without ulceration. A regimen that incorporates adalimumab can thus be used to treat ACR after intestinal transplantation. Larger multicenter studies are needed to show the full efficacy of this therapeutic regimen.

  17. The effect of cold ischemia time on delayed graft function and acute rejection in kidney transplantation.

    PubMed

    Sert, Ismail; Colak, Hulya; Tugmen, Cem; Dogan, Sait Murat; Karaca, Cezmi

    2014-09-01

    The objective of this study is to evaluate the impact of cold ischemia time (CIT) on delayed graft function (DGF) and acute rejection (AR) among deceased donor kidney transplant recipients. The medical records of 111 patients who underwent kidney transplantation from deceased donors between November 1994 and July 2009 were retrospectively analyzed. DGF was observed in 54% of the patients and the prevalence of AR in the first year after transplantation was 9.9%. The incidence of DGF was higher among patients with longer CIT. There was no correlation between CIT and AR episodes. Higher body weight of recipients and donors, history of prior blood transfusion and advanced donor age were related with DGF. Patients with DGF had higher serum creatinine levels at the first, third and fifth years. There was a negative correlation between recipient body weight and creatinine clearance at the first year. CIT has an important role in the development of DGF as a modifiable risk factor. Moreover, donors with advanced age and higher body weight as well as recipients with higher body weight and history of blood transfusions are at risk for the development of DGF. Prevention of DGF may help to improve graft function at the first, third and fifth years and shorten the hospital stay.

  18. Exogenous Lipocalin 2 Ameliorates Acute Rejection in a Mouse Model of Renal Transplantation

    PubMed Central

    Ashraf, M. I.; Schwelberger, H. G.; Brendel, K. A.; Feurle, J.; Andrassy, J.; Kotsch, K.; Regele, H.; Pratschke, J.; Maier, H. T.

    2016-01-01

    Abstract Lipocalin 2 (Lcn2) is rapidly produced by damaged nephron epithelia and is one of the most promising new markers of renal injury, delayed graft function and acute allograft rejection (AR); however, the functional importance of Lcn2 in renal transplantation is largely unknown. To understand the role of Lcn2 in renal AR, kidneys from Balb/c mice were transplanted into C57Bl/6 mice and vice versa and analyzed for morphological and physiological outcomes of AR at posttransplantation days 3, 5, and 7. The allografts showed a steady increase in intensity of interstitial infiltration, tubulitis and periarterial aggregation of lymphocytes associated with a substantial elevation in serum levels of creatinine, urea and Lcn2. Perioperative administration of recombinant Lcn2:siderophore:Fe complex (rLcn2) to recipients resulted in functional and morphological amelioration of the allograft at day 7 almost as efficiently as daily immunosuppression with cyclosporine A (CsA). No significant differences were observed in various donor–recipient combinations (C57Bl/6 wild‐type and Lcn2−/−, Balb/c donors and recipients). Histochemical analyses of the allografts showed reduced cell death in recipients treated with rLcn2 or CsA. These results demonstrate that Lcn2 plays an important role in reducing the extent of kidney AR and indicate the therapeutic potential of Lcn2 in transplantation. PMID:26595644

  19. Biological mechanism analysis of acute renal allograft rejection: integrated of mRNA and microRNA expression profiles

    PubMed Central

    Huang, Shi-Ming; Zhao, Xia; Zhao, Xue-Mei; Wang, Xiao-Ying; Li, Shan-Shan; Zhu, Yu-Hui

    2014-01-01

    Objectives: Renal transplantation is the preferred method for most patients with end-stage renal disease, however, acute renal allograft rejection is still a major risk factor for recipients leading to renal injury. To improve the early diagnosis and treatment of acute rejection, study on the molecular mechanism of it is urgent. Methods: MicroRNA (miRNA) expression profile and mRNA expression profile of acute renal allograft rejection and well-functioning allograft downloaded from ArrayExpress database were applied to identify differentially expressed (DE) miRNAs and DE mRNAs. DE miRNAs targets were predicted by combining five algorithm. By overlapping the DE mRNAs and DE miRNAs targets, common genes were obtained. Differentially co-expressed genes (DCGs) were identified by differential co-expression profile (DCp) and differential co-expression enrichment (DCe) methods in Differentially Co-expressed Genes and Links (DCGL) package. Then, co-expression network of DCGs and the cluster analysis were performed. Functional enrichment analysis for DCGs was undergone. Results: A total of 1270 miRNA targets were predicted and 698 DE mRNAs were obtained. While overlapping miRNA targets and DE mRNAs, 59 common genes were gained. We obtained 103 DCGs and 5 transcription factors (TFs) based on regulatory impact factors (RIF), then built the regulation network of miRNA targets and DE mRNAs. By clustering the co-expression network, 5 modules were obtained. Thereinto, module 1 had the highest degree and module 2 showed the most number of DCGs and common genes. TF CEBPB and several common genes, such as RXRA, BASP1 and AKAP10, were mapped on the co-expression network. C1R showed the highest degree in the network. These genes might be associated with human acute renal allograft rejection. Conclusions: We conducted biological analysis on integration of DE mRNA and DE miRNA in acute renal allograft rejection, displayed gene expression patterns and screened out genes and TFs that may

  20. Expression of hemopexin in acute rejection of rat liver allograft identified by serum proteomic analysis.

    PubMed

    Xu, Min; Tan, Changjun; Hu, Jinwu; Alwahsh, Salamah Mohammad; Yan, Jun; Hu, Jie; Dai, Zhi; Wang, Zheng; Zhou, Jian; Fan, Jia; Huang, Xiaowu

    2014-07-01

    Acute rejection (AR) and acceptance of allograft after liver transplantation (LTx) remain critical issues that need addressing to improve prognosis. We therefore performed rat orthotopic LTx and proteomic analyses to screen for immune response-related biomarkers in sera. Markers identified were validated at the mRNA and/or protein levels, and the molecules of interest were functionally explored. Compared with syngeneic controls, signs of AR as well as spontaneous acceptance were observed in hematoxylin and eosin-stained sections of liver allografts. In accordance with the severity of AR, 30 protein spots displaying significant changes in abundance were identified using two-dimensional differential gel electrophoresis. Ultimately, 14 serum proteins were sequenced and five spots of interest were identified as hemopexin (HPX). Expression of HPX was significantly and inversely associated with the severity of AR at both the mRNA and protein levels. In vitro, Mt-1, Ho-1, Fth, Ifn-γ, and Il-17 transcripts were significantly upregulated in lysates of lymphocytes stimulated with HPX, whereas Il-10 markedly was remarkably downregulated. Interferon-γ, IL-10, and IL-17 proteins in the supernatant of HPX-stimulated lymphocytes were significantly altered in keeping with the mRNA level. Our data facilitated the generation of a proteomic profile to enhance the understanding of rat liver AR. In view of finding that the HPX serum level is negatively associated with the severity of AR of rat liver allograft, we propose that in vitro treatment with HPX regulates cytokine expression in rat lymphocytes.

  1. Treatment of acute antibody-mediated rejection using bortezomib: a case report.

    PubMed

    Sin, Yong-Hun; Kim, Yong-Jin; Oh, Joon Seok; Lee, Jin Ho; Kim, Seong Min; Kim, Joong Kyung

    2015-07-01

    Here we report the successful treatment of acute antibody-mediated rejection (AMR) with bortezomib. Bortezomib rescue treatment was administered after a 42-year-old woman failed to respond to steroid pulse and plasmapheresis with intravenous immunoglobulin (IVIG). The patient underwent a second renal transplantation with a deceased donor kidney. She was treated pre-operatively with rituximab (200 mg/body) and underwent plasmapheresis twice (day-1 and operation day) because ELISA screening revealed that her pre-operative peak panel reactive antibody (PRA) composition was 100% class I and 100% class II and 15 times of cross-match positive history during the waiting period for transplantation. The patients received induction therapy with Simulect (an IL-2-blocking agent). A 1-hour protocol biopsy revealed C4d-positivity and mild peritubular capillary inflammation. This was suggestive of early AMR-associated changes. After transplantation, the patient underwent plasmaphereses (nine times) with low-dose IVIG (2 mg/kg). Despite this treatment regimen, serum creatinine levels increased to 3.4 mg/dL on post-transplant day 15. A second graft biopsy was performed, which showed overt AMR with glomerulitis, peritubular capillary inflammation and no C4d deposition. On post-operative day (POD) 22, treatment with four doses of bortezomib (1.3 mg/m(2) ) was initiated with the patient's consent. On POD 55, renal function had recovered and serum creatinine was 1.5 mg/dL. In summary, bortezomib was administered as a rescue treatment for a patient who developed AMR that was refractory to a combination of plasmaphereses with low-dose IVIG and preemptive administration of rituximab.

  2. Total body irradiation of donors can alter the course of tolerance and induce acute rejection in a spontaneous tolerance rat liver transplantation model.

    PubMed

    Zhang, YeWei; Zhao, HeWei; Bo, Lin; Yang, YinXue; Lu, Xiang; Sun, JingFeng; Wen, JianFei; He, Xia; Yin, GuoWen

    2012-09-01

    Liver transplantation is an established therapy for end-stage liver diseases. Graft rejection occurs unless the recipient receives immunosuppression after transplantation. This study aimed to explore the mechanism of acute rejection of liver allografts in rats pre-treated with total body irradiation to eliminate passenger lymphocytes and to define the role of CD4(+)CD25(+) regulatory T cells in the induction of immunotolerance in the recipient. Male Lewis rats were used as donors and male DA rats were recipients. Rats were randomly assigned to the following four groups: control group, homogeneity liver transplantation group, idio-immunotolerance group and acute rejection group. After transplantation, the survival time of each group, serum alanine aminotransferase, total bilirubin levels, number of Foxp3(+)CD4(+)CD25(+) regulatory T cells, expression of glucocorticoid-induced tumor necrosis factor receptor on T cell subgroups, histopathology of the hepatic graft and spleen cytotoxic T lymphocyte lytic activity were measured. In the acute rejection group, where donors were preconditioned with total body irradiation before liver transplantation, all recipients died between day 17 and day 21. On day 14, serum alanine aminotransferase increased significantly to (459.2±76.9) U L(-1), total bilirubin increased to (124.1±33.7) μmol L(-1) (P<0.05) and the ratio of Foxp3(+)CD4(+)CD25(+) regulatory T cells decreased significantly to 1.50%±0.50% (P<0.05) compared with the other groups. Analysis of the T cell subpopulations in the acute rejection group varied from the other groups. Histological analysis showed typical changes of acute rejection in the acute rejection group only. Preconditioning of the donors with total body irradiation eliminated passenger lymphocytes of the liver graft, and thus affected the course of tolerance and induced acute rejection after liver transplantation.

  3. A Comparative Analysis of Bronchial Stricture Following Lung Transplantation in Recipients With and Without Early Acute Rejection

    PubMed Central

    Castleberry, Anthony W.; Worni, Mathias; Kuchibhatla, Maragatha; Lin, Shu S.; Snyder, Laurie D.; Shofer, Scott L.; Palmer, Scott M.; Pietrobon, Ricardo S.; Davis, R. Duane; Hartwig, Matthew G.

    2014-01-01

    Background Risk factors and outcomes of bronchial stricture following lung transplantation are not well defined. An association between acute rejection and development of stricture has been suggested in small case series. We evaluated this relationship using a large, national registry. Methods All lung transplants between 04/1994 and 12/2008 per the United Network for Organ Sharing database were analyzed. Generalized linear models were used to determine the association between early rejection and development of stricture after adjusting for potential confounders. The association of stricture with postoperative lung function and overall survival was also evaluated. Results 9,335 patients were included for analysis. The incidence of stricture was 11.5% (=1,077/9,335) with no significant change in incidence during the study period (p=0.13). Early rejection was associated with a significantly greater incidence of stricture [adjusted odds ratio (AOR) 1.40, 95% confidence interval (CI) 1.22 - 1.61; p<0.0001]. Male gender, restrictive lung disease, and pre-transplant requirement for hospitalization were also associated with stricture. Those who developed stricture had and a lower postoperative peak percent predicted forced expiratory volume at one second (median 74% vs. 86% for bilateral transplants only, p<0.0001), shorter unadjusted survival (median 6.09 vs. 6.82 years, p<0.001) and increased risk of death after adjusting for potential confounders (adjusted hazard ratio 1.13, CI 1.03 - 1.23, p=0.007). Conclusions Early rejection is associated with an increased incidence of stricture. Recipients with stricture demonstrate worse postoperative lung function and survival. Prospective studies may be warranted to further assess causality and the potential for coordinated rejection and stricture surveillance strategies to improve postoperative outcomes. PMID:23870829

  4. Treatment of steroid-resistant acute renal allograft rejection with alemtuzumab.

    PubMed

    van den Hoogen, M W F; Hesselink, D A; van Son, W J; Weimar, W; Hilbrands, L B

    2013-01-01

    Steroid-resistant renal allograft rejections are commonly treated with rabbit antithymocyte globulin (RATG), but alemtuzumab could be an effective, safe and more convenient alternative. Adult patients with steroid-resistant renal allograft rejection treated with alemtuzumab (15-30 mg s.c. on 2 subsequent days) from 2008 to 2012 (n = 11) were compared to patients treated with RATG (2.5-4.0 mg/kg bodyweight i.v. for 10-14 days; n = 20). We assessed treatment-failure (graft loss, lack of improvement of graft function or need for additional anti-rejection treatment), infections during the first 3 months after treatment and infusion-related side effects. In both groups, the median time-interval between rejection and transplantation was 2 weeks, and approximately 75% of rejections were classified as Banff-IIA or higher. Three alemtuzumab-treated patients (27%) experienced treatment failure, compared to eight RATG treated patients (40%, p = 0.70). There was no difference in the incidence of infections. There were mild infusion-related side-effects in three alemtuzumab-treated patients (27%), and more severe infusion-related side effects in 17 RATG-treated patients (85%, p = 0.013). Drug related costs of alemtuzumab-treatment were lower than of RATG-treatment (€1050 vs. €2024; p < 0.01). Alemtuzumab might be an effective therapy for steroid-resistant renal allograft rejections. In contrast to RATG, alemtuzumab is nearly devoid of infusion-related side-effects. These data warrant a prospective trial.

  5. Increased BK viremia and progression to BK-virus nephropathy following high-dose intravenous immunoglobulin for acute cellular rejection.

    PubMed

    Boonyapredee, Maytee; Knight, Kendral; Little, Dustin

    2014-06-01

    BK virus nephropathy and cellular rejection are common causes of allograft dysfunction in renal transplant recipients. The two can be difficult to distinguish on allograft biopsy and can be present simultaneously. Management of the patient with coexistent BK infection and rejection is complicated by the conflicting ideals of decreasing immunosuppression to treat the former and increasing immunosuppression to treat the latter. The authors present the case of a 57-year-old renal transplant recipient who underwent allograft biopsy 8 weeks post-transplant for evaluation of increased serum creatinine in the setting of BK viremia (BKV). Biopsy revealed Banff classification 1b acute cellular rejection, with insufficient evidence to diagnose BK virus-associated nephropathy. The patient was administered intravenous immune globulin (IVIG), with no other changes in immunosuppressive therapy. Plasma and urine BK increased exponentially following IVIG administration, and allograft function further deteriorated. Repeat biopsy showed overt BK viral nephropathy, and BKV and creatinine decreased only after reduction in immunosuppression and initiation of leflunomide. Although case series have suggested a potential role for IVIG in the setting of BK infection, further study is needed to define the safety and efficacy of this approach.

  6. Gene silencing of 4-1BB by RNA interference inhibits acute rejection in rats with liver transplantation.

    PubMed

    Shi, Yang; Hu, Shuqun; Song, Qingwei; Yu, Shengcai; Zhou, Xiaojun; Yin, Jun; Qin, Lei; Qian, Haixin

    2013-01-01

    The 4-1BB signal pathway plays a key role in organ transplantation tolerance. In this study, we have investigated the effect of gene silencing of 4-1BB by RNA interference (RNAi) on the acute rejection in rats with liver transplantation. The recombination vector of lentivirus that contains shRNA targeting the 4-1BB gene (LV-sh4-1BB) was constructed. The liver transplantation was performed using the two-cuff technique. Brown-Norway (BN) recipient rats were infected by the recombinant LVs. The results showed that gene silencing of 4-1BB by RNAi downregulated the 4-1BB gene expression of the splenic lymphocytes in vitro, and the splenic lymphocytes isolated from the rats with liver transplantation. LV-sh4-1BB decreased the plasma levels of liver injury markers including AST, ALT, and BIL and also decreased the level of plasma IL-2 and IFN- γ in recipient rats with liver transplantation. Lentivirus-mediated delivery of shRNA targeting 4-1BB gene prolonged the survival time of recipient and alleviated the injury of liver morphology in recipient rats with liver transplantation. In conclusion, our results demonstrate that gene silencing of 4-1BB by RNA interference inhibits the acute rejection in rats with liver transplantation.

  7. Acute allograft rejection following interferon therapy for hepatitis C in recipients who have returned to dialysis after kidney transplant failure: case study.

    PubMed

    Fabrizi, Fabrizio; D'Ambrosio, Roberta; Pallotti, Francesco; Berardinelli, Luisa; Messa, Piergiorgio; Martin, Paul; Aghemo, Alessio

    2014-11-01

    Interferon-based therapy remains the gold standard for hepatitis C in patients with chronic kidney disease; however, due to the high rate of IFN-induced rejection after transplant, treatment of HCV-infected kidney transplant recipients is recommended only in particular circumstances. We report the case of a 45-year-old Caucasian female with chronic hepatitis C (genotype 1b) who returned to hemodialysis following the complete functional loss of her kidney transplant. She started combination antiviral therapy with peg-IFN-α2a (135 mcg sc weekly) plus ribavirin (200 mg daily) nine months after the re-initiation of hemodialysis. Antiviral therapy was neither effective nor safe; ribavirin was stopped at week 38 due to hemolytic anemia; on-treatment HCV breakthrough was observed at week 48; and acute rejection occurred after four months of IFN-based therapy. Diagnosis of acute allograft rejection was suspected on the grounds of clinical, radiographic, and laboratory data. Allograft nephrectomy was then performed and histology showed acute-on-chronic rejection. This is an uncommon case of IFN-associated kidney rejection in an allograft recipient who had functional loss of her graft and had returned to hemodialysis. In view of the risk of rejection of renal allograft, and the limited efficacy of IFN-based treatment of hepatitis C, physicians should be aware of effective treatment with oral anti-viral agents and avoid the use of IFN in patients on maintenance dialysis with failed renal allograft.

  8. CD8 T-cell recognition of acquired alloantigen promotes acute allograft rejection

    PubMed Central

    Harper, Simon J. F.; Ali, Jason M.; Wlodek, Elizabeth; Negus, Marg C.; Harper, Ines G.; Chhabra, Manu; Qureshi, M. Saeed; Mallik, Mekhola; Bolton, Eleanor; Bradley, J. Andrew; Pettigrew, Gavin J.

    2015-01-01

    Adaptive CD8 T-cell immunity is the principal arm of the cellular alloimmune response, but its development requires help. This can be provided by CD4 T cells that recognize alloantigen “indirectly,” as self-restricted allopeptide, but this process remains unexplained, because the target epitopes for CD4 and CD8 T-cell recognition are “unlinked” on different cells (recipient and donor antigen presenting cells (APCs), respectively). Here, we test the hypothesis that the presentation of intact and processed MHC class I alloantigen by recipient dendritic cells (DCs) (the “semidirect” pathway) allows linked help to be delivered by indirect-pathway CD4 T cells for generating destructive cytotoxic CD8 T-cell alloresponses. We show that CD8 T-cell–mediated rejection of murine heart allografts that lack hematopoietic APCs requires host secondary lymphoid tissue (SLT). SLT is necessary because within it, recipient dendritic cells can acquire MHC from graft parenchymal cells and simultaneously present it as intact protein to alloreactive CD8 T cells and as processed peptide alloantigen for recognition by indirect-pathway CD4 T cells. This enables delivery of essential help for generating cytotoxic CD8 T-cell responses that cause rapid allograft rejection. In demonstrating the functional relevance of the semidirect pathway to transplant rejection, our findings provide a solution to a long-standing conundrum as to why SLT is required for CD8 T-cell allorecognition of graft parenchymal cells and suggest a mechanism by which indirect-pathway CD4 T cells provide help for generating effector cytotoxic CD8 T-cell alloresponses at late time points after transplantation. PMID:26420874

  9. Delayed Cytotoxic T Lymphocyte-Associated Protein 4-Immunoglobulin Treatment Reverses Ongoing Alloantibody Responses and Rescues Allografts From Acute Rejection.

    PubMed

    Young, J S; Chen, J; Miller, M L; Vu, V; Tian, C; Moon, J J; Alegre, M-L; Sciammas, R; Chong, A S

    2016-08-01

    Antibody-mediated rejection has emerged as the leading cause of late graft loss in kidney transplant recipients, and inhibition of donor-specific antibody production should lead to improved transplant outcomes. The fusion protein cytotoxic T lymphocyte-associated protein 4-immunoglobulin (CTLA4-Ig) blocks T cell activation and consequently inhibits T-dependent B cell antibody production, and the current paradigm is that CTLA4-Ig is effective with naïve T cells and less so with activated or memory T cells. In this study, we used a mouse model of allosensitization to investigate the efficacy of continuous CTLA4-Ig treatment, initiated 7 or 14 days after sensitization, for inhibiting ongoing allospecific B cell responses. Delayed treatment with CTLA4-Ig collapsed the allospecific germinal center B cell response and inhibited alloantibody production. Using adoptively transferred T cell receptor transgenic T cells and a novel approach to track endogenous graft-specific T cells, we demonstrate that delayed CTLA4-Ig minimally inhibited graft-specific CD4(+) and T follicular helper responses. Remarkably, delaying CTLA4-Ig until day 6 after transplantation in a fully mismatched heart transplant model inhibited alloantibody production and prevented acute rejection, whereas transferred hyperimmune sera reversed the effects of delayed CTLA4-Ig. Collectively, our studies revealed the unexpected efficacy of CTLA4-Ig for inhibiting ongoing B cell responses even when the graft-specific T cell response was robustly established. PMID:26928966

  10. Noninvasive allograft imaging of acute rejection: evaluation of (131)I-anti-CXCL10 mAb.

    PubMed

    Cheng, Dayan; Sun, Hukui; Liang, Ting; Zhang, Chao; Song, Jing; Hou, Guihua

    2015-02-01

    The purpose of this study was to investigate the use of iodine-131-labeled anti-CXCL10 mAb as tracer targeted at CXCL10 to detect acute rejection (AR) with mice model. Expression of CXCL10 was proved by RT-PCR, ELISA, and immunochemistry staining. All groups were submitted to whole-body autoradioimaging and ex vivo biodistribution studies after tail vein injection of (131)I-anti-CXCL10 mAb. The highest concentration/expression of CXCL10 was detected in allograft tissue compared with allograft treated with tacrolimus and isograft control. Tacrolimus could obviously inhibit the rejection of allograft. Allograft could be obviously imaged at all checking points, much clearer than the other two groups. The biodistribution results showed the highest uptake of radiotracer in allograft. T/NT (target/nontarget) ratio was 4.15 ± 0.25 at 72 h, apparently different from allograft treated with tacrolimus (2.29 ± 0.10), P < 0.05. These data suggest that CXCL10 is a promising target for early stage AR imaging and (131)I-CXCL10 mAb can successfully image AR and monitor the effect of immunosuppressant.

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

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

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

  12. Mixed lymphocyte cultures can predict TCR Vbeta repertoires of T cells infiltrating kidney transplants during acute rejection episodes.

    PubMed

    Paraoan, Marius T; Bakran, Ali; Hammad, Abdul; Sells, Robert A; Christmas, Stephen E

    2005-12-27

    Alloreactive T cell populations can show skewing of T-cell antigen receptor (TCR) Vbeta gene usage. The aims of the experiments were to compare in vivo and in vitro T cell alloresponses against donor alloantigens for TCR Vbeta gene usage. T-cell cultures from renal biopsies taken during acute rejection and pretransplant mixed lymphocyte cultures (MLC) were established from five renal transplant patients. TCR Vbeta gene usage, assessed with Vbeta family specific antibodies, showed that up to five different Vbeta families were significantly expanded. In four of five cases, there was close concordance between Vbeta families expanded from the biopsy and in MLC. T-cell clones from one renal biopsy were specific for the mismatched donor alloantigen and showed similar TCR Vbeta gene usage to the original T-cell line. The results show very similar patterns of TCR Vbeta gene usage in alloreactive T cells generated ex vivo or in vitro.

  13. Polymorphisms in the lectin pathway of complement activation influence the incidence of acute rejection and graft outcome after kidney transplantation.

    PubMed

    Golshayan, Déla; Wójtowicz, Agnieszka; Bibert, Stéphanie; Pyndiah, Nitisha; Manuel, Oriol; Binet, Isabelle; Buhler, Leo H; Huynh-Do, Uyen; Mueller, Thomas; Steiger, Jürg; Pascual, Manuel; Meylan, Pascal; Bochud, Pierre-Yves

    2016-04-01

    There are conflicting data on the role of the lectin pathway of complement activation and its recognition molecules in acute rejection and outcome after transplantation. To help resolve this we analyzed polymorphisms and serum levels of lectin pathway components in 710 consecutive kidney transplant recipients enrolled in the nationwide Swiss Transplant Cohort Study, together with all biopsy-proven rejection episodes and 1-year graft and patient survival. Functional mannose-binding lectin (MBL) levels were determined in serum samples, and previously described MBL2, ficolin 2, and MBL-associated serine protease 2 polymorphisms were genotyped. Low MBL serum levels and deficient MBL2 diplotypes were associated with a higher incidence of acute cellular rejection during the first year, in particular in recipients of deceased-donor kidneys. This association remained significant (hazard ratio 1.75, 95% confidence interval 1.18-2.60) in a Cox regression model after adjustment for relevant covariates. In contrast, there was no significant association with rates of antibody-mediated rejection, patient death, early graft dysfunction or loss. Thus, results in a prospective multicenter contemporary cohort suggest that MBL2 polymorphisms result in low MBL serum levels and are associated with acute cellular rejection after kidney transplantation. Since MBL deficiency is a relatively frequent trait in the normal population, our findings may lead to individual risk stratification and customized immunosuppression.

  14. Heterotopic transplantation of glycerin-preserved trachea: effect of respiratory epithelium desquamation on acute rejection.

    PubMed

    Saueressig, M G; Edelweiss, M I A; Souza, F H; Moreschi, A H; Savegnago, F L; Macedo Neto, A V

    2005-07-01

    An effective preservation method and decreased rejection are essential for tracheal transplantation in the reconstruction of large airway defects. Our objective in the present study was to evaluate the antigenic properties of glycerin-preserved tracheal segments. Sixty-one tracheal segments (2.4 to 3.1 cm) were divided into three groups: autograft (N = 21), fresh allograft (N = 18) and glycerin-preserved allograft (N = 22). Two segments from different groups were implanted into the greater omentum of dogs (N = 31). After 28 days, the segments were harvested and analyzed for mononuclear infiltration score and for the presence of respiratory epithelium. The fresh allograft group presented the highest score for mononuclear infiltration (1.78 +/- 0.43, P < or = 0.001) when compared to the autograft and glycerin-preserved allograft groups. In contrast to the regenerated epithelium observed in autograft segments, all fresh allografts and glycerin-preserved allografts had desquamation of the respiratory mucosa. The low antigenicity observed in glycerin segments was probably the result of denudation of the respiratory epithelium and perhaps due to the decrease of major histocompatibility complex class II antigens.

  15. Renal and Cardiac Endothelial Heterogeneity Impact Acute Vascular Rejection in Pig-to-Baboon Xenotransplantation

    PubMed Central

    Knosalla, C.; Yazawa, K.; Behdad, A.; Bodyak, N.; Shang, H.; Bühler, L.; Houser, S.; Gollackner, B.; Griesemer, A.; Schmitt-Knosalla, I.; Schuurman, H.-J.; Awwad, M.; Sachs, D. H.; Cooper, D. K. C.; Yamada, K.; Usheva, A.; Robson, S. C.

    2010-01-01

    Xenograft outcomes are dictated by xenoantigen expression, for example, Gal α 1, 3Gal (Gal), but might also depend on differing vascular responses. We investigated whether differential vascular gene expression in kidney and cardiac xenografts correlate with development of thrombotic microangiopathy (TM) and consumptive coagulation (CC). Immunosuppressed baboons underwent miniswine or hDAF pig kidney (n = 6) or heart (n = 7), or Gal-transferase gene-knockout (GalT-KO) (thymo)kidney transplantation (n = 14). Porcine cDNA miniarrays determined donor proinflammatory, apoptosis-related and vascular coagulant/fibrinolytic gene expression at defined time points; validated by mRNA, protein levels and immunopathology. hDAF-transgenic and GalT-KO xenografts, (particularly thymokidneys) exhibited prolonged survival. CC was seen with Gal-expressing porcine kidneys (3 of 6), only 1 of 7 baboons post-cardiac xenotransplantation and was infrequent following GalT-KO grafts (1 of 14). Protective-type genes (heme oxygenase-I, superoxide dismutases and CD39) together with von Willebrand factor and P-selectin were upregulated in all renal grafts. Transcriptional responses in Gal-expressing xenografts were comparable to those seen in the infrequent GalT-KO rejection. In cardiac xenografts, fibrin deposition was associated with increased plasminogen activator inhibitor-1 expression establishing that gene expression profiles in renal and cardiac xenografts differ in a quantitative manner. These findings suggest that therapeutic targets may differ for renal and cardiac xenotransplants. PMID:19422330

  16. Heterotopic transplantation of glycerin-preserved trachea: effect of respiratory epithelium desquamation on acute rejection.

    PubMed

    Saueressig, M G; Edelweiss, M I A; Souza, F H; Moreschi, A H; Savegnago, F L; Macedo Neto, A V

    2005-07-01

    An effective preservation method and decreased rejection are essential for tracheal transplantation in the reconstruction of large airway defects. Our objective in the present study was to evaluate the antigenic properties of glycerin-preserved tracheal segments. Sixty-one tracheal segments (2.4 to 3.1 cm) were divided into three groups: autograft (N = 21), fresh allograft (N = 18) and glycerin-preserved allograft (N = 22). Two segments from different groups were implanted into the greater omentum of dogs (N = 31). After 28 days, the segments were harvested and analyzed for mononuclear infiltration score and for the presence of respiratory epithelium. The fresh allograft group presented the highest score for mononuclear infiltration (1.78 +/- 0.43, P < or = 0.001) when compared to the autograft and glycerin-preserved allograft groups. In contrast to the regenerated epithelium observed in autograft segments, all fresh allografts and glycerin-preserved allografts had desquamation of the respiratory mucosa. The low antigenicity observed in glycerin segments was probably the result of denudation of the respiratory epithelium and perhaps due to the decrease of major histocompatibility complex class II antigens. PMID:16007278

  17. Localization of C-X-C and C-C chemokines to renal tubular epithelial cells in human kidney transplants is not confined to acute cellular rejection.

    PubMed

    Sibbring, J S; Sharma, A; McDicken, I W; Sells, R A; Christmas, S E

    1998-12-01

    Chemokines are important mediators of leucocyte chemoattraction to inflammatory sites. Previous work has shown that the expression of some chemokines is upregulated during renal transplant rejection. The objectives of the present study were to determine whether chemokine expression is increased during renal transplant rejection. Immunohistochemistry was used to localize the C-X-C (alpha) chemokine interleukin-8 (IL-8) and the C-C (beta) chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1beta (MIP-1beta) in 30 needle biopsies of human kidney transplants taken for diagnosis of renal dysfunction. Urine samples from transplant patients taken immediately prior to biopsy were assayed for chemokine content using enzyme-linked immunosorbent assays (ELISAs). Results from groups of patients having different clinicopathological diagnoses were then compared. All three chemokines were detected in most renal transplant biopsies showing acute cellular rejection but, although infiltrating leucocytes were often positive, staining was predominantly localized to renal tubular epithelium. Staining for MCP-1 was generally weaker than for the other chemokines, and collecting tubules were usually stained more strongly than proximal convoluted tubules. Tubular epithelial staining was also found in biopsies from patients without signs of acute cellular rejection. There were significantly higher amounts of IL-8 in the urine of patients with acute cellular rejection, even when patients with urinary tract infections were excluded, but mean titres of urinary MIP-1beta did not differ between patient groups. This was also found when titres were normalized for urine volume and creatinine levels. Production of IL-8, MCP-1 and MIP-1beta is not confined to kidney transplants showing acute cellular rejection, and may be a relatively nonspecific response of tubular epithelial cells to renal damage.

  18. A 3’-UTR Polymorphism in Soluble Epoxide Hydrolase Gene Is Associated with Acute Rejection in Renal Transplant Recipients

    PubMed Central

    Gervasini, Guillermo; García-Cerrada, Montserrat; Coto, Eliecer; Vergara, Esther; García-Pino, Guadalupe; Alvarado, Raul; Fernández-Cavada, Maria Jesús; Suárez-Álvarez, Beatriz; Barroso, Sergio; Doblaré, Emilio; Díaz-Corte, Carmen; López-Larrea, Carlos; Cubero, Juan Jose

    2015-01-01

    Background and Purpose Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites that play a protective role against damaging processes that may occur after re-oxygenation of the graft. We aimed to investigate whether the presence of functional polymorphisms in the gene encoding soluble epoxy hydrolase (EPHX2), which metabolizes EETs to less active compounds, may play a role in the outcome of renal transplantation. Methods In a group of 259 Caucasian renal transplant recipients and 183 deceased donors, we determined the presence of three common EPHX2 SNPs, namely rs41507953 (K55R), rs751141 (R287Q) and rs1042032 A/G. Associations with parameters of graft function and the incidence of acute rejection were retrospectively investigated throughout the first year after grafting by logistic regression adjusting for clinical and demographic variables. Results Carriers of the rs1042032 GG genotype displayed significantly lower estimated glomerular filtration rate (eGFR) (38.15 ± 15.57 vs. 45.99 ± 16.05; p = 0.04) and higher serum creatinine values (1.57 ± 0.58 vs. 1.30 ± 0.47 g/dL; p=0.02) one year after grafting, compared to patients carrying the wildtype A-allele. The same GG genotype was also associated to increased risk of acute rejection. Interestingly, this association was observed for the genotype of both recipients [OR =6.34 (1.35-29.90); p = 0.015] and donors [OR = 5.53 (1.10-27.80); p=0.042]. A statistical model including both genotypes along with other meaningful demographic and clinical variables resulted in an increased significance for the association with the recipients’ genotype [OR=8.28 (1.21-74.27); p=0.031]. Conclusions Our results suggest that genetic variability in the EETs-metabolizing gene, EPHX2, may have a significant impact on the outcome of deceased-donor renal transplantation. PMID:26230946

  19. RNA Profiling in Human and Murine Transplanted Hearts: Identification and Validation of Therapeutic Targets for Acute Cardiac and Renal Allograft Rejection

    PubMed Central

    Van Aelst, L. N. L.; Summer, G.; Li, S.; Gupta, S. K.; Heggermont, W.; De Vusser, K.; Carai, P.; Naesens, M.; Van Cleemput, J.; Van de Werf, F.; Vanhaecke, J.; Thum, T.; Waer, M.; Papageorgiou, A.‐P.; Schroen, B.

    2015-01-01

    Acute cellular rejection (ACR) is the adverse response of the recipient's immune system against the allogeneic graft. Using human surveillance endomyocardial biopsies (EMBs) manifesting ACR and murine allogeneic grafts, we profiled implicated microRNAs (miRs) and mRNAs. MiR profiling showed that miR‐21, ‐142‐3p, ‐142‐5p, ‐146a, ‐146b, ‐155, ‐222, ‐223, and ‐494 increased during ACR in humans and mice, whereas miR‐149‐5p decreased. mRNA profiling revealed 70 common differentially regulated transcripts, all involved in immune signaling and immune‐related diseases. Interestingly, 33 of 70 transcripts function downstream of IL‐6 and its transcription factor spleen focus forming virus proviral integration oncogene (SPI1), an established target of miR‐155, the most upregulated miR in human EMBs manifesting rejection. In a mouse model of cardiac transplantation, miR‐155 absence and pharmacological inhibition attenuated ACR, demonstrating the causal involvement and therapeutic potential of miRs. Finally, we corroborated our miR signature in acute cellular renal allograft rejection, suggesting a nonorgan specific signature of acute rejection. We concluded that miR and mRNA profiling in human and murine ACR revealed the shared significant dysregulation of immune genes. Inflammatory miRs, for example miR‐155, and transcripts, in particular those related to the IL‐6 pathway, are promising therapeutic targets to prevent acute allograft rejection. PMID:26249758

  20. Prediction of Renal Allograft Acute Rejection Using a Novel Non-Invasive Model Based on Acoustic Radiation Force Impulse.

    PubMed

    Yang, Cheng; Jin, Yunjie; Wu, Shengdi; Li, Long; Hu, Mushuang; Xu, Ming; Rong, Ruiming; Zhu, Tongyu; He, Wanyuan

    2016-09-01

    Point shear wave elastography based on acoustic radiation force impulse is a novel technology used to quantify tissue stiffness by measuring shear wave speed. A total of 115 kidney transplantation recipients were consecutively enrolled in this prospective study. The patients were subdivided into two groups using 1 mo post-transplantation as the cutoff time for determining the development of acute rejection (AR). Shear wave speed was significantly higher in the AR group than in the non-AR group. We created a model called SEV, comprising shear wave speed, estimated glomerular filtration rate and kidney volume change, that could successfully discriminate patients with or without AR. The area under the receiver operating characteristic curve of SEV was 0.89, which was higher than values for other variables; it was even better in patients within 1 mo post-transplantation (0.954), but was lower than the estimated glomerular filtration rate in patients after 1 mo post-transplantation. Therefore, the SEV model may predict AR after renal transplantation with a high degree of accuracy, and it may be more useful in the early post-operative stage after renal transplantation. PMID:27267289

  1. Differential diagnosis of acute rejection and chronic cyclosporine nephropathy after rat renal transplantation by detection of endothelial microparticles (EMP).

    PubMed

    Cui, Jiewei; Yang, Jing; Cao, Weike; Sun, Yi

    2010-12-01

    Endothelial microparticles (EMP) are small vesicles smaller than 1.0μm, released from endothelial cells (EC) during their activation and (or) apoptosis. The assay of the level of elevated EMP is a new approach to evaluate the dysfunction of endothelial cell. EMP can be classified into several types according to their membrane molecular, and the levels of various types of EMP may be different. As the most cost-effective immunodepressant, cyclosporine A (CsA) has been used widely in organ transplantation. But its dose is hard to control, under-medication may cause the acute rejection (AR) and overdose may cause chronic cyclosporine nephropathy (CCN). The cyclosporine A (CsA) caused CCN and the AR caused renal injury after renal transplantation are both vascular diseases related with endothelial dysfunction, and up to now, there is still no effective method to distinguish the two kinds of diseases. Owing to distinct pathogenesis of the two kinds of vascular diseases, the level of each type of EMP originated from vascular endothelial cells may be different. We hypothesize that maybe we can distinguish them by detecting the different levels of some types of EMP which is also related with vascular disease, and we propose to prove our hypothesis through animal experiment. If our hypothesis is proved, it will be more helpful for clinicians to adjust the dose of CsA promptly according to the differential diagnosis of the two kinds of diseases.

  2. Serial measurement of Doppler hepatic hemodynamic parameters for the diagnosis of acute rejection after live donor liver transplantation.

    PubMed

    Sugimoto, Hiroyuki; Kato, Koichi; Hirota, Masashi; Takeda, Shin; Kamei, Hideya; Nakamura, Taro; Kiuchi, Tetsuya; Nakao, Akimasa

    2009-09-01

    To elucidate the role of Doppler hepatic hemodynamic parameters as surrogate markers of acute rejection (AR) after live donor liver transplantation (LDLT), serial Doppler measurements were prospectively performed during the first 2 weeks after LDLT to compare the longitudinal hepatic hemodynamic changes between patients with histologically proven AR and patients without histologically proven AR. Forty-six patients that had undergone adult-to-adult LDLT using a right lobe graft were enrolled in this study. The portal venous maximum velocity (PVV; cm/second), portal venous flow volume, hepatic arterial peak systolic velocity, hepatic arterial pulsatility index, hepatic venous maximum velocity, hepatic venous pulsatility index, and splenic arterial pulsatility index were measured. Fourteen patients were diagnosed by biopsy to have clinically relevant AR. Markedly increased PVV was seen soon after surgery and gradually decreased in both patients with clinically relevant AR and patients without clinically relevant AR. This serial change of decreasing PVV was significantly greater in patients with clinically relevant AR (P < 0.0001). After postoperative day 6, the PVV in patients with clinically relevant AR was significantly lower than that in patients without clinically relevant AR (PVV on postoperative day 6: 35.6 +/- 21.3 versus 58.3 +/- 27.1 cm/second, respectively, P = 0.0080). A PVV cutoff value of 20.2 cm/second demonstrated the best accuracy for predicting clinically relevant AR. The sensitivity and specificity for predicting clinically relevant AR were 92.9% and 87.1%, respectively. The area under the curve was 0.94. In conclusion, serial Doppler measurement of hepatic parameters in LDLT is useful for the diagnosis of clinically relevant AR. Clinically relevant AR should therefore be suspected when a marked unexpected decrease in the PVV is observed.

  3. Expression of vascular endothelial growth factor and basic fibroblast growth factor in acute rejection reaction following rat orthotopic liver transplantation.

    PubMed

    Zhang, Changsong; Yang, Guangshun; Lu, Dewen; Ling, Yang; Chen, Guihua; Zhou, Tianbao

    2014-08-01

    The aim of the present study was to investigate the expression levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in acute rejection reaction (ARR) following orthotopic liver transplantation in a rat model. Serum VEGF and bFGF levels were detected using ELISA, and their expression levels in liver and spleen tissues were determined using immunohistochemistry. The mRNA expression levels of VEGF and bFGF were detected by conducting a quantitative polymerase chain reaction during the ARR following orthotopic liver transplantation. The expression levels of VEGF and bFGF in the serum 3 days following liver transplantation were significantly higher compared with those in the other groups (1 and 7 days following transplantation; P<0.01). In addition, the numbers of cells in the liver tissue that were shown to be positive for the expression VEGF and bFGF using immunohistochemistry were significantly higher 3 days following transplantation than at the other time points (P<0.0001). Furthermore, the numbers of cells positive for VEGF and bFGF expression in the spleen detected 3 days following the transplantation surgery were also significantly higher compared with those at the other time points (P<0.01). VEGF and bFGF mRNA expression levels were also increased from 1 day following the surgery and reached a peak at day 3, prior to declining gradually and remaining at a relatively high level. VEGF and bFGF mRNA expression levels changed dynamically, by peaking and then declining, in ARR following orthotopic liver transplantation. These changes may have an important impact on angiogenesis and the inflammatory reaction, and the identification of these changes increases the current understanding of ARR following orthotopic liver transplantation.

  4. Normalizing Rejection.

    PubMed

    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. PMID:26041785

  5. Rejection episodes.

    PubMed

    Koyama, H; Cecka, J M

    1992-01-01

    Based upon analyses of 40,671 kidney transplants reported to the UNOS Scientific Renal Transplant Registry between October 1987 and August 1992: 1. Twenty-four percent of the 21,923 recipients of first cadaver grafts experienced one or more rejection episodes during their transplant hospitalization, 52% during the first 6 months. At 12 months, only 40% of patients remained rejection-free. Patients who experienced any rejection during the first 6 months had a 72% 1-year graft survival rate compared with 95% for those who remained rejection-free (p < 0.001). 2. Recipients of transplants from living donors had a significantly lower incidence of rejection episodes. There was a clear effect of histocompatibility in comparing the incidence of rejection in HLA-identical sibling transplants (8% at discharge and 32% at 1 year) with that in 1-haplotype disparate transplants (22% at discharge and 52% at 1 year, p < 0.01 at each time point). Rejections were reported for 25% of transplants from other living donors at discharge and for 56% at 1 year, similar to the figures for cadaver transplants. 3. Histocompatibility also influenced the incidence of rejection in first cadaver-donor transplants. Only 15% of recipients of 0-HLA-A,B mismatched kidneys had rejection episodes reported at discharge, compared with 26% of those who received kidneys completely mismatched for HLA-A,B antigens (p < 0.01). At 1 year, 56% of HLA-A,B matched patients remained rejection-free, whereas only 35% of those mismatched for 4 antigens had no reported rejection through the first year (p < 0.01). Considering HLA-DR antigen mismatches, 19% of the 0-antigen mismatched group had rejection episodes at discharge, versus 28% for those with 2 HLA-DR mismatches (p < 0.01), and at 1 year, the percentage who were rejection-free decreased from 48% to 40% and 34% with 0, 1, and 2 HLA-DR mismatches, respectively. 4. The incidence of rejection episodes decreased as the recipient's age increased. Patients under age

  6. Clinical usefulness of gene-expression profile to rule out acute rejection after heart transplantation: CARGO II

    PubMed Central

    Crespo-Leiro, Maria G.; Stypmann, Jörg; Schulz, Uwe; Zuckermann, Andreas; Mohacsi, Paul; Bara, Christoph; Ross, Heather; Parameshwar, Jayan; Zakliczyński, Michal; Fiocchi, Roberto; Hoefer, Daniel; Colvin, Monica; Deng, Mario C.; Leprince, Pascal; Elashoff, Barbara; Yee, James P.; Vanhaecke, Johan

    2016-01-01

    Aims A non-invasive gene-expression profiling (GEP) test for rejection surveillance of heart transplant recipients originated in the USA. A European-based study, Cardiac Allograft Rejection Gene Expression Observational II Study (CARGO II), was conducted to further clinically validate the GEP test performance. Methods and results Blood samples for GEP testing (AlloMap®, CareDx, Brisbane, CA, USA) were collected during post-transplant surveillance. The reference standard for rejection status was based on histopathology grading of tissue from endomyocardial biopsy. The area under the receiver operating characteristic curve (AUC-ROC), negative (NPVs), and positive predictive values (PPVs) for the GEP scores (range 0–39) were computed. Considering the GEP score of 34 as a cut-off (>6 months post-transplantation), 95.5% (381/399) of GEP tests were true negatives, 4.5% (18/399) were false negatives, 10.2% (6/59) were true positives, and 89.8% (53/59) were false positives. Based on 938 paired biopsies, the GEP test score AUC-ROC for distinguishing ≥3A rejection was 0.70 and 0.69 for ≥2–6 and >6 months post-transplantation, respectively. Depending on the chosen threshold score, the NPV and PPV range from 98.1 to 100% and 2.0 to 4.7%, respectively. Conclusion For ≥2–6 and >6 months post-transplantation, CARGO II GEP score performance (AUC-ROC = 0.70 and 0.69) is similar to the CARGO study results (AUC-ROC = 0.71 and 0.67). The low prevalence of ACR contributes to the high NPV and limited PPV of GEP testing. The choice of threshold score for practical use of GEP testing should consider overall clinical assessment of the patient's baseline risk for rejection. PMID:26746629

  7. Monitoring Pharmacologically Induced Immunosuppression by Immune Repertoire Sequencing to Detect Acute Allograft Rejection in Heart Transplant Patients: A Proof-of-Concept Diagnostic Accuracy Study

    PubMed Central

    Valantine, Hannah A.; Penland, Lolita; Luikart, Helen; Strehl, Calvin; Cohen, Garrett; Khush, Kiran K.; Quake, Stephen R.

    2015-01-01

    Background 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. Methods and Findings 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

  8. β-cell-targeted blockage of PD1 and CTLA4 pathways prevents development of autoimmune diabetes and acute allogeneic islets rejection

    PubMed Central

    El Khatib, Moustafa; Sakuma, Toshie; Tonne, Jason M.; Mohamed, Magid S.; Holditch, Sara J.; Lu, Brian; Kudva, Yogish C.; Ikeda, Yasuhiro

    2015-01-01

    Protection of beta cells from autoimmune destruction potentially cures type 1 diabetes mellitus (T1D). During antigen presentation, interactions between cytotoxic T-lymphocyte antigen-4 (CTLA4) and B7 molecules, or programmed death 1 (PD1) and its ligand PDL1, negatively regulate immune responses in a non-redundant manner. Here, we employed beta cell-targeted adeno-associated virus serotype 8 (AAV8)-based vectors to over-express an artificial PDL1-CTLA4Ig polyprotein or IL10. Beta cell-targeted expression of PDL1-CTLA4Ig or IL10 preserved beta cell mass and protected NOD mice from T1D development. When NOD mice were treated with vectors at early onset of hyperglycemia, PDL1-CTLA4Ig or IL10 alone failed to normalize the early onset of hyperglycemia. When drug-induced diabetic mice received MHC-matched allo-islets, with or without pretreatment of the PDL1-CTLA4Ig-expressing vector, PDL1-CTLA4Ig-expressing islets were protected from rejection for at least 120 days. Similarly, transplantation of PDL1-CTLA4Ig-expressing MHC-matched islets into mice with established T1D resulted in protection of allo-islets from acute rejection, although islet grafts were eventually rejected. Thus, the present study demonstrates the potent immuno-suppressive effects of beta cell-targeted PDL1-CTLA4Ig overexpression against T1D development and allo-islet rejection. The gene-based simultaneous inhibition of PD1 and CTLA4 pathways provides a unique strategy for immunosuppression-free tissue/organ transplantation, especially in the setting of no established autoimmunity. PMID:25786871

  9. Association between the presence of anti-HLA antibodies with acute rejection and chronic allograft nephropathy in the first year after kidney transplantation.

    PubMed

    Toresan, R; Manfro, R C; Proença, M C C; Veronese, F J V; Salim, P H; da Silva, D M; Ribeiro, A R; Edelweiss, M I A; Pegas, K L; Jobim, L F J

    2008-04-01

    The clinical relevance of anti-HLA antibodies following kidney transplantation has been a recent focus of research. Patients who present anti-HLA antibodies in the posttransplantation period have shown higher incidences of acute rejection episodes (ARE) and chronic allograft nephropathy (CAN). The objective of this study was to evaluate the presence of anti-HLA antibodies during the first year after kidney transplantation and their association with the occurrence of ARE and CAN. Eighty-eight kidney transplant recipients were evaluated for the presence of IgG anti-HLA antibodies using an enzyme-linked immunosorbent assay (LAT-M and LAT-1240, One Lambda Inc, Calif, United States). Protocol kidney biopsies were performed in consenting patients. ARE and CAN were diagnosed by clinical, laboratory, and histopathological criteria. Anti-HLA antibodies were observed in 20 (22.7%) patients. At 1 year follow-up, 26.1% presented ARE and 51.2% developed CAN. Nine patients (45%) with antibodies developed ARE as opposed to 20.6% without antibodies and 64.7% developed CAN as opposed to 47.8% of those without antibodies. In the histological analysis, the anti-HLA antibodies were associated with Banff IIA ARE (P = .001) and Banff grade II CAN (P = .012). Routine posttransplantation search for antibodies may identify cases at higher risk for acute and chronic rejection, and perhaps help to tailor the immunosuppressive regimen. PMID:18454996

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

    PubMed

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

    2014-01-01

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

  11. High frequency of central memory regulatory T cells allows detection of liver recipients at risk of early acute rejection within the first month after transplantation.

    PubMed

    Boix-Giner, Francisco; Millan, Olga; San Segundo, David; Muñoz-Cacho, Pedro; Mancebo, Esther; Llorente, Santiago; Rafael-Valdivia, Lourdes; Rimola, Antoni; Fábrega, Emilio; Mrowiec, Anna; Allende, Luis; Minguela, Alfredo; Bolarín, Jose M; Paz-Artal, Estela; López-Hoyos, Marcos; Brunet, Mercé; Muro, Manuel

    2016-02-01

    Several studies have analyzed the potential of T regulatory cells (Treg cells) as biomarkers of acute rejection (AR). The aim of the present multicenter study was to correlate the percentage of peripheral Treg cells in liver graft recipients drawn at baseline up to 12 months after transplantation with the presence of AR. The percentage of central memory (cm) Treg cells (CD4(+)CD25(high)CD45RO(+)CD62L(+)) was monitored at pre-transplant and at 1 and 2 weeks, and 1, 2, 3 and 6 months and 1 year post-transplantation. The same validation standard operating procedures were used in all participating centers. Fifteen patients developed AR (23.4%). Hepatitis C virus recurrence was observed in 16 recipients, who displayed low peripheral blood cmTreg levels compared with patients who did not. A steady increase of cmTregs was observed during the first month after transplantation with statistically significant differences between AR and non-AR patients. The high frequency of memory Treg cells allowed us to monitor rejection episodes during the first month post-transplantation. On the basis of these data, we developed a prediction model for assessing risk of AR that can provide clinicians with useful information for managing patients individually and customizing immunosuppressive therapies.

  12. Immuno-histological assessment of sub-clinical acute and borderline rejection in renal allograft recipients: Data from a transplant center in India.

    PubMed

    Badwal, Sonia; Kumar, Arun; Hooda, A K; Varma, P P

    2015-11-01

    This single-center study was carried out on living related and unrelated renal transplant recipients (RTRs) to evaluate the usefulness of surveillance biopsies in monitoring stable renal allografts using immuno-histological markers for immune-activation. This is a prospective, longitudinal study. Protocol biopsies of 60 RTRs with stable graft function were evaluated at three, six and 12 months post-transplant. Immuno-histological evaluation was carried out using immune-activation markers (perforins, granzyme and interleukin-2R), phenotypic markers (CD-3 and CD-20), viral markers and C4d. The demographic and clinical profile was recorded for each patient. All cases of acute sub-clinical rejection (SCR) were treated and borderline SCR cases were followed-up without treatment. SCR at three and six months post-transplant was evident in 16.7% and 3.7% of RTRs, respectively. Positive statistical association of SCR was seen with HLA-DR mismatches, whereas patients receiving induction therapy and tacrolimus-based immunosuppression exhibited a lower incidence of SCR. T cell phenotype with persistent expression of immune-activation markers exhibited positive statistical association with interstitial fibrosis and tubular atrophy at 12-month follow-up biopsy. The mean creatinine levels were significantly lower in the protocol biopsy group than the non-protocol biopsy group. No significant difference was found between the mean creatinine levels of the SCR group after treatment and the non-SCR cases within the protocol biopsy group. Early treatment of sub-clinical acute rejection leads to better functional outcomes. However, persistent immune-activation is associated with chronicity and may have implications on long-term graft survival.

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

    PubMed Central

    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

  14. Rejected applications

    PubMed Central

    2014-01-01

    Objective: To review membership application materials (especially rejected applications) to the American Academy of Neurology (AAN) during its formative years (1947–1953). Methods: Detailed study of materials in the AAN Historical Collection. Results: The author identified 73 rejected applications. Rejected applicants (71 male, 2 female) lived in 25 states. The largest number was for the Associate membership category (49). These were individuals “in related fields who have made and are making contributions to the field of neurology.” By contrast, few applicants to Active membership or Fellowship status were rejected. The largest numbers of rejectees were neuropsychiatrists (19), neurosurgeons (16), and psychiatrists (14). Conclusion: The AAN, established in the late 1940s, was a small and politically vulnerable organization. A defining feature of the fledgling society was its inclusiveness; its membership was less restrictive than that of the older American Neurological Association. At the same time, the society needed to preserve its core as a neurologic society rather than one of psychiatry or neurosurgery. Hence, the balance between inclusiveness and exclusive identity was a difficult one to maintain. The Associate membership category, more than any other, was at the heart of this issue of self-definition. Associate members were largely practitioners of psychiatry or neurosurgery. Their membership was a source of consternation and was to be carefully been held in check during these critical formative years. PMID:24944256

  15. Should IFN-γ, IL-17 and IL-2 be considered predictive biomarkers of acute rejection in liver and kidney transplant? Results of a multicentric study.

    PubMed

    Millán, O; Rafael-Valdivia, L; San Segundo, D; Boix, F; Castro-Panete, M J; López-Hoyos, M; Muro, M; Valero-Hervás, D; Rimola, A; Navasa, M; Muñoz, P; Miras, M; Andrés, A; Guirado, L; Pascual, J; Brunet, M

    2014-10-01

    Acute rejection (AR) remains a major challenge in organ transplantation, and there is a need for predictive biomarkers. In the present multicenter study, we prospectively examined a series of biomarkers in liver and kidney recipients. Intracellular expression of IFN-γ, IL-17 and IL-2 and IL-17 soluble production were evaluated both pre-transplantation and post-transplantation (1st and 2nd week, 1st, 2nd and 3rd month). 142 transplant patients (63 liver/79 kidney) were included in the study. Twenty-eight recipients (14 liver/14 kidney) developed AR. Pre- and post-transplantation intracellular expression of %IFN-γ(+) in CD4(+)CD69(+) and in CD8(+)CD69(+) and soluble IL17 identified liver and kidney transplant patients at high risk of AR. Pre-transplantation, %IL-2(+) in CD8(+)CD69(+) also identified kidney patients at high risk. We constructed pre- and post-transplantation risk prediction models, based on a composite panel of biomarkers, which could provide the basis for future studies and will be a useful tool for the selection and adjustment of immunosuppressive treatments.

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

    PubMed

    Ming, Yingzi; Hu, Juan; Luo, Qizhi; Ding, Xiang; Luo, Weiguang; Zhuang, Quan; Zou, Yizhou

    2015-01-01

    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.

  17. RNAi-mediated silencing of HLA A2 suppressed acute rejection against human fibroblast xenografts in the striatum of 6-OHDA lesioned rats.

    PubMed

    Liang, Caixia; Xu, Yunzhi; Zheng, Deyu; Sun, Xiaohong; Xu, Qunyuan; Duan, Deyi

    2016-08-15

    Major histocompatibility complex class l (MHC I) molecules play a role in determining whether transplanted cells will be accepted or rejected, and masking of MHC I on donor cells has been found useful for immunoprotection of neural xenografts. In the present study, primary human embryonic lung fibroblasts (HELF), HELF treated with lentivirus-mediated small interfering RNAs (siRNAs) targeting human leukocyte antigen A2 (HLA A2, MHC I in humans) (siHELF), and rat embryonic lung fibroblasts (RELF) were stereotaxically grafted into the striatum of 6-hydroxydopamine lesioned rats to explore whether knockdown of HLA A2 could reduce host immune responses against xenografts. Before lentiviral infection, the cells were transduced with retroviruses harboring tyrosine hydroxylase cDNA. Knockdown of HLA A2 protein was examined by Western blotting. The immune responses (the number of CD4 and CD8 T-cells in the brain and peripheral blood), glial reaction, and survival of human fibroblasts were quantitatively evaluated by flow cytometry and immunohistochemistry at 4d, 2w, and 6w post-graft. Animal behaviors were assessed by counting apomorphine-induced rotations pre- and post-grafts. It was shown that a lower level of HLA A2 was observed in siHELF grafts than in HELF grafts, and knockdown of HLA A2 decreased rat immune responses, as indicated by less remarkable increases in the number of CD8 and CD4 T-cells in the brain and the ratio of CD4:CD8 T-cells in the peripheral blood in rats grafted with siHELF. Rats grafted with siHELF exhibited a significant improvement in motor asymmetry post-transplantation and a better survival of human fibroblasts at 2w. The increasing number of activated microglia and the decreasing number of astrocytes were found in three groups of rats post-implantation. These data suggested that RNAi-mediated knockdown of HLA A2 could suppress acute rejection against xenogeneic human cell transplants in the rat brain. PMID:27397073

  18. Effect of nifedipine on renal transplant rejection.

    PubMed

    Nicholson, M L; Dennis, M J; Beckingham, I J; Smith, S J

    1993-10-01

    The effect of early nifedipine therapy on acute renal allograft rejection was studied in 170 adult cadaveric transplant recipients. Acute rejection occurring in the first 3 months after transplantation was diagnosed by Tru-cut biopsy and the severity of each rejection episode assessed histologically. The incidence of acute rejection was significantly lower in patients treated with nifedipine (29 of 80; 36 per cent) than in controls (52 of 90; 58 per cent) (P < 0.01) and there was a higher proportion of histologically mild rejection episodes in the former group (P < 0.01). Multivariate analysis confirmed that nifedipine exerted a significant independent effect on the incidence of early acute rejection. Other factors identified in the multivariate model as influencing rejection were human leucocyte antigen (HLA) matching at the DR locus, blood level of cyclosporin during the first week, HLA matching at the B locus, donor age and donor sex. The 1-year graft survival rate was 88.6 per cent in patients given nifedipine and 63.8 per cent in controls (P < 0.02). These data suggest that nifedipine therapy has a useful role in human renal transplantation.

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

    PubMed Central

    2012-01-01

    Background Acute kidney allograft rejection is a major cause for declining graft function and has a negative impact on the long-term graft survival. The majority (90%) of acute rejections are T-cell mediated and, therefore, the anti-rejection therapy targets T-cell-mediated mechanisms of the rejection process. However, there is increasing evidence that intragraft B-cells are also important in the T-cell-mediated rejections. First, a significant proportion of patients with acute T-cell-mediated rejection have B-cells present in the infiltrates. Second, the outcome of these patients is inferior, which has been related to an inferior response to the conventional anti-rejection therapy. Third, treatment of these patients with an anti-CD20 antibody (rituximab) improves the allograft outcome as reported in single case observations and in one small study. Despite the promise of these observations, solid evidence is required before incorporating this treatment option into a general treatment recommendation. Methods/Design The RIACT study is designed as a randomized, double-blind, placebo-controlled, parallel group multicenter Phase III study. The study examines whether rituximab, in addition to the standard treatment with steroid-boli, leads to an improved one-year kidney allograft function, compared to the standard treatment alone in patients with acute T-cell mediated tubulointerstitial rejection and significant B-cell infiltrates in their biopsies. A total of 180 patients will be recruited. Discussion It is important to clarify the relevance of anti-B cell targeting in T-cell mediated rejection and answer the question whether this novel concept should be incorporated in the conventional anti-rejection therapy. Trial registration Clinical trials gov. number: NCT01117662 PMID:23101480

  20. High proportion of CD95(+) and CD38(+) in cultured CD8(+) T cells predicts acute rejection and infection, respectively, in kidney recipients.

    PubMed

    Mancebo, Esther; Castro, María José; Allende, Luís M; Talayero, Paloma; Brunet, Mercè; Millán, Olga; Guirado, Luís; López-Hoyos, Marcos; San Segundo, David; Rodrigo, Emilio; Muñoz, Pedro; Boix Giner, Francisco; Llorente Viñas, Santiago; Muro-Amador, Manuel; Paz-Artal, Estela

    2016-02-01

    The aim of this study was to find noninvasive T-cell markers able to predict rejection or infection risk after kidney transplantation. We prospectively examined T-lymphocyte subsets after cell culture stimulation (according to CD38, CD69, CD95, CD40L, and CD25 expression) in 79 first graft recipients from four centers, before and after transplantation. Patients were followed up for one year. Patients who rejected within month-1 (n=10) showed high pre-transplantation and week-1 post-transplantation percentages of CD95(+), in CD4(+) and CD8(+) T-cells (P<0.001 for all comparisons). These biomarkers conferred independent risk for early rejection (HR:5.05, P=0.061 and HR:75.31, P=0.004; respectively). The cut-off values were able to accurately discriminate between rejectors and non-rejectors and Kaplan-Meier curves showed significantly different free-of-rejection time rates (P<0.005). Patients who rejected after the month-1 (n=4) had a higher percentage of post-transplantation CD69(+) in CD8(+) T-cells than non-rejectors (P=0.002). Finally, patients with infection (n=41) previously showed higher percentage of CD38(+) in CD8(+) T-cells at all post-transplantation times evaluated, being this increase more marked in viral infections. A cut-off of 59% CD38(+) in CD8(+) T-cells at week-1, week-2 and month-2 reached 100% sensitivity for the detection of subsequent viral infections. In conclusion, predictive biomarkers of rejection and infection risk after transplantation were detected that could be useful for the personalized care of kidney recipients.

  1. Association of HLA-G promoter and 14-bp insertion-deletion variants with acute allograft rejection and end-stage renal disease.

    PubMed

    Misra, M K; Prakash, S; Kapoor, R; Pandey, S K; Sharma, R K; Agrawal, S

    2013-11-01

    The aim of this study was to investigate the HLA-G 14-bp insertion/deletion (I/D) polymorphism among end-stage renal disease (ESRD) patients. Cytomegalovirus (CMV) infection, acute allograft rejection (AR) and overall survival after renal transplantation was investigated in 300 ESRD patients and 302 age, sex and ethnicity-matched controls. Sequencing was performed to evaluate the impact of HLA-G promoter region single-nucleotide polymorphisms (SNPs) whereas semi-quantitative PCR method was used to determine the probable HLA-G expression pattern among ESRD and AR cases. Further, soluble human leukocyte antigen (HLA)-G (sHLA-G) expression levels were compared in AR vs non-AR cases in the light of HLA-G 14-bp I/D polymorphism. Increased risk was found for 14-bp D/D (deletion-DD) genotype and 14-bp D allele [DD: odds ratio (OR) = 1.46, 95% confidence interval (CI) = 1.03-2.06, P value = 0.0358; D: OR = 1.29, 95% CI = 1.03-1.62, P value = 0.0277], respectively for ESRD and CMV infection (DD: OR = 2.70, 95% CI = 1.45-5.05, P value = 0.0021; D: OR = 1.94, 95% CI = 1.22-3.08, P value = 0.0052). Nearly fourfold (OR = 3.62, 95%CI = 1.61-8.14, p = 0.0039) risk was observed for 14-bp I/I (insertion-II) genotype for AR. Survival analysis showed increased overall survival (OS) (AR or death) for 14-bp D/D genotype. HLA-G promoter region sequencing was carried out among 60 ESRD patients and 100 normal controls which showed increased risk for -964 G>A, -725 C>G/T and -486 A>C SNPs. -964 G>A and -725 C>G/T SNPs showed risk association for AR patients. High level of HLA-G transcripts was observed among non-AR patients. Further soluble HLA-G (sHLA-G) showed increased levels in ESRD patients (mean ± SEM; 62.16 ± 2.43 U/ml) as compared to controls (mean ± SEM; 21.06 ± 3.89 U/ml) (P = <0.0001). The 14-bp I/I, 14-bp I/D and 14-bp D/D genotypes showed significantly higher levels of sHLA-G among non-AR as

  2. [Diagnosis of rejection in a transplanted liver].

    PubMed

    Sticová, Eva; Honsová, Eva

    2015-01-01

    Despite advances in immunosupressive therapy rejection remains the most common complication of liver transplantation in both the early and the late post-transplant period. Unlike other solid organs, liver graft rejection has some specific characteristics likely attributable to the unique immunobiologic properties and the remarkable regenerative capabilities of liver parenchyma. Acute cellular rejection is the most frequent type of the rejection episode in the liver allograft, whereas chronic (ductopenic) rejection and humoral rejection are uncommon. Since the clinical findings are not entirely characteristic, histopathological evaluation of liver biopsy remains the gold standard in the diagnosis of rejection. However, the close cooperation between the pathologist and the clinician is essential for the correct interpretation of morphologic changes.

  3. Machine perfusion following static cold storage preservation in kidney transplantation: donor-matched pair analysis of the prognostic impact of longer pump time.

    PubMed

    Ciancio, Gaetano; Gaynor, Jeffrey J; Sageshima, Junichiro; Roth, David; Kupin, Warren; Guerra, Giselle; Tueros, Lissett; Zarak, Alberto; Hanson, Lois; Ganz, Susan; Chen, Linda; Ruiz, Phillip; Livingstone, Alan S; Burke, George W

    2012-01-01

    The impact of machine perfusion (MP) time on kidney transplant outcome is mixed in previous studies using multivariable analyses. In an analysis of 66 pairs of donor-matched adult, first transplant recipients (N = 132) with identical donor characteristics except for pump time, tests of association of shorter versus longer pump time (first versus second kidney removed) by delayed graft function(DGF), slow graft function(SGF), and biopsy proven acute rejection(BPAR) were performed using McNemar's test. Freedom-from-BPAR, graft and patient survival, and renal function were also compared. Mean ± SD pump times for paired recipients with first and second kidneys were 22.7 ± 7.3 h and 31.2 ± 7.9 h, respectively (mean difference: 8.5 ± 4.5 h, P < .000001). There was no significant impact of pump time on DGF or SGF, with discordant pairs favoring less SGF with longer pump time (N.S.). The incidence of BPAR during the first 12 months post-transplant yielded a borderline difference favoring longer pump time (P = .09), and freedom-from-BPAR during the first 12 months was significantly more favorable for longer pump times (95% vs. 84%, P = 0.04). No differences were observed in graft and patient survival, and renal function. While offering significantly favorable protection from BPAR, this analysis of donor-matched recipient pairs corroborates longer MP (pump) times having no unfavorable effect on other clinical outcomes.

  4. Mouse kidney transplantation: models of allograft rejection.

    PubMed

    Tse, George H; Hesketh, Emily E; Clay, Michael; Borthwick, Gary; Hughes, Jeremy; Marson, Lorna P

    2014-01-01

    Rejection of the transplanted kidney in humans is still a major cause of morbidity and mortality. The mouse model of renal transplantation closely replicates both the technical and pathological processes that occur in human renal transplantation. Although mouse models of allogeneic rejection in organs other than the kidney exist, and are more technically feasible, there is evidence that different organs elicit disparate rejection modes and dynamics, for instance the time course of rejection in cardiac and renal allograft differs significantly in certain strain combinations. This model is an attractive tool for many reasons despite its technical challenges. As inbred mouse strain haplotypes are well characterized it is possible to choose donor and recipient combinations to model acute allograft rejection by transplanting across MHC class I and II loci. Conversely by transplanting between strains with similar haplotypes a chronic process can be elicited were the allograft kidney develops interstitial fibrosis and tubular atrophy. We have modified the surgical technique to reduce operating time and improve ease of surgery, however a learning curve still needs to be overcome in order to faithfully replicate the model. This study will provide key points in the surgical procedure and aid the process of establishing this technique.

  5. Mouse Kidney Transplantation: Models of Allograft Rejection

    PubMed Central

    Clay, Michael; Borthwick, Gary; Hughes, Jeremy; Marson, Lorna P.

    2014-01-01

    Rejection of the transplanted kidney in humans is still a major cause of morbidity and mortality. The mouse model of renal transplantation closely replicates both the technical and pathological processes that occur in human renal transplantation. Although mouse models of allogeneic rejection in organs other than the kidney exist, and are more technically feasible, there is evidence that different organs elicit disparate rejection modes and dynamics, for instance the time course of rejection in cardiac and renal allograft differs significantly in certain strain combinations. This model is an attractive tool for many reasons despite its technical challenges. As inbred mouse strain haplotypes are well characterized it is possible to choose donor and recipient combinations to model acute allograft rejection by transplanting across MHC class I and II loci. Conversely by transplanting between strains with similar haplotypes a chronic process can be elicited were the allograft kidney develops interstitial fibrosis and tubular atrophy. We have modified the surgical technique to reduce operating time and improve ease of surgery, however a learning curve still needs to be overcome in order to faithfully replicate the model. This study will provide key points in the surgical procedure and aid the process of establishing this technique. PMID:25350513

  6. "Science" Rejects Postmodernism.

    ERIC Educational Resources Information Center

    St. Pierre, Elizabeth Adams

    2002-01-01

    The National Research Council report, "Scientific Research in Education," claims to present an inclusive view of sciences in responding to federal attempts to legislate educational research. This article asserts that it narrowly defines science as positivism and methodology as quantitative, rejecting postmodernism and omitting other theories. Uses…

  7. The Polymorphism −308G/A of Tumor Necrosis Factor-α Gene Modulates the Effect of Immunosuppressive Treatment in First Kidney Transplant Subjects Who Suffer an Acute Rejection

    PubMed Central

    Sánchez-Fructuoso, Ana Isabel; Pérez-Flores, Isabel; Valero, Rosalia; Moreno, Maria Angeles; Fernandez-Arquero, Miguel; Urcelay, Elena; Fernández-Pérez, Cristina

    2016-01-01

    The −308G/A SNP of tumor necrosis factor-alpha (TNF-α) gene affects TNF-α production. As its impact on transplant outcome remains open to debate, we decided to genotype it in a cohort of transplant subjects. A retrospective analysis of 439 first kidney recipients randomly divided into two subgroups (discovery and validation cohorts) was performed to identify the best predictors of acute rejection (AR). The effect on transplant outcome was analyzed by an adjusted logistic regression model. Carriers of the A allele, associated with elevated TNF-α production, presented a higher risk of AR (OR = 2.78; 95% CI = 1.40–5.51). Logistic regression analyses for AR showed an interaction between the polymorphism and treatment with thymoglobulin (p-interaction = 0.03). In recipients who did not receive thymoglobulin, carriers of A allele had higher risk of AR (OR = 4.05; 95% CI = 1.76–9.28). Moreover, carriers of A allele not treated with thymoglobulin presented higher risk of AR than those who received thymoglobulin (OR = 13.74; 95% CI = 1.59–118.7). The AUC of the model in the discovery cohort was 0.70 and in the validation cohort was 0.69. Our findings indicate that the −308G/A TNF-α polymorphism is associated with AR risk and it modulates the effectiveness of thymoglobulin treatment. This pharmacogenetic effect lets us propose this SNP as a useful predictor biomarker to tailor immunosuppressive regimens. PMID:27777962

  8. Soothing the Sting of Rejection.

    ERIC Educational Resources Information Center

    Campbell, Joan Daniels

    1990-01-01

    Preventing rejection of a student by his/her peers and helping the child to cope with such rejection are ever-present challenges for teachers. Suggestions are given by teachers who have successfully dealt with students who were rejected by classmates. (IAH)

  9. Heat rejection system

    DOEpatents

    Smith, Gregory C.; Tokarz, Richard D.; Parry, Jr., Harvey L.; Braun, Daniel J.

    1980-01-01

    A cooling system for rejecting waste heat consists of a cooling tower incorporating a plurality of coolant tubes provided with cooling fins and each having a plurality of cooling channels therein, means for directing a heat exchange fluid from the power plant through less than the total number of cooling channels to cool the heat exchange fluid under normal ambient temperature conditions, means for directing water through the remaining cooling channels whenever the ambient temperature rises above the temperature at which dry cooling of the heat exchange fluid is sufficient and means for cooling the water.

  10. Escaping from Rejection

    PubMed Central

    Lynch, Raymond J.; Platt, Jeffrey L.

    2009-01-01

    Summary Those engaged in clinical transplantation and transplantation immunology have always taken as a central objective the elucidation of means to prevent graft rejection by the recipient immune system. Conceptually, such mechanisms stem from the concept of Paul Ehrlich that all organisms can selectively avoid autotoxicity; i.e. they exhibit horror autotoxicus. Some mechanisms of horror autotoxicus now understood. T lymphocytes and B lymphocytes recognize foreign antigens but not some auto-antigens. Clonal deletion generates lacunae in what is otherwise a virtually limitless potential to recognize antigens. We call this mechanism structural tolerance. Where imperfections in structural tolerance allow self-recognition, the full activation of lymphocytes and generation of effector activity depends on delivery of accessory signals generated by infection and/or injury. The absence of accessory signals prevents or even suppresses immunological responses. We call this dichotomy of responsiveness conditional tolerance. When, despite structural and conditional tolerance, effector activity perturbs autologous cells, metabolism changes in ways that protect against injury. We use the term accommodation to refer to this acquired protection against injury. Structural and conditional tolerance and accommodation overlap in such a way that potentially toxic products can be generated to control microorganisms and neutralize toxins without overly damaging adjacent cells. The central challenge in transplantation, then, should be the orchestration of structural and conditional tolerance and accommodation in such a way that toxic products can still be generated for defense while preserving graft function and survival. Since the earliest days of transplantation, immunobiologists have sought means by which to prevent recognition and rejection of foreign tissue. The goal of these strategies is the retention of recipient immune function while selectively avoiding graft injury. While

  11. Diagnostic criteria of antibody-mediated rejection in kidney transplants.

    PubMed

    Mosquera Reboredo, J M; Vázquez Martul, E

    2011-01-01

    The diagnosis and treatment of anti-donor antibody-mediated rejection or humoral rejection (ABMR) is one of the main discussions at the moment in kidney transplantation. The search for histopathological markers that help us to diagnose ABMR has been more problematic, in contrast to the histological expression of cellular or tubulointerstitial rejection. Although the relationship between post-transplant anti-donor antibodies and the allograft's prognosis has been a topic of discussion for a long time, led in the main by P.Terasaki, it was not until the beginning of 1990s when P. Halloran studied the humoral mechanisms of rejection in greater depth. Feutch described the importance of C4d deposits as a marker that shows a humoral mechanism of allograft rejection in 1993. As a result of many studies carried out, the Banff consensus group established some diagnostic histopathological criteria of acute (ABMR) in 2003. These have been modified slightly in later meetings of the group. Furthermore, in 2005 this same working group looked at the physiopathological mechanisms causing chronic allograft failure in more detail and established the criteria defining chronic humoral rejection. In this review, we are trying to update any useful histopathological criteria for diagnosing acute and chronic ABMR.

  12. Optimizing rejection readouts in a corneal allograft transplantation model

    PubMed Central

    Hildebrand, Antonia; Böhringer, Daniel; Betancor, Paola Kammrath; Schlunck, Günther; Reinhard, Thomas

    2016-01-01

    Purpose To evaluate the feasibility of anterior segment spectral domain optic coherence tomography (ASOCT) as rejection readout in a keratoplasty mouse model and to compare ASOCT against the current standard (i.e., a clinical score system). Furthermore, to compare both approaches with respect to intra- and inter-individual observer variability and to calculate a critical point that distinguishes between rejection and non-rejection in ASOCT analysis. Methods Allogeneic penetrating keratoplasties (PKs) were performed using C3H/He donor mice and BALB/c recipient mice; syngeneic transplantations served as controls using BALB/c donors and recipients. Corneal graft rejection was determined with a clinical score. ASOCT was used to determine the central thickness of the corneal grafts in the same animals. The rejection status was corroborated with histopathological examination. Results The median survival time (MST) of the corneal allografts in the wild-type BALB/c mice was 12 days. Allogeneic transplantation led to a 100% rejection rate, whereas signs of rejection after syngeneic transplantation appeared in up to 20% of the mice. Central corneal thickness (CCT) determination via customized software revealed a direct correlation with the clinical score. Receiver operating curve (ROC) analysis confirmed CCT as a valid surrogate for rejection. Calculation of the area under the curve (AUC) revealed a value of 0.88 with an optimal cut-off at 267 pixels. Conclusions An increase in the CCT during acute allogeneic corneal graft rejection significantly correlated with the clinical surrogate parameter “corneal opacity.” ASOCT not only generates source data, but also analysis of the ASOCT data shows lower readout variability and fewer interpreter variations than the clinical score commonly used to define the time point of graft rejection in mice. PMID:27777504

  13. Autophagy in allografts rejection: A new direction?

    PubMed

    Sun, Hukui; Cheng, Dayan; Ma, Yuanyuan; Wang, Huaiquan; Liang, Ting; Hou, Guihua

    2016-03-18

    Despite the introduction of new and effective immunosuppressive drugs, acute cellular graft rejection is still a major risk for graft survival. Modulating the dosage of immunosuppressive drugs is not a good choice for all patients, new rejection mechanisms discovery are crucial to limit the inflammatory process and preserve the function of the transplant. Autophagy, a fundamental cellular process, can be detected in all subsets of lymphocytes and freshly isolated naive T lymphocytes. It is required for the homeostasis and function of T lymphocytes, which lead to cell survival or cell death depending on the context. T cell receptor (TCR) stimulation and costimulator signals induce strong autophagy, and autophagy deficient T cells leads to rampant apoptosis upon TCR stimulation. Autophagy has been proved to be activated during ischemia-reperfusion (I/R) injury and associated with grafts dysfunction. Furthermore, Autophagy has also emerged as a key mechanism in orchestrating innate and adaptive immune response to self-antigens, which relates with negative selection and Foxp3(+) Treg induction. Although, the role of autophagy in allograft rejection is unknown, current data suggest that autophagy indeed sweeps across both in the graft organs and recipients lymphocytes after transplantation. This review presents the rationale for the hypothesis that targeting the autophagy pathway could be beneficial in promoting graft survival after transplantation. PMID:26876576

  14. Autophagy in allografts rejection: A new direction?

    PubMed

    Sun, Hukui; Cheng, Dayan; Ma, Yuanyuan; Wang, Huaiquan; Liang, Ting; Hou, Guihua

    2016-03-18

    Despite the introduction of new and effective immunosuppressive drugs, acute cellular graft rejection is still a major risk for graft survival. Modulating the dosage of immunosuppressive drugs is not a good choice for all patients, new rejection mechanisms discovery are crucial to limit the inflammatory process and preserve the function of the transplant. Autophagy, a fundamental cellular process, can be detected in all subsets of lymphocytes and freshly isolated naive T lymphocytes. It is required for the homeostasis and function of T lymphocytes, which lead to cell survival or cell death depending on the context. T cell receptor (TCR) stimulation and costimulator signals induce strong autophagy, and autophagy deficient T cells leads to rampant apoptosis upon TCR stimulation. Autophagy has been proved to be activated during ischemia-reperfusion (I/R) injury and associated with grafts dysfunction. Furthermore, Autophagy has also emerged as a key mechanism in orchestrating innate and adaptive immune response to self-antigens, which relates with negative selection and Foxp3(+) Treg induction. Although, the role of autophagy in allograft rejection is unknown, current data suggest that autophagy indeed sweeps across both in the graft organs and recipients lymphocytes after transplantation. This review presents the rationale for the hypothesis that targeting the autophagy pathway could be beneficial in promoting graft survival after transplantation.

  15. Emotional responses to interpersonal rejection

    PubMed Central

    Leary, Mark R.

    2015-01-01

    A great deal of human emotion arises in response to real, anticipated, remembered, or imagined rejection by other people. Because acceptance by other people improved evolutionary fitness, human beings developed biopsychological mechanisms to apprise them of threats to acceptance and belonging, along with emotional systems to deal with threats to acceptance. This article examines seven emotions that often arise when people perceive that their relational value to other people is low or in potential jeopardy, including hurt feelings, jealousy, loneliness, shame, guilt, social anxiety, and embarrassment. Other emotions, such as sadness and anger, may occur during rejection episodes, but are reactions to features of the situation other than low relational value. The article discusses the evolutionary functions of rejection-related emotions, neuroscience evidence regarding the brain regions that mediate reactions to rejection, and behavioral research from social, developmental, and clinical psychology regarding psychological and behavioral concomitants of interpersonal rejection. PMID:26869844

  16. Emotional responses to interpersonal rejection.

    PubMed

    Leary, Mark R

    2015-12-01

    A great deal of human emotion arises in response to real, anticipated, remembered, or imagined rejection by other people. Because acceptance by other people improved evolutionary fitness, human beings developed biopsychological mechanisms to apprise them of threats to acceptance and belonging, along with emotional systems to deal with threats to acceptance. This article examines seven emotions that often arise when people perceive that their relational value to other people is low or in potential jeopardy, including hurt feelings, jealousy, loneliness, shame, guilt, social anxiety, and embarrassment. Other emotions, such as sadness and anger, may occur during rejection episodes, but are reactions to features of the situation other than low relational value. The article discusses the evolutionary functions of rejection-related emotions, neuroscience evidence regarding the brain regions that mediate reactions to rejection, and behavioral research from social, developmental, and clinical psychology regarding psychological and behavioral concomitants of interpersonal rejection.

  17. Is Duplex-Ultrasound a useful tool in defining rejection episodes in composite tissue allograft transplants?

    PubMed

    Loizides, Alexander; Kronberger, Irmgard-Elisabeth; Plaikner, Michaela; Gruber, Hannes

    2015-12-01

    Immunologic reactions in transplanted organs are in more or less all allograft patients detectable: clear parameters exist as e.g. in renal transplants where the clearance power reduces by rejection. On the contrary, in composite tissue allografts clear and objective indicators stating a rejection episode lack. We present the case of a hand-transplanted subject with signs of acute transplant rejection diagnosed by means of Duplex Ultrasound and confirmed by biopsy.

  18. Private Information and Insurance Rejections

    PubMed Central

    Hendren, Nathaniel

    2013-01-01

    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. PMID:24187381

  19. Private Information and Insurance Rejections.

    PubMed

    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.

  20. Do Scientists Really Reject God?

    ERIC Educational Resources Information Center

    Scott, Eugenie C.

    1998-01-01

    Suggests that the title of the recent Larson and Witham article in the journal Nature, "Leading Scientists Still Reject God", is premature and without reliable data upon which to base it. (Author/CCM)

  1. ENDOTHELIAL CELLS IN ALLOGRAFT REJECTION

    PubMed Central

    Al-Lamki, Rafia S.; Bradley, John R.; Pober, Jordan S.

    2008-01-01

    In organ transplantation, blood borne cells and macromolecules (e.g. antibodies) of the host immune system are brought into direct contact with the endothelial cell (EC) lining of graft vessels. In this location, graft ECs play several roles in allograft rejection, including the initiation of rejection responses by presentation of alloantigen to circulating T cells; the development of inflammation and thrombosis; and as targets of injury and agents of repair. PMID:19034000

  2. Updates on antibody-mediated rejection in intestinal transplantation

    PubMed Central

    Wu, Guo-Sheng

    2016-01-01

    Antibody-mediated rejection (ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation (ITx). Compelling evidence indicates that donor-specific antibodies can mediate and promote acute and chronic rejection after ITx. However, diagnostic criteria for ABMR after ITx have not been established yet and the mechanisms of antibody-mediated graft injury are not well-known. Effective approaches to prevent and treat ABMR are required to improve long-term outcomes of intestine recipients. Clearly, ABMR after ITx has become an important area for research and clinical investigation. PMID:27683635

  3. Updates on antibody-mediated rejection in intestinal transplantation.

    PubMed

    Wu, Guo-Sheng

    2016-09-24

    Antibody-mediated rejection (ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation (ITx). Compelling evidence indicates that donor-specific antibodies can mediate and promote acute and chronic rejection after ITx. However, diagnostic criteria for ABMR after ITx have not been established yet and the mechanisms of antibody-mediated graft injury are not well-known. Effective approaches to prevent and treat ABMR are required to improve long-term outcomes of intestine recipients. Clearly, ABMR after ITx has become an important area for research and clinical investigation. PMID:27683635

  4. Updates on antibody-mediated rejection in intestinal transplantation

    PubMed Central

    Wu, Guo-Sheng

    2016-01-01

    Antibody-mediated rejection (ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation (ITx). Compelling evidence indicates that donor-specific antibodies can mediate and promote acute and chronic rejection after ITx. However, diagnostic criteria for ABMR after ITx have not been established yet and the mechanisms of antibody-mediated graft injury are not well-known. Effective approaches to prevent and treat ABMR are required to improve long-term outcomes of intestine recipients. Clearly, ABMR after ITx has become an important area for research and clinical investigation.

  5. Membrane rejection of nitrogen compounds

    NASA Technical Reports Server (NTRS)

    Lee, S.; Lueptow, R. M.

    2001-01-01

    Rejection characteristics of nitrogen compounds were examined for reverse osmosis, nanofiltration, and low-pressure reverse osmosis membranes. The rejection of nitrogen compounds is explained by integrating experimental results with calculations using the extended Nernst-Planck model coupled with a steric hindrance model. The molecular weight and chemical structure of nitrogen compounds appear to be less important in determining rejection than electrostatic properties. The rejection is greatest when the Donnan potential exceeds 0.05 V or when the ratio of the solute radius to the pore radius is greater than 0.8. The transport of solute in the pore is dominated by diffusion, although convective transport is significant for organic nitrogen compounds. Electromigration contributes negligibly to the overall solute transport in the membrane. Urea, a small organic compound, has lower rejection than ionic compounds such as ammonium, nitrate, and nitrite, indicating the critical role of electrostatic interaction in rejection. This suggests that better treatment efficiency for organic nitrogen compounds can be obtained after ammonification of urea.

  6. Proteomics for rejection diagnosis in renal transplant patients: Where are we now?

    PubMed Central

    Gwinner, Wilfried; Metzger, Jochen; Husi, Holger; Marx, David

    2016-01-01

    Rejection is one of the key factors that determine the long-term allograft function and survival in renal transplant patients. Reliable and timely diagnosis is important to treat rejection as early as possible. Allograft biopsies are not suitable for continuous monitoring of rejection. Thus, there is an unmet need for non-invasive methods to diagnose acute and chronic rejection. Proteomics in urine and blood samples has been explored for this purpose in 29 studies conducted since 2003. This review describes the different proteomic approaches and summarizes the results from the studies that examined proteomics for the rejection diagnoses. The potential limitations and open questions in establishing proteomic markers for rejection are discussed, including ongoing trials and future challenges to this topic. PMID:27011903

  7. The role of the graft endothelium in transplant rejection: evidence that endothelial activation may serve as a clinical marker for the development of chronic rejection.

    PubMed

    Denton, M D; Davis, S F; Baum, M A; Melter, M; Reinders, M E; Exeni, A; Samsonov, D V; Fang, J; Ganz, P; Briscoe, D M

    2000-11-01

    In this review, we discuss the role of the allograft endothelium in the recruitment and activation of leukocytes during acute and chronic rejection. We discuss associations among endothelial activation responses, the expression of adhesion molecules, chemokines and chemokine receptors, and rejection; and we propose that endothelial vascular cellular adhesion molecule-1 (VCAM-1) may be used as a surrogate marker of acute rejection and allograft vasculopathy. In addition, we describe potential mechanistic interpretations of persistent endothelial cell (EC) expression of major histocompatibility complex (MHC) class II molecules in allorecognition. The graft endothelium may provide an antigen-specific signal to transmigrating, previously activated, T cells and may induce B7 expression on locally transmigrating leukocytes to promote costimulation. Taken together, these functions of the EC provide it with a potent regulatory role in rejection and in the maintenance of T-cell activation via the direct and/or the indirect pathways of allorecognition.

  8. MDMA decreases the effects of simulated social rejection.

    PubMed

    Frye, Charles G; Wardle, Margaret C; Norman, Greg J; de Wit, Harriet

    2014-02-01

    3-4-Methylenedioxymethamphetamine (MDMA) increases self-reported positive social feelings and decreases the ability to detect social threat in faces, but its effects on experiences of social acceptance and rejection have not been determined. We examined how an acute dose of MDMA affects subjective and autonomic responses to simulated social acceptance and rejection. We predicted that MDMA would decrease subjective responses to rejection. On an exploratory basis, we also examined the effect of MDMA on respiratory sinus arrhythmia (RSA), a measure of parasympathetic cardiac control often thought to index social engagement and emotional regulation. Over three sessions, healthy adult volunteers with previous MDMA experience (N=36) received capsules containing placebo, 0.75 or 1.5 mg/kg of MDMA under counter-balanced double-blind conditions. During expected peak drug effect, participants played two rounds of a virtual social simulation task called "Cyberball" during which they experienced acceptance in one round and rejection in the other. During the task we also obtained electrocardiograms (ECGs), from which we calculated RSA. After each round, participants answered questionnaires about their mood and self-esteem. As predicted, MDMA decreased the effect of simulated social rejection on self-reported mood and self-esteem and decreased perceived intensity of rejection, measured as the percent of ball tosses participants reported receiving. Consistent with its sympathomimetic properties, MDMA decreased RSA as compared to placebo. Our finding that MDMA decreases perceptions of rejection in simulated social situations extends previous results indicating that MDMA reduces perception of social threat in faces. Together these findings suggest a cognitive mechanism by which MDMA might produce pro-social behavior and feelings and how the drug might function as an adjunct to psychotherapy. These phenomena merit further study in non-simulated social environments.

  9. Perturbations in the Urinary Exosome in Transplant Rejection

    SciTech Connect

    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

  10. A Zero-Reject System.

    ERIC Educational Resources Information Center

    Rowley, Jo Anne

    The handbook describes the Project FIND Zero-Reject Model for identifying and serving handicapped children in Texas's Gregory-Portland Independent School District. A Flow Chart of the system is provided, and the following components are discussed (sample subtopics in parentheses): needs assessment, staffing patterns (responsibilities of directors,…

  11. Augmented orbiter heat rejection study

    NASA Technical Reports Server (NTRS)

    Hixon, C. W.

    1981-01-01

    Spacecraft radiator concepts are presented that relieve attitude restrictions required by the shuttle orbiter space radiator for baseline and extended capability STS missions. Cost effective heat rejection kits are considered which add additional capability in the form of attached spacelab radiators or a deployable radiator module.

  12. B cells assist allograft rejection in the deficiency of protein kinase c-theta.

    PubMed

    Yan, Wenwei; Xu, Rui; Ma, Lian Li; Han, Wei; Geevarghese, Sunil K; Williams, Phillip E; Sciammas, Roger; Chong, Anita S; Yin, Deng Ping

    2013-09-01

    We have previously shown that mice deficient in protein kinase C theta (PKCθ) have the ability to reject cardiac allografts, but are susceptible to tolerance induction. Here we tested role of B cells in assisting alloimmune responses in the absence of PKCθ. Mouse cardiac allograft transplantations were performed from Balb/c (H-2d) to PKCθ knockout (PKCθ(-/-)), PKCθ and B cell double-knockout (PBDK, H-2b) mice and wild-type (WT) C57BL/6 (H-2b) mice. PBDK mice spontaneously accepted the allografts with the inhibition of NF-κB activation in the donor cardiac allograft. Anti-B cell antibody (rituximab) significantly delayed allograft rejection in PKCθ(-/-), but not in WT mice. Co-transfer of PKCθ(-/-) T plus PKCθ(-/-) B cells or primed sera triggered allograft rejection in Rag1(-/-) mice, and only major histocompatibility complex class II-enriched B cells, but not class I-enriched B cells, were able to promote rejection. This, together with the inability of PKCθ(-/-) and CD28(-/-) double-deficient (PCDK) mice to acutely reject allografts, suggested that an effective cognate interaction between PKCθ(-/-) T and B cells for acute rejection is CD28 molecule dependent. We conclude that T-B cell interactions synergize with PKCθ(-/-) T cells to mediate acute allograft rejection.

  13. A Critical Analysis of Rejection in Vascularized Composite Allotransplantation: Clinical, Cellular and Molecular Aspects, Current Challenges, and Novel Concepts

    PubMed Central

    Sarhane, Karim A.; Tuffaha, Sami H.; Broyles, Justin M.; Ibrahim, Amir E.; Khalifian, Saami; Baltodano, Pablo; Santiago, Gabriel F.; Alrakan, Mohammed; Ibrahim, Zuhaib

    2013-01-01

    Advances in microsurgical techniques and immunomodulatory protocols have contributed to the expansion of vascularized composite allotransplantation (VCA) with very encouraging immunological, functional, and cosmetic results. Rejection remains however a major hurdle that portends serious threats to recipients. Rejection features in VCA have been described in a number of studies, and an international consensus on the classification of rejection was established. Unfortunately, current available diagnostic methods carry many shortcomings that, in certain cases, pose a great diagnostic challenge to physicians especially in borderline rejection cases. In this review, we revisit the features of acute skin rejection in hand and face transplantation at the clinical, cellular, and molecular levels. The multiple challenges in diagnosing rejection and in defining chronic and antibody-mediated rejection in VCA are then presented, and we finish by analyzing current research directions and novel concepts aiming at improving available diagnostic measures. PMID:24324470

  14. A phase II trial of partially incompatible bone marrow transplantation for high-risk acute lymphoblastic leukaemia in children: prevention of graft rejection with anti-LFA-1 and anti-CD2 antibodies. Société Française de Greffe de Moelle Osseuse.

    PubMed

    Cavazzana-Calvo, M; Bordigoni, P; Michel, G; Esperou, H; Souillet, G; Leblanc, T; Stephan, J L; Vannier, J P; Mechinaud, F; Reiffers, J; Vilmer, E; Landman-Parker, J; Benkerrou, M; Baruchel, A; Pico, J; Bernaudin, F; Bergeron, C; Plouvier, E; Thomas, C; Wijdenes, J; Lacour, B; Blanche, S; Fischer, A

    1996-04-01

    Bone marrow transplantation (BMT) from matched sibling donors has been useful for the treatment of acute lymphoblastic leukaemia in children with a poor prognosis but is not available to more than two-thirds of patients who do not have a matched allogeneic donor. This study was undertaken to assess one strategy of marrow graft rejection prevention when alternative marrow sources such as HLA-phenoidentical unrelated volunteers and HLA-partially incompatible relatives were used. Results have been compared with two matched groups of children with the same risks factors and disease status who underwent HLA-genoidentical or autologous BMT. The conditioning regimen was the same for the three groups of patients; in the study group anti-LFA-1 and anti-CD2 monoclonal antibodies combined with T-cell depletion of the marrow was added to prevent graft rejection and graft-versus-host disease. Nineteen patients were included and followed for a median of 25 months (14 months to 3 years). Bone marrow engraftment occurred in 83% of the evaluable patients. Post-transplantation infectious diseases were the most frequent causes of death in the study group, occurring in 31% of patients. No fatal infections occurred in the two control groups. Post-transplantation relapse of leukaemia occurred in 26% of study group's patients, in 58% of autologous BMT control group's patients and 5% of HLA-genoidentical allogeneic group's patients. The event-free survival was 83% in the HLA-genoidentical control group, and 30% and 24% in the study group and in the autologous control group, respectively. In conclusion, a high rate of engraftment was achieved by the use of anti-LFA-1 and anti CD2 antibodies. Occurrence of a long-lasting immunodeficiency, however, led to a high incidence of lethal infections and relapses. Combined approaches are therefore to be investigated accelerating immune reconstitution after transplantations of T-depleted HLA partially incompatible marrow.

  15. Rejection and indirect revascularization of glycerin-preserved tracheal implant.

    PubMed

    Saueressig, Maurício G; Moreschi, Alexandre H; Barbosa, Gilberto V; Edelweiss, Maria I A; de Souza, Felipe H; Savegnago, Fabrício L; de Macedo Neto, Amarílio V

    2003-09-01

    The objective of the following study was to evaluate antigenicity, malacia and revascularization in glycerin-preserved canine tracheal allografts. Trachea with six cartilage rings (2.4 to 3.1 cm) were distributed in three study groups: autograft (21), allograft (18) and glycerin-preserved (22). We implanted two segments from different groups in the greater omentum of dogs. After 28 days, latex was injected in the canine aorta before the segments were harvested. We evaluated number of sectors with functional vessels, number of vessels dyed in the submucosa, acute arteritis score, incidence of acute rejection, cartilage lesion score, and malacia. The autograft group had a larger number of dyed vessels than the glycerin-preserved group. The autograft group also had a higher average number of quadrants with functional vessels than the allograft group and the glycerin-preserved group. The allograft group had a higher mean score for acute arteritis than the autograft group and more acute rejection than the glycerin-preserved group. The cartilage lesion score did not show any significant difference between groups. Malacia was not observed in any tracheal segment. Overall, the glycerin-preserved tracheal implant had low antigenicity and good rigidity, but showed incomplete revascularization.

  16. Rejection and indirect revascularization of glycerin-preserved tracheal implant.

    PubMed

    Saueressig, Maurício G; Moreschi, Alexandre H; Barbosa, Gilberto V; Edelweiss, Maria I A; de Souza, Felipe H; Savegnago, Fabrício L; de Macedo Neto, Amarílio V

    2003-09-01

    The objective of the following study was to evaluate antigenicity, malacia and revascularization in glycerin-preserved canine tracheal allografts. Trachea with six cartilage rings (2.4 to 3.1 cm) were distributed in three study groups: autograft (21), allograft (18) and glycerin-preserved (22). We implanted two segments from different groups in the greater omentum of dogs. After 28 days, latex was injected in the canine aorta before the segments were harvested. We evaluated number of sectors with functional vessels, number of vessels dyed in the submucosa, acute arteritis score, incidence of acute rejection, cartilage lesion score, and malacia. The autograft group had a larger number of dyed vessels than the glycerin-preserved group. The autograft group also had a higher average number of quadrants with functional vessels than the allograft group and the glycerin-preserved group. The allograft group had a higher mean score for acute arteritis than the autograft group and more acute rejection than the glycerin-preserved group. The cartilage lesion score did not show any significant difference between groups. Malacia was not observed in any tracheal segment. Overall, the glycerin-preserved tracheal implant had low antigenicity and good rigidity, but showed incomplete revascularization. PMID:14514556

  17. 7 CFR 58.136 - Rejected milk.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 3 2013-01-01 2013-01-01 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...

  18. 7 CFR 58.136 - Rejected milk.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 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...

  19. 7 CFR 58.136 - Rejected milk.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 3 2014-01-01 2014-01-01 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...

  20. 7 CFR 58.136 - Rejected milk.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 3 2012-01-01 2012-01-01 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...

  1. 7 CFR 58.136 - Rejected milk.

    Code of Federal Regulations, 2010 CFR

    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...

  2. Peer Group Rejection and Children's Outgroup Prejudice

    ERIC Educational Resources Information Center

    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…

  3. Social Causes and Consequences of Rejection Sensitivity

    ERIC Educational Resources Information Center

    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…

  4. Role of anti-vimentin antibodies in allograft rejection.

    PubMed

    Rose, Marlene L

    2013-11-01

    Production of anti-vimentin antibodies (AVA) after solid organ transplantation are common. Although classically thought to be expressed mainly within the cytosol, recent evidence demonstrates that extracellular or cell surface expression of vimentin is not unusual. This review examines the evidence to assess whether AVA contribute to allograft pathology. Clinical studies suggest that AVA are associated with cardiac allograft vasculopathy in heart transplant recipients. Studies in non-human primates confirm that production of AVA after renal and heart transplantation are not inhibited by Cyclosporine. Experimental studies have demonstrated that mice pre-immunised with vimentin undergo accelerated acute rejection and vascular intimal occlusion of cardiac allografts. Adoptive transfer of hyperimmune sera containing AVA into B-cell-knock-out mice caused accelerated rejection of allografted hearts, this is clear evidence that antibodies to vimentin accelerate rejection. AVA act in concert with the alloimmune response and AVA do not damage syngeneic or native heart allografts. Confocal microscopy of allografted organs in vimentin immunised mice shows extensive expression of vimentin on endothelial cells, apoptotic leukocytes and platelet/leukocyte conjugates, co-localising with C4d. One explanation for the ability of AVA to accelerate rejection would be fixation of complement within the graft and subsequent pro-inflammatory effects; there may also be interactions with platelets within the vasculature.

  5. Extracorporeal Photochemotherapy as a Challenging Treatment for Cutaneous T-Cell Lymphoma, Acute and Chronic Graft-versus-Host Disease, Organ Rejection and T-Lymphocyte-Mediated Autoimmune Diseases

    PubMed Central

    Perseghin, Paolo

    2008-01-01

    Summary 20 years ago, in 1987, Edelson and co-workers published their first report on the effectiveness of a new procedure, called extracorporeal photochemotherapy (ECP), in patients with advanced stage cutaneous T-cell lymphoma (CTCL). The positive response (>70% overall) achieved in those patients encouraged several groups to try out this new technology in other T-lymphocyte-mediated autoimmune diseases and a number of dermatological diseases, which sometimes gave conflicting results. In the following years, ECP obtained FDA approval as first line treatment in CTCL. In the 1990s ECP was applied to acute and chronic graft-versus-host disease (GvHD) refractory to conventional immunosuppressive therapy and proved to be effective in >60% of cases of this larger patient population. Today, although the effectiveness of ECP in GvHD is generally acknowledged, this is mainly based on retrospective or observational studies, as data from large, randomized multicenter trials, has yet to be published. Moreover, ECP's real mechanism of action and optimal treatment schedule are still under investigation. The aim of this review is to summarize knowledge acquired to date about ECP. PMID:21547105

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

    PubMed

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

    2010-12-01

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

  7. Extended Active Disturbance Rejection Controller

    NASA Technical Reports Server (NTRS)

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

    2014-01-01

    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.

  8. Extended Active Disturbance Rejection Controller

    NASA Technical Reports Server (NTRS)

    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.

  9. Extended active disturbance rejection controller

    NASA Technical Reports Server (NTRS)

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

    2012-01-01

    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.

  10. Imaging of cardiac allograft rejection in dogs using indium-111 monoclonal antimyosin Fab

    SciTech Connect

    Addonizio, L.J.; Michler, R.E.; Marboe, C.; Esser, P.E.; Johnson, L.L.; Seldin, D.W.; Gersony, W.M.; Alderson, P.O.; Rose, E.A.; Cannon, P.J.

    1987-03-01

    The acute rejection of cardiac allografts is currently diagnosed by the presence of myocyte necrosis on endomyocardial biopsy. We evaluated the efficacy of noninvasive scintigraphic imaging with indium-111-labeled anticardiac myosin Fab fragments (indium-111 antimyosin) to detect and quantify cardiac allograft rejection. Six dogs that had intrathoracic heterotopic cardiac allograft transplantation were injected with indium-111 antimyosin and planar and single photon emission computed tomographic (SPECT) images were obtained in various stages of acute and subacute rejection. Four dogs had an allograft older than 8 months and had been on long-term immunosuppressive therapy; two dogs had an allograft less than 2 weeks old and were not on immunosuppressive therapy. Count ratios comparing heterotopic with native hearts were calculated from both SPECT images and in vitro scans of excised and sectioned hearts and were compared with the degree of rejection scored by an independent histopathologic review. Indium-111 antimyosin uptake was not visible in planar or SPECT images of native hearts. Faint diffuse uptake was apparent in cardiac allografts during long-term immunosuppression and intense radioactivity was present in hearts with electrocardiographic evidence of rejection. The heterotopic to native heart count ratios in SPECT images correlated significantly with the count ratios in the excised hearts (r = 0.93) and with the histopathologic rejection score (r = 0.97). The distribution of indium-111 antimyosin activity in right and left ventricles corresponded to areas of histopathologic abnormalities.

  11. Chronic Renal Transplant Rejection and Possible Anti-Proliferative Drug Targets

    PubMed Central

    Usman, Muhammad

    2015-01-01

    The global prevalence of renal transplants is increasing with time, and renal transplantation is the only definite treatment for end-stage renal disease. We have limited the acute and late acute rejection of kidney allografts, but the long-term survival of renal tissues still remains a difficult and unanswered question as most of the renal transplants undergo failure within a decade of their transplantation. Among various histopathological changes that signify chronic allograft nephropathy (CAN), tubular atrophy, fibrous thickening of the arteries, fibrosis of the kidney interstitium, and glomerulosclerosis are the most important. Moreover, these structural changes are followed by a decline in the kidney function as well. The underlying mechanism that triggers the long-term rejection of renal transplants involves both humoral and cell-mediated immunity. T cells, with their related cytokines, cause tissue damage. In addition, CD 20+ B cells and their antibodies play an important role in the long-term graft rejection. Other risk factors that predispose a recipient to long-term graft rejection include HLA-mismatching, acute episodes of graft rejection, mismatch in donor-recipient age, and smoking. The purpose of this review article is the analyze current literature and find different anti-proliferative agents that can suppress the immune system and can thus contribute to the long-term survival of renal transplants. The findings of this review paper can be helpful in understanding the long-term survival of renal transplants and various ways to improve it. PMID:26677426

  12. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence.

    PubMed

    Sellarés, J; de Freitas, D G; Mengel, M; Reeve, J; Einecke, G; Sis, B; Hidalgo, L G; Famulski, K; Matas, A; Halloran, P F

    2012-02-01

    We prospectively studied kidney transplants that progressed to failure after a biopsy for clinical indications, aiming to assign a cause to every failure. We followed 315 allograft recipients who underwent indication biopsies at 6 days to 32 years posttransplant. Sixty kidneys progressed to failure in the follow-up period (median 31.4 months). Failure was rare after T-cell-mediated rejection and acute kidney injury and common after antibody-mediated rejection or glomerulonephritis. We developed rules for using biopsy diagnoses, HLA antibody and clinical data to explain each failure. Excluding four with missing information, 56 failures were attributed to four causes: rejection 36 (64%), glomerulonephritis 10 (18%), polyoma virus nephropathy 4 (7%) and intercurrent events 6 (11%). Every rejection loss had evidence of antibody-mediated rejection by the time of failure. Among rejection losses, 17 of 36 (47%) had been independently identified as nonadherent by attending clinicians. Nonadherence was more frequent in patients who progressed to failure (32%) versus those who survived (3%). Pure T-cell-mediated rejection, acute kidney injury, drug toxicity and unexplained progressive fibrosis were not causes of loss. This prospective cohort indicates that many actual failures after indication biopsies manifest phenotypic features of antibody-mediated or mixed rejection and also underscores the major role of nonadherence.

  13. The long-term influence of repetitive cellular cardiac rejections on left ventricular longitudinal myocardial deformation in heart transplant recipients.

    PubMed

    Clemmensen, Tor Skibsted; Løgstrup, Brian Bridal; Eiskjaer, Hans; Høyer, Søren; Poulsen, Steen Hvitfeldt

    2015-04-01

    The aim of the study was to evaluate the long-term influence of repeated acute cellular rejections on left ventricular longitudinal deformation in heart transplantation (HTX) patients. One hundred and seventy-eight HTX patients were included in the study. Rejections were classified according to the International Society of Heart and Lung Transplantation (ISHLT) classification (0R-3R). Patients were divided into three groups according to rejection scores (RSs). Group 1: <50% of biopsies with 1R rejection and no ≥2R rejections; Group 2: ≥50% of biopsies with 1R rejection or one biopsy with ≥2R rejection; Group 3: ≥Two biopsies with ≥2R rejections. All patients had a comprehensive echocardiographic examination and coronary angiography. We found significantly decreasing global longitudinal strain (GLS) comparing to rejection groups (GLS group 1: -16.8 ± 2.4 (%); GLS group 2: -15.9 ± 3.3 (%); GLS group 3: -14.5 ± 2.9 (%), P = 0.0003). After excluding patients with LVEF < 50% or vasculopathy, GLS was still significantly reduced according to RS groups (P = 0.0096). Total number of 1R and 2R rejections correlated significant to GLS in a linear regression model. In contrast, we found fractional shortening and LVEF to be unaffected by repeated rejections. In conclusion, repeated cardiac rejections lead to impaired graft function as detected by decreasing magnitude of GLS. In contrast, traditional systolic graft function surveillance by LVEF did not correlate to rejection burden.

  14. 21 CFR 1230.47 - Rejected containers.

    Code of Federal Regulations, 2010 CFR

    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...

  15. Who Doesn't Reject the Rejectee?

    ERIC Educational Resources Information Center

    Cockriel, Irwin W.; Fox, Randy J.

    1976-01-01

    This article reports on the utility of sociometrics for the teacher, particularly in determining who will not reject a generally rejected classmate. A study on teachers' ability to predict such students indicated teachers were not very good at predicting either rejectees, or accepting students. Implications and suggestions are discussed. (NG)

  16. An adaptive algorithm for noise rejection.

    PubMed

    Lovelace, D E; Knoebel, S B

    1978-01-01

    An adaptive algorithm for the rejection of noise artifact in 24-hour ambulatory electrocardiographic recordings is described. The algorithm is based on increased amplitude distortion or increased frequency of fluctuations associated with an episode of noise artifact. The results of application of the noise rejection algorithm on a high noise population of test tapes are discussed.

  17. Image rejects/retakes--radiographic challenges.

    PubMed

    Waaler, D; Hofmann, B

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  19. Rejection of pharmaceuticals by forward osmosis membranes.

    PubMed

    Jin, Xue; Shan, Junhong; Wang, Can; Wei, Jing; Tang, Chuyang Y

    2012-08-15

    Rejection of four pharmaceutical compounds, carbamazepine, diclofenac, ibuprofen and naproxen, by forward osmosis (FO) membranes was investigated in this study. For the first time, the rejection efficiency of the pharmaceutical compounds was compared between commercial cellulose triacetate (CTA) based membranes and thin film composite (TFC) polyamide based membranes. The rejection behavior was related to membrane interfacial properties, physicochemical characteristics of the pharmaceutical molecules and feed solution pH. TFC polyamide membranes exhibited excellent overall performance, with high water flux, excellent pH stability and great rejection of all pharmaceuticals investigated (>94%). For commercial CTA based FO membranes, hydrophobic interaction between the compounds and membranes exhibited strong influence on their rejection under acidic conditions. The pharmaceuticals rejection was well correlated to their hydrophobicity (log D). Under alkaline conditions, both electrostatic repulsion and size exclusion contributed to the removal of deprotonated molecules. The pharmaceuticals rejection by CTA-HW membrane at pH 8 followed the order: diclofenac (99%)>carbamazepine (95%)>ibuprofen (93%) ≈ naproxen (93%). These results can be important for FO membrane synthesis, modification and their application in water purification. PMID:22640821

  20. Pericytes, microvasular dysfunction, and chronic rejection.

    PubMed

    Kloc, Malgorzata; Kubiak, Jacek Z; Li, Xian C; Ghobrial, Rafik M

    2015-04-01

    Chronic rejection of transplanted organs remains the main obstacle in the long-term success of organ transplantation. Thus, there is a persistent quest for development of antichronic rejection therapies and identification of novel molecular and cellular targets. One of the potential targets is the pericytes, the mural cells of microvessels, which regulate microvascular permeability, development, and maturation by controlling endothelial cell functions and regulating tissue fibrosis and inflammatory response. In this review, we discuss the potential of targeting pericytes in the development of microvasular dysfunction and the molecular pathways involved in regulation of pericyte activities for antichronic rejection intervention.

  1. Pericytes, microvasular dysfunction and chronic rejection

    PubMed Central

    Kloc, Malgorzata; Kubiak, Jacek Z.; Li, Xian C.; Ghobrial, Rafik M.

    2014-01-01

    Chronic rejection of transplanted organs remains the main obstacle in the long-term success of organ transplantation. Thus, there is a persistent quest for development of anti-chronic rejection therapies and identification of novel molecular and cellular targets. One of the potential targets is the pericytes, the mural cells of microvessels, which regulate microvascular permeability, development and maturation by controlling endothelial cell functions and regulating tissue fibrosis and inflammatory response. In this review we discuss the potential of targeting pericytes in development of microvasular dysfunction and the molecular pathways involved in regulation of pericyte activities for anti-chronic rejection intervention. PMID:25793439

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

    PubMed Central

    Boucher, Anne; Collette, Suzon; Senécal, Lynne

    2016-01-01

    In renal transplantation, treatment options for antibody-mediated rejection are limited. Here, we report a case of severe AMR treated with eculizumab. A 50-year-old woman known for end stage kidney disease secondary to IgA nephropathy received a kidney transplant from a 50-year-old deceased donor. At 5 months after transplantation, she presented with acute graft dysfunction and biopsy showed a severe antibody-mediated rejection associated with thrombotic microangiopathy. Despite an aggressive conventional immunosuppressive regimen, signs of rejection persisted and the patient was treated with 3 doses of eculizumab. Following the therapy, markers of TMA improved and graft function stabilized. However, ongoing signs of rejection remained in the repeated biopsy. In kidney transplantation, eculizumab is an expensive treatment and its role in the treatment of antibody-mediated rejection remains to be determined. PMID:27478676

  3. Both rejection and tolerance of allografts can occur in the absence of secondary lymphoid tissues.

    PubMed

    Kant, Cavit D; Akiyama, Yoshinobu; Tanaka, Katsunori; Shea, Susan; Yamada, Yohei; Connolly, Sarah E; Marino, Jose; Tocco, Georges; Benichou, Gilles

    2015-02-01

    In this study, we showed that aly/aly mice, which are devoid of lymph nodes and Peyer's patches, acutely rejected fully allogeneic skin and heart grafts. They mounted potent inflammatory direct alloresponses but failed to develop indirect alloreactivity after transplantation. Remarkably, skin allografts also were rejected acutely by splenectomized aly/aly (aly/aly-spl(-)) mice devoid of all secondary lymphoid organs. In these recipients, the rejection was mediated by alloreactive CD8(+) T cells presumably primed in the bone marrow. In contrast, cardiac transplants were not rejected by aly/aly-spl(-) mice. Actually, aly/aly-spl(-) mice that spontaneously accepted a heart allotransplant and displayed donor-specific tolerance also accepted skin grafts from the same, but not a third-party, donor via a mechanism involving CD4(+) regulatory T cells producing IL-10 cytokine. Therefore, direct priming of alloreactive T cells, as well as rejection and regulatory tolerance of allogeneic transplants, can occur in recipient mice lacking secondary lymphoid organs.

  4. Interplay between immune responses to HLA and non-HLA self-antigens in allograft rejection.

    PubMed

    Angaswamy, Nataraju; Tiriveedhi, Venkataswarup; Sarma, Nayan J; Subramanian, Vijay; Klein, Christina; Wellen, Jason; Shenoy, Surendra; Chapman, William C; Mohanakumar, T

    2013-11-01

    Recent studies strongly suggest an increasing role for immune responses against self-antigens (Ags) which are not encoded by the major histocompatibility complex in the immunopathogenesis of allograft rejection. Although, improved surgical techniques coupled with improved methods to detect and avoid sensitization against donor human leukocyte antigen (HLA) have improved the immediate and short term function of transplanted organs. However, acute and chronic rejection still remains a vexing problem for the long term function of the transplanted organ. Immediately following organ transplantation, several factors both immune and non immune mechanisms lead to the development of local inflammatory milieu which sets the stage for allograft rejection. Traditionally, development of antibodies (Abs) against mismatched donor HLA have been implicated in the development of Ab mediated rejection. However, recent studies from our laboratory and others have demonstrated that development of humoral and cellular immune responses against non-HLA self-Ags may contribute in the pathogenesis of allograft rejection. There are reports demonstrating that immune responses to self-Ags especially Abs to the self-Ags as well as cellular immune responses especially through IL17 has significant pro-fibrotic properties leading to chronic allograft failure. This review summarizes recent studies demonstrating the role for immune responses to self-Ags in allograft immunity leading to rejection as well as present recent evidence suggesting there is interplay between allo- and autoimmunity leading to allograft dysfunction.

  5. The role of the macrophage in cardiac allograft rejection in the rat.

    PubMed

    MacPherson, G G; Christmas, S E

    1984-01-01

    Macrophages (MO) are a well-recognized component of the cellular infiltrate in first-set (acute) allograft rejections. Definition of their actual role in the mediation of rejection depends on showing that they are present in sufficient numbers and at relevant sites in rejecting grafts, that they are capable of mediating damage to graft tissues, and that their absence interfere with rejection. We have used rat heart allografts to investigate these questions. Normal rejection takes 7 days. By this time the MO is the major infiltrating cell and large numbers are present close to myocardial cells. In some cases they appear to push pseudopodia into the cell. Neither they, or other cell types, appear to be interacting with endothelial cells. MO extracted from rejecting allografts are potent secretors of plasminogen activator but show poor glass adherence and phagocytic ability compared to resident peritoneal cells. Graft MO are able to damage beating heart cells in vitro; their activity is not immunologically specific. Peritoneal MO from rats immunised with allogeneic spleen cells and MO grown in vitro from bone marrow in the absence of allostimulators behave similarly. Manipulation of MO behaviour was attempted with rabbit anti-rat MO serum. This did not prolong allograft survival and did not significantly depress blood monocyte levels. 750 rads irradiation prolonged graft survival usually until the death of the animal. Rejection could be restored with small lymphocytes from a normal rat, and the addition of bone-marrow cells had no effect. However, hearts rejected by animals given irradiation and lymphocytes alone contained as many MO as those rejected by normal animals, despite a reduction in blood monocyte levels to less than 5% of normal. We conclude that MO are present in large numbers and at relevant sites in rejecting allografts, and that they show features of activation and have a cytotoxic capability against relevant target cells. However, present approaches

  6. DIPS organic rankine cycle heat rejection system

    SciTech Connect

    Pearson, R.

    1987-01-01

    The paper presents the results of an optimization study performed on the heat rejection system for a space based ORC power system using an isotope heat source. The radiator sizing depends on the heat rejection temperature, radiator configuration, and radiator properties such as the fin effectiveness, emissivity, and absorptivity. The optimization analysis to evaluate the effect of each of these parameters on the system weight and area is presented.

  7. Interpersonal rejection as a determinant of anger and aggression.

    PubMed

    Leary, Mark R; Twenge, Jean M; Quinlivan, Erin

    2006-01-01

    This article reviews the literature on the relationship between interpersonal rejection and aggression. Four bodies of research are summarized: laboratory experiments that manipulate rejection, rejection among adults in everyday life, rejection in childhood, and individual differences that may moderate the relationship. The theoretical mechanisms behind the effect are then explored. Possible explanations for why rejection leads to anger and aggression include: rejection as a source of pain, rejection as a source of frustration, rejection as a threat to self-esteem, mood improvement following aggression, aggression as social influence, aggression as a means of reestablishing control, retribution, disinhibition, and loss of self-control. PMID:16768650

  8. Image rejects in general direct digital radiography

    PubMed Central

    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

  9. Role of complement and NK cells in antibody mediated rejection.

    PubMed

    Akiyoshi, Takurin; Hirohashi, Tsutomu; Alessandrini, Alessandro; Chase, Catherine M; Farkash, Evan A; Neal Smith, R; Madsen, Joren C; Russell, Paul S; Colvin, Robert B

    2012-12-01

    Despite extensive research on T cells and potent immunosuppressive regimens that target cellular mediated rejection, few regimens have been proved to be effective on antibody-mediated rejection (AMR), particularly in the chronic setting. C4d deposition in the graft has been proved to be a useful marker for AMR; however, there is an imperfect association between C4d and AMR. While complement has been considered as the main player in acute AMR, the effector mechanisms in chronic AMR are still debated. Recent studies support the role of NK cells and direct effects of antibody on endothelium cells in a mechanism suggesting the presence of a complement-independent pathway. Here, we review the history, currently available systems and progress in experimental animal research. Although there are consistent findings from human and animal research, transposing the experimental results from rodent to human has been hampered by the differences in endothelial functions between species. We briefly describe the findings from patients and compare them with results from animals, to propose a combined perspective.

  10. Micro and Nanoparticle Drug Delivery Systems for Preventing Allotransplant Rejection

    PubMed Central

    Fisher, James D.; Acharya, Abhinav P.; Little, Steven R.

    2015-01-01

    Despite decades of advances in transplant immunology, tissue damage caused by acute allograft rejection remains the primary cause of morbidity and mortality in the transplant recipient. Moreover, the long-term sequelae of lifelong immunosuppression leaves patients at risk for developing a host of other deleterious conditions. Controlled drug delivery using micro- and nanoparticles (MNPs) is an effective way to deliver higher local doses of a given drug to specific tissues and cells while mitigating systemic effects. Herein, we review several descriptions of MNP immunotherapies aimed at prolonging allograft survival. We also discuss developments in the field of biomimetic drug delivery that use MNP constructs to induce and recruit our bodies' own suppressive immune cells. Finally, we comment on the regulatory pathway associated with these drug delivery systems. Collectively, it is our hope the studies described in this review will help to usher in a new era of immunotherapy in organ transplantation. PMID:25937032

  11. Rejection of pharmaceuticals by nanofiltration (NF) membranes: Effect of fouling on rejection behaviour

    NASA Astrophysics Data System (ADS)

    Mahlangu, T. O.; Msagati, T. A. M.; Hoek, E. M. V.; Verliefde, A. R. D.; Mamba, B. B.

    The aim of this study was to investigate the effects of membrane fouling by sodium alginate, latex and a combination of alginate + latex on the rejection behaviour of salts and organics. Sodium chloride and caffeine were selected to represent salts and organics, respectively. The effects of the presence of calcium chloride on the fouling behaviour and rejection of solutes were investigated. The results revealed that the salt rejection by virgin membranes was 47% while that of caffeine was 85%. Fouling by alginate, latex and combined alginate-latex resulted in flux decline of 25%, 37% and 17%, respectively. The addition of Ca2+ aggravated fouling and resulted in further flux decline to 37%. Fouling decreased salt rejection, an observation that was further aggravated by the addition on Ca2+. However, it was also observed that fouling with alginate and calcium and with latex and calcium minimised salt rejection by 30% and 31%, respectively. This reduction in salt rejection was attributed to the decrease in permeate flux (since rejection is a function of flux). There was a slight increase in caffeine rejection when the membrane was fouled with latex particles. Moreover, the presence of foulants on the membrane resulted in a decrease in the surface charge of the membrane. The results of this study have shown that the NF 270 membrane can be used to treat water samples contaminated with caffeine and other organic compounds that have physicochemical properties similar to those of caffeine.

  12. Large Solar-Rejection Filter

    NASA Technical Reports Server (NTRS)

    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

  13. Solar dynamic space power system heat rejection

    NASA Technical Reports Server (NTRS)

    Carlson, A. W.; Gustafson, E.; Mclallin, K. L.

    1986-01-01

    A radiator system concept is described that meets the heat rejection requirements of the NASA Space Station solar dynamic power modules. The heat pipe radiator is a high-reliability, high-performance approach that is capable of erection in space and is maintainable on orbit. Results are present of trade studies that compare the radiator system area and weight estimates for candidate advanced high performance heat pipes. The results indicate the advantages of the dual-slot heat pipe radiator for high temperature applications as well as its weight-reduction potential over the range of temperatures to be encountered in the solar dynamic heat rejection systems.

  14. Immunological analogy between allograft rejection, recurrent abortion and pre-eclampsia - the same basic mechanism?

    PubMed

    Wilczyński, Jacek R

    2006-07-01

    There are still controversies concerning the role of immunological mechanisms engaged both in recurrent abortions (RA) and pre-eclampsia (PE). According to some opinions, recurrent miscarriage is comparable to organ-specific autoimmune disease. Analysis of immune reactions shows that graft rejection shares many similar mechanisms with RA and PE. This fact allows us to conclude that rejection of transplanted alloantigenic organs and pregnancy loss have probably the same evolutionary origin. Subsets and functions of immunocompetent cells (T CD4, suppressor gammadeltaT, cytotoxic T CD8, Treg, Tr1, uterine NK cells), over-activation of innate immunity (activation of NK cytotoxic cells, macrophages, neutrophils and complement), changes of Th1/Th2 cytokine balance (IL-2, IL-12, IL-15, IL-18, IFNgamma, TNFalpha vs. IL-4, IL-10, TGFbeta), importance of HLA-G molecule, CD200/CD200R interaction, over-expression of adhesion molecules, fgl2 prothrombinase activation and stimulation of IDO and HO expression, all suggest that RA and PE are syndromes of fetal allograft rejection, and not organ-specific autoimmune diseases. According to that supposition, an analogy might exist between acute graft rejection and recurrent abortion, and between chronic graft rejection and pre-eclampsia. PMID:16829304

  15. Examining Social Acceptance & Rejection. FPG Snapshot #44

    ERIC Educational Resources Information Center

    FPG Child Development Institute, 2007

    2007-01-01

    This FPG Snapshot summarizes the findings of a study, published in the November 2006 issue of the "Journal of Educational Psychology," that examined whether children with disabilities are accepted or rejected by their classmates in inclusive classrooms. Specifically, the study examined two sets of related questions: (1) Are individual children…

  16. Development of enhanced sulfur rejection processes

    SciTech Connect

    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.

  17. Development of enhanced sulfur rejection processes

    SciTech Connect

    Yoon, R.H.; Luttrell, G.; Adel, G.; Richardson, P.E.

    1993-03-23

    Research at Virginia Tech led to two complementary concepts for improving the removal of inorganic sulfur from much of the Eastern US coals. One controls the surface properties of coal pyrite (FeS[sub 2]) by electrochemical-.potential control, referred to as the Electrochemically Enhanced Sulfur Rejection (EESR) Process: The second controls the flotation of middlings, i.e., particles composed of pyrite with coal inclusions by using polymeric reagents to react with pyrite and convert the middlings to hydrophilic particles, and is termed the Polymer Enhanced Sulfur Rejection (PESR) Process. These new concepts are based on recent research establishing the two main reasons why flotation fails to remove more than about 50% of the pyritic sulfur from coal: superficial oxidization of liberated pyrite to form polysulfide oxidation products so that a part of the liberated pyrite floats with the coal; and hydrophobic coal inclusions in the middlings dominating their flotation so that the middlings also float with the coal. These new pyritic-sulfur rejection processes do not require significant modifications of existing coal preparation facilities, enhancing their adoptability by the coal industry. It is believed that they can be used simultaneously to achieve both free pyrite and locked pyrite rejection.

  18. Guidelines for proposals to conserve or reject

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The scientific journal Taxon is the medium for the publication of proposals to conserve or reject scientific names of plants based on the International Code of Botanical Nomenclature (ICBN). The first formal guidelines for the preparation of such proposals appeared in 1994; these were updated in 200...

  19. Automatic Rejection Of Multimode Laser Pulses

    NASA Technical Reports Server (NTRS)

    Tratt, David M.; Menzies, Robert T.; Esproles, Carlos

    1991-01-01

    Characteristic modulation detected, enabling rejection of multimode signals. Monitoring circuit senses multiple longitudinal mode oscillation of transversely excited, atmospheric-pressure (TEA) CO2 laser. Facility developed for inclusion into coherent detection laser radar (LIDAR) system. However, circuit described of use in any experiment where desireable to record data only when laser operates in single longitudinal mode.

  20. Is the bitter rejection response always adaptive?

    PubMed

    Glendinning, J I

    1994-12-01

    The bitter rejection response consists of a suite of withdrawal reflexes and negative affective responses. It is generally assumed to have evolved as a way to facilitate avoidance of foods that are poisonous because they usually taste bitter to humans. Using previously published studies, the present paper examines the relationship between bitterness and toxicity in mammals, and then assesses the ecological costs and benefits of the bitter rejection response in carnivorous, omnivorous, and herbivorous (grazing and browsing) mammals. If the bitter rejection response accurately predicts the potential toxicity of foods, then one would expect the threshold for the response to be lower for highly toxic compounds than for nontoxic compounds. The data revealed no such relationship. Bitter taste thresholds varied independently of toxicity thresholds, indicating that the bitter rejection response is just as likely to be elicited by a harmless bitter food as it is by a harmful one. Thus, it is not necessarily in an animal's best interest to have an extremely high or low bitter threshold. Based on this observation, it was hypothesized that the adaptiveness of the bitter rejection response depends upon the relative occurrence of bitter and potentially toxic compounds in an animal's diet. Animals with a relatively high occurrence of bitter and potentially toxic compounds in their diet (e.g., browsing herbivores) were predicted to have evolved a high bitter taste threshold and tolerance to dietary poisons. Such an adaptation would be necessary because a browser cannot "afford" to reject all foods that are bitter and potentially toxic without unduly restricting its dietary options. At the other extreme, animals that rarely encounter bitter and potentially toxic compounds in their diet (e.g., carnivores) were predicted to have evolved a low bitter threshold. Carnivores could "afford" to utilize such a stringent rejection mechanism because foods containing bitter and potentially

  1. Is the bitter rejection response always adaptive?

    PubMed

    Glendinning, J I

    1994-12-01

    The bitter rejection response consists of a suite of withdrawal reflexes and negative affective responses. It is generally assumed to have evolved as a way to facilitate avoidance of foods that are poisonous because they usually taste bitter to humans. Using previously published studies, the present paper examines the relationship between bitterness and toxicity in mammals, and then assesses the ecological costs and benefits of the bitter rejection response in carnivorous, omnivorous, and herbivorous (grazing and browsing) mammals. If the bitter rejection response accurately predicts the potential toxicity of foods, then one would expect the threshold for the response to be lower for highly toxic compounds than for nontoxic compounds. The data revealed no such relationship. Bitter taste thresholds varied independently of toxicity thresholds, indicating that the bitter rejection response is just as likely to be elicited by a harmless bitter food as it is by a harmful one. Thus, it is not necessarily in an animal's best interest to have an extremely high or low bitter threshold. Based on this observation, it was hypothesized that the adaptiveness of the bitter rejection response depends upon the relative occurrence of bitter and potentially toxic compounds in an animal's diet. Animals with a relatively high occurrence of bitter and potentially toxic compounds in their diet (e.g., browsing herbivores) were predicted to have evolved a high bitter taste threshold and tolerance to dietary poisons. Such an adaptation would be necessary because a browser cannot "afford" to reject all foods that are bitter and potentially toxic without unduly restricting its dietary options. At the other extreme, animals that rarely encounter bitter and potentially toxic compounds in their diet (e.g., carnivores) were predicted to have evolved a low bitter threshold. Carnivores could "afford" to utilize such a stringent rejection mechanism because foods containing bitter and potentially

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

    PubMed

    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. PMID:27344009

  3. Rejection of Cardiac Xenografts Transplanted from α 1,3-Galactosyltransferase Gene-Knockout (GalT-KO) Pigs to Baboons

    PubMed Central

    Hisashi, Y.; Yamada, K.; Kuwaki, K.; Tseng, Y.-L; Dor, F. J. M. F.; Houser, S. L; Robson, S. C.; Schuurman, H.-J.; Cooper, D. K. C.; Sachs, D. H.; Colvin, R. B.; Shimizu, A.

    2010-01-01

    The use of α 1,3-galactosyltransferase gene-knockout (GalT-KO) swine donors in discordant xenotransplantation has extended the survival of cardiac xenografts in baboons following transplantation. Eight baboons received heterotopic cardiac xenografts from GalT-KO swine and were treated with a chronic immunosuppressive regimen. The pathologic features of acute humoral xenograft rejection (AHXR), acute cellular xenograft rejection (ACXR) and chronic rejection were assessed in the grafts. No hyperacute rejection developed and one graft survived up to 6 months after transplantation. However, all GalT-KO heart grafts underwent graft failure with AHXR, ACXR and/or chronic rejection. AHXR was characterized by interstitial hemorrhage and multiple thrombi in vessels of various sizes. ACXR was characterized by TUNEL+ graft cell injury with the infiltration of T cells (including CD3 and TIA-1+ cytotoxic T cells), CD4+ cells, CD8+ cells, macrophages and a small number of B and NK cells. Chronic xenograft vasculopathy, a manifestation of chronic rejection, was characterized by arterial intimal thickening with TUNEL+ dead cells, antibody and complement deposition, and/or cytotoxic T-cell infiltration. In conclusion, despite the absence of the Gal epitope, acute and chronic antibody and cell-mediated rejection developed in grafts, maintained by chronic immunosupression, presumably due to de novo responses to non-Gal antigens. PMID:19032222

  4. Changes in Self-Definition Impede Recovery From Rejection.

    PubMed

    Howe, Lauren C; Dweck, Carol S

    2016-01-01

    Previous research highlights how adept people are at emotional recovery after rejection, but less research has examined factors that can prevent full recovery. In five studies, we investigate how changing one's self-definition in response to rejection causes more lasting damage. We demonstrate that people who endorse an entity theory of personality (i.e., personality cannot be changed) report alterations in their self-definitions when reflecting on past rejections (Studies 1, 2, and 3) or imagining novel rejection experiences (Studies 4 and 5). Further, these changes in self-definition hinder post-rejection recovery, causing individuals to feel haunted by their past, that is, to fear the recurrence of rejection and to experience lingering negative affect from the rejection. Thus, beliefs that prompt people to tie experiences of rejection to self-definition cause rejection's impact to linger. PMID:26498977

  5. Changes in Self-Definition Impede Recovery From Rejection.

    PubMed

    Howe, Lauren C; Dweck, Carol S

    2016-01-01

    Previous research highlights how adept people are at emotional recovery after rejection, but less research has examined factors that can prevent full recovery. In five studies, we investigate how changing one's self-definition in response to rejection causes more lasting damage. We demonstrate that people who endorse an entity theory of personality (i.e., personality cannot be changed) report alterations in their self-definitions when reflecting on past rejections (Studies 1, 2, and 3) or imagining novel rejection experiences (Studies 4 and 5). Further, these changes in self-definition hinder post-rejection recovery, causing individuals to feel haunted by their past, that is, to fear the recurrence of rejection and to experience lingering negative affect from the rejection. Thus, beliefs that prompt people to tie experiences of rejection to self-definition cause rejection's impact to linger.

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

    PubMed Central

    Ayduk, Özlem; Gyurak, Anett; Luerssen, Anna

    2014-01-01

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

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

    PubMed Central

    Bourier, Felix; Kühne, Louisa; Banas, Miriam C.; Rümmele, Petra; Wurm, Simone; Banas, Bernhard

    2016-01-01

    Objective 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. Results 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. Conclusion 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

  8. Recipient Myd88 Deficiency Promotes Spontaneous Resolution of Kidney Allograft Rejection.

    PubMed

    Lerret, Nadine M; Li, Ting; Wang, Jiao-Jing; Kang, Hee-Kap; Wang, Sheng; Wang, Xueqiong; Jie, Chunfa; Kanwar, Yashpal S; Abecassis, Michael M; Luo, Xunrong; Zhang, Zheng

    2015-11-01

    The myeloid differentiation protein 88 (MyD88) adapter protein is an important mediator of kidney allograft rejection, yet the precise role of MyD88 signaling in directing the host immune response toward the development of kidney allograft rejection remains unclear. Using a stringent mouse model of allogeneic kidney transplantation, we demonstrated that acute allograft rejection occurred equally in MyD88-sufficient (wild-type [WT]) and MyD88(-/-) recipients. However, MyD88 deficiency resulted in spontaneous diminution of graft infiltrating effector cells, including CD11b(-)Gr-1(+) cells and activated CD8 T cells, as well as subsequent restoration of near-normal renal graft function, leading to long-term kidney allograft acceptance. Compared with T cells from WT recipients, T cells from MyD88(-/-) recipients failed to mount a robust recall response upon donor antigen restimulation in mixed lymphocyte cultures ex vivo. Notably, exogenous IL-6 restored the proliferation rate of T cells, particularly CD8 T cells, from MyD88(-/-) recipients to the proliferation rate of cells from WT recipients. Furthermore, MyD88(-/-) T cells exhibited diminished expression of chemokine receptors, specifically CCR4 and CXCR3, and the impaired ability to accumulate in the kidney allografts despite an otherwise MyD88-sufficient environment. These results provide a mechanism linking the lack of intrinsic MyD88 signaling in T cells to the effective control of the rejection response that results in spontaneous resolution of acute rejection and long-term graft protection.

  9. Preventing T cell rejection of pig xenografts.

    PubMed

    Higginbotham, Laura; Ford, Mandy L; Newell, Kenneth A; Adams, Andrew B

    2015-11-01

    Xenotransplantation is a potential solution to the limited supply of donor organs. While early barriers to xenograft acceptance, such as hyperacute rejection, are now largely avoided through genetic engineering, the next frontier in successful xenograft survival will require prevention of T cell-mediated rejection. Most successful immunosuppressive regimens in xenotransplantation utilize T cell depletion with antibody therapy. Additionally, the use of T cell costimulatory blockade - specifically blockade of the CD40-CD154 pathway - shows promise with several reports of long-term xenograft survival. Additional therapies, such as transgenic expression of T cell coinhibitory molecules or transfer of immunomodulatory cells to promote tolerance, may be necessary to achieve reliable long-term xenograft acceptance. Further studies in pre-clinical models are essential in order to optimize these regimens prior to trials in patients.

  10. Multimodal physiological sensor for motion artefact rejection.

    PubMed

    Goverdovsky, Valentin; Looney, David; Kidmose, Preben; Mandic, Danilo P

    2014-01-01

    This work introduces a novel physiological sensor, which combines electrical and mechanical modalities in a co-located arrangement, to reject motion-induced artefacts. The mechanically sensitive element consists of an electret condenser microphone containing a light diaphragm, allowing it to detect local mechanical displacements and disregard large-scale whole body movements. The electrically sensitive element comprises a highly flexible membrane, conductive on one side and insulating on the other. It covers the sound hole of the microphone, thereby forming an isolated pocket of air between the membrane and the diaphragm. The co-located arrangement of the modalities allows the microphone to sense mechanical disturbances directly through the electrode, thus providing an accurate proxy to artefacts caused by relative motion between the skin and the electrode. This proxy is used to reject such artefacts in the electrical physiological signals, enabling enhanced recording quality in wearable health applications.

  11. Adolescent social rejection alters pain processing in a CB1 receptor dependent manner.

    PubMed

    Schneider, Peggy; Pätz, Monique; Spanagel, Rainer; Schneider, Miriam

    2016-07-01

    Experiences of social rejection represent a major source of distress and in particular peer rejection during adolescence has been implicated in various psychiatric disorders. Moreover, experimentally induced acute social rejection alters pain perception in humans, implicating overlapping neurocircuits for social and physical pains. We recently demonstrated that rearing of adolescent Wistar rats with inadequate, less playful play partners (Fischer 344) persistently decreases pain sensitivity, although the detailed mechanisms mediating the aversiveness during the social encounter remained unsettled. With the present study we examined the behavioral performance during acute interaction of female adolescent Wistar rats with either age-matched same-strain partners or rats from the Fischer 344 strain. We here identify the low responsiveness upon playful attacks, which appears to be characteristic for social play in the Fischer 344 strain, as one of the main aversive components for adolescent Wistar animals during cross-strain encounters, which subsequently diminishes thermal pain reactivity. A detailed behavioral analysis further revealed increased ultrasonic vocalization at 50kHz and an increased frequency of playful attacks for adolescent Wistar animals paired with a Fischer 344 rat compared to same-strain control pairs. Finally, an acute injection of a subthreshold dose of the cannabinoid type 1 receptor inverse agonist/antagonist SR141716 before the social encounter abolished enhanced play-soliciting behavior in Wistar/Fischer 344 pairs as well as the behavioral consequences of the rejection experience in adolescent Wistar rats, further emphasizing an important modulatory role of the endocannabinoid system in mediating the effects of social behavior and social pain. PMID:27157075

  12. Active disturbance rejection controller for chemical reactor

    SciTech Connect

    Both, Roxana; Dulf, Eva H.; Muresan, Cristina I.

    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.

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

    PubMed

    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.

  14. 43 CFR 3141.6-6 - Rejection of bid.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) LEASING IN SPECIAL TAR SAND AREAS Leasing in Special Tar Sand Areas § 3141.6-6 Rejection of bid. If the high bid is rejected for failure by the...

  15. 43 CFR 3141.6-6 - Rejection of bid.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) LEASING IN SPECIAL TAR SAND AREAS Leasing in Special Tar Sand Areas § 3141.6-6 Rejection of bid. If the high bid is rejected for failure by the...

  16. 43 CFR 3141.6-6 - Rejection of bid.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) LEASING IN SPECIAL TAR SAND AREAS Leasing in Special Tar Sand Areas § 3141.6-6 Rejection of bid. If the high bid is rejected for failure by the...

  17. 43 CFR 3141.6-6 - Rejection of bid.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) LEASING IN SPECIAL TAR SAND AREAS Leasing in Special Tar Sand Areas § 3141.6-6 Rejection of bid. If the high bid is rejected for failure by the...

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

    ERIC Educational Resources Information Center

    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.…

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

    PubMed Central

    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 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 three 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 fourth 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. PMID:20649367

  20. Detection of cytomegalovirus and human herpesvirus-6 DNA in liver biopsy specimens and their correlation with rejection after liver transplantation.

    PubMed

    Guardia-Silva, A C; Stucchi, R S B; Sampaio, A M; Milan, A; Costa, S C B; Boin, I F S F

    2012-10-01

    Cytomegalovirus (CMV) and human herpesvirus-6 (HHV-6) reactivation after transplantation put patients at an increased risk of graft rejection mainly among those who receive organs that are positive in their donor biopsies. The aim of this study was to investigate the presence of CMV and HHV-6 DNA in liver biopsy specimens from the donors and from their grafts for correlation with rejection after transplantation. We followed 41 liver transplantation patients whose samples were evaluated using nested-polymerase chain reactions (N-PCR). Twenty-one (51%) of the 41 studied patients experienced rejection; 4/21 (19%) were CMV positive in the donor biopsy specimens and remained positive; another 5 subjects became positive. The patients who received organs from donors with biopsies positive for CMV demonstrated a trend to develop graft rejection after transplantation (Fisher's exact test [P = .0591] with significant results on univariate and multivariate analysis [P = .042]). Eight of the 21 who experienced rejection episodes were HHV-6 positive in the donor biopsy but there was no statistical significance CMV DNA diagnosed in liver donor biopsies remained positive posttransplantation in liver biopsy recipients; it was considered a tendency to develop acute cellular rejection after transplantation.

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

    PubMed

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

    2011-06-01

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

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

    PubMed

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

    2011-06-01

    Antibody-mediated rejection (AMR) continues to present a challenge for the survival of the cardiac allograft. AMR appears to be on the rise, likely secondary to changing trends in clinical practice, including selection of patients for transplantation on mechanical circulatory support and development of more effective combinations of immunosuppressive drugs against acute cellular rejection. Most current strategies are aimed at treating acute AMR, but the treatment of chronic AMR is still not well defined. Clinically, AMR can often be more severe than cellular rejection and more difficult to treat, often not responding to typical protocols of increased immunosuppression. Complex steps involved in the antibody response allows for several potential targets for therapeutic intervention, including suppression of T and B cells, elimination of circulating antibodies, and inhibition of residual antibodies. Existing evidence suggests a multiregimen approach is the best option. Sustenance of accommodation and induction of tolerance could be viewed as viable options if adequate immune surveillance can be achieved in this setting. This review discusses the challenges in treating AMR and provides a critical analysis of current and possible future therapies. PMID:21474341

  3. Identification of platelet-derived growth factor A and B chains in human renal vascular rejection.

    PubMed Central

    Alpers, C. E.; Davis, C. L.; Barr, D.; Marsh, C. L.; Hudkins, K. L.

    1996-01-01

    Platelet-derived growth factor (PDGF) exists as a dimer composed of two homologous but distinct peptides termed PDGF-A and -B chains, and may exist as AA, AB, and BB isoforms. The PDGF-B chain has been implicated as a mediator of renal vascular rejection by virtue of up-regulated expression of its receptor, PDGF beta-receptor, in affected arteries. A role for PDGF-A chain in mediating intimal proliferation has been suggested in human atherosclerosis (Rekhter MD, Gordon D: Does platelet-derived growth factor-A chain stimulate proliferation of arterial mesenchymal cells in human atherosclerotic plaques? Circ Res 1994, 75:410), but no studies of this molecule in human renal allograft injury have been reported to date. We used two polyclonal antisera to detect expression of PDGF-A chain and one monoclonal antibody to detect PDGF-B chain by immunohistochemistry in fixed, paraffin-embedded tissue from 1) normal adult kidneys, 2) a series of renal transplant biopsies chosen to emphasize features of vascular rejection, and 3) allograft nephrectomies. Immunohistochemistry was correlated with in situ hybridization on adjacent, formalin fixed tissue sections from nephrectomies utilizing riboprobes made from PDGF-A and -B chain cDNA. PDGF-A chain is widely expressed by medial smooth muscle cells of normal and rejecting renal arterial vessels of all sizes by immunohistochemistry and in situ hybridization. PDGF-A chain is also expressed by a population of smooth muscle cells (shown by double immunolabeling with an antibody to alpha-smooth muscle actin) comprising the intima in chronic vascular rejection. In arteries demonstrating acute rejection, up-regulated expression of PDGF-A chain by endothelial cells was detected by both immunohistochemistry and in situ hybridization. In contrast, PDGF-B chain was identified principally in infiltrating monocytes within the rejecting arteries, similar to its localization in infiltrating monocytes in human atherosclerosis. Although less

  4. Solar Rejection Filter for Large Telescopes

    NASA Technical Reports Server (NTRS)

    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

  5. Why Goethe rejected Newton's theory of light.

    PubMed

    Treisman, M

    1996-01-01

    Observations that he himself had made persuaded Goethe to reject Newton's theory of light and to put forward an alternative theory of the colour phenomena seen with a prism. Duck has argued that Goethe's attack on Newton's theory rested on valid experimental observations that appeared to present a difficulty for Newton's theory but to support his own views on colour. Duck has also proposed that these observations may be accounted for as an instance of the Bezold-Brücke phenomenon. It is argued here that this explanation is invalid and that two other features of colour processing can explain Goethe's observations.

  6. Confidence and rejection in automatic speech recognition

    NASA Astrophysics Data System (ADS)

    Colton, Larry Don

    Automatic speech recognition (ASR) is performed imperfectly by computers. For some designated part (e.g., word or phrase) of the ASR output, rejection is deciding (yes or no) whether it is correct, and confidence is the probability (0.0 to 1.0) of it being correct. This thesis presents new methods of rejecting errors and estimating confidence for telephone speech. These are also called word or utterance verification and can be used in wordspotting or voice-response systems. Open-set or out-of-vocabulary situations are a primary focus. Language models are not considered. In vocabulary-dependent rejection all words in the target vocabulary are known in advance and a strategy can be developed for confirming each word. A word-specific artificial neural network (ANN) is shown to discriminate well, and scores from such ANNs are shown on a closed-set recognition task to reorder the N-best hypothesis list (N=3) for improved recognition performance. Segment-based duration and perceptual linear prediction (PLP) features are shown to perform well for such ANNs. The majority of the thesis concerns vocabulary- and task-independent confidence and rejection based on phonetic word models. These can be computed for words even when no training examples of those words have been seen. New techniques are developed using phoneme ranks instead of probabilities in each frame. These are shown to perform as well as the best other methods examined despite the data reduction involved. Certain new weighted averaging schemes are studied but found to give no performance benefit. Hierarchical averaging is shown to improve performance significantly: frame scores combine to make segment (phoneme state) scores, which combine to make phoneme scores, which combine to make word scores. Use of intermediate syllable scores is shown to not affect performance. Normalizing frame scores by an average of the top probabilities in each frame is shown to improve performance significantly. Perplexity of the wrong

  7. Rejection of cardiac allografts by T cells expressing a restricted repertoire of T-cell receptor V beta genes.

    PubMed Central

    Shirwan, H; Barwari, L; Cramer, D V

    1997-01-01

    We have recently shown that T cells infiltrating cardiac allografts early in graft rejection use a limited T-cell receptor (TCR) V beta repertoire. In this study we tested whether this limited repertoire of V beta genes is important for graft rejection. A cell line, AL2-L3, was established from LEW lymphocytes infiltrating ACI heart allografts 2 days after transplantation. This cell line is composed of CD4+ T cells that primarily recognize the class II RTI.B major histocompatibility complex (MHC) molecule expressed by the donor graft. This cell line precipitated acute rejection of donor hearts with a median survival time (MST) of 10.5 days following adoptive transfer to sublethally irradiated LEW recipients. This rate of graft rejection was significantly (P < 0.0007) accelerated when compared with a MST of 60 days for allografts in irradiated control recipients. The AL2-L3-mediated acceleration of graft rejection was donor specific as WF third-party heart allografts were rejected with a delayed tempo (MST = 28.5 days). The V beta repertoire of this cell line was primarily restricted to the expression of V beta 4, 15 and 19 genes. The nucleotide sequence analysis of the beta-chain cDNAs from this cell line demonstrated that the restricted use of the V gene repertoire was not shared with the N, D and J regions. A wide variety of CDR3 loops and J beta genes were used in association with selected V beta genes. These data provide evidence for the role a restricted repertoire of V beta genes plays in cardiac allograft rejection in this model. The restricted usage of the V beta repertoire in an early T-cell response to allografts may provide the opportunity to therapeutically disrupt the rejection reaction by targeting selected T-cell populations for elimination at the time of organ transplantation. Images Figure 2 PMID:9176111

  8. Rejection sensitivity polarizes striatal-medial prefrontal activity when anticipating social feedback

    PubMed Central

    Powers, Katherine E.; Somerville, Leah H.; Kelley, William M.; Heatherton, Todd F.

    2014-01-01

    As a social species, humans are acutely aware of cues that signal inclusionary status. The present study characterizes behavioral and neural responses when individuals anticipate social feedback. Across two functional magnetic resonance imaging studies, participants (N = 42) made social judgments about supposed peers and then received feedback from those individuals. Of particular interest was the neural activity occurring when participants were awaiting social feedback. During this anticipatory period, increased neural activity was observed in the ventral striatum (VS), a central component of the brain’s reward circuitry, and dorsomedial prefrontal cortex (dmPFC), a brain region implicated in mentalizing about others. Individuals high in rejection sensitivity exhibited greater responses in both the VS and dmPFC when anticipating positive feedback. These findings provide initial insight into the neural mechanisms involved in anticipating social evaluations, as well as the cognitive processes that underlie rejection sensitivity. PMID:23859650

  9. 75 FR 32490 - Issues in the Development of Medical Products for the Prophylaxis and/or Treatment of Acute...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-08

    ... Prophylaxis and/or Treatment of Acute Antibody Mediated Rejection in Kidney Transplant Recipients; Public... prophylaxis and/or treatment of acute antibody mediated rejection (AMR) in kidney transplant recipients. This public workshop is intended to provide information for and gain perspective from health care...

  10. Effect of reverse chimerism on rejection in clinical transplantation.

    PubMed

    Bolado, Pedro; Landin, Luis

    2013-11-01

    Chimerism may enable allografts to survive when immunosuppressive therapy is administered at low levels or is even absent. Reverse chimerism (RC) is focused on intragraft chimerism that repopulates the allograft with cells of recipient origin. We aimed to identify and analyze current clinical evidence on RC and the presence of endothelial RC and tissue-specific RC. A total of 33 clinical reports on cardiac, kidney, liver, and lung transplants published between 1972 and 2012 that focused on RC were included in a systematic review. Liver allografts presented with the highest percentage of endothelial RC and lung allografts by far the lowest. Tissue-specific RC was present in most of the recipients, but at very low levels. There were also cardiac and kidney allografts with chimerism, but the functionality of the cells of recipient origin was questionable. We were unable to determine whether RC was a trigger for or a result of acute rejection. Further clinical research should focus on outcomes to evaluate the clinical relevance of this form of chimerism in transplantation.

  11. Precision Subtypes of T Cell-Mediated Rejection Identified by Molecular Profiles

    PubMed Central

    Kadota, Paul Ostrom; Hajjiri, Zahraa; Finn, Patricia W.; Perkins, David L.

    2015-01-01

    Among kidney transplant recipients, the treatment of choice for acute T cell-mediated rejection (TCMR) with pulse steroids or antibody protocols has variable outcomes. Some rejection episodes are resistant to an initial steroid pulse, but respond to subsequent antibody protocols. The biological mechanisms causing the different therapeutic responses are not currently understood. Histological examination of the renal allograft is considered the gold standard in the diagnosis of acute rejection. The Banff Classification System was established to standardize the histopathological diagnosis and to direct therapy. Although widely used, it shows variability among pathologists and lacks criteria to guide precision individualized therapy. The analysis of the transcriptome in allograft biopsies, which we analyzed in this study, provides a strategy to develop molecular diagnoses that would have increased diagnostic precision and assist the development of individualized treatment. Our hypothesis is that the histological classification of TCMR contains multiple subtypes of rejection. Using R language algorithms to determine statistical significance, multidimensional scaling, and hierarchical, we analyzed differential gene expression based on microarray data from biopsies classified as TCMR. Next, we identified KEGG functions, protein–protein interaction networks, gene regulatory networks, and predicted therapeutic targets using the integrated database ConsesnsusPathDB (CPDB). Based on our analysis, two distinct clusters of biopsies termed TCMR01 and TCMR02 were identified. Despite having the same Banff classification, we identified 1933 differentially expressed genes between the two clusters. These genes were further divided into three major groups: a core group contained within both the TCMR01 and TCMR02 subtypes, as well as genes unique to TCMR01 or TCMR02. The subtypes of TCMR utilized different biological pathways, different regulatory networks and were predicted to

  12. Adolescent peer-rejection persistently alters pain perception and CB1 receptor expression in female rats.

    PubMed

    Schneider, Peggy; Hannusch, Christin; Schmahl, Christian; Bohus, Martin; Spanagel, Rainer; Schneider, Miriam

    2014-02-01

    Peer-interactions are particularly important during adolescence and teenagers display enhanced sensitivity toward rejection by peers. Social rejection has been shown to induce alterations in pain perception in humans. However, the neurobiological consequences of adolescent social rejection have yet to be extensively characterized, and no appropriate animal model is available. Here, we propose inadequate playful interactions in adolescent rats as a novel animal model for social peer-rejection and examine potential long-term consequences into adulthood. Acute social pairing of female adolescent Wistar rats with an age-matched rat from the less playful Fischer344 strain was found to alter social play and decrease pain reactivity, indicating Fischer rats as inadequate social partners for Wistar animals. Therefore, in a second experiment, adolescent female Wistar rats were either reared with another Wistar rat (adequate social rearing; control) or with a Fischer rat (inadequate social rearing; play-deprived). Beginning on day 50, all Wistar rats were group housed with same-strain partners and tested for behavioral, neurobiological and endocrine differences in adulthood. Playful peer-interactions were decreased during adolescence in play-deprived animals, without affecting social contact behavior. Consequently, adult play-deprived rats showed decreased pain sensitivity and increased startle reactivity compared to controls, but did not differ in activity, anxiety-related behavior or social interaction. Both groups also differed in their endocrine stress-response, and expression levels of the cannabinoid CB1 receptor were increased in the thalamus, whereas FAAH levels were decreased in the amygdala. The present animal model therefore represents a novel approach to assess the long-term consequences of peer-rejection during adolescence. PMID:23669059

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

    PubMed Central

    Kusumesh, Rakhi; Vanathi, Murugesan

    2015-01-01

    Purpose: Early presentation of rejection facilitates early initiation of treatment which can favor a reversible rejection and better outcome. We analyzed the incidence, clinical features including rejection-treatment period and outcomes following graft rejection in our series of pediatric corneal graft. Materials and Methods: Case records of pediatric penetrating keratoplasty (PK) were reviewed retrospectively, and parameters noted demographic profile, indication of surgery, surgery-rejection period, rejection-treatment interval, graft outcome, and complications. Results: PK was performed in 66 eyes of 66 children <12 years, with an average follow-up of 21.12 ± 11.36 months (range 4-48 month). The median age at the time of surgery was 4.0 years (range 2 months to 12 years). Most of the children belonged to rural background. Scarring after keratitis (22, 33.4%) was the most common indication. Graft rejection occurred in eight eyes (12.12%) (acquired nontraumatic - 3, congenital hereditary endothelial dystrophy [CHED] - 2, nonCHED - 1, congenital glaucoma - 1, regraft - 1). The mean surgery-rejection period was 10.5 ± 7.3 months and mean rejection-treatment interval was 10.9 ± 7.02 days. 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. PMID:25709272

  14. Use of a SQUID array to detect T-cells with magnetic nanoparticles in determining transplant rejection

    NASA Astrophysics Data System (ADS)

    Flynn, Edward R.; Bryant, H. C.; Bergemann, Christian; Larson, Richard S.; Lovato, Debbie; Sergatskov, Dmitri A.

    2007-04-01

    Acute rejection in organ transplant is signaled by the proliferation of T-cells that target and kill the donor cells requiring painful biopsies to detect rejection onset. An alternative non-invasive technique is proposed using a multi-channel superconducting quantum interference device (SQUID) magnetometer to detect T-cell lymphocytes in the transplanted organ labeled with magnetic nanoparticles conjugated to antibodies specifically attached to lymphocytic ligand receptors. After a magnetic field pulse, the T-cells produce a decaying magnetic signal with a characteristic time of the order of a second. The extreme sensitivity of this technique, 10 5 cells, can provide early warning of impending transplant rejection and monitor immune-suppressive chemotherapy.

  15. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 ...

  16. Interference rejection techniques in spread spectrum communications

    NASA Astrophysics Data System (ADS)

    Milstein, Laurence B.

    1988-06-01

    It is argued that the ability of a spread-spectrum system to withstand interference, both intentional and unintentional, is probably its greatest asset. Any spread spectrum receiver can only suppress a given amount of interference; if the level of interference becomes too great, the system will not function properly. Even under these latter circumstances, however, other techniques, which enhance the performance of the system over and above the performance improvement that comes automatically to systems simply from using spread spectrum, are available for use. These techniques typically involve some type of additional signal processing and are examined here. Two general types of narrowband interference suppression schemes are discussed and an overview is presented for several other techniques. The two classes of rejection schemes emphasized are (1) those based on least-mean-square estimation techniques, and (2) those based on transform-domain processing structures.

  17. Girls' use of defense mechanisms following peer rejection.

    PubMed

    Sandstrom, Marlene J; Cramer, Phebe

    2003-08-01

    This study explores the relation between girls' social adjustment and their use of defense mechanisms. We recruited girls representing four sociometric status classifications (rejected, neglected, average, and popular), and assessed their use of defense mechanisms both before and after encountering a peer rejection experience in the laboratory. We hypothesized that increasing degrees of social maladjustment would be associated with higher levels of defense use, particularly after encountering a rejection experience. Our results supported these hypotheses. There was a significant negative relationship between social adjustment and defense use, both prior to and immediately following the rejection experience. Categorical analyses revealed that rejected and neglected girls used more defenses following the rejection experience than did popular and average girls.

  18. Total lymphoid irradiation for treatment of intractable cardiac allograft rejection

    SciTech Connect

    Hunt, S.A.; Strober, S.; Hoppe, R.T.; Stinson, E.B. )

    1991-03-01

    The ability of postoperative total lymphoid irradiation to reverse otherwise intractable cardiac allograft rejection was examined in a group of 10 patients in whom conventional rejection therapy (including pulsed steroids and monoclonal or polyclonal anti-T-cell antibody therapy) had failed to provide sustained freedom from rejection. Follow-up periods range from 73 to 1119 days since the start of total lymphoid irradiation. No patient died or sustained serious morbidity because of the irradiation. Three patients have had no further rejection (follow-up periods, 105 to 365 days). Two patients died--one in cardiogenic shock during the course of total lymphoid irradiation, the other with recurrent rejection caused by noncompliance with his medical regimen. Total lymphoid irradiation appears to be a safe and a moderately effective immunosuppressive modality for 'salvage' therapy of cardiac allograft rejection unresponsive to conventional therapy.

  19. WILLIAM SEAL REJECTING AN INCOMPLETE OR IMPROPERLY SET BEARDSLEY AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    WILLIAM SEAL REJECTING AN INCOMPLETE OR IMPROPERLY SET BEARDSLEY AND PIPER ROTOMOLD CORMATIC CORE. - Southern Ductile Casting Company, Core Making, 2217 Carolina Avenue, Bessemer, Jefferson County, AL

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

    PubMed

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

    2015-03-01

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

  1. The PGR Catalog of Objects Rejected from the PG Survey (``PG Rejects'')

    NASA Astrophysics Data System (ADS)

    Wade, R. A.; Green, R. F.; Stark, M. A.

    2005-12-01

    The Palomar-Green (PG) survey for ultraviolet-excess objects generated many candidate UV-excess objects that ultimately were not included in the final PG catalog (Green, Schmidt & Liebert 1986). These candidates were chosen based on their preliminary photographic U-B color, but low-resolution classification spectra showed zero-redshift K-line or G-band absorption or other indicators that the objects were ``cool'', so they were ultimately rejected. Nevertheless, among these ``PG Rejects'' are interesting individual objects, including a DAZB white dwarf, some composite spectrum binaries, and numerous metal-poor sdF/sdG subdwarfs. While the PG Rejects do not comprise a statistically complete sample, it is estimated that several percent, i.e., dozens, of the 1125 PGR objects will be of individual interest as examples of rare classes of stars. Most of the objects have not been studied before. We introduce the forthcoming master catalog of ``PGR'' objects, which will make this finding list available to a wider audience. We discuss some of the interesting objects found so far in the catalog, and present aggregate data to summarize some properties of the PGR stars. Supported in part by NASA grants.

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

    PubMed

    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.

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

    PubMed Central

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

    2004-01-01

    Vascular adhesion protein-1 (VAP-1) has been shown to mediate lymphocyte adhesion to endothelia at sites of inflammation, but its functional role in vivo has not been tested in any rodent model. Here we report the effects of VAP-1 blockade on rat liver allograft rejection. BN recipients of PVG liver allografts (known to develop acute rejection by day 7) were treated with 2 mg/kg anti-VAP-1 (a new anti-rat VAP-1 mAb 174–5) or isotype-matched irrelevant antibody (NS1) every other day (n = 6/group) and one group with anti-VAP-1 2 mg/kg daily (n = 7). On day 7, samples were collected for transplant aspiration cytology, histology, and immunohistochemistry. Lymphocyte infiltration to the graft was clearly affected by VAP-blockade. The total inflammation, mainly the number of active lymphoid cells, in transplant aspiration cytology was significantly decreased in animals treated with anti-VAP-1 (4.7 ± 1.0 and 2.4 ± 1.0 corrected increment units, respectively) compared to control (6.6 ± 1.0) (P < 0.05). In histology, the intensity of portal inflammation was significantly decreased (P < 0.05). The amount of T cells expressing activation markers diminished. This is the first demonstration in any prolonged in vivo model that VAP-1 plays an important role in lymphocyte infiltration to sites of inflammation, and, in particular, liver allograft rejection. PMID:15579442

  4. Expression of decoy receptor 3 in kidneys is associated with allograft survival after kidney transplant rejection

    PubMed Central

    Weng, Shuo-Chun; Shu, Kuo-Hsiung; Wu, Ming-Ju; Wen, Mei-Chin; Hsieh, Shie-Liang; Chen, Nien-Jung; Tarng, Der-Cherng

    2015-01-01

    Decoy receptor 3 (DcR3) expression in kidneys has been shown to predict progression of chronic kidney disease. We prospectively investigated a cohort comprising 96 renal transplant recipients (RTRs) undergoing graft kidney biopsies. Computer-assisted quantitative immunohistochemical staining value of DcR3 in renal tubular epithelial cells (RTECs) was used to determine the predictive role of DcR3 in kidney disease progression. The primary end point was doubling of serum creatinine and/or graft failure. A multivariate Cox proportional hazards model was used to assess the risk of DcR3 expression in rejected kidney grafts toward the renal end point. In total, RTRs with kidney allograft rejection were evaluated and the median follow-up was 30.9 months. The greater expression of DcR3 immunoreactivity in RTECs was correlated with a higher rate of the histopathological concordance of acute T cell-mediated rejection. Compared with 65 non-progressors, 31 progressors had higher DcR3 expression (HDE) regardless of the traditional risk factors. Cox regression analysis showed HDE was significantly associated with the risk of renal end point with a hazard ratio of 3.19 (95% confidence interval, 1.40 to 7.27; P = 0.006) after adjusting for other variables. In repetitive biopsies, HDE in tissue showed rapid kidney disease progression due to persistent inflammation. PMID:26335204

  5. Perturbations in the Urinary Exosome in Transplant Rejection

    PubMed Central

    Sigdel, Tara K.; Ng, Yolanda W.; Lee, Sangho; Nicora, Carrie D.; Qian, Wei-Jun; Smith, Richard D.; Camp, David G.; Sarwal, Minnie M.

    2015-01-01

    Background: 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. Methods: Urine exosomes were isolated by centrifugal filtration of urine samples collected from kidney transplant patients with and without acute rejection (AR), which were biopsy matched. The proteomes of unfractionated whole urine (Uw) and urine exosomes (Ue) underwent mass spectroscopy-based quantitative proteomics analysis. The proteome data were analyzed for significant differential protein abundances in AR. Results: A total of 1018 proteins were identified in Uw and 349 proteins in Ue. Two hundred seventy-nine 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. Eleven Ue proteins, functionally involved in an inflammatory and stress response, were more abundant in urine samples from patients with AR, three of which are exclusive to the Ue fraction. Ue AR-specific biomarkers (1) were also detected in Uw, but since they were observed at significantly lower abundances in Uw, they were not significant for AR in Uw. Conclusion: 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

  6. 48 CFR 1514.404 - Rejection of bids.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Rejection of bids. 1514.404 Section 1514.404 Federal Acquisition Regulations System ENVIRONMENTAL PROTECTION AGENCY CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 1514.404 Rejection of bids....

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

    ERIC Educational Resources Information Center

    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…

  8. 18 CFR 50.8 - Acceptance/rejection of applications.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ELECTRIC TRANSMISSION FACILITIES § 50.8 Acceptance/rejection of applications. (a) Applications will be... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Acceptance/rejection of applications. 50.8 Section 50.8 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY...

  9. 18 CFR 50.8 - Acceptance/rejection of applications.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... ELECTRIC TRANSMISSION FACILITIES § 50.8 Acceptance/rejection of applications. (a) Applications will be... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Acceptance/rejection of applications. 50.8 Section 50.8 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY...

  10. 37 CFR 1.113 - Final rejection or action.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Applicant and Further Consideration § 1.113 Final rejection or action. (a) On the second or any subsequent... in the case of rejection of any claim (§ 41.31 of this title), or to amendment as specified in §...

  11. 37 CFR 1.113 - Final rejection or action.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Applicant and Further Consideration § 1.113 Final rejection or action. (a) On the second or any subsequent... in the case of rejection of any claim (§ 41.31 of this title), or to amendment as specified in §...

  12. 37 CFR 1.113 - Final rejection or action.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Applicant and Further Consideration § 1.113 Final rejection or action. (a) On the second or any subsequent... in the case of rejection of any claim (§ 41.31 of this title), or to amendment as specified in §...

  13. 48 CFR 14.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Rejection of individual... of individual bids. (a) Any bid that fails to conform to the essential requirements of the invitation... total price of the bid, but the prices for individual line items as well. (g) Any bid may be rejected...

  14. 48 CFR 814.404-2 - Rejection of individual bids.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Rejection of individual... Rejection of individual bids. (a) When a contracting officer finds a bid that is being considered for an... nonresponsive an individual bid that is not in compliance with the Government's bid acceptance time,...

  15. Preadolescent Friendship and Peer Rejection as Predictors of Adult Adjustment.

    ERIC Educational Resources Information Center

    Bagwell, Catherine L.; Newcomb, Andrew F.; Bukowski, William M.

    1998-01-01

    Compared adjustment of 30 young adults who had a stable, reciprocal best friend in fifth grade and 30 who did not. Found that lower peer rejection uniquely predicted overall life status adjustment. Friended preadolescents had higher general self-worth in adulthood, even after controlling for perceived preadolescence competence. Peer rejection and…

  16. Heterosexual Rejection and Mate Choice: A Sociometer Perspective

    PubMed Central

    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. PMID:26648898

  17. Process Demands of Rejection Mechanisms of Recognition Memory

    ERIC Educational Resources Information Center

    Odegard, Timothy N.; Koen, Joshua D.; Gama, Jorge M.

    2008-01-01

    A surge of research has been conducted to examine memory editing mechanisms that help distinguish accurate from inaccurate memories. In the present experiment, the authors examined the ability of participants to use novelty detection, recollection rejection, and plausibility judgments to reject lures presented on a recognition memory test.…

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

    ERIC Educational Resources Information Center

    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. 25 CFR 163.18 - Acceptance and rejection of bids.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Acceptance and rejection of bids. 163.18 Section 163.18 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GENERAL FORESTRY REGULATIONS Forest Management and Operations § 163.18 Acceptance and rejection of bids. (a) The high bid received...

  20. 25 CFR 163.18 - Acceptance and rejection of bids.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Acceptance and rejection of bids. 163.18 Section 163.18 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GENERAL FORESTRY REGULATIONS Forest Management and Operations § 163.18 Acceptance and rejection of bids. (a) The high bid received...

  1. 25 CFR 163.18 - Acceptance and rejection of bids.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Acceptance and rejection of bids. 163.18 Section 163.18 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GENERAL FORESTRY REGULATIONS Forest Management and Operations § 163.18 Acceptance and rejection of bids. (a) The high bid received...

  2. 25 CFR 163.18 - Acceptance and rejection of bids.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Acceptance and rejection of bids. 163.18 Section 163.18 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GENERAL FORESTRY REGULATIONS Forest Management and Operations § 163.18 Acceptance and rejection of bids. (a) The high bid received...

  3. 25 CFR 163.18 - Acceptance and rejection of bids.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Acceptance and rejection of bids. 163.18 Section 163.18 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GENERAL FORESTRY REGULATIONS Forest Management and Operations § 163.18 Acceptance and rejection of bids. (a) The high bid received...

  4. Aggressive and Nonaggressive Rejected Students: An Analysis of Their Differences

    ERIC Educational Resources Information Center

    Lopez, Estefania Estevez; Olaizola, Juan Herrero; Ferrer, Belen Martinez; Ochoa, Gonzalo Musitu

    2006-01-01

    The present study aimed to analyze differences between aggressive and nonaggressive rejected students in four sets of variables: personal, family, school, and social. Participants in the study were 843 Spanish adolescents ranging in age from 11 to 16 years old, of whom 47% were boys. Results indicated that these two subgroups of rejected students…

  5. 7 CFR 70.35 - Rejection of application.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) VOLUNTARY GRADING OF POULTRY PRODUCTS AND RABBIT PRODUCTS Grading of Poultry Products and Rabbit Products Application for Grading Service § 70.35 Rejection of application. (a) Any application for grading service may be rejected by...

  6. 48 CFR 2919.505 - Rejecting Small Business Administration recommendations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Rejecting Small Business... LABOR SOCIOECONOMIC PROGRAMS SMALL BUSINESS AND SMALL DISADVANTAGED BUSINESS CONCERNS Set-Asides for Small Business 2919.505 Rejecting Small Business Administration recommendations. When the...

  7. 48 CFR 2919.505 - Rejecting Small Business Administration recommendations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Rejecting Small Business... LABOR SOCIOECONOMIC PROGRAMS SMALL BUSINESS AND SMALL DISADVANTAGED BUSINESS CONCERNS Set-Asides for Small Business 2919.505 Rejecting Small Business Administration recommendations. When the...

  8. Continuous improvement in nitrogen rejection unit design

    SciTech Connect

    O`Brien, J.V.; Maloney, J.J.

    1997-12-31

    The design and fabrication of Nitrogen Rejection Units (NRU) has advanced considerably over the past 15 years. Improvements have been made in all aspects of producing an NRU plant and cold box. This paper presents the primary areas involved that have seen these improvements. (1) Process design: the two-column process has been superseded by an approach which utilizes multiple flash drums and one column. This leads to a smaller and lower cost cold box. With low nitrogen content feeds, the prefractionater recovers half the methane as a high pressure residue gas and reduces the cold box size. (2) Mechanical Design: improved software enables the design process to be more accurate, eliminate piping and equipment interferences, reduce the size of the box and save design time. (3) Manufacturing: the interfacing of the 3D software design tools and the manufacturing process enables the shop floor personnel to reduce the manufacturing time by 10%. All of these individual improvements have reduced the real cost of an NRU substantially over the past 15 years.

  9. South African court rejects country's new constitution.

    PubMed

    1996-09-20

    Fundamental principles designed to ensure that South Africa's new constitution upholds a wide range of individual rights and freedoms and establishes a responsive government with a balanced separation of powers, including recognition of the role of traditional tribal leadership, were adopted into the current interim constitution shortly before the 1994 free elections which brought Nelson Mandela and the African National Congress to power. In a judgement issued on September 6, 1996, South Africa's Constitutional Court rejected the country's new draft constitution, arguing that it failed to meet the standards of nine of the 34 principles established at the Kempton Park negotiations. The Constitutional Assembly is comprised of a joint meeting of the National Assembly and Senate. One of the court's major objections to the constitution concerned the proposed structure of rule, which was seen to give inadequate power to South Africa's nine provinces as compared with the national government. However, the bill of rights was almost entirely upheld. The bill would create a favorable environment for legalized abortion and guarantee a universal right of access to health care, including reproductive health services

  10. Similarity principle and rejection of Gibbs paradox

    NASA Astrophysics Data System (ADS)

    Lin, Shu-Kun

    2000-03-01

    Gibbs Paradox says that entropy of mixing or assembling decreases discotinuously with the increase in the property similarity. After the rejection of the Gibbs paradox statement (see papers cited at website http://www.mdpi.org/lin/), the similarity principle has been developed: If all the other conditions remain constant, the higher the similarity among the components is, the higher value of entropy of the mixing, the assembling or the chemical bond formation process will be, the more spontaneous the mixing, the assembling or the chemical bond formation process will be, and the more stable the mixture, the assemblage or the chemical bond will be. The similarity principle is very useful. If one wants to mix substances, increase the similarity (of relevant properties); if one plans to separate the substances as phases, reduce their similarity! Then, the desirable processes of mixing or separation will happen spontaneously. Normally by changing temperature ( similarity is related to Boltzmann factor) and pressure, one can control the similarity and in turn, direct the process towards the desired direction. Higher temperature and pressure leads to higher similarity. This theory is important in understanding molecular recognition, self-organization, molecular assembling and molecular replication.

  11. Equal overall rejection rate in pre-transplant flow-cytometric cross-match negative and positive adult recipients in liver transplantation.

    PubMed

    Matinlauri, Irma H; Höckerstedt, Krister A; Isoniemi, Helena M

    2005-10-01

    T cell IgG flow-cytometric cross-matches (FCXM) using 48 stored pre-transplant patient serum samples and 40 stored serum samples collected 3 wk after liver transplantation and frozen spleen cells of cadaveric donors in 48 consecutive liver transplantations were performed retrospectively. T cell IgG FCXM using pre-transplant serum samples was compared with 46 complement-dependent lymphocytotoxic cross-matches (CDCXM) performed at the time of transplantation. Clinical relevance of these tests was evaluated in relation to acute rejection, 1-, 3- and 5-yr graft and patient survival. The incidence of positive FCXM was 33% (16 of 48) and 13% (six of 46) by CDCXM. The median time of acute rejection was 29 d after transplantation in FCXM positive group (range 13-101 d) and 22 d in FCXM negative group (range 7-157 d, NS). Rejection rate was similar in 16 pre-transplant FCXM positive patients (eight of 16, 50%) compared with six pre-transplant CDCXM positive patients (three of six, 50%; NS). Recipients having graft rejection tended to be more often pre-transplant FCXM positive (eight of 21, 38%) than CDCXM positive (three of 21, 14%), but the difference was not significant (p > 0.1). No difference was found in the positive predictive value in relation to acute rejection between positive FCXM and CDCXM (69% vs. 50%; NS). Furthermore there was no correlation between post-transplant positive FCXM and acute rejection. No difference was found between pre-transplant T cell IgG FCXM positive and negative recipients in relation to graft or patient survival. Our findings are supportive for little risk associated with preformed donor-specific antibodies in liver transplantation.

  12. Rejection Sensitivity and Adolescents’ Perceptions of Romantic Interactions

    PubMed Central

    Norona, Jerika C.; Salvatore, Joseph F.; Welsh, Deborah P.; Darling, Nancy

    2014-01-01

    Rejection sensitivity – the tendency to expect, perceive, and overreact to rejection by others – is linked with individuals’ expectations that their romantic partners’ behaviors have negative intent, even if, perhaps, such behaviors could be considered neutral when observed by another. The aim of the present study was to test this proposition, derived from rejection sensitivity theory, using a Video-Recall Procedure with adolescent couples in the US (N = 386 adolescents, 50% girls). We examined whether adolescents who were more sensitive to rejection perceived their romantic partners’ behaviors as more conflictual than when viewed by trained, third-party observers. Findings suggest that, at the micro-analytic level, higher rejection sensitivity is associated with adolescents’ heightened perception of their romantic partners as conflictual when compared to observers, who more often coded the same behaviors as neutral rather than conflictual. Implications for adolescent mental health and well-being are discussed. PMID:25282535

  13. A rejection method for selection of scattered states

    NASA Astrophysics Data System (ADS)

    Lawson, William S.

    1994-05-01

    A rejection method is presented that sidesteps much of the labor necessary in the usual techniques for choosing a scattered state after an electron-phonon collision with full band structure. The phonon wave number is chosen randomly, then tested to see if the resultant collision will satisfy energy conservation to within some accuracy. If not, the collision is rejected, and if so, then the wave number is adjusted in order to enforce energy conservation more precisely. The price one pays is in a high rejection rate. If the cost of a rejection is small, however, this rejection rate can be tolerated. This method will not compete with analytical models (near valley minima), but may outperform the more usual techniques. Accuracies of a few percent are practical. Simulations were preformed with the first conduction band of gallium arsenide.

  14. Solar dynamic heat rejection technology. Task 1: System concept development

    NASA Technical Reports Server (NTRS)

    Gustafson, Eric; Carlson, Albert W.

    1987-01-01

    The results are presented of a concept development study of heat rejection systems for Space Station solar dynamic power systems. The heat rejection concepts are based on recent developments in high thermal transport capacity heat pipe radiators. The thermal performance and weights of each of the heat rejection subsystems is addressed in detail, and critical technologies which require development tests and evaluation for successful demonstration are assessed and identified. Baseline and several alternate heat rejection system configurations and optimum designs are developed for both Brayton and Rankine cycles. The thermal performance, mass properties, assembly requirements, reliability, maintenance requirements and life cycle cost are determined for each configuration. A specific design was then selected for each configuration which represents an optimum design for that configuration. The final recommendations of heat rejection system configuration for either the Brayton or Rankine cycles depend on the priorities established for the evaluation criteria.

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

    PubMed

    Valladares Linares, Rodrigo; Yangali-Quintanilla, Victor; Li, Zhenyu; Amy, Gary

    2011-12-15

    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. PMID:22055122

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

    PubMed

    Valladares Linares, Rodrigo; Yangali-Quintanilla, Victor; Li, Zhenyu; Amy, Gary

    2011-12-15

    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.

  17. Ischemia-Reperfusion Injury Enhances Lymphatic Endothelial VEGFR3 and Rejection in Cardiac Allografts.

    PubMed

    Dashkevich, A; Raissadati, A; Syrjälä, S O; Zarkada, G; Keränen, M A I; Tuuminen, R; Krebs, R; Anisimov, A; Jeltsch, M; Leppänen, V-M; Alitalo, K; Nykänen, A I; Lemström, K B

    2016-04-01

    Organ damage and innate immunity during heart transplantation may evoke adaptive immunity with serious consequences. Because lymphatic vessels bridge innate and adaptive immunity, they are critical in immune surveillance; however, their role in ischemia-reperfusion injury (IRI) in allotransplantation remains unknown. We investigated whether the lymphangiogenic VEGF-C/VEGFR3 pathway during cardiac allograft IRI regulates organ damage and subsequent interplay between innate and adaptive immunity. We found that cardiac allograft IRI, within hours, increased graft VEGF-C expression and lymphatic vessel activation in the form of increased lymphatic VEGFR3 and adhesion protein expression. Pharmacological VEGF-C/VEGFR3 stimulation resulted in early lymphatic activation and later increase in allograft inflammation. In contrast, pharmacological VEGF-C/VEGFR3 inhibition during cardiac allograft IRI decreased early lymphatic vessel activation with subsequent dampening of acute and chronic rejection. Genetic deletion of VEGFR3 specifically in the lymphatics of the transplanted heart recapitulated the survival effect achieved by pharmacological VEGF-C/VEGFR3 inhibition. Our results suggest that tissue damage rapidly changes lymphatic vessel phenotype, which, in turn, may shape the interplay of innate and adaptive immunity. Importantly, VEGF-C/VEGFR3 inhibition during solid organ transplant IRI could be used as lymphatic-targeted immunomodulatory therapy to prevent acute and chronic rejection. PMID:26689983

  18. Nature of hyperacute (accelerated second set) rejection in dog renal allografts and effects of heparin on rejection process.

    PubMed

    Amery, A H; Pegrum, G D; Risdon, R A; Williams, G

    1973-02-24

    Renal allografts were exchanged between unrelated mongrel dogs after previous sensitization with skin and kidney grafts from the same donors. Rapid rejection of the renal allografts was associated with the accumulation of platelets and leucocytes in the peritubular and glomerular capillaries but fibrin deposition was not demonstrated.Heparin infusion delayed but did not prevent the rejection process.

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

    ERIC Educational Resources Information Center

    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…

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

    PubMed Central

    Kawamoto, Taishi; Nittono, Hiroshi; Ura, Mitsuhiro

    2015-01-01

    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. PMID:26483750

  1. Acute Bronchitis

    MedlinePlus

    ... tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis get better within several days. But your ... that cause colds and the flu often cause acute bronchitis. These viruses spread through the air when ...

  2. Separate neural representations for physical pain and social rejection.

    PubMed

    Woo, Choong-Wan; Koban, Leonie; Kross, Ethan; Lindquist, Martin A; Banich, Marie T; Ruzic, Luka; Andrews-Hanna, Jessica R; Wager, Tor D

    2014-01-01

    Current theories suggest that physical pain and social rejection share common neural mechanisms, largely by virtue of overlapping functional magnetic resonance imaging (fMRI) activity. Here we challenge this notion by identifying distinct multivariate fMRI patterns unique to pain and rejection. Sixty participants experience painful heat and warmth and view photos of ex-partners and friends on separate trials. FMRI pattern classifiers discriminate pain and rejection from their respective control conditions in out-of-sample individuals with 92% and 80% accuracy. The rejection classifier performs at chance on pain, and vice versa. Pain- and rejection-related representations are uncorrelated within regions thought to encode pain affect (for example, dorsal anterior cingulate) and show distinct functional connectivity with other regions in a separate resting-state data set (N = 91). These findings demonstrate that separate representations underlie pain and rejection despite common fMRI activity at the gross anatomical level. Rather than co-opting pain circuitry, rejection involves distinct affective representations in humans. PMID:25400102

  3. Separate neural representations for physical pain and social rejection

    PubMed Central

    Woo, Choong-Wan; Koban, Leonie; Kross, Ethan; Lindquist, Martin A.; Banich, Marie T.; Ruzic, Luka; Andrews-Hanna, Jessica R.; Wager, Tor D.

    2014-01-01

    Current theories suggest that physical pain and social rejection share common neural mechanisms, largely by virtue of overlapping functional magnetic resonance imaging (fMRI) activity. Here we challenge this notion by identifying distinct multivariate fMRI patterns unique to pain and rejection. Sixty participants experience painful heat and warmth and view photos of ex-partners and friends on separate trials. FMRI pattern classifiers discriminate pain and rejection from their respective control conditions in out-of-sample individuals with 92% and 80% accuracy. The rejection classifier performs at chance on pain, and vice versa. Pain-and rejection-related representations are uncorrelated within regions thought to encode pain affect (for example, dorsal anterior cingulate) and show distinct functional connectivity with other regions in a separate resting-state data set (N = 91). These findings demonstrate that separate representations underlie pain and rejection despite common fMRI activity at the gross anatomical level. Rather than co-opting pain circuitry, rejection involves distinct affective representations in humans. PMID:25400102

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

    NASA Technical Reports Server (NTRS)

    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.

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

    NASA Astrophysics Data System (ADS)

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

    1998-07-01

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

  6. Separate neural representations for physical pain and social rejection.

    PubMed

    Woo, Choong-Wan; Koban, Leonie; Kross, Ethan; Lindquist, Martin A; Banich, Marie T; Ruzic, Luka; Andrews-Hanna, Jessica R; Wager, Tor D

    2014-01-01

    Current theories suggest that physical pain and social rejection share common neural mechanisms, largely by virtue of overlapping functional magnetic resonance imaging (fMRI) activity. Here we challenge this notion by identifying distinct multivariate fMRI patterns unique to pain and rejection. Sixty participants experience painful heat and warmth and view photos of ex-partners and friends on separate trials. FMRI pattern classifiers discriminate pain and rejection from their respective control conditions in out-of-sample individuals with 92% and 80% accuracy. The rejection classifier performs at chance on pain, and vice versa. Pain- and rejection-related representations are uncorrelated within regions thought to encode pain affect (for example, dorsal anterior cingulate) and show distinct functional connectivity with other regions in a separate resting-state data set (N = 91). These findings demonstrate that separate representations underlie pain and rejection despite common fMRI activity at the gross anatomical level. Rather than co-opting pain circuitry, rejection involves distinct affective representations in humans.

  7. Ferritin as an early marker of graft rejection after allogeneic hematopoietic stem cell transplantation in pediatric patients.

    PubMed

    Döring, Michaela; Cabanillas Stanchi, Karin Melanie; Feucht, Judith; Queudeville, Manon; Teltschik, Heiko-Manuel; Lang, Peter; Feuchtinger, Tobias; Handgretinger, Rupert; Müller, Ingo

    2016-01-01

    Diagnosis of adverse events following hematopoietic stem cell transplantation (HSCT) is mainly assigned to clinical symptoms or biopsies and thus rather unspecific and/or invasive. Studies indicate a distinct role of serum ferritin in HSCT and its correlation with adverse events such as graft-versus-host disease (GvHD), veno-occlusive disease (VOD), or infections. However, published data on the relevance of ferritin as a prognostic marker for post-transplant adverse events is rare, especially in pediatric patients. The present study analyzes ferritin plasma concentrations of 138 pediatric patients after HSCT between 2007 and 2010 including the control group (n = 21). Given the initial results regarding ferritin as a significant predictor for acute graft rejection after allogeneic HSCT in 9 of the 138 pediatric patients, serum ferritin of all pediatric patients (n = 27) who experienced graft rejection between 2007 and 2014 was analyzed. In addition, laboratory parameters including C-reactive protein (CRP), lactate dehydrogenase (LDH), fibrinogen, and D-dimer as possible differentiation markers for graft rejection were determined. In 24 (88.9 %) of the 27 pediatric patients with graft rejection, a significant increase of ferritin levels was observed 1 to 7 days prior to (P < 0.0001) and at the time of graft rejection (P < 0.0001). Moreover, there was an increase of D-dimer, CRP, LDH, and fibrinogen 1-7 days before graft rejection. Ferritin increased significantly at time of VOD (P = 0.0067), at time of intestinal (P < 0.0001) and skin GvHD (P < 0.0001), and at time of sepsis (P = 0.0005) and bacteremia (P = 0.0029). Ferritin might serve as a readily available identification marker for differentiation and identification of adverse events after HSCT in combination with other laboratory markers. PMID:26611853

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

    PubMed

    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. Stress, rejection, and hormones: Cortisol and progesterone reactivity to laboratory speech and rejection tasks in women and men

    PubMed Central

    Gaffey, Allison E.; Wirth, Michelle M.

    2014-01-01

    Stress and social rejection have important impacts on health. Among the mechanisms implicated are hormonal systems such as the hypothalamic-pituitary-adrenal (HPA) axis, which produces cortisol in humans. Current research employs speech stressors and social rejection stressors to understand hormonal responses in a laboratory setting. However, it is not clear whether social rejection stressors elicit hormonal reactivity. In addition to cortisol, progesterone has been highlighted as a potential stress- and affiliation-related hormone in humans. In the present study, 131 participants (70 men and 61 women) were randomly assigned to be exposed to one of four conditions: standardized speech stressor; speech control; social rejection task; or a control (inclusion) version of the social rejection task. Saliva samples were collected throughout the study to measure cortisol and progesterone. As hypothesized, we found the expected increase in cortisol in the speech stressor, and we also found that the social rejection task did not increase cortisol, underscoring the divergence between unpleasant experiences and HPA axis activity. However, we did not find evidence for progesterone increase either during the speech- or social rejection tasks. Compared with past studies on progesterone and stress in humans, the present findings present a mixed picture. Future work is needed to delineate the contexts and types of manipulations which lead to progesterone increases in humans. PMID:25580228

  10. Lentivirus IL-10 gene therapy down-regulates IL-17 and attenuates mouse orthotopic lung allograft rejection.

    PubMed

    Hirayama, S; Sato, M; Loisel-Meyer, S; Matsuda, Y; Oishi, H; Guan, Z; Saito, T; Yeung, J; Cypel, M; Hwang, D M; Medin, J A; Liu, M; Keshavjee, S

    2013-06-01

    The purpose of the study was to examine the effect of lentivirus-mediated IL-10 gene therapy to target lung allograft rejection in a mouse orthotopic left lung transplantation model. IL-10 may regulate posttransplant immunity mediated by IL-17. Lentivirus-mediated trans-airway luciferase gene transfer to the donor lung resulted in persistent luciferase activity up to 6 months posttransplant in the isograft (B6 to B6); luciferase activity decreased in minor-mismatched allograft lungs (B10 to B6) in association with moderate rejection. Fully MHC-mismatched allograft transplantation (BALB/c to B6) resulted in severe rejection and complete loss of luciferase activity. In minor-mismatched allografts, IL-10-encoding lentivirus gene therapy reduced the acute rejection score compared with the lentivirus-luciferase control at posttransplant day 28 (3.0 ± 0.6 vs. 2.0 ± 0.6 (mean ± SD); p = 0.025; n = 6/group). IL-10 gene therapy also significantly reduced gene expression of IL-17, IL-23, and retinoic acid-related orphan receptor (ROR)-γt without affecting levels of IL-12 and interferon-γ (IFN-γ). Cells expressing IL-17 were dramatically reduced in the allograft lung. In conclusion, lentivirus-mediated IL-10 gene therapy significantly reduced expression of IL-17 and other associated genes in the transplanted allograft lung and attenuated posttransplant immune responses after orthotopic lung transplantation. PMID:23601206

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

    SciTech Connect

    De Nardo, D.; Scibilia, G.; Macchiarelli, A.G.; Cassisi, A.; Tonelli, E.; Papalia, U.; Gallo, P.; Antolini, M.; Pitucco, G.; Reale, A. )

    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.

  12. Stem Cells Transplanted in Monkeys without Anti-Rejection Drugs

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_160989.html Stem Cells Transplanted in Monkeys Without Anti-Rejection Drugs Scientists say goal is to create banks of stem cells that could be used for any human patient ...

  13. 7 CFR 56.24 - Rejection of application

    Code of Federal Regulations, 2010 CFR

    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)...

  14. Outside advantage: can social rejection fuel creative thought?

    PubMed

    Kim, Sharon H; Vincent, Lynne C; Goncalo, Jack A

    2013-08-01

    Eminently creative people working in fields as disparate as physics and literature refer to the experience of social rejection as fuel for creativity. Yet, the evidence of this relationship is anecdotal, and the psychological process that might explain it is as yet unknown. We theorize that the experience of social rejection may indeed stimulate creativity but only for individuals with an independent self-concept. In 3 studies, we show that individuals who hold an independent self-concept performed more creatively after social rejection relative to inclusion. We also show that this boost in creativity is mediated by a differentiation mind-set, or salient feelings of being different from others. Future research might investigate how the self-concept--for example, various cultural orientations-may shape responses to social rejection by mitigating some of the negative consequences of exclusion and potentially even motivating creative exploration. PMID:22889163

  15. Emotional responses to rejection of gestures of intergroup reconciliation.

    PubMed

    Harth, Nicole Syringa; Hornsey, Matthew J; Barlow, Fiona Kate

    2011-06-01

    Four experiments examine the emotional and attitudinal consequences of victim group rejection of a gesture of reconciliation from a transgressor group. Participants were reminded about an ingroup transgression and were told that their ingroup provided an apology (Studies 1 and 4) or an offer of repair (Studies 2 and 3). The authors varied whether the victim group rejected or accepted these gestures. As predicted, rejection resulted in greater anger and lower levels of satisfaction directed toward the victim group. Victim group response had little systematic effect on anxiety or shame, however. Appraisals of the response as illegitimate mediated the effects of victim group response (Studies 3 and 4). Furthermore, Study 4 showed that the emotional backlash toward victim groups who reject an offer of reconciliation leads to heightened racism and reduced intentions to financially compensate victim groups. Implications for how groups reconcile in the face of historical transgressions are discussed.

  16. Rotating reverse osmosis: a dynamic model for flux and rejection

    NASA Technical Reports Server (NTRS)

    Lee, S.; Lueptow, R. M.

    2001-01-01

    Reverse osmosis (RO) is a compact process for the removal of ionic and organic pollutants from contaminated water. However, flux decline and rejection deterioration due to concentration polarization and membrane fouling hinders the application of RO technology. In this study, a rotating cylindrical RO membrane is theoretically investigated as a novel method to reduce polarization and fouling. A dynamic model based on RO membrane transport incorporating concentration polarization is used to predict the performance of rotating RO system. Operating parameters such as rotational speed and transmembrane pressure play an important role in determining the flux and rejection in rotating RO. For a given geometry, a rotational speed sufficient to generate Taylor vortices in the annulus is essential to maintain high flux as well as high rejection. The flux and rejection were calculated for wide range of operating pressures and rotational speeds. c 2001 Elsevier Science B.V. All rights reserved.

  17. Liquid droplet radiators for heat rejection in space

    NASA Technical Reports Server (NTRS)

    Mattick, A. T.; Hertzberg, A.

    1980-01-01

    A radiator for heat rejection in space is described which utilizes a stream of liquid droplets to radiate waste heat. The large surface area per mass makes the liquid droplet radiator at least an order of magnitude lighter than tube and fin radiators. Generation and collection of the droplets, as well as heat transfer to the liquid, can be achieved with modest extensions of conventional technology. Low vapor pressure liquids are available which cover a radiating temperature range 250-1000 K with negligible evaporation losses. The droplet radiator may be employed for a wide range of heat rejection applications in space. Three applications - heat rejection for a high temperature Rankine cycle, cooling of photovoltaic cells, and low temperature heat rejection for refrigeration in space illustrate the versatility of the radiator.

  18. Fate of manuscripts rejected for publication in the AJR.

    PubMed

    Chew, F S

    1991-03-01

    The fate of rejected manuscripts that were originally submitted to the American Journal of Roentgenology (AJR) during the first 5 months of 1986 was investigated to learn whether, when, and where they had been published. AJR, a peer-reviewed journal of diagnostic radiology with a circulation of over 21,000, annually publishes about 500 papers and receives over 11,500 citations. MEDLINE searches conducted 45 to 54 months after the dates of rejection by AJR located 162 (64%) published papers out of a consecutive series of 254 manuscripts rejected by AJR, including 69% of the rejected major papers and 62% of the rejected case reports. The papers had been published in 30 different radiologic and 27 different nonradiologic journals. Most of these journals published fewer papers, had smaller circulations, and had lower impact factors (a ratio of citations received to papers published) than AJR does. The mean time lapse between rejection by AJR and publication in other journals was 15 months. The delay in publication was greater for papers published in nonradiologic and foreign journals than for papers published in radiologic and American journals. The results of this study indicate that rejection of a manuscript by a peer-reviewed journal such as AJR delays but by no means precludes publication. At least 82% of the major papers and 70% of the case reports that are submitted to AJR are eventually published, either in AJR or elsewhere. Because a scientific paper represents not only many hours of writing and manuscript preparation but also a great investment of research time and resources, authors are reluctant to abandon rejected manuscripts. In the majority of cases, submission to other journals gains acceptance and publication. PMID:1899764

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

    PubMed

    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. PMID:20402451

  20. B cells mediate chronic allograft rejection independently of antibody production.

    PubMed

    Zeng, Qiang; Ng, Yue-Harn; Singh, Tripti; Jiang, Ke; Sheriff, Khaleefathullah A; Ippolito, Renee; Zahalka, Salwa; Li, Qi; Randhawa, Parmjeet; Hoffman, Rosemary A; Ramaswami, Balathiripurasundari; Lund, Frances E; Chalasani, Geetha

    2014-03-01

    Chronic rejection is the primary cause of long-term failure of transplanted organs and is often viewed as an antibody-dependent process. Chronic rejection, however, is also observed in mice and humans with no detectable circulating alloantibodies, suggesting that antibody-independent pathways may also contribute to pathogenesis of transplant rejection. Here, we have provided direct evidence that chronic rejection of vascularized heart allografts occurs in the complete absence of antibodies, but requires the presence of B cells. Mice that were deficient for antibodies but not B cells experienced the same chronic allograft vasculopathy (CAV), which is a pathognomonic feature of chronic rejection, as WT mice; however, mice that were deficient for both B cells and antibodies were protected from CAV. B cells contributed to CAV by supporting splenic lymphoid architecture, T cell cytokine production, and infiltration of T cells into graft vessels. In chimeric mice, in which B cells were present but could not present antigen, both T cell responses and CAV were markedly reduced. These findings establish that chronic rejection can occur in the complete absence of antibodies and that B cells contribute to this process by supporting T cell responses through antigen presentation and maintenance of lymphoid architecture.

  1. [Aggression homicide and rejection homicide: a communicative classification of homicide].

    PubMed

    Mitterauerl, Bernhard; Griebnitz, Ernst; Rothuber, Helfried

    2006-01-01

    Based on a 10-year sample of homicides (n = 50), the hypothesis was tested that it is possible to differentiate between aggression and rejection homicide. The aggression homicide results from the offender/victim relationship, which is no longer accepted for some reason. In contrast, in the rejection homicide the offender radically strives for a goal which can only be reached if the victim is eliminated. Based on forensic-psychiatric expert opinions (n = 50), the case analyses yielded 31 aggression homicides and 18 rejection homicides, one case could not be classified. Aggression homicides differed significantly from the rejection homicides with regard to their main motives. Hate in quarrel (n = 8), violent occupation of the victim (n = 7), delusions (n = 5), revenge (n = 3), self-defence (n = 2), and jealousy (n = 1) characterized the aggression homicides, whereas rejection homicides were dominated by economic motives (n = 14). Two offenders intended to get rid of the victim and one offender wanted to rescue a third person. From a forensic-psychiatric point of view, the pertinent statistical data (social data, diagnosis, criminal responsibility) are reported and the significance of the differentiation between aggression homicide and rejection homicide for medico-legal or criminological case profiling and for the prognosis of the risk potential is discussed.

  2. Influence of biofouling on pharmaceuticals rejection in NF membrane filtration.

    PubMed

    Botton, Sabrina; Verliefde, Arne R D; Quach, Nhut T; Cornelissen, Emile R

    2012-11-15

    The effects of biomass attachment and growth on the surface characteristics and organic micropollutants rejection performance of nanofiltration membranes were investigated in a pilot installation. Biomass growth was induced by dosing of a readily biodegradable carbon source resulting in the formation of a biofouling in the investigated membrane elements. Surface properties and rejection behaviour of a biofouled and virgin membrane were investigated and compared in terms of surface charge, surface energy and hydrophobicity. The last two were accomplished by performing contact angle measurements on fully hydrated membrane surfaces, in order to mimic the operating conditions of a membrane in contact with water. Compared to a virgin membrane, deposition and growth of biofilm did slightly alter the surface charge, which became more negative, and resulted in a higher hydrophilicity of the membrane surface. In addition, the presence of the negatively charged biofilm induced accumulation of positively charged pharmaceuticals within the biomass layer, which probably also hindered back diffusion. This caused a reduction in rejection efficiency of positively charged solutes but did not alter rejection of neutral and negatively charged pharmaceuticals. Pharmaceuticals rejection was found to positively correlate with the specific free energy of interaction between virgin or biofouled membranes and pharmaceuticals dissolved in the water phase. The rejection values obtained with both virgin and biofouled membranes were compared and found in good agreement with the predictions calculated with a solute transport model earlier developed for high pressure filtration processes. PMID:22960036

  3. The use of antibody to complement protein C5 for salvage treatment of severe antibody-mediated rejection.

    PubMed

    Locke, J E; Magro, C M; Singer, A L; Segev, D L; Haas, M; Hillel, A T; King, K E; Kraus, E; Lees, L M; Melancon, J K; Stewart, Z A; Warren, D S; Zachary, A A; Montgomery, R A

    2009-01-01

    Desensitized patients are at high risk of developing acute antibody-mediated rejection (AMR). In most cases, the rejection episodes are mild and respond to a short course of plasmapheresis (PP) / low-dose IVIg treatment. However, a subset of patients experience severe AMR associated with sudden onset oliguria. We previously described the utility of emergent splenectomy in rescuing allografts in patients with this type of severe AMR. However, not all patients are good candidates for splenectomy. Here we present a single case in which eculizumab, a complement protein C5 antibody that inhibits the formation of the membrane attack complex (MAC), was used combined with PP/IVIg to salvage a kidney undergoing severe AMR. We show a marked decrease in C5b-C9 (MAC) complex deposition in the kidney after the administration of eculizumab.

  4. Preferential accumulation of T helper cells but not cytotoxic T cells characterizes benign subclinical rejection of human liver allografts.

    PubMed

    Baumann, Anna K; Schlue, Jerome; Noyan, Fatih; Hardtke-Wolenski, Matthias; Lehner, Frank; Barg-Hock, Hannelore; Klempnauer, Juergen; Manns, Michael P; Taubert, Richard; Jaeckel, Elmar

    2016-07-01

    Subclinical rejection (SCR) is a common event in protocol biopsies after liver transplantation (LT). So far the interpretation of the underlying histological changes and clinical significance is limited. Previous studies were restricted to SCR manifestations within the first weeks after transplantation with limited follow-up. We analyzed clinical data from our prospective protocol biopsy program and found late SCR (at least 3 months after transplantation) to be a common event (41/94 patients). SCR manifested much later than acute cellular rejection (ACR). In the second year after transplantation, the SCR incidence in protocol biopsies reached a plateau of approximately 25% and remained at this level until the latest observed manifestations more than 5 years after transplantation. During a median follow-up of 32 months after SCR, no acute or chronic rejection, relevant graft fibrosis, graft loss, or liver-related death occurred even without specific therapy for SCR. Immunophenotyping of liver biopsies during SCR showed that similar to ACR, the composition of intrahepatic T cells depended on the severity of histological rejection. However, SCR showed a different pattern of infiltrating T cells with a stronger accumulation of CD4(+) cells, an increasing CD4(+) /CD8(+) ratio, and an increasing CD4(+) forkhead box P3 (FOXP3)(+) regulatory T cell (Treg)/CD8(+) ratio, which was not seen in ACR. These intrahepatic T cell patterns were not reflected in the peripheral blood. In conclusion, late SCR after LT has a good clinical prognosis, and it seems safe to leave it untreated. This benign clinical course compared to ACR is associated with intrahepatic T cell infiltration patterns showing less cytotoxic T cells and more CD4(+) FOXP3(+) Tregs. Liver Transplantation 22 943-955 2016 AASLD.

  5. A common blood gene assay predates clinical and histological rejection in kidney and heart allografts.

    PubMed

    Sarwal, Minnie; Sigdel, Tara

    2013-01-01

    We assayed our recently defined blood gene panel, diagnostic for kidney and cardiac acute rejection (AR), for its ability to predict biopsy-confirmed renal and cardiac AR prior to clinical or histological AR detection. We utilized a subset of 63 patients from our recent studies with biopsy-confirmed AR (n=40 kidney AR, n=23 cardiacAR) who had paired blood samples collected within 6 months before and after AR. Blood samples were analyzed by quantitative polymerase chain reaction (QPCR) for 10 genes, modeled across differing panels of 5 genes for kidney and heart AR to classify each sample with a quantitative prediction score for rejection. The performance accuracy of the 5-gene panels for AR were compared to the only commercially available QPCR blood assay (AlloMap). A blood gene-based molecular call for AR was made -3 months prior to the histological AR diagnosis in both kidney (92% predicted probability) and cardiac (80% predicted probability) transplant patients and outperformed the AlloMapTM blood test for accuracy and sensitivity [area under the curve (AUC)=0.917 for the kidney 5 genes and 0.915 for the cardiac 5 genes versus an AUC=0.72 for AlloMap]. Serial, posttransplant, targeted profiling of blood samples for a set of 10 genes provides a means to identify kidney and heart transplant recipients at high risk for graft dysfunction and, in the absence of immunosuppression customization, fated to advance to histological rejection and increased graft and patient morbidity.

  6. Clinical and pathological features of kidney transplant patients with concurrent polyomavirus nephropathy and rejection-associated endarteritis

    PubMed Central

    McGregor, Stephanie M; Chon, W James; Kim, Lisa; Chang, Anthony; Meehan, Shane M

    2015-01-01

    AIM: To describe the clinicopathologic features of concurrent polyomavirus nephropathy (PVN) and endarteritis due to rejection in renal allografts. METHODS: We searched our electronic records database for cases with transplant kidney biopsies demonstrating features of both PVN and acute rejection (AR). PVN was defined by the presence of typical viral cytopathic effect on routine sections and positive polyomavirus SV40 large-T antigen immunohistochemistry. AR was identified by endarteritis (v1 by Banff criteria). All cases were subjected to chart review in order to determine clinical presentation, treatment course and outcomes. Outcomes were recorded with a length of follow-up of at least one year or time to nephrectomy. RESULTS: Of 94 renal allograft recipients who developed PVN over an 11-year period at our institution, we identified 7 (7.4%) with viral cytopathic changes, SV40 large T antigen staining, and endarteritis in the same biopsy specimen, indicative of concurrent PVN and AR. Four arose after reduction of immunosuppression (IS) (for treatment of PVN in 3 and tuberculosis in 1), and 3 patients had no decrease of IS before developing simultaneous concurrent disease. Treatment consisted of reduced oral IS and leflunomide for PVN, and anti-rejection therapy. Three of 4 patients who developed endarteritis in the setting of reduced IS lost their grafts to rejection. All 3 patients with simultaneous PVN and endarteritis cleared viremia and were stable at 1 year of follow up. Patients with endarteritis and PVN arising in a background of reduced IS had more severe rejection and poorer outcome. CONCLUSION: Concurrent PVN and endarteritis may be more frequent than is currently appreciated and may occur with or without prior reduction of IS. PMID:26722657

  7. The composition of the microbiota modulates allograft rejection.

    PubMed

    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.

  8. The composition of the microbiota modulates allograft rejection

    PubMed Central

    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

    2016-01-01

    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. PMID:27322054

  9. [Cyclosporin, toxicity and efficacy in rejection of liver allografts in the rat].

    PubMed

    Settaf, A; Gugenheim, J; Lahlou, M K; Gigou, M; Capron-Laudereau, M; Charpentier, B; Reynes, M; Lokiec, F; Bismuth, H

    1989-01-01

    52 orthotopic liver transplants were performed in DA to lewis rat strain combination, in order to appreciate cyclosporine toxicity, and efficacy at doses of 10 mg/kg day (G II) and 20 mg/kg/day (GIII) compared to liver allografts in DA/lewis rats. The first signs of cyclosporine hepatotoxicity are biological (increased plasma level of bilirubine and transaminase) that were noticed at the dose of 20 mg/kg/day. Histological signs (cells inclusion, hepatocytic necrosis) appeared late and were less constant as well as difficult to assert creatinine plasma level was the best reflect of cyclosporine nephrotoxicity. Renal toxicity was practically constant at the dose of 20 mg/kg/day. In spite of renal and hepatic toxicity, cyclosporin by itself, allows the abolition of the acute rejection of liver allografts in the rat.

  10. Liver transplant complications in hepatitis C infected recipients: recurrence versus rejection.

    PubMed

    Gehrau, Ricardo C; Mas, Valeria R; Suh, Jihee L; Maluf, Daniel G

    2014-07-01

    Despite improvement on outcomes post liver transplantation (LT), complications such as HCV recurrence (HCV-rec) and acute cellular rejection (ACR) continue to be a challenge for transplant physicians. Accurate diagnostic tools to better dissect between those complications post-LT are crucial for prompt and correct diagnosis and treatment. It is well known that the overlapping features of clinical and histo-pathological characteristics between these conditions turn difficult the appropriate differential diagnosis. Recently, new technological advances had supported the field of biomarker discovery in many diseases. Disease biomarkers capable to differentiate ACR versus HCV-rec post-LT is a long waited task in the transplant community. This editorial describes and discusses potential biomarkers of disease differentiation including recent reports in the field of genomics, proteomics, immunohistochemistry among other technologies.

  11. De novo expression of fetal ED-A(+) fibronectin and B (+) tenascin-C splicing variants in human cardiac allografts: potential impact for targeted therapy of rejection.

    PubMed

    Franz, Marcus; Matusiak-Brückner, Monika; Richter, Petra; Grün, Katja; Ziffels, Barbara; Neri, Dario; Maschek, Hansjörg; Schulz, Uwe; Pfeil, Alexander; Jung, Christian; Figulla, Hans R; Gummert, Jan; Berndt, Alexander; Renner, André

    2014-10-01

    Management of acute and especially chronic rejection after human cardiac transplantation is still challenging. Chronic rejection, represented by allograft vasculopathy (CAV) and cardiac interstitial fibrosis (CIF) is known to cause severe long-term complications. Rejection associated tissue-remodelling entails the reoccurrence of fetal variants of Fibronectin (Fn) and Tenascin-C (Tn-C), which are virtually absent in adult human organs. In a rat model, an extensive re-expression could be demonstrated for ED-A(+) Fn with spatial association to CAV and CIF. Thus, it is of great interest to investigate the cardiac tissue expression and distribution in human samples. From 48 heart transplanted patients, 64 tissue specimens derived from right ventricular biopsies were available. Histopathological analysis was performed according to the International Society for Heart and Lung Transplantation (ISHLT) guidelines for the detection of acute rejection. By immunohistochemistry, protein expression of ED-A(+) Fn, B(+) Tn-C, alpha-smooth muscle actin, CD31 and CD45 was assessed and analysed semiquantitatively. Co-localisation studies were performed by means of immunofluorescence double labelling. Histopathological analysis of the 64 samples revealed different ISHLT grades (0R in 36 cases, 1R in 20 cases and 2R in 8 cases). There was a distinct and quantitatively relevant re-occurrence of ED-A(+) Fn and B(+) Tn-C in most samples. Semi-quantitative evaluation did not show any correlation to the acute rejection grade for all markers. Interestingly, significant correlations to the extent of inflammation could be shown for ED-A(+) Fn (r = 0.442, p = 0.000) and B(+) Tn-C (r = 0.408, p = 0.001) as well as between both proteins (r = 0.663, p = 0.000). A spatial association of ED-A(+) Fn and B(+) Tn-C to CAV and CIF could be demonstrated. A relevant re-occurrence of ED-A(+) Fn and B(+) Tn-C following human heart transplantation could be demonstrated with spatial association to

  12. 40 CFR 205.57-7 - Acceptance and rejection of batch sequence.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Acceptance and rejection of batch....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 based upon the number of rejected...

  13. 40 CFR 205.57-7 - Acceptance and rejection of batch sequence.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Acceptance and rejection of batch....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 based upon the number of rejected...

  14. 40 CFR 205.57-7 - Acceptance and rejection of batch sequence.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Acceptance and rejection of batch....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 based upon the number of rejected...

  15. 40 CFR 205.57-7 - Acceptance and rejection of batch sequence.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Acceptance and rejection of batch....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 based upon the number of rejected...

  16. Relational Victimization and Rejection Sensitivity: The Long-Term Impact of Social Hurt

    ERIC Educational Resources Information Center

    Mellin, Elizabeth A.

    2012-01-01

    The Rejection Sensitivity Model is used to examine the social antecedents to expectations of rejection among adults. College students (N = 314) completed measures of relational victimization and rejection sensitivity. Results indicate that relational victimization is significantly related to rejection sensitivity for women. Implications for…

  17. Demonstration of An Image Rejection Mixer for High Frequency Applications (26-36 GHz)

    NASA Technical Reports Server (NTRS)

    Bankston, Cheryl D.; Carlstrom, John E.

    1999-01-01

    A new high frequency image-rejection mixer was successfully tested in a 26-36 GHz band receiver. This paper briefly describes the motivation for implementation of an image rejection mixer in a receiver system, the basic operation of an image rejection mixer, and the development and testing of an image rejection mixer for a high frequency, cryogenic receiver system.

  18. Protection against hyperacute xenograft rejection of transgenic rat hearts expressing human decay accelerating factor (DAF) transplanted into primates.

    PubMed Central

    Charreau, B.; Ménoret, S.; Tesson, L.; Azimzadeh, A.; Audet, M.; Wolf, P.; Marquet, R.; Verbakel, C.; Ijzermans, J.; Cowan, P.; Pearse, M.; d'Apice, A.; Soulillou, J. P.; Anegon, I.

    1999-01-01

    BACKGROUND: Production of transgenic pigs for multiple transgenes is part of a potential strategy to prevent immunological events involved in xenograft rejection. Use of a genetically engineerable rodent as a donor in primates could allow testing in vivo of the effects of different transgenes on controlling xenograft rejection. As a first step in the development of a donor containing multiple transgenes, transgenic rats for human decay-accelerating factor (DAF) were used as heart donors to test their resistance against complement (C)-mediated rejection by non-human primates. MATERIALS AND METHODS: Transgenic rats were generated by using a construct containing the human DAF cDNA under the transcriptional control of the endothelial cell (EC)-specific human ICAM-2 promoter. DAF expression was evaluated by immunohistology and by FACS analysis of purified ECs. Resistance of transgenic hearts against C-mediated damage was evaluated by ex vivo perfusion with human serum and by transplantation into cynomolgus monkeys. RESULTS: Immunohistological analysis of DAF expression in several organs from two transgenic lines showed uniform expression on the endothelium of all blood vessels. ECs purified from transgenic hearts showed 50% DAF expression compared to human ECs and >70% reduction of C-dependent cell lysis compared to control rat ECs. Hemizygous transgenic hearts perfused with human serum showed normal function for >60 min vs. 11. 2 +/- 1.7 min in controls. Hemi- or homozygous transgenic hearts transplanted into cynomolgus monkeys showed longer survival (15.2 +/- 7 min and >4.5 hr, respectively) than controls (5.5 +/- 1.4 min). In contrast to hyperacutely rejected control hearts, rejected homozygous DAF hearts showed signs of acute vascular rejection (AVR) characterized by edema, hemorrhage, and an intense PMN infiltration. CONCLUSIONS: We demonstrate that endothelial-specific DAF expression increased heart transplant survival in a rat-to-primate model of

  19. Data augmentation for models based on rejection sampling

    PubMed Central

    Rao, Vinayak; Lin, Lizhen; Dunson, David B.

    2016-01-01

    We present a data augmentation scheme to perform Markov chain Monte Carlo inference for models where data generation involves a rejection sampling algorithm. Our idea is a simple scheme to instantiate the rejected proposals preceding each data point. The resulting joint probability over observed and rejected variables can be much simpler than the marginal distribution over the observed variables, which often involves intractable integrals. We consider three problems: modelling flow-cytometry measurements subject to truncation; the Bayesian analysis of the matrix Langevin distribution on the Stiefel manifold; and Bayesian inference for a nonparametric Gaussian process density model. The latter two are instances of doubly-intractable Markov chain Monte Carlo problems, where evaluating the likelihood is intractable. Our experiments demonstrate superior performance over state-of-the-art sampling algorithms for such problems. PMID:27279660

  20. Allograft rejection in cattle with bovine leukocyte adhesion deficiency.

    PubMed

    Müller, K E; Rutten, V P; Becker, C K; Hoek, A; Bernadina, W E; Wentink, G H; Figdor, C G

    1995-09-01

    In the present investigation cell-mediated immunity in animals with bovine leukocyte adhesion deficiency (BLAD) was studied by means of skin transplantation experiments. Autograft and allograft behaviour in animals with BLAD was compared with the behaviour of simultaneously transplanted autografts and allografts in healthy controls. Allograft survival time was prolonged in three BLAD cattle (28, 30, and 72 days) compared to six healthy controls (12-14 days). When transplantations were repeated on one animal with BLAD using skin grafts from the same donor, accelerated rejection was observed (allograft survival time decreased from 72 days at primary to 35 days at secondary and to 21 days at tertiary transplantation), suggesting the development of immunological memory. Graft-infiltrating lymphocytes that were obtained from allograft biopsies during the period of rejection, were shown to be from recipient origin (beta 2-integrin negative). Our findings demonstrate that, although prolonged allograft survival is observed in cattle with BLAD, skin allografts are ultimately rejected. PMID:8533316

  1. Self-contained heat rejection module for future spacecraft

    NASA Technical Reports Server (NTRS)

    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.

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

    SciTech Connect

    Nakamura, H.; Gress, R.E. )

    1990-02-01

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

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

    PubMed

    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.

  4. A Longitudinal Study of Rejecting and Autonomy-Restrictive Parenting, Rejection Sensitivity, and Socioemotional Symptoms in Early Adolescents.

    PubMed

    Rowe, Susan L; Gembeck, Melanie J Zimmer; Rudolph, Julia; Nesdale, Drew

    2015-08-01

    Rejection sensitivity (RS) has been defined as the tendency to readily perceive and overreact to interpersonal rejection. The primary aim of this study was to test key propositions of RS theory, namely that rejecting experiences in relationships with parents are antecedents of early adolescents' future RS and symptomatology. We also expanded this to consider autonomy-restrictive parenting, given the importance of autonomy in early adolescence. Participants were 601 early adolescents (age 9 to 13 years old, 51% boys) from three schools in Australia. Students completed questionnaires at school about parent and peer relationships, RS, loneliness, social anxiety, and depression at two times with a 14-month lag between assessments. Parents also reported on adolescents' difficulties at Time 1 (T1). It was anticipated that more experience of parental rejection, coercion, and psychological control would be associated with adolescents' escalating RS and symptoms over time, even after accounting for peer victimisation, and that RS would mediate associations between parenting and symptoms. Structural equation modelling supported these hypotheses. Parent coercion was associated with adolescents' increasing symptoms of social anxiety and RS over time, and parent psychological control was associated with increasing depressive symptoms over time. Indirect effects via RS were also found, with parent rejection and psychological control linked to higher T1 RS, which was then associated with increasing loneliness and RS. Lastly, in a separate model, peer victimisation and RS, but not parenting practices, were positively associated with concurrent parent reports of adolescents' difficulties.

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

    SciTech Connect

    De Geronimo, Gianluigi

    2014-11-18

    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. Method and apparatus for analog pulse pile-up rejection

    SciTech Connect

    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.

  7. Solar dynamic organic Rankine cycle heat rejection system simulation

    NASA Technical Reports Server (NTRS)

    Havens, V. N.; Ragaller, D. R.; Namkoong, D.

    1987-01-01

    The use of a rotary fluid management device (RFMD) and shear flow condenser for two-phase fluid management in microgravity organic Rankine cycle (ORC) applications is examined. A prototype of the proposed Space Station ORC heat rejection system was constructed to evaluate the performance of the inventory control method. The design and operation of the RFMD, shear flow condenser, and inventory control fluid accumulator are described. A schematic diagram of the ORC, RFMD, and condenser, and a functional diagram of the heat rejection system for the ORC are presented.

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

    PubMed Central

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

    2014-01-01

    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 as compared to low (HRS vs. LRS) individuals displayed a resistance to extinction of the conditioned response to angry faces, but not to neutral faces or non-social 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. PMID:23914767

  9. Solar dynamic organic Rankine cycle heat rejection system simulation

    NASA Astrophysics Data System (ADS)

    Havens, V. N.; Ragaller, D. R.; Namkoong, D.

    The use of a rotary fluid management device (RFMD) and shear flow condenser for two-phase fluid management in microgravity organic Rankine cycle (ORC) applications is examined. A prototype of the proposed Space Station ORC heat rejection system was constructed to evaluate the performance of the inventory control method. The design and operation of the RFMD, shear flow condenser, and inventory control fluid accumulator are described. A schematic diagram of the ORC, RFMD, and condenser, and a functional diagram of the heat rejection system for the ORC are presented.

  10. Graft-Infiltrating Macrophages Adopt an M2 Phenotype and Are Inhibited by Purinergic Receptor P2X7 Antagonist in Chronic Rejection.

    PubMed

    Wu, C; Zhao, Y; Xiao, X; Fan, Y; Kloc, M; Liu, W; Ghobrial, R M; Lan, P; He, X; Li, X C

    2016-09-01

    Macrophages exhibit diverse phenotypes and functions; they are also a major cell type infiltrating chronically rejected allografts. The exact phenotypes and roles of macrophages in chronic graft loss remain poorly defined. In the present study, we used a mouse heart transplant model to examine macrophages in chronic allograft rejection. We found that treatment of C57BL/6 mice with CTLA4 immunoglobulin fusion protein (CTLA4-Ig) prevented acute rejection of a Balb/c heart allograft but allowed chronic rejection to develop over time, characterized by prominent neointima formation in the graft. There was extensive macrophage infiltration in the chronically rejected allografts, and the graft-infiltrating macrophages expressed markers associated with M2 cells but not M1 cells. In an in vitro system in which macrophages were polarized into either M1 or M2 cells, we screened phenotypic differences between M1 and M2 cells and identified purinergic receptor P2X7 (P2x7r), an adenosine triphosphate (ATP)-gated ion channel protein that was preferentially expressed by M2 cells. We further showed that blocking the P2x7r using oxidized ATP (oATP) inhibited M2 induction in a dose-dependent fashion in vitro. Moreover, treatment of C57BL/6 recipients with the P2x7r antagonist oATP, in addition to CTLA4-Ig treatment, inhibited graft-infiltrating M2 cells, prevented transplant vasculopathy, and induced long-term heart allografts survival. These findings highlight the importance of the P2x7r-M2 axis in chronic rejection and establish P2x7r as a potential therapeutic target in suppression of chronic rejection. PMID:27575724

  11. Long-term follow-up of 100 high-risk renal transplant recipients converted from calcineurin inhibitors to sirolimus: a single center experience.

    PubMed

    Halim, M A; Al-Otaibi, T; Johny, K V; Hamid, M H; Tawab, K A; Balaha, M A; Abraham, M; Said, T; Nair, M P; Al-Waheeb, S; Al-Muzairai, I; Nampoory, M R N

    2009-06-01

    While conversion of stable renal transplant recipients (RTR) from calcineurin inhibitors (CNI) to sirolimus (SRL) is safe and effective, it is still under investigation for recent, high-risk cases. We studied the long-term effects of conversion of high-risk subjects maintained on a CNI, mycophenolate mofetil, plus steroid regimen to SRL, mycophenolate mofetil, plus steroid on graft and patient outcomes. We retrospectively reviewed the first 100 RTR converted to SRL treatment over approximately 5 years. The main indications for conversion were biopsy-proven acute rejection (BPAR), CNI toxicity, CNI elimination, and acute-tubular necrosis (ATN). Exclusion criteria were limited to bone marrow suppression. The overall mean +/- SD age was 38.5 +/- 15.6 years, including pediatric and geriatric age groups. Mean +/- SD body mass index (BMI) was 28.99 +/- 8.0 and 40% had a BMI > 30. There were 40% RTR from deceased donors and 60% showed 4 to 6 HLA mismatches. Preconversion total BPAR and steroid-resistant rejection incidences were 35% and 14%, respectively. Mean +/- SD time to start of SRL was 11.9 +/- 22.8 months posttransplantation. Proteinuria > 2 g/d, leukopenia, and hyperlipidemia increased significantly after conversion (P = .001, P = .0003, and P = .0001, respectively). Patient and graft survivals were 95% and 90%, respectively. There was significant improvement in graft function postconversion (P < .0001). There was a high incidence of side effects and cases of SRL discontinuation. Multivariate analysis demonstrated the influence of bone marrow suppression, obesity, hyperlipidemia, nutritional status, proteinuria, and graft function on graft and patient outcomes. We concluded that conversion from CNI to SRL was effective among high-risk RTR, but with a high incidence of adverse events during long-term follow-up.

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  14. Bone marrow-derived T lymphocytes responsible for allograft rejection

    SciTech Connect

    Senjanovic, M.; Marusic, M.

    1984-08-01

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

  15. Compact filtering monopole patch antenna with dual-band rejection.

    PubMed

    Kim, Sun-Woong; Choi, Dong-You

    2016-01-01

    In this paper, a compact ultra-wideband patch antenna with dual-band rejection is proposed. The proposed antenna filters 3.3-3.8 GHz WiMAX and 5.15-5.85 GHz WLAN by respectively rejecting these bands through a C-shaped slit and a λg/4 resonator. The λg/4 resonator is positioned as a pair, centered around the microstrip line, and a C-type slit is inserted into an elliptical patch. The impedance bandwidth of the proposed antenna is 2.9-9.3 GHz, which satisfies the bandwidth for ultra-wideband communication systems. Further, the proposed antenna provides dual-band rejection at two bands: 3.2-3.85 and 4.7-6.03 GHz. The radiation pattern of the antenna is omnidirectional, and antenna gain is maintained constantly while showing -8.4 and -1.5 dBi at the two rejected bands, respectively. PMID:27386331

  16. Solar collector apparatus having increased energy rejection during stagnation

    DOEpatents

    Moore, S.W.

    1981-01-16

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

  17. Solar collector apparatus having increased energy rejection during stagnation

    DOEpatents

    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.

  18. Project Zero Reject Manual: Strategies in Child Find.

    ERIC Educational Resources Information Center

    Gilliam, Deborah F. Carpenter; And Others

    The report describes Project Zero Reject, a cooperative effort between the Dallas (TX) Independent School District and the Dallas County Mental Health Mental Retardation Center to locate handicapped children not receiving educational services and to develop a computerized information system for planning regarding these children. Awareness efforts…

  19. 7 CFR 1956.84 - Approval or rejection.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS...) PROGRAM REGULATIONS (CONTINUED) DEBT SETTLEMENT Debt Settlement-Farm Loan Programs and Multi-Family... is rejected will be notified of appeal rights pursuant to 7 CFR part 11....

  20. Compact filtering monopole patch antenna with dual-band rejection.

    PubMed

    Kim, Sun-Woong; Choi, Dong-You

    2016-01-01

    In this paper, a compact ultra-wideband patch antenna with dual-band rejection is proposed. The proposed antenna filters 3.3-3.8 GHz WiMAX and 5.15-5.85 GHz WLAN by respectively rejecting these bands through a C-shaped slit and a λg/4 resonator. The λg/4 resonator is positioned as a pair, centered around the microstrip line, and a C-type slit is inserted into an elliptical patch. The impedance bandwidth of the proposed antenna is 2.9-9.3 GHz, which satisfies the bandwidth for ultra-wideband communication systems. Further, the proposed antenna provides dual-band rejection at two bands: 3.2-3.85 and 4.7-6.03 GHz. The radiation pattern of the antenna is omnidirectional, and antenna gain is maintained constantly while showing -8.4 and -1.5 dBi at the two rejected bands, respectively.

  1. Characteristics of Rejection Letters and Their Effects on Job Applicants.

    ERIC Educational Resources Information Center

    Jablin, Fredric M.; Krone, Kathleen

    1984-01-01

    Describes the structural and content characteristics of actual employment rejection letters (sent following job screening interviews) and analyzes their impact on applicants' feelings about themselves and about the letters. Concludes that few of the letter characteristics affected applicants' feelings about themselves, but that a number were…

  2. Examining Appearance-Based Rejection Sensitivity during Early Adolescence

    ERIC Educational Resources Information Center

    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…

  3. Chlorine-resistant composite membranes with high organic rejection

    DOEpatents

    McCray, Scott B.; Friesen, Dwayne T.; Barss, Robert P.; Nelson, Leslie D.

    1996-01-01

    A method for making a chlorine-resistant composite polyamide membrane having high organic rejection, the essential step of which comprises treating a conventional composite membrane with an acyl halide. The novel membrane is especially suitable for the treatment of water containing chlorine or lower molecular weight organic compounds.

  4. Addressing Issues of Peer Rejection in Child-Centered Classrooms.

    ERIC Educational Resources Information Center

    Matthews, Mona W.

    1996-01-01

    Notes that children ignored or rebuffed by their peers may be denied access to learning opportunities involving peer interaction. Describes how the sociometric dynamics in one classroom affected three children. Suggests implementations to minimize negative impact of peer rejection including identifying sociometric patterns, and then utilizing…

  5. Maternal Predictors of Rejecting Parenting and Early Adolescent Antisocial Behavior

    ERIC Educational Resources Information Center

    Trentacosta, Christopher J.; Shaw, Daniel S.

    2008-01-01

    The present study examined relations among maternal psychological resources, rejecting parenting, and early adolescent antisocial behavior in a sample of 231 low-income mothers and their sons with longitudinal assessments from age 18 months to 12 years. The maternal resources examined were age at first birth, aggressive personality, and empathy.…

  6. 14 CFR 29.62 - Rejected takeoff: Category A.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Flight Performance § 29.62 Rejected takeoff: Category A... critical engine failure is recognized and the rotorcraft is landed and brought to a complete stop on the... until the rotorcraft is on the ground. Secondary controls located on the primary control may not be...

  7. 14 CFR 29.62 - Rejected takeoff: Category A.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Flight Performance § 29.62 Rejected takeoff: Category A... critical engine failure is recognized and the rotorcraft is landed and brought to a complete stop on the... until the rotorcraft is on the ground. Secondary controls located on the primary control may not be...

  8. 7 CFR 58.12 - When application may be rejected.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) GRADING AND INSPECTION... Governing the Inspection and Grading Services of Manufactured or Processed Dairy Products Inspection Or Grading Service § 58.12 When application may be rejected. An application for inspection or grading...

  9. Heat Rejection from a Variable Conductance Heat Pipe Radiator Panel

    NASA Technical Reports Server (NTRS)

    Jaworske, D. A.; Gibson, M. A.; Hervol, D. S.

    2012-01-01

    A titanium-water heat pipe radiator having an innovative proprietary evaporator configuration was evaluated in a large vacuum chamber equipped with liquid nitrogen cooled cold walls. The radiator was manufactured by Advanced Cooling Technologies, Inc. (ACT), Lancaster, PA, and delivered as part of a Small Business Innovative Research effort. The radiator panel consisted of five titanium-water heat pipes operating as thermosyphons, sandwiched between two polymer matrix composite face sheets. The five variable conductance heat pipes were purposely charged with a small amount of non-condensable gas to control heat flow through the condenser. Heat rejection was evaluated over a wide range of inlet water temperature and flow conditions, and heat rejection was calculated in real-time utilizing a data acquisition system programmed with the Stefan-Boltzmann equation. Thermography through an infra-red transparent window identified heat flow across the panel. Under nominal operation, a maximum heat rejection value of over 2200 Watts was identified. The thermal vacuum evaluation of heat rejection provided critical information on understanding the radiator s performance, and in steady state and transient scenarios provided useful information for validating current thermal models in support of the Fission Power Systems Project.

  10. The effects of rejection sensitivity on reactive and proactive aggression.

    PubMed

    Jacobs, Nicky; Harper, Brit

    2013-01-01

    The aim of this research was to use a pure measure of aggression to clarify whether rejection sensitive children exhibit higher levels of aggressive behavior than those who are not as rejection sensitive and to examine whether the components of rejection sensitivity (RS) vary according to the types of aggression. A total of 287 Australian primary school students aged between 9 and 12 completed self-report measures of RS and aggression. As expected, RS and its components, angry and anxious expectations of rejection, were linked to generalized aggression (GA) in adolescents, with angry expectations being more strongly associated with GA and in particular, proactive aggression. As expected, RS predicted reactive aggression better than it did proactive aggression and a three-way interaction was found whereby the relationship between the type of RS and aggression differed as a function of the type of aggression. The present study offers new evidence to support the theory that RS is predictive of aggressive behavior in children and clarifies some confusion about the attributional affect and processes behind this behavior. The findings both support and extend existing research in the areas of RS and aggression. PMID:23090847

  11. Experiences of Familial Acceptance–Rejection Among Transwomen of Color

    PubMed Central

    Koken, Juline A.; Bimbi, David S.; Parsons, Jeffrey T.

    2010-01-01

    Because of the stigma associated with transgenderism, many transwomen (biological males who identify as female or transgender) experience rejection or abuse at the hands of their parents and primary caregivers as children and adolescents. The Parental Acceptance–Rejection (PAR) theory indicates that a child's experience of rejection may have a significant impact on their adult lives. The purpose of this study was to conduct a qualitative analysis of adult transwomen of color's experiences with caregivers, guided by PAR theory. Twenty transwomen of color completed semi-structured interviews exploring the reaction of their parents and primary caregivers to their gender. While many participants reported that at least one parent or close family member responded with warmth and acceptance, the majority confronted hostility and aggression; reports of neglect and undifferentiated rejection were also common. Many transwomen were forced out of their homes as adolescents or chose to leave, increasing their risk of homelessness, poverty, and associated negative sequelae. Future research is needed to explore how families come to terms with having a transgender child and how best to promote acceptance of such children. PMID:20001144

  12. Rejecting Admission Offers to a Selective Math and Science School

    ERIC Educational Resources Information Center

    Jones, Brent M.

    2014-01-01

    An exploratory study of applicants who rejected admission to the Texas Academy of Mathematics and Science (TAMS) is described in this article. TAMS is a residential early college entry program at the University of North Texas in Denton. Up to 600 mathematically talented sophomores apply to TAMS each year and among the 200 selectees, a predictable…

  13. 45 CFR 1180.36 - Rejection of an application.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Rejection of an application. 1180.36 Section 1180.36 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES INSTITUTE OF MUSEUM AND LIBRARY SERVICES GRANTS REGULATIONS General...

  14. Fate of Manuscripts Rejected From the Red Journal

    SciTech Connect

    Holliday, Emma B.; Yang, George; Jagsi, Reshma; Hoffman, Karen E.; Bennett, Katherine Egan; Grace, Calley; Zietman, Anthony L.

    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

  15. Vicarious Group-Based Rejection: Creating a Potentially Dangerous Mix of Humiliation, Powerlessness, and Anger

    PubMed Central

    Veldhuis, Tinka M.; Gordijn, Ernestine H.; Veenstra, René; 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 rejection was followed by two main studies on vicarious group-based rejection. It was found that merely observing rejection of ingroup members can trigger feelings of humiliation that are equally intense as those experienced in response to personal rejection. Moreover, given that the rejection is explicit, vicariously experienced feelings of humiliation can be accompanied by powerlessness and anger. Potentially, this combination of emotions could be an important source of offensive action against rejecters. PMID:24759901

  16. Differential gene expression pattern in biopsies with renal allograft pyelonephritis and allograft rejection.

    PubMed

    Oghumu, Steve; Nori, Uday; Bracewell, Anna; Zhang, Jianying; Bott, Cherri; Nadasdy, Gyongyi M; Brodsky, Sergey V; Pelletier, Ronald; Satoskar, Abhay R; Nadasdy, Tibor; Satoskar, Anjali A

    2016-09-01

    Differentiating acute pyelonephritis (APN) from acute rejection (AR) in renal allograft biopsies can sometimes be difficult because of overlapping clinical and histologic features, lack of positive urine cultures,and variable response to antibiotics. We wanted to study differential gene expression between AR and APN using biopsy tissue. Thirty-three biopsies were analyzed using NanoString multiplex platform and PCR (6 transplant baseline biopsies, 8 AR, 15 APN [8 culture positive, 7 culture negative], and 4 native pyelonephritis [NP]). Additional 22 biopsies were tested by PCR to validate the results. CXCL9, CXCL10, CXCL11, and IDO1 were the top differentially expressed genes, upregulated in AR. Lactoferrin (LTF) and CXCL1 were higher in APN and NP. No statistically significant difference in transcript levels was seen between culture-positive and culture-negative APN biopsies. Comparing the overall mRNA signature using Ingenuity pathway analysis, interferon-gamma emerged as the dominant upstream regulator in AR and allograft APN, but not in NP (which clustered separately). Our study suggests that chemokine pathways in graft APN may differ from NP and in fact resemble AR, due to a component of alloreactivity, resulting in variable response to antibiotic treatment. Therefore, cautious addition of steroids might help in resistant cases of graft APN.

  17. 21 CFR 111.170 - What requirements apply to rejected components, packaging, and labels, and to rejected products...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production and Process Control... or Labeling as a Dietary Supplement § 111.170 What requirements apply to rejected components... a dietary supplement (and for distribution rather than for return to the supplier), that is...

  18. 21 CFR 111.170 - What requirements apply to rejected components, packaging, and labels, and to rejected products...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production and Process Control... or Labeling as a Dietary Supplement § 111.170 What requirements apply to rejected components... a dietary supplement (and for distribution rather than for return to the supplier), that is...

  19. 21 CFR 111.170 - What requirements apply to rejected components, packaging, and labels, and to rejected products...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production and Process Control... or Labeling as a Dietary Supplement § 111.170 What requirements apply to rejected components... a dietary supplement (and for distribution rather than for return to the supplier), that is...

  20. 21 CFR 111.170 - What requirements apply to rejected components, packaging, and labels, and to rejected products...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production and Process Control... or Labeling as a Dietary Supplement § 111.170 What requirements apply to rejected components... a dietary supplement (and for distribution rather than for return to the supplier), that is...

  1. 21 CFR 111.170 - What requirements apply to rejected components, packaging, and labels, and to rejected products...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production and Process Control... or Labeling as a Dietary Supplement § 111.170 What requirements apply to rejected components... a dietary supplement (and for distribution rather than for return to the supplier), that is...

  2. Agreement in Mother and Father Acceptance-Rejection, Warmth, and Hostility/Rejection/Neglect of Children across Nine Countries

    PubMed Central

    Putnick, Diane L.; Bornstein, Marc H.; Lansford, Jennifer E.; Chang, Lei; Deater-Deckard, Kirby; Di Giunta, Laura; Gurdal, Sevtap; Dodge, Kenneth A.; Malone, Patrick S.; Oburu, Paul; Pastorelli, Concetta; Skinner, Ann T.; Sorbring, Emma; Tapanya, Sombat; Uribe Tirado, Liliana Maria; Zelli, Arnaldo; Alampay, Liane Peña; Al-Hassan, Suha M.; Bacchini, Dario; Bombi, Anna Silvia

    2011-01-01

    We assessed whether mothers’ and fathers’ self-reports of acceptance-rejection, warmth, and hostility/rejection/neglect (HRN) of their pre-adolescent children differ cross-nationally and relative to the gender of the parent and child in 10 communities in 9 countries, including China, Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States (N = 998 families). Mothers and fathers in all countries reported a high degree of acceptance and warmth, and a low degree of HRN, but countries also varied. Mothers reported greater acceptance of children than fathers in China, Italy, Sweden, and the United States, and these effects were accounted for by greater self-reported warmth in mothers than fathers in China, Italy, the Philippines, Sweden, and Thailand and less HRN in mothers than fathers in Sweden. Fathers reported greater warmth than mothers in Kenya. Mother and father acceptance-rejection were moderately correlated. Relative levels of mother and father acceptance and rejection appear to be country specific. PMID:23024576

  3. Banff Borderline Changes Suspicious for Acute T Cell-Mediated Rejection: Where Do We Stand?

    PubMed

    Becker, J U; Chang, A; Nickeleit, V; Randhawa, P; Roufosse, C

    2016-09-01

    The definition of Banff Borderline became ambiguous when the Banff 2005 consensus modified the lower threshold from i1t1 (10-25% interstitial inflammation with mild tubulitis) to i0t1 (0-10% interstitial inflammation with mild tubulitis). We conducted a worldwide survey among members of the Renal Pathology Society about their approach to this diagnostic category. A web-based survey was sent out to all 503 current members (153 respondents). A database search yielded which threshold for Banff i was applied in the most influential manuscripts about Borderline. Among the 139 nephropathologists using the Borderline category, 67% use the Banff 1997 definition, requiring Banff i1. Thirty-seven percent admitted to sometimes exaggerating Banff i in the presence of tubulitis, to reach a diagnosis of Borderline. Forty-eight percent were dissatisfied with the definition of Borderline. The majority of the most influential manuscripts used the 1997 definition, contrary to the current one. There is considerable dissatisfaction with Borderline, and practice in Banff i thresholds is variable. Until additional studies inform a revision, we suggest leaving it to each pathologist's discretion whether to use i0 or i1 as the minimal threshold. In order to avoid future ambiguity, a web-based synopsis of all scattered current Banff definitions and rules should be created. PMID:26988137

  4. Modified active disturbance rejection control for time-delay systems.

    PubMed

    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.

  5. Rejection of false saturation data in optical pulse-oximeter

    NASA Astrophysics Data System (ADS)

    Scalise, Lorenzo; Marchionni, Paolo; Carnielli, Virgilio

    2010-04-01

    Pulse oximetry (PO) is a non-invasive medical device used for monitoring of the arterial oxygen saturation (SaO2) and in particular of haemoglobin oxygenation in blood. Oxygen saturation is commonly used in any setting where the patient blood oxygen saturation is unstable, including Neonatal Intensive Care Unit (NICU). The main factor affecting PO's output data is the presence of voluntary or involuntary motion artifacts or imperfect skin-sensor contact. Various methods have been employed to reject motion artifact but have met with little success. The aim of the present work is to propose a novel measurement procedure for real-time monitoring and validation of the oxygen saturation data as measured in standard pulse oxymeter. The procedure should be able to individuate and reject erroneous saturation data due to incorrect transducer-skin contact or motion artifact. In the case of short sequences of rejected SpO2 data (time duration< 8s), we report on an algorithm able to substitute the sequence of rejected data with the "most-probable" (rescued) SpO2 data. In total we have analyzed 14 patient for a total of 310 hr, 43 min and 15s, equivalent to a total number of samples of 1118595. For our study, we were interested to download heart rate measured with the ECG (HRECG), the heart rate as measured by the pulse oximeter (HRSAT) and the SpO2 value. In order to remove the erroneous SpO2 values reported in the rough data in coincidence of motion artifact (top, right), we have implemented a specific algorithm which provides at the output a new sequence of SpO2 data (validated SpO2 data). With the aim to "rescue" SpO2 value rejected by the previously presented algorithm, we have implemented an algorithm able to provide the "most-probable" SpO2 values in the case of single rejected values or in the case of short sequences of invalidated data (< 8 s). From these data it is possible to observe how in the 6.8% of the observation time the SpO2 data measured by the pulse oximeter

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

    NASA Technical Reports Server (NTRS)

    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.

  7. Rejection sensitivity and disruption of attention by social threat cues

    PubMed Central

    Berenson, Kathy R.; Gyurak, Anett; Ayduk, Özlem; Downey, Geraldine; Garner, Matthew J.; Mogg, Karin; Bradley, Brendan P.; Pine, Daniel S.

    2009-01-01

    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. PMID:20160869

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

    PubMed

    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. PMID:24135203

  9. Cosmic-Ray Rejection by Linear Filtering of Single Images

    NASA Astrophysics Data System (ADS)

    Rhoads, James E.

    2000-05-01

    We present a convolution-based algorithm for finding cosmic rays in single well-sampled astronomical images. The spatial filter used is the point-spread function (approximated by a Gaussian) minus a scaled delta function, and cosmic rays are identified by thresholding the filtered image. This filter searches for features with significant power at spatial frequencies too high for legitimate objects. Noise properties of the filtered image are readily calculated, which allows us to compute the probability of rejecting a pixel not contaminated by a cosmic ray (the false alarm probability). We demonstrate that the false alarm probability for a pixel containing object flux will never exceed the corresponding probability for a blank-sky pixel, provided we choose the convolution kernel appropriately. This allows confident rejection of cosmic rays superposed on real objects. Identification of multiple-pixel cosmic-ray hits can be enhanced by running the algorithm iteratively, replacing flagged pixels with the background level at each iteration.

  10. Self-excitation in Francis runner during load rejection

    NASA Astrophysics Data System (ADS)

    Moisan, É.; Giacobbi, D.-B.; Gagnon, M.; Léonard, F.

    2014-03-01

    Typically, transients such as load rejection generate only a few high vibration cycles in Francis runners. However, in the cases presented in this study, a sustained vibration around a natural frequency was observed on three (3) homologous Francis runners of different sizes during such events. The first two (2) runners were equipped with strain gauges on the blades and displacement sensors positioned circumferentially in the bottom ring and head cover around the runner labyrinth seals. The third runner was monitored only with displacement sensors on non-rotating components. The data from the first two (2) runners provided a better understanding of the parameters influencing the appearance of the high amplitude vibrations and allowed the implementation of a test plan to circumvent the phenomenon during commissioning of the third runner. Based on the measured data, the distributor's closing parameters were optimized to eliminate the vibration observed during load rejection on most of the operating range and reduce it significantly at full load.

  11. Composite disturbance rejection control based on generalized extended state observer.

    PubMed

    Zhang, Yanjun; Zhang, Jun; Wang, Lu; Su, Jianbo

    2016-07-01

    Traditional extended state observer (ESO) design method does not focus on analysis of system reconstruction strategy. The prior information of the controlled system cannot be used for ESO implementation to improve the control accuracy. In this paper, composite disturbance rejection control strategy is proposed based on generalized ESO. First, the disturbance rejection performance of traditional ESO is analyzed to show the essence of the reconstruction strategy. Then, the system is reconstructed based on the equivalent disturbance model. The generalized ESO is proposed based on the reconstructed model, while convergence of the proposed ESO is analyzed along with the outer loop feedback controller. Simulation results on a second order mechanical system show that the proposed generalized ESO can deal with the external disturbance with known model successfully. Experiment of attitude tracking task on an aircraft is also carried out to show the effectiveness of the proposed method. PMID:27129764

  12. Centered CW interference rejection using spread spectrum techniques

    NASA Technical Reports Server (NTRS)

    Scholtz, R. A.

    1980-01-01

    A mathematical model is developed for the rejection of CW interference by spread spectrum techniques. When this interference is known to be exactly at the carrier frequency of the spread spectrum signal, this information can be used to design optimal IF filtering prior to despreading. The application of this approach to the pilot beam receiver of the Solar Power Satellite is considered as an example.

  13. Spectral anomaly methods for aerial detection using KUT nuisance rejection

    NASA Astrophysics Data System (ADS)

    Detwiler, R. S.; Pfund, D. M.; Myjak, M. J.; Kulisek, J. A.; Seifert, C. E.

    2015-06-01

    This work discusses the application and optimization of a spectral anomaly method for the real-time detection of gamma radiation sources from an aerial helicopter platform. Aerial detection presents several key challenges over ground-based detection. For one, larger and more rapid background fluctuations are typical due to higher speeds, larger field of view, and geographically induced background changes. As well, the possible large altitude or stand-off distance variations cause significant steps in background count rate as well as spectral changes due to increased gamma-ray scatter with detection at higher altitudes. The work here details the adaptation and optimization of the PNNL-developed algorithm Nuisance-Rejecting Spectral Comparison Ratios for Anomaly Detection (NSCRAD), a spectral anomaly method previously developed for ground-based applications, for an aerial platform. The algorithm has been optimized for two multi-detector systems; a NaI(Tl)-detector-based system and a CsI detector array. The optimization here details the adaptation of the spectral windows for a particular set of target sources to aerial detection and the tailoring for the specific detectors. As well, the methodology and results for background rejection methods optimized for the aerial gamma-ray detection using Potassium, Uranium and Thorium (KUT) nuisance rejection are shown. Results indicate that use of a realistic KUT nuisance rejection may eliminate metric rises due to background magnitude and spectral steps encountered in aerial detection due to altitude changes and geographically induced steps such as at land-water interfaces.

  14. Vibroacoustic Analysis of Large Heat Rejection Radiators for Future Spacecraft

    NASA Technical Reports Server (NTRS)

    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.

  15. Reverse osmosis membrane of high urea rejection properties. [water purification

    NASA Technical Reports Server (NTRS)

    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.

  16. [Chronic rejection: Differences and similarities in various solid organ transplants].

    PubMed

    Suhling, H; Gottlieb, J; Bara, C; Taubert, R; Jäckel, E; Schiffer, M; Bräsen, J H

    2016-01-01

    In this paper, chronic rejections after transplantation of the lungs, heart, liver, and kidney are described. Chronic allograft dysfunction (CAD) plays an important role in all of these transplantations and has a significant influence on patient survival. The pathophysiological reasons for CAD varies greatly in the various organs.Chronic lung allograft dysfunction (CLAD) is the most important determinant of survival and quality of life after lung transplantation. Diagnosis is based on lung function, especially forced expiratory flow in 1 s (FEV1) decline. Prevention, early detection, and rapid treatment are extremely important. Azithromycin and extracorporeal photopheresis are commonly used for treatment because they usually positively influence the progression of lung remodeling.The expression for chronic rejection of the heart is cardiac allograft vasculopathy (CAV). Immunological and nonimmunological factors are important for its development. Due to limited therapeutic options, prevention is of utmost importance (administration of mTOR inhibitors and minimizing cardiovascular risk factors).The mid- and long-term survival rates after liver transplantation have hardly changed in recent decades, which is an indication of the difficulty in diagnosing chronic graft dysfunction. Chronic ductopenic rejection accounts for a small proportion of late graft dysfunction. Idiopathic posttransplant hepatitis and de novo autoimmune hepatitis are important in addition to recurrence of the underlying disease that led to transplantation.Chronic allograft nephropathy is the result of severe rejection which cumulates in increasing fibrosis with remodeling. The earliest possible diagnosis and therapy is currently the only option. Diagnosis is based on evidence of donor-specific antibodies and histological findings.

  17. Experimental demonstrations of organic Rankine cycle waste heat rejection systems

    NASA Astrophysics Data System (ADS)

    Bland, Timothy J.; Lacey, P. Douglas

    Two phase fluid management is an important factor in the successful design of organic Rankine cycle (ORC) power conversion systems for space applications. The evolution of the heat rejection system approach from a jet condenser, through a rotary jet condenser, to a rotary fluid management device (RFMD) with a surface condenser has been described in a previous paper. Some of the test programs that were used to prove the validity of the selected approach are described.

  18. Dynamic positioning system based on active disturbance rejection technology

    NASA Astrophysics Data System (ADS)

    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.

  19. Detection of cardiac allograft rejection using radionuclide techniques

    SciTech Connect

    Addonizio, L.J. )

    1990-09-01

    The results of the investigations in the search for a radionuclide technique to detect rejection have, thus far, not found any method that can be applied clinically. Functional studies are not sensitive enough, unless further work on the quantitative volume changes shows consistent correlation. Routine myocardial imaging agents such as {sup 67}Ga, {sup 99}TcPP, or the perfusion agent, {sup 201}Tl are clearly not specific enough to detect rejection until the grafts are nearly lost. Radiolabeled lymphocyte studies show promise, in that lymphocytes are intimately involved in the rejection process. However, there needs to be further research to determine if the specificity of the technique can isolate those patients who require treatment. The data involving labeled antimyosin antibody fragments indicate that they can specifically detect myocyte necrosis that occurs on the microscopic level. However, it may also be too sensitive a technique for transplanted hearts, which are so immunologically active at baseline to determine when treatment is necessary.30 references.

  20. Optical axis jitter rejection for double overlapped adaptive optics systems

    NASA Astrophysics Data System (ADS)

    Luo, Qi; Luo, Xi; Li, Xinyang

    2016-04-01

    Optical axis jitters, or vibrations, which arise from wind shaking and structural oscillations of optical platforms, etc., cause a deleterious impact on the performance of adaptive optics systems. When conventional integrators are utilized to reject such high frequency and narrow-band disturbance, the benefits are quite small despite their acceptable capabilities to reject atmospheric turbulence. In our case, two suits of complete adaptive optics systems called double overlapped adaptive optics systems (DOAOS) are used to counteract both optical jitters and atmospheric turbulence. A novel algorithm aiming to remove vibrations is proposed by resorting to combine the Smith predictor and notch filer. With the help of loop shaping method, the algorithm will lead to an effective and stable controller, which makes the characteristics of error transfer function close to notch filters. On the basis of the spectral analysis of observed data, the peak frequency and bandwidth of vibrations can be identified in advance. Afterwards, the number of notch filters and their parameters will be determined using coordination descending method. The relationship between controller parameters and filtering features is discussed, and the robustness of the controller against varying parameters of the control object is investigated. Preliminary experiments are carried out to validate the proposed algorithms. The overall control performance of DOAOS is simulated. Results show that time delays are a limit of the performance, but the algorithm can be successfully implemented on our systems, which indicate that it has a great potential to reject jitters.

  1. Three-year efficacy and safety results from a study of everolimus versus mycophenolate mofetil in de novo renal transplant patients.

    PubMed

    Vítko, Stefan; Margreiter, Raimund; Weimar, Willem; Dantal, Jacques; Kuypers, Dirk; Winkler, Michael; Øyen, Ole; Viljoen, Hendrik G; Filiptsev, Pavel; Sadek, Sami; Li, Yulan; Cretin, Nathalie; Budde, Klemens

    2005-10-01

    Everolimus 1.5 or 3 mg/day was compared with mycophenolate mofetil (MMF) 2 g/day in a randomized, multicenter 36-month trial in de novo renal allograft recipients (n = 588) receiving cyclosporine microemulsion (CsA) and corticosteroids. The study was double-blind until all patients had completed 12 months, then open-label. By 36 months, graft loss occurred in 7.2, 16.7 and 10.7% of patients in the everolimus 1.5, 3 mg/day, and MMF groups, respectively (p = 0.0048 for everolimus 1.5 mg/day vs. 3 mg/day); efficacy failure (biopsy-proven acute rejection (BPAR), graft loss, death or lost to follow-up) occurred in 33.0, 38.9 and 37.2% of patients (p = 0.455 overall), respectively. Mortality and incidence of BPAR were comparable in all groups. Creatinine values were higher in everolimus groups, requiring a protocol amendment that recommended lower CsA exposure. Diarrhea, lymphocele, peripheral edema and hyperlipidemia were more common among everolimus-treated patients, whereas viral infections, particularly cytomegalovirus infection, increased in the MMF group. Overall safety and tolerability were better with MMF and everolimus 1.5 mg/day than with everolimus 3 mg/day. In conclusion, at 36 months, an immunosuppressive regimen containing everolimus 1.5 mg/day had equivalent patient, and graft survival and rejection rates compared with MMF in de novo renal transplant recipients, whereas everolimus 3 mg/day had inferior graft survival. Renal dysfunction in everolimus cohorts necessitates close monitoring. PMID:16162203

  2. Three-year efficacy and safety results from a study of everolimus versus mycophenolate mofetil in de novo renal transplant patients.

    PubMed

    Vítko, Stefan; Margreiter, Raimund; Weimar, Willem; Dantal, Jacques; Kuypers, Dirk; Winkler, Michael; Øyen, Ole; Viljoen, Hendrik G; Filiptsev, Pavel; Sadek, Sami; Li, Yulan; Cretin, Nathalie; Budde, Klemens

    2005-10-01

    Everolimus 1.5 or 3 mg/day was compared with mycophenolate mofetil (MMF) 2 g/day in a randomized, multicenter 36-month trial in de novo renal allograft recipients (n = 588) receiving cyclosporine microemulsion (CsA) and corticosteroids. The study was double-blind until all patients had completed 12 months, then open-label. By 36 months, graft loss occurred in 7.2, 16.7 and 10.7% of patients in the everolimus 1.5, 3 mg/day, and MMF groups, respectively (p = 0.0048 for everolimus 1.5 mg/day vs. 3 mg/day); efficacy failure (biopsy-proven acute rejection (BPAR), graft loss, death or lost to follow-up) occurred in 33.0, 38.9 and 37.2% of patients (p = 0.455 overall), respectively. Mortality and incidence of BPAR were comparable in all groups. Creatinine values were higher in everolimus groups, requiring a protocol amendment that recommended lower CsA exposure. Diarrhea, lymphocele, peripheral edema and hyperlipidemia were more common among everolimus-treated patients, whereas viral infections, particularly cytomegalovirus infection, increased in the MMF group. Overall safety and tolerability were better with MMF and everolimus 1.5 mg/day than with everolimus 3 mg/day. In conclusion, at 36 months, an immunosuppressive regimen containing everolimus 1.5 mg/day had equivalent patient, and graft survival and rejection rates compared with MMF in de novo renal transplant recipients, whereas everolimus 3 mg/day had inferior graft survival. Renal dysfunction in everolimus cohorts necessitates close monitoring.

  3. 40 CFR 204.57-7 - Acceptance and rejection of batch sequence.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Acceptance and rejection of batch... § 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...

  4. 40 CFR 204.57-7 - Acceptance and rejection of batch sequence.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Acceptance and rejection of batch... § 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...

  5. 40 CFR 204.57-7 - Acceptance and rejection of batch sequence.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Acceptance and rejection of batch... § 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...

  6. 40 CFR 205.57-6 - Acceptance and rejection of batches.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Acceptance and rejection of batches... Acceptance and rejection of batches. (a) The batch from which a batch sample is selected will be accepted or rejected based upon the number of failing vehicles in the batch sample. A sufficient number of test...

  7. 40 CFR 205.57-6 - Acceptance and rejection of batches.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Acceptance and rejection of batches... Acceptance and rejection of batches. (a) The batch from which a batch sample is selected will be accepted or rejected based upon the number of failing vehicles in the batch sample. A sufficient number of test...

  8. 40 CFR 204.57-7 - Acceptance and rejection of batch sequence.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Acceptance and rejection of batch... § 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...

  9. 40 CFR 205.57-6 - Acceptance and rejection of batches.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Acceptance and rejection of batches... Acceptance and rejection of batches. (a) The batch from which a batch sample is selected will be accepted or rejected based upon the number of failing vehicles in the batch sample. A sufficient number of test...

  10. 40 CFR 204.57-7 - Acceptance and rejection of batch sequence.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Acceptance and rejection of batch... § 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...

  11. 40 CFR 205.57-6 - Acceptance and rejection of batches.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Acceptance and rejection of batches... Acceptance and rejection of batches. (a) The batch from which a batch sample is selected will be accepted or rejected based upon the number of failing vehicles in the batch sample. A sufficient number of test...

  12. Interactions between Rejection Sensitivity and Supportive Relationships in the Prediction of Adolescents' Internalizing Difficulties

    ERIC Educational Resources Information Center

    McDonald, Kristina L.; Bowker, Julie C.; Rubin, Kenneth H.; Laursen, Brett; Duchene, Melissa S.

    2010-01-01

    Rejection sensitivity, the tendency to anxiously or angrily expect rejection, is associated with internalizing difficulties during childhood and adolescence. The primary goal of the present study was to examine whether supportive parent-child relationships and friendships moderate associations that link angry and anxious rejection sensitivity to…

  13. Peer-Social Attributions and Self-Efficacy of Peer-Rejected Preadolescents.

    ERIC Educational Resources Information Center

    Toner, Mark A.; Munro, Don

    1996-01-01

    Examined whether peer-rejected preadolescents differ from nonrejected groups (average, popular, neglected) in their explanations for peer-social events and their perceived control of outcomes. Found that rejected children were inclined to forego credit for acceptance, to ascribe rejection to persistent factors, and to perceive lower control of…

  14. 41 CFR 102-38.210 - What happens when bids have been rejected?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... have been rejected? 102-38.210 Section 102-38.210 Public Contracts and Property Management Federal... OF PERSONAL PROPERTY Bids Acceptance of Bids § 102-38.210 What happens when bids have been rejected? You may re-offer items for which all bids have been rejected at the same sale, if possible, or...

  15. Extension of the Rejection Sensitivity Construct to the Interpersonal Functioning of Gay Men

    ERIC Educational Resources Information Center

    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…

  16. 47 CFR 1.773 - Petitions for suspension or rejection of new tariff filings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Petitions for suspension or rejection of new... Petitions for suspension or rejection of new tariff filings. (a) Petition—(1) Content. Petitions seeking investigation, suspension, or rejection of a new or revised tariff filing or any provision thereof shall...

  17. 47 CFR 1.773 - Petitions for suspension or rejection of new tariff filings.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false Petitions for suspension or rejection of new... Petitions for suspension or rejection of new tariff filings. (a) Petition—(1) Content. Petitions seeking investigation, suspension, or rejection of a new or revised tariff filing or any provision thereof shall...

  18. The neural correlates of correctly rejecting lures during memory retrieval: the role of item relatedness.

    PubMed

    Bowman, Caitlin R; Dennis, Nancy A

    2015-06-01

    Successful memory retrieval is predicated not only on recognizing old information, but also on correctly rejecting new information (lures) in order to avoid false memories. Correctly rejecting lures is more difficult when they are perceptually or semantically related to information presented at study as compared to when lures are distinct from previously studied information. This behavioral difference suggests that the cognitive and neural basis of correct rejections differs with respect to the relatedness between lures and studied items. The present study sought to identify neural activity that aids in suppressing false memories by examining the network of brain regions underlying correct rejection of related and unrelated lures. Results showed neural overlap in the right hippocampus and anterior parahippocampal gyrus associated with both related and unrelated correct rejections, indicating that some neural regions support correctly rejecting lures regardless of their semantic/perceptual characteristics. Direct comparisons between related and unrelated correct rejections showed that unrelated correct rejections were associated with greater activity in bilateral middle and inferior temporal cortices, regions that have been associated with categorical processing and semantic labels. Related correct rejections showed greater activation in visual and lateral prefrontal cortices, which have been associated with perceptual processing and retrieval monitoring. Thus, while related and unrelated correct rejections show some common neural correlates, related correct rejections are driven by greater perceptual processing whereas unrelated correct rejections show greater reliance on salient categorical cues to support quick and accurate memory decisions. PMID:25862563

  19. Acute gastroenteritis.

    PubMed

    Graves, Nancy S

    2013-09-01

    Acute gastroenteritis is a common infectious disease syndrome, causing a combination of nausea, vomiting, diarrhea, and abdominal pain. There are more than 350 million cases of acute gastroenteritis in the United States annually and 48 million of these cases are caused by foodborne bacteria. Traveler's diarrhea affects more than half of people traveling from developed countries to developing countries. In adult and pediatric patients, the prevalence of Clostridium difficile is increasing. Contact precautions, public health education, and prudent use of antibiotics are necessary goals in decreasing the prevalence of Clostridium difficle. Preventing dehydration or providing appropriate rehydration is the primary supportive treatment of acute gastroenteritis.

  20. Acute Bronchitis

    MedlinePlus

    ... bronchitis? Acute bronchitis is almost always caused by viruses that attack the lining of the bronchial tree ... infection. As your body fights back against these viruses, more swelling occurs and more mucus is produced. ...

  1. Acute Pericarditis

    MedlinePlus

    ... large pericardial effusions). Acute pericarditis usually responds to colchicine or NSAIDs (such as aspirin and ibuprofen ) taken ... reduce pain but relieves it by reducing inflammation. Colchicine also decreases the chance of pericarditis returning later. ...

  2. Beneficiation of limestone plant rejects for value addition.

    PubMed

    Jena, M S; Sahu, P; Dash, P; Mohanty, J K

    2013-11-15

    Investigations were carried out on lime stone rejects (-1mm) generated at a lime stone washing plant in southern India. These rejects contain 12.09% CaO, 2.95% MgO, 10.73% Al2O3, 4.99% Fe2O3, 43.05% SiO2 and 24.92% LOI. Mineralogical studies including SEM-EDAX, XRD, FTIR and TGA were conducted to confirm relative distribution of minerals in the flotation feed and products. These studies revealed that feed sample consists of quartz and calcite as the major minerals with minor amounts of montmorillonite and dolomite whereas flotation concentrate dominantly consists of calcite, and tailings mostly of quartz and montmorillonite. A commercial grade sodium silicate, oleic acid and MIBC were used as depressant, collector and frother respectively in flotation studies. The effects of different operating parameters were evaluated for both conventional and column flotation. Two stage conventional cell flotation results indicate that a cleaner concentrate of 42.50% lime (CaO) content could be obtained at a yield of 15.65%. The lime (CaO) content of the concentrate was further enhanced up to 44.23% at 20.73% yield using single stage column flotation. The column flotation is more efficient in comparison to the conventional cell for treating this sample. A process flowsheet was developed to treat these rejects based on the studies carried out. This process can minimize the waste generation and the concentrate generated during this process can be directly utilized in the Indian cement industries. PMID:24035797

  3. A novel robust disturbance rejection anti-windup framework

    NASA Astrophysics Data System (ADS)

    Li, Guang; Herrmann, Guido; Stoten, David P.; Tu, Jiaying; Turner, Matthew C.

    2011-01-01

    In this article, we propose a novel anti-windup (AW) framework for coping with input saturation in the disturbance rejection problem of stable plant systems. This framework is based on the one developed by Weston and Postlethwaite (W&P) (Weston, P.F., and Postlethwaite, I. (2000), 'Linear Conditioning for Systems Containing Saturating Actuators', Automatica, 36, 1347-1354). The new AW-design improves the disturbance rejection performance over the design framework usually suggested for the coprime-factorisation based W&P-approach. Performance improvement is achieved by explicitly incorporating a transfer function, which represents the effect of the disturbance on the nonlinear loop, into the AW compensator synthesis. An extra degree of freedom is exploited for the coprime factorisation, resulting in an implicitly computed multivariable algebraic loop for the AW-implementation. Suggestions are made to overcome the algebraic loop problem via explicit computation. Furthermore, paralleling the results of former work (Turner, M.C., Herrmann, G., and Postlethwaite, I. (2007), 'Incorporating Robustness Requirements into Antiwindup Design', IEEE Transactions on Automatic Control, 52, 1842-1855), the additive plant uncertainty is incorporated into the AW compensator synthesis, by using a novel augmentation for the disturbance rejection problem. In this new framework, it is shown that the internal model control (IMC) scheme is optimally robust, as was the case in Turner, Herrmann, and Postlethwaite (2007) and Zheng and Morari (Zheng, A., and Morari, M. (1994), 'Anti-windup using Internal Model Control', International Journal of Control, 60, 1015-1024). The new AW approach is applied to the control of dynamically substructured systems (DSS) subject to external excitation signals and actuator limits. The benefit of this approach is demonstrated in the simulations for a small-scale building mass damper DSS and a quasi-motorcycle DSS.

  4. Correlation filter for target detection and noise and clutter rejection

    NASA Astrophysics Data System (ADS)

    Goo, Gee-In

    1996-03-01

    This study was motivated by the infrared search and tracking (IRST) project. The investigation seeks to develop a technique that could detect the presence of a moving target in a cloud cluttered environment. Particularly, the signals, noise and clutters are unknown to the system. Thus, the correlation technique for image processing was developed, demonstrating its ability to detect moving targets of one pixel in size such as missiles and planes. A real-time image processor using this correlation technique was implemented. A Panoramic Imaging System, a 512 by 480 image processor at 30 frames per second was demonstrated. The demonstrated imaging system was operating at 120 mops (million operations per second) using an assembly- line processor architecture. The successful investigation of the correlation technique for image processing led to the developments of a correlation filter and the inspiration to develop the generalized filter. From the investigation, the author found that the Kalman filter, the Weiner filter and the correlation filter are special cases of a generalized filter. These filters can be related through a cost function in the constrained gain matrix of a generalized filter. However, in developing the correlation filter and the real-time imager, the correlation filter was observed to be a very effective noise and clutter rejecter and yet a very powerful detector. The filter was successfully applied to detection of pixel sized targets in noisy and cluttered IR images. Also it has been successfully applied to detection of intruders in cluttered, trees and bushes, video and IR images in security systems. This paper presents the derivation of the correlation filter for detection and estimation of unknown signals in unknown noise. Several noise rejection and cluttered rejection examples are presented.

  5. New Monolithic High Solar Rejection EUV Transmission Filter

    NASA Astrophysics Data System (ADS)

    Fleury-Frenette, Karl; Renotte, Etienne; Lenaerts, C.; Rossi, Laurence; Jacques, Lionel; Halain, Jean-Philippe; Rochus, Pierre

    A new high solar rejection transmission filter for the extreme UV has been developed for the Solar Orbiter Extreme Ultraviolet Imager (EUI). To provide enhanced resilience to high thermal load, a monolithic architecture approach has been taken in order to limit the thermal contact resistance between the filtering sub-micron thin film, its supporting mesh, and holding frame. Some aspects of the manufacturing process involving thin film deposition and photolithography will be presented along with optical performance and space environmental test results. New avenues for improving the thermo-optical properties of the filter will also be discussed.

  6. Motivated Rejection of (Climate) Science: Causes, Tools, and Effects

    NASA Astrophysics Data System (ADS)

    Lewandowsky, S.

    2015-12-01

    Although the relevant scientific community long ago settled on the conclusion that human economic activities are causing climate change through the emission of greenhouse gases, a small but vocal number of dissenters remains unconvinced by the evidence. I examine the cognitive and motivational factors that underlie the rejection of scientific evidence, and I illustrate the techniques by which contrarians seek to shape public debate and mislead the public. I also suggest that contrarian activities have seeped into the scientific community and have arguably altered the interpretation of the risks posed by climate change.

  7. TRC (Texas Railroad Commission) rejects gas storage project financing plans

    SciTech Connect

    Not Available

    1980-08-11

    TRC has rejected Valero Transmission Co.'s plan to finance a 5 billion cu ft underground storage facility already under construction in Wharton County, TX. The fee application, dismissed without prejudice to Valero's filing another application, would have added $0.015/1000 cu ft for the first nine years of operation before dropping to $0.014/1000 cu ft in the tenth year. The TRC commissioners decided that the costs underlying this proposed fee schedule were too speculative to be passed on to pipeline customers.

  8. ANALYSIS AND REJECTION SAMPLING OF WRIGHT-FISHER DIFFUSION BRIDGES

    PubMed Central

    Schraiber, Joshua G.; Griffiths, Robert C.; Evans, Steven N.

    2013-01-01

    We investigate the properties of a Wright-Fisher diffusion process started from frequency x at time 0 and conditioned to be at frequency y at time T. Such a process is called a bridge. Bridges arise naturally in the analysis of selection acting on standing variation and in the inference of selection from allele frequency time series. We establish a number of results about the distribution of neutral Wright-Fisher bridges and develop a novel rejection sampling scheme for bridges under selection that we use to study their behavior. PMID:24001410

  9. Active rejection of persistent disturbances in flexible space structures

    NASA Technical Reports Server (NTRS)

    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.

  10. Design and Modeling of a Variable Heat Rejection Radiator

    NASA Technical Reports Server (NTRS)

    Miller, Jennifer R.; Birur, Gajanana C.; Ganapathi, Gani B.; Sunada, Eric T.; Berisford, Daniel F.; Stephan, Ryan

    2011-01-01

    Variable Heat Rejection Radiator technology needed for future NASA human rated & robotic missions Primary objective is to enable a single loop architecture for human-rated missions (1) Radiators are typically sized for maximum heat load in the warmest continuous environment resulting in a large panel area (2) Large radiator area results in fluid being susceptible to freezing at low load in cold environment and typically results in a two-loop system (3) Dual loop architecture is approximately 18% heavier than single loop architecture (based on Orion thermal control system mass) (4) Single loop architecture requires adaptability to varying environments and heat loads

  11. Inertial-space disturbance rejection for robotic manipulators

    NASA Technical Reports Server (NTRS)

    Holt, Kevin

    1992-01-01

    The disturbance rejection control problem for a 6-DOF (degree of freedom) PUMA manipulator mounted on a 3-DOF platform is investigated. A control algorithm is designed to track the desired position and attitude of the end-effector in inertial space, subject to unknown disturbances in the platform axes. Conditions for the stability of the closed-loop system are derived. The performance of the controller is compared for step, sinusoidal, and random disturbances in the platform rotational axis and in the neighborhood of kinematic singularities.

  12. Disturbance Rejection Based Test Rocket Control System Design and Validation

    NASA Astrophysics Data System (ADS)

    Yang, H.; Zhang, S.; Li, T.; Zhang, Y.

    2015-09-01

    This paper presents a novel design and validation for the three-channel attitude controller of a STT test rocket based on the extended state observer approach. The uniform second order integral-chain state space model is firstly established for the control variable of the angle of attack, angle of sideslip and roll angle. Combined with the pole placement, the extended state observer is applied to the disturbance rejection design of the attitude controller. Through numerical and hardware-in-the-loop simulation with uncertainties considered, the effectiveness and robustness of the controller are illustrated and verified. Finally, the performance of the controller is validated by flight-test with satisfactory results.

  13. Thermal storage for industrial process and reject heat

    NASA Technical Reports Server (NTRS)

    Duscha, R. A.; Masica, W. J.

    1978-01-01

    Industrial production uses about 40 percent of the total energy consumed in the United States. The major share of this is derived from fossil fuel. Potential savings of scarce fuel is possible through the use of thermal energy storage (TES) of reject or process heat for subsequent use. Three especially significant industries where high temperature TES appears attractive - paper and pulp, iron and steel, and cement are discussed. Potential annual fuel savings, with large scale implementation of near-term TES systems for these three industries, is nearly 9,000,000 bbl of oil.

  14. Thermal storage for industrial process and reject heat

    NASA Technical Reports Server (NTRS)

    Duscha, R. A.; Masica, W. J.

    1978-01-01

    Industrial production uses about 40% of the total energy consumed in the United States. The major share of this is derived from fossil fuel. Potential savings of scarce fuel is possible through the use of thermal energy storage (TES) of reject or process heat for subsequent use. Results of study contracts awarded by the Department of Energy (DOE) and managed by the NASA Lewis Research Center have identified three especially significant industries where high temperature TES appears attractive - paper and pulp, iron and steel, and cement. Potential annual fuel savings with large scale implementation of near-term TES systems for these three industries is nearly 9 million bbl of oil.

  15. PD1-Expressing T Cell Subsets Modify the Rejection Risk in Renal Transplant Patients

    PubMed Central

    Pike, Rebecca; Thomas, Niclas; Workman, Sarita; Ambrose, Lyn; Guzman, David; Sivakumaran, Shivajanani; Johnson, Margaret; Thorburn, Douglas; Harber, Mark; Chain, Benny; Stauss, Hans J.

    2016-01-01

    We tested whether multi-parameter immune phenotyping before or after renal ­transplantation can predict the risk of rejection episodes. Blood samples collected before and weekly for 3 months after transplantation were analyzed by multi-parameter flow cytometry to define 52 T cell and 13 innate lymphocyte subsets in each sample, producing more than 11,000 data points that defined the immune status of the 28 patients included in this study. Principle component analysis suggested that the patients with histologically confirmed rejection episodes segregated from those without rejection. Protein death 1 (PD-1)-expressing subpopulations of regulatory and conventional T cells had the greatest influence on the principal component segregation. We constructed a statistical tool to predict rejection using a support vector machine algorithm. The algorithm correctly identified 7 out of 9 patients with rejection, and 14 out of 17 patients without rejection. The immune profile before transplantation was most accurate in determining the risk of rejection, while changes of immune parameters after transplantation were less accurate in discriminating rejection from non-rejection. The data indicate that pretransplant immune subset analysis has the potential to identify patients at risk of developing rejection episodes, and suggests that the proportion of PD1-expressing T cell subsets may be a key indicator of rejection risk. PMID:27148254

  16. Sugar or spice: Using I3 metatheory to understand how and why glucose reduces rejection-related aggression.

    PubMed

    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.

  17. Rejection as a call to arms: inter-racial hostility and support for political action as outcomes of race-based rejection in majority and minority groups.

    PubMed

    Barlow, Fiona Kate; Sibley, Chris G; Hornsey, Matthew J

    2012-03-01

    Both majority and minority group members fear race-based rejection, and respond by disparaging the groups that they expect will reject them. It is not clear, however, how this process differs in minority and majority groups. Using large representative samples of White (N= 4,618) and Māori (N= 1,163) New Zealanders, we found that perceptions of race-based rejection predicted outgroup negativity in both groups, but in different ways and for different reasons. For White (but not Māori) New Zealanders, increased intergroup anxiety partially mediated the relationship between cognitions of rejection and outgroup negativity. Māori who expected to be rejected on the basis of their race reported increased ethnic identification and, in part through this, increased support for political action benefiting their own group. This finding supports collective-action models of social change in historically disadvantaged minority groups.

  18. Salt rejection and water transport through boron nitride nanotubes.

    PubMed

    Hilder, Tamsyn A; Gordon, Daniel; Chung, Shin-Ho

    2009-10-01

    Nanotube-based water-purification devices have the potential to transform the field of desalination and demineralization through their ability to remove salts and heavy metals without significantly affecting the fast flow of water molecules. Boron nitride nanotubes have shown superior water flow properties compared to carbon nanotubes, and are thus expected to provide a more efficient water purification device. Using molecular dynamics simulations it is shown that a (5, 5) boron nitride nanotube embedded in a silicon nitride membrane can, in principle, obtain 100% salt rejection at concentrations as high as 1 M owing to a high energy barrier while still allowing water molecules to flow at a rate as high as 10.7 water molecules per nanosecond (or 0.9268 L m(-2) h(-1)). Furthermore, ions continue to be rejected under the influence of high hydrostatic pressures up to 612 MPa. When the nanotube radius is increased to 4.14 A the tube becomes cation-selective, and at 5.52 A the tube becomes anion-selective. PMID:19582727

  19. Heat Rejection Concepts for Brayton Power Conversion Systems

    NASA Technical Reports Server (NTRS)

    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.

  20. Heat Rejection Concepts for Lunar Fission Surface Power Applications

    NASA Technical Reports Server (NTRS)

    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.

  1. Heat pipe heat rejection system. [for electrical batteries

    NASA Technical Reports Server (NTRS)

    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.

  2. Salt rejection and water transport through boron nitride nanotubes.

    PubMed

    Hilder, Tamsyn A; Gordon, Daniel; Chung, Shin-Ho

    2009-10-01

    Nanotube-based water-purification devices have the potential to transform the field of desalination and demineralization through their ability to remove salts and heavy metals without significantly affecting the fast flow of water molecules. Boron nitride nanotubes have shown superior water flow properties compared to carbon nanotubes, and are thus expected to provide a more efficient water purification device. Using molecular dynamics simulations it is shown that a (5, 5) boron nitride nanotube embedded in a silicon nitride membrane can, in principle, obtain 100% salt rejection at concentrations as high as 1 M owing to a high energy barrier while still allowing water molecules to flow at a rate as high as 10.7 water molecules per nanosecond (or 0.9268 L m(-2) h(-1)). Furthermore, ions continue to be rejected under the influence of high hydrostatic pressures up to 612 MPa. When the nanotube radius is increased to 4.14 A the tube becomes cation-selective, and at 5.52 A the tube becomes anion-selective.

  3. Automatic misclassification rejection for LDA classifier using ROC curves.

    PubMed

    Menon, Radhika; Di Caterina, Gaetano; Lakany, Heba; Petropoulakis, Lykourgos; Conway, Bernard A; Soraghan, John J

    2015-08-01

    This paper presents a technique to improve the performance of an LDA classifier by determining if the predicted classification output is a misclassification and thereby rejecting it. This is achieved by automatically computing a class specific threshold with the help of ROC curves. If the posterior probability of a prediction is below the threshold, the classification result is discarded. This method of minimizing false positives is beneficial in the control of electromyography (EMG) based upper-limb prosthetic devices. It is hypothesized that a unique EMG pattern is associated with a specific hand gesture. In reality, however, EMG signals are difficult to distinguish, particularly in the case of multiple finger motions, and hence classifiers are trained to recognize a set of individual gestures. However, it is imperative that misclassifications be avoided because they result in unwanted prosthetic arm motions which are detrimental to device controllability. This warrants the need for the proposed technique wherein a misclassified gesture prediction is rejected resulting in no motion of the prosthetic arm. The technique was tested using surface EMG data recorded from thirteen amputees performing seven hand gestures. Results show the number of misclassifications was effectively reduced, particularly in cases with low original classification accuracy.

  4. fMRI artefact rejection and sleep scoring toolbox.

    PubMed

    Leclercq, Yves; Schrouff, Jessica; Noirhomme, Quentin; Maquet, Pierre; Phillips, Christophe

    2011-01-01

    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

  5. Nationalism and patriotism: national identification and out-group rejection.

    PubMed

    Mummendey, A; Klink, A; Brown, R

    2001-06-01

    It is argued that the differentiation between nationalism and patriotism proposed in the literature can be seen as analogous to judgments based on different types of comparisons: intergroup comparisons with other nations are associated with intergroup behaviour that corresponds to nationalism, whereas temporal or standard comparisons are linked with behaviour that corresponds to patriotism. Four studies (N = 103, 107, 96 and 105) conducted in Germany and Britain examined the hypothesis that national identification and in-group evaluation only show a reliable relationship with out-group rejection under an intergroup comparison orientation. Participants were primed with either an intergroup comparison, a temporal comparison or no explicit comparison orientation. A subsequent questionnaire assessed in-group (own country) identification, in-group evaluation (i.e. national pride) and rejection of national out-groups. Across all four studies, both in-group identification and in-group evaluation show a stronger correlation with out-group derogation if participants were primed with an intergroup comparison orientation compared to temporal and control conditions. Results are discussed with regard to nationalism and patriotism as well as Hinkle and Brown's (1990) model on relational vs. autonomous orientations.

  6. Implementation and Rejection of Industrial Steam System Energy Efficiency Measures

    SciTech Connect

    Therkelesen, Peter; McKane, Aimee

    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.

  7. Aire deficiency promotes TRP-1-specific immune rejection of melanoma.

    PubMed

    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.

  8. Diagnosis of early pancreas graft failure via antibody-mediated rejection: single-center experience with 256 pancreas transplantations.

    PubMed

    de Kort, H; Mallat, M J K; van Kooten, C; de Heer, E; Brand-Schaaf, S H; van der Wal, A M; Roufosse, C; Roelen, D L; Bruijn, J A; Claas, F H; de Fijter, J W; Bajema, I M

    2014-04-01

    Early pancreas graft loss is usually attributed to technical failure while the possibility of antibody-mediated rejection (AMR) is generally overlooked. To investigate the role of AMR in early pancreas graft loss, we retrospectively assessed 256 patients with simultaneous pancreas-kidney transplantation (SPK) between 1985 and 2010 at our institute. We included 33 SPK patients who lost their pancreas graft <1 year after transplantation. AMR was diagnosed based on donor-specific antibodies, C4d and histology in 7 cases, 8 cases were suspicious for AMR and 18 pancreas graft losses were not due to AMR. Acute AMR occurred >1 month after transplantation in 6/7 cases, whereas all other causes typically led to loss <1 month after transplantation. Thrombotic lesions occurred equally among the 33 cases. In 12/18 concurrent kidney specimens, the diagnostic results paralleled those of the pancreas graft. All patients with acute AMR of the pancreas graft lost their renal grafts <1 year after transplantation. In the setting of a thrombotic event, histopathological analysis of early pancreas graft loss is advisable to rule out the possibility of AMR, particularly because a diagnosis of acute AMR has important consequences for renal graft outcomes.

  9. Successful application of MARS therapy in a 7 year-old patient with hepatic chronic rejection and severe cholestatic syndrome.

    PubMed

    Voiculescu, Mihai; Ioanitescu, Simona; Rusu, Elena; Micu, Diana; Mihaila, Mariana; Micu, Laurentiu

    2002-06-01

    Liver transplant currently represents the therapeutic method for irreversible acute and chronic liver diseases without any other available therapy. In some cases, before or after liver transplantation, it is necessary to replace the functions of the liver. We report the case of a 7 year-old female patient with type I glycogenosis who was transplanted in July 2001 using living-related donor transplantation and who developed chronic rejection two months later. In this case, we used MARS (Molecular Adsorbents Recirculating System) detoxification therapy to optimise the patient's clinical and biological status and to create a bridge that allowed the patient's survival until retransplantation was available. The therapy was well tolerated, with no major incidents. We noted favourable clinical effects and significant improvement in serum bilirubin level, urea nitrogen level and serum creatinine level. We consider that MARS treatment is a temporary solution for patients with acute and acute-on-chronic liver failure, indicated in those cases with real chances of recovery of the hepatic functions or in patients on the liver transplantation waiting list.

  10. Immune mechanisms in organ allograft rejection. V. Pivotal role of the cytotoxic-suppressor T cell subset in the rejection of heart grafts bearing isolated class I disparities in the inbred rat

    SciTech Connect

    Lowry, R.P.; Forbes, R.D.; Blackburn, J.H.; Marghesco, D.M.

    1985-11-01

    The cellular requirements for rejection of heart grafts bearing isolated major histocompatibility complex (MHC) subregion RT1A-encoded class I disparities was assessed by adoptive transfer. Sublethally irradiated (780 rads) (PVG X WF)F1 recipients of irradiated PVG-RT1r1 heart grafts were selectively reconstituted with spleen cells from syngeneic donors previously sensitized with two sequential PVG-RT1r1 skin grafts. PVG-RT1r1 heart grafts were rejected acutely in recipients reconstituted with 10 X 10(6) unfractionated immune spleen cells or inocula (5 X 10(6) cells) depleted of SIg+ cells, but additional depletion of cytotoxic T cells and their precursors resulted in marked prolongation of graft survival. Reducing the reconstituting inocula from 4 X 10(6) to 2.5 X 10(6) spleen cells prolonged graft survival to that observed in unreconstituted recipients. Additional studies were performed to define the immunologic basis for prolonged survival of PVG-RT1r1 heart grafts in homozygous PVG recipients. Although lymphoid cells of naive PVG failed to proliferate on coculture with irradiated PVG-RT1r1, bulk cultures yielding but weak and variable CTL generation, lymphoid cells from specifically sensitized PVG proliferated and generated greater cytotoxic T lymphocyte (CTL) activity under identical conditions, strongly suggesting, therefore, that prolonged heart graft survival in this strain combination is related to low CTL precursor frequency.

  11. Chronic transplantation immunity in newts: temperature susceptibility of an effector phase in allo-skin graft rejection.

    PubMed

    Kinefuchi, Kenjiroh; Kushida, Yoshihiro; Johnouchi, Masato; Shimizu, Yuiko; Ohneda, Hikaru; Fujii, Masato; Hosono, Masamichi

    2011-07-01

    Urodele amphibians are unique due to their greatly reduced immune responsiveness compared to bony fishes, which show acute immune responsiveness. In newts, the mean survival time of allogenic skin grafts in the transplantation immunity was 48.8 ± 8.3 days at 25°C, suggesting that it occurs in a chronic manner. The graft rejection process was categorized into three stages: a latent stage with frequent blood circulation, or the immune induction phase; a vascular stoppage stage with dominant infiltrating cells of T cells; and a rejection stage showing the change of the dominant cells to monocytes/macrophages, probably as effector cells, tetntatively referred to as the immune effector phase. The immune induction phase is susceptible to the cyclophosphamide (CY) mitosis inhibitor, but not to a temperature shift from 18 to 27°C, while the immune effector phase is susceptible to temperature shifts, but not CY-treatment, although the temperature shift failed to shorten the graft survival time to less than 25 days, which nearly equals that of the secondary set of grafts where the lack of complete blood circulation is remarkable and graft rejection is resistant to CY-treatment. In contrast, a very low temperature (5-10°C) completely prevented effector generation in newts; in frogs, however, it is reported that such low temperatures did not prevent the generation of effectors. Taken together, these data suggest that chronic responses in newts are due to effector cells other than cytotoxic T cells; possible effector cells are discussed.

  12. Relational victimization, loneliness and depressive symptoms: indirect associations via self and peer reports of rejection sensitivity.

    PubMed

    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.

  13. Extension of the rejection sensitivity construct to the interpersonal functioning of gay men.

    PubMed

    Pachankis, John E; Goldfried, Marvin R; Ramrattan, Melissa E

    2008-04-01

    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 test the mediating effect of internalized homophobia on the relationship between parental rejection of one's sexual orientation and sensitivity to future gay-related rejection. The present data support this mediational model and also establish rejection sensitivity's unique contribution to unassertive interpersonal behavior in the context of internalized homophobia and parental rejection. The authors conclude that gay-related rejection sensitivity is a useful construct for clinicians working with gay men given the impact that past gay-related rejection can have on their gay clients' present cognitive-affective-behavioral functioning. The authors discuss the possibility of revising rejection-prone schemas in clinical work with gay men. Future research is necessary to further examine the internal processing and interpersonal functioning of gay men by using existing constructs (or modifications of them) that are likely to be particularly relevant to the unique concerns of this population. PMID:18377126

  14. Anti-huCD20 Antibody Therapy for Antibody-Mediated Rejection of Renal Allografts in a Mouse Model

    PubMed Central

    Abe, Toyofumi; Ishii, Daisuke; Gorbacheva, Victoria; Kohei, Naoki; Tsuda, Hidetoshi; Tanaka, Toshiaki; Dvorina, Nina; Nonomura, Norio; Takahara, Shiro; Valujskikh, Anna; Baldwin, William M.; Fairchild, Robert L.

    2016-01-01

    We have reported that B6.CCR5−/− mice reject renal allografts with high serum donor-specific antibody (DSA) titers and marked C4d deposition in grafts, features consistent with AMR. B6.huCD20/CCR5−/− mice, where human CD20 expression is restricted to B cells, rejected A/J renal allografts by day 26 post-transplant with DSA first detected in serum on day 5 post-transplant and increased thereafter. Recipient treatment with anti-huCD20 mAb prior to the transplant and weekly up to 7 weeks post-transplant promoted long-term allograft survival (> 100 days) with low DSA titers. To investigate the effect of B cell depletion at the time serum DSA was first detected, recipients were treated with anti-huCD20 mAb on days 5, 8 and 12 post-transplant. This regimen significantly reduced DSA titers and graft inflammation on day 15 post-transplant and prolonged allograft survival > 60 days. However, DSA returned to the titers observed in control treated recipients by day 30 post-transplant and histological analyses on day 60 post-transplant indicated severe interstitial fibrosis. These results indicate that anti-huCD20 mAb had the greatest effect as a prophylactic treatment and that the distinct kinetics of DSA responses accounts for acute renal allograft failure versus the development of fibrosis. PMID:25731734

  15. De Novo Production of K-α1 Tubulin Specific Antibodies: Role in Chronic Lung Allograft Rejection

    PubMed Central

    Goers, Trudie A.; Ramachandran, Sabarinathan; Aloush, Aviva; Trulock, Elbert; Patterson, G. Alexander; Mohanakumar, T.

    2009-01-01

    Lung transplantation is the treatment option for a variety of end stage pulmonary diseases. Post transplant development of antibodies (Abs) against donor HLA and non-HLA antigens 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 antigen that is distinct from HLA. Further, de novo production of anti-epithelial cell antibody precedes clinical onset of BOS. N-terminal sequencing and BLASTX analysis as well as blocking with K-alpha1 tubulin specific antibody identified the epithelial antigen as K-α1 tubulin. Binding of the de novo produced anti-K-α1 tubulin antibodies 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 fibro-proliferation, the central events in immunopathogenesis of BOS following human lung transplantation. PMID:18354170

  16. What Protects Rejected Adolescents from Also Being Bullied by Their Peers? The Moderating Role of Peer-Valued Characteristics

    ERIC Educational Resources Information Center

    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…

  17. Independent component analysis for underwater lidar clutter rejection

    NASA Astrophysics Data System (ADS)

    Illig, David W.; Jemison, William D.; Mullen, Linda J.

    2016-05-01

    This work demonstrates a new statistical approach towards backscatter "clutter" rejection for continuous-wave underwater lidar systems: independent component analysis. Independent component analysis is a statistical signal processing technique which can separate a return of interest from clutter in a statistical domain. After highlighting the statistical processing concepts, we demonstrate that underwater lidar target and backscatter returns have very different distributions, facilitating their separation in a statistical domain. Example profiles are provided showing the results of this separation, and ranging experiment results are presented. In the ranging experiment, performance is compared to a more conventional frequency-domain filtering approach. Target tracking is maintained to 14.5 attenuation lengths in the laboratory test tank environment, a 2.5 attenuation length improvement over the baseline.

  18. Air-core grid for scattered x-ray rejection

    DOEpatents

    Logan, C.M.; Lane, S.M.

    1995-10-03

    The invention is directed to a grid used in x-ray imaging applications to block scattered radiation while allowing the desired imaging radiation to pass through, and to process for making the grid. The grid is composed of glass containing lead oxide, and eliminates the spacer material used in prior known grids, and is therefore, an air-core grid. The glass is arranged in a pattern so that a large fraction of the area is open allowing the imaging radiation to pass through. A small pore size is used and the grid has a thickness chosen to provide high scatter rejection. For example, the grid may be produced with a 200 {micro}m pore size, 80% open area, and 4 mm thickness. 2 figs.

  19. MONITORING WASTE HEAT REJECTION TO THE ENVIRONMENT VIA REMOTE SENSING

    SciTech Connect

    Garrett, A

    2009-01-13

    Nuclear power plants typically use waste heat rejection systems such as cooling lakes and natural draft cooling towers. These systems are designed to reduce cooling water temperatures sufficiently to allow full power operation even during adverse meteorological conditions. After the power plant is operational, the performance of the cooling system is assessed. These assessments usually rely on measured temperatures of the cooling water after it has lost heat to the environment and is being pumped back into the power plant (cooling water inlet temperature). If the cooling system performance is not perceived to be optimal, the utility will collect additional data to determine why. This paper discusses the use of thermal imagery collected from aircraft and satellites combined with numerical simulation to better understand the dynamics and thermodynamics of nuclear power plant waste heat dissipation systems. The ANS meeting presentation will discuss analyses of several power plant cooling systems based on a combination of remote sensing data and hydrodynamic modeling.

  20. [Immunosuppressives to prevent rejection reactions after allogeneic corneal transplantation].

    PubMed

    Lapp, T; Maier, P; Birnbaum, F; Schlunck, G; Reinhard, T

    2014-03-01

    In order to prevent rejection of an allogeneic corneal transplant after perforating (high risk) keratoplasty, active agents from different classes of pharmacological substances are used, as with solid organ transplantation. In addition to glucocorticoids, antiproliferative agents, small molecule inhibitors and antibodies, those belonging to the group of macrolides with their many derivatives represent an interesting class of substances in this context. As a supplement to cyclosporin A (CSA) the most successful macrolide in transplantation medicine, animal experiments are currently being carried out to test newer macrolide derivatives, such as sanglifehrin A (SFA). This overview describes the classes of drugs and modes of action of currently administered standard medications in the clinical routine and new developments are presented.

  1. Study of a heat rejection system using capillary pumping

    NASA Technical Reports Server (NTRS)

    Neal, L. G.; Wanous, D. J.; Clausen, O. W.

    1971-01-01

    Results of an analytical study investigating the application of capillary pumping to the heat rejection loop of an advanced Rankine cycle power conversion system are presented. The feasibility of the concept of capillary pumping as an alternate to electromagnetic pumping is analytically demonstrated. Capillary pumping is shown to provide a potential for weight and electrical power saving and reliability through the use of redundant systems. A screen wick pump design with arterial feed lines was analytically developed. Advantages of this design are high thermodynamic and hydrodynamic efficiency, which provide a lightweight easily packaged system. Operational problems were identified which must be solved for successful application of capillary pumping. The most important are the development of start up and shutdown procedures, and development of a means of keeping noncondensibles from the system and of earth-bound testing procedures.

  2. Heat-rejection design for large concentrating solar arrays

    NASA Technical Reports Server (NTRS)

    French, E. P.

    1980-01-01

    This paper considers the effect of heat rejection devices (radiators) on the performance and cost of large concentrating solar arrays for space application. Overall array characteristics are derived from the weight, cost, and performance of four major components; namely primary structure, optics/secondary structure, radiator, and solar panel. An ideal concentrator analysis is used to establish general cost and performance trends independent of specific array design. Both passive and heat-pipe radiation are evaluated, with an incremental cost-of-power approach used in the evaluation. Passive radiators are found to be more cost effective with silicon than with gallium arsenide (GaAs) arrays. Representative concentrating arrays have been evaluated for both near-term and advanced solar cell technology. Minimum cost of power is achieved at geometric concentration ratios in the range 2 to 6.

  3. Analysis techniques for background rejection at the Majorana Demonstrator

    SciTech Connect

    Cuestra, Clara; Rielage, Keith Robert; Elliott, Steven Ray; Xu, Wenqin; Goett, John Jerome III

    2015-06-11

    The MAJORANA Collaboration is constructing the MAJORANA DEMONSTRATOR, an ultra-low background, 40-kg modular HPGe detector array to search for neutrinoless double beta decay in 76Ge. In view of the next generation of tonne-scale Ge-based 0νββ-decay searches that will probe the neutrino mass scale in the inverted-hierarchy region, a major goal of the MAJORANA DEMONSTRATOR is to demonstrate a path forward to achieving a background rate at or below 1 count/tonne/year in the 4 keV region of interest around the Q-value at 2039 keV. The background rejection techniques to be applied to the data include cuts based on data reduction, pulse shape analysis, event coincidences, and time correlations. The Point Contact design of the DEMONSTRATOR's germanium detectors allows for significant reduction of gamma background.

  4. Air-core grid for scattered x-ray rejection

    DOEpatents

    Logan, Clinton M.; Lane, Stephen M.

    1995-01-01

    The invention is directed to a grid used in x-ray imaging applications to block scattered radiation while allowing the desired imaging radiation to pass through, and to process for making the grid. The grid is composed of glass containing lead oxide, and eliminates the spacer material used in prior known grids, and is therefore, an air-core grid. The glass is arranged in a pattern so that a large fraction of the area is open allowing the imaging radiation to pass through. A small pore size is used and the grid has a thickness chosen to provide high scatter rejection. For example, the grid may be produced with a 200 .mu.m pore size, 80% open area, and 4 mm thickness.

  5. Analysis techniques for background rejection at the MAJORANA DEMONSTRATOR

    SciTech Connect

    Cuesta, C.; Buuck, M.; Detwiler, J. A.; Gruszko, J.; Guinn, I. S.; Leon, J.; Robertson, R. G. H.; Abgrall, N.; Bradley, A. W.; Chan, Y-D.; Mertens, S.; Poon, A. W. P.; Arnquist, I. J.; Hoppe, E. W.; Kouzes, R. T.; LaFerriere, B. D.; Orrell, J. L.; Avignone, F. T.; Baldenegro-Barrera, C. X.; Bertrand, F. E.; and others

    2015-08-17

    The MAJORANA Collaboration is constructing the MAJORANA DEMONSTRATOR, an ultra-low background, 40- kg modular HPGe detector array to search for neutrinoless double beta decay in {sup 76}Ge. In view of the next generation of tonne-scale Ge-based 0νβ β-decay searches that will probe the neutrino mass scale in the inverted-hierarchy region, a major goal of the MAJORANA DEMONSTRATOR is to demonstrate a path forward to achieving a background rate at or below 1 count/tonne/year in the 4 keV region of interest around the Q-value at 2039 keV. The background rejection techniques to be applied to the data include cuts based on data reduction, pulse shape analysis, event coincidences, and time correlations. The Point Contact design of the DEMONSTRATOR’s germanium detectors allows for significant reduction of gamma background.

  6. Plant data comparisons for Comanche Peak 50% load rejection transient

    SciTech Connect

    Boatwright, W.J.; Choe, W.G.; Hiltbrand, D.W.; Devore, C.V.

    1994-12-31

    The RETRAN-02 codes is used for the transient and accident analysis. Benchmarks have been performed in order to qualify the Comanche Pear Steam electric station (CPSES) RETRAN-02 model, particularly the protection and control systems , reactivity feedback, noding, and primary-to-secondary heat transfer modeling. The 50% load rejection test was performed as part of the initial start-up test sequence for CPSES-1. The results of this analysis demonstrate that the RETRAN-02 model of CPSES-1 allows for quite good predictions of (1) the primary-to-secondary heat transfer rate; (2) the core power response, including the reactivity feedback effects due to changes in moderator and fuel temperatures and control rod position; and (3) the rod control model, which correctly simulates actual plant response in which the control rods are inserted and withdrawn in response to temperature and power error signals.

  7. Life cycle cost assessment of future low heat rejection engines

    NASA Technical Reports Server (NTRS)

    Petersen, D. R.

    1986-01-01

    The Adiabatic Diesel Engine Component Development (ADECD) represents a project which has the objective to accelerate the development of highway truck engines with advanced technology aimed at reduced fuel consumption. The project comprises three steps, including the synthesis of a number of engine candidate designs, the coupling of each with a number of systems for utilizing exhaust gas energy, and the evaluation of each combination in terms of desirability. Particular attention is given to the employed evaluation method and the development of this method. The objective of Life Cycle Cost (LCC) evaluation in the ADECD program was to select the best from among 42 different low heat rejection engine (LHRE)/exhaust energy recovery system configurations. The LCC model is discussed along with a maintenance cost model, the evaluation strategy, the selection of parameter ranges, and a full factorial analysis.

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

    PubMed

    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.

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

    PubMed

    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. PMID:26637661

  10. Rats rapidly reject diets deficient in essential amino acids.

    PubMed

    Koehnle, Thomas J; Russell, Matthew C; Gietzen, Dorothy W

    2003-07-01

    Omnivores must obtain diets balanced with respect to amino acids to support growth and protein synthesis. The standard paradigm used to study behavioral responses to amino acid deficiency combines deficient diets with dietary novelty. The objective of this study was to examine the effects of amino acid deficiency on the first meal of rats without the confounding effects of novelty. We report on a series of five studies of feeding behavior in rats. Rats were fed low protein diets for 5-7 d and then exposed to diets with and without essential amino acids. Rats consistently demonstrated recognition of essential amino acid deficiency within the first meal by a significant reduction in first meal duration, rejecting the deficient diets after just 12-16 min exposure. This is the first report of a rapid effect of amino acid-deficient diets without the confounding effects of dietary novelty.

  11. Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.

    1972-01-01

    For many decades two types of acute pancreatitis have been recognized: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary α-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess. PMID:4559467

  12. Noninvasive detection of human cardiac transplant rejection with indium-111 antimyosin (Fab) imaging

    SciTech Connect

    Frist, W.; Yasuda, T.; Segall, G.; Khaw, B.A.; Strauss, H.W.; Gold, H.; Stinson, E.; Oyer, P.; Baldwin, J.; Billingham, M.

    1987-11-01

    Diagnosis of rejection after cardiac transplantation is currently made by right ventricular endomyocardial biopsy. To evaluate antimyosin imaging as a noninvasive means of detecting human cardiac rejection, the Fab fragment of murine monoclonal antimyosin antibodies was labeled with indium-111 and given intravenously to 18 patients (age 45 +/- 12 years) in 20 studies 7 days to 9 years after transplantation. Endomyocardial biopsy specimens were obtained at the time of each imaging study. Eight patients had positive scans confirmed by biopsy as rejection, and eight patients had negative scans and no evidence of rejection on biopsy. Discordance was observed in four studies, two with positive scans and no rejection on biopsy and two with negative scans and positive biopsy. The sensitivity, specificity, and overall accuracy of the technique were each 80%. Imaging with radiolabeled antimyosin antibody Fab fragments may be of value in the noninvasive identification of rejection in the cardiac transplant recipient.

  13. Mouse model of alloimmune-induced vascular rejection and transplant arteriosclerosis.

    PubMed

    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.

  14. Reactions to Discrimination, Stigmatization, Ostracism, and Other Forms of Interpersonal Rejection

    PubMed Central

    Richman, Laura Smart; Leary, Mark R.

    2009-01-01

    This article describes a new model that provides a framework for understanding people’s reactions to threats to social acceptance and belonging as they occur in the context of diverse phenomena such as rejection, discrimination, ostracism, betrayal, and stigmatization. People’s immediate reactions are quite similar across different forms of rejection in terms of negative affect and lowered self-esteem. However, following these immediate responses, people’s reactions are influenced by construals of the rejection experience that predict 3 distinct motives for prosocial, antisocial, and socially avoidant behavioral responses. The authors describe the relational, contextual, and dispositional factors that affect which motives determine people’s reactions to a rejection experience and the ways in which these 3 motives may work at cross-purposes. The multimotive model accounts for the myriad ways in which responses to rejection unfold over time and offers a basis for the next generation of research on interpersonal rejection. PMID:19348546

  15. Adaptive filtering for ECG rejection from surface EMG recordings.

    PubMed

    Marque, C; Bisch, C; Dantas, R; Elayoubi, S; Brosse, V; Pérot, C

    2005-06-01

    Surface electromyograms (EMG) of back muscles are often corrupted by electrocardiogram (ECG) signals. This noise in the EMG signals does not allow to appreciate correctly the spectral content of the EMG signals and to follow its evolution during, for example, a fatigue process. Several methods have been proposed to reject the ECG noise from EMG recordings, but seldom taking into account the eventual changes in ECG characteristics during the experiment. In this paper we propose an adaptive filtering algorithm specifically developed for the rejection of the electrocardiogram corrupting surface electromyograms (SEMG). The first step of the study was to choose the ECG electrode position in order to record the ECG with a shape similar to that found in the noised SEMGs. Then, the efficiency of different algorithms were tested on 28 erector spinae SEMG recordings. The best algorithm belongs to the fast recursive least square family (FRLS). More precisely, the best results were obtained with the simplified formulation of a FRLS algorithm. As an application of the adaptive filtering, the paper compares the evolutions of spectral parameters of noised or denoised (after adaptive filtering) surface EMGs recorded on erector spinae muscles during a trunk extension. The fatigue test was analyzed on 16 EMG recordings. After adaptive filtering, mean initial values of energy and of mean power frequency (MPF) were significantly lower and higher respectively. The differences corresponded to the removal of the ECG components. Furthermore, classical fatigue criteria (increase in energy and decrease in MPF values over time during the fatigue test) were better observed on the denoised EMGs. The mean values of the slopes of the energy-time and MPF-time linear relationships differed significantly when established before and after adaptive filtering. These results account for the efficacy of the adaptive filtering method proposed here to denoise electrophysiological signals.

  16. Generation of suppressive blood cells for control of allograft rejection.

    PubMed

    Kleist, Christian; Sandra-Petrescu, Flavius; Jiga, Lucian; Dittmar, Laura; Mohr, Elisabeth; Greil, Johann; Mier, Walter; Becker, Luis E; Lang, Peter; Opelz, Gerhard; Terness, Peter

    2015-05-01

    Our previous studies in rats showed that incubation of monocytic dendritic cells (DCs) with the chemotherapeutic drug mitomycin C (MMC) renders the cells immunosuppressive. Donor-derived MMC-DCs injected into the recipient prior to transplantation prolonged heart allograft survival. Although the generation of DCs is labour-intensive and time-consuming, peripheral blood mononuclear cells (PBMCs) can be easily harvested. In the present study, we analyse under which conditions DCs can be replaced by PBMCs and examine their mode of action. When injected into rats, MMC-incubated donor PBMCs (MICs) strongly prolonged heart allograft survival. Removal of monocytes from PBMCs completely abrogated their suppressive effect, indicating that monocytes are the active cell population. Suppression of rejection was donor-specific. The injected MICs migrated into peripheral lymphoid organs and led to an increased number of regulatory T-cells (Tregs) expressing cluster of differentiation (CD) markers CD4 and CD25 and forkhead box protein 3 (FoxP3). Tolerance could be transferred to syngeneic recipients with blood or spleen cells. Depletion of Tregs from tolerogenic cells abrogated their suppressive effect, arguing for mediation of immunosuppression by CD4⁺CD25⁺FoxP3⁺ Tregs. Donor-derived MICs also prolonged kidney allograft survival in pigs. MICs generated from donor monocytes were applied for the first time in humans in a patient suffering from therapy-resistant rejection of a haploidentical stem cell transplant. We describe, in the present paper, a simple method for in vitro generation of suppressor blood cells for potential use in clinical organ transplantation. Although the case report does not allow us to draw any conclusion about their therapeutic effectiveness, it shows that MICs can be easily generated and applied in humans.

  17. Adult stem cell plasticity: will engineered tissues be rejected?

    PubMed Central

    Fang, Te-Chao; Alison, Malcolm R; Wright, Nicholas A; Poulsom, Richard

    2004-01-01

    The dogma that adult tissue-specific stem cells remain committed to supporting only their own tissue has been challenged; a new hypothesis, that adult stem cells demonstrate plasticity in their repertoires, is being tested. This is important because it seems possible that haematopoietic stem cells, for example, could be exploited to generate and perhaps deliver cell-based therapies deep within existing nonhaematopoietic organs. Much of the evidence for plasticity derives from histological studies of tissues from patients or animals that have received grafts of cells or whole organs, from a donor bearing (or lacking) a definitive marker. Detection in the recipient of appropriately differentiated cells bearing the donor marker is indicative of a switch in phenotype of a stem cell or a member of a transit amplifying population or of a differentiated cell. In this review, we discuss evidence for these changes occurring but do not consider the molecular basis of cell commitment. In general, the extent of engraftment is low but may be increased if tissues are damaged. In model systems of liver regeneration, the repeated application of a selection pressure increases levels of engraftment considerably; how this occurs is unclear. Cell fusion plays a part in regeneration and remodelling of the liver, skeletal muscle and even regions of the brain. Genetic disease may be amenable to some forms of cell therapy, yet immune rejection will present challenges. Graft-vs.-host disease will continue to present problems, although this may be avoided if the cells were derived from the recipient or they were tolerized. Despite great expectations for cellular therapies, there are indications that attempts to replace missing proteins could be confounded simply by the development of specific immunity that rejects the new phenotype. PMID:15255965

  18. Rejection Thresholds in Chocolate Milk: Evidence for Segmentation.

    PubMed

    Harwood, Meriel L; Ziegler, Gregory R; Hayes, John E

    2012-10-01

    Bitterness is generally considered a negative attribute in food, yet many individuals enjoy some bitterness in products like coffee or chocolate. In chocolate, bitterness arises from naturally occurring alkaloids and phenolics found in cacao. Fermentation and roasting help develop typical chocolate flavor and reduce the intense bitterness of raw cacao by modifying these bitter compounds. As it becomes increasingly common to fortify chocolate with `raw' cacao to increase the amount of healthful phytonutrients, it is important to identify the point at which the concentration of bitter compounds becomes objectionable, even to those who enjoy some bitterness. Classical threshold methods focus on the presence or absence of a sensation rather than acceptability or hedonics. A new alternative, the rejection threshold, was recently described in the literature. Here, we sought to quantify and compare differences in Rejection Thresholds (RjT) and Detection Thresholds (DT) in chocolate milk spiked with a food safe bitterant (sucrose octaacetate). In experiment 1, a series of paired preference tests was used to estimate the RjT for bitterness in chocolate milk. In a new group of participants (experiment 2), we determined the RjT and DT using the forced choice ascending method of limits. In both studies, participants were segmented on the basis of self-declared preference for milk or dark solid chocolate. Based on sigmoid fits of the indifference-preference function, the RjT was ~2.3 times higher for those preferring dark chocolate than the RjT for those preferring milk chocolate in both experiments. In contrast, the DT for both groups was functionally identical, suggesting that differential effects of bitterness on liking of chocolate products are not based on the ability to detect bitterness in these products.

  19. Rejection sensitivity mediates the relationship between social anxiety and body dysmorphic concerns.

    PubMed

    Fang, Angela; Asnaani, Anu; Gutner, Cassidy; Cook, Courtney; Wilhelm, Sabine; Hofmann, Stefan G

    2011-10-01

    The goal of this study was to examine the role of rejection sensitivity in the relationship between social anxiety and body dysmorphic concerns. To test our hypothesis that rejection sensitivity mediates the link between social anxiety and body dysmorphic concerns, we administered self-report questionnaires to 209 student volunteers. Consistent with our prediction, rejection sensitivity partially mediated the relationship between social anxiety symptoms and body dysmorphic concerns. The implications of the overlap between these constructs are discussed.

  20. Inhibition of allograft rejection by anti-T-cell receptor-alpha beta monoclonal antibodies preserving resistance to bacterial infection.

    PubMed Central

    Eto, M; Yoshikai, Y; Nishimura, Y; Hiromatsu, K; Maeda, T; Nomoto, K; Kong, Y Y; Kubo, R T; Kumazawa, J; Nomoto, K

    1994-01-01

    Anti-CD3 monoclonal antibody (mAb) has been administered in clinical organ transplantation to reverse acute allograft rejection; however, severe immunodeficiency can result from such mAb treatment and cause an increased incidence of opportunistic infections. Therefore, new model systems are required in order to establish better methods for suppressing allograft rejection while preserving resistance to opportunistic infections. In this study, we compared the effects of the in vivo administration of anti-T-cell receptor-alpha beta (TcR alpha beta) mAb, H57-597, with those of anti-CD3 mAb, 145-2C11. Much to our surprise, the in vivo administration of anti-TcR alpha beta mAb prior to skin grafting led to a longer allograft survival than that of anti-CD3 mAb at any of the comparable dosages examined. In the lymphoid organs of mice treated with anti-TcR alpha beta mAb, TcR alpha beta-bearing cells were almost completely depleted, while TcR gamma delta-bearing cells remained at a relatively increased level on day 14 after anti-TcR alpha beta mAb treatment. The in vitro stimulation by anti-TcR gamma delta mAb clearly showed that such TcR gamma delta-bearing cells were functionally intact. Furthermore, the mice treated with anti-TcR alpha beta mAb, but not anti-CD3 mAb, were observed to be resistant to infection with Listeria monocytogenes. Finally, treatment with H57-597, but not with 145-2C11, led to a marked prolongation of skin allograft survival in the thymectomized mice. These results strongly suggest that anti-TcR alpha beta mAb, which partially preserved anti-bacterial resistance, may be more effective in preventing graft rejection than anti-CD3 mAb in the periphery, and indicate that anti-TcR alpha beta mAb may thus be potentially applicable for human transplantation. In addition, these results also indicate that the TcR gamma delta-bearing cells alone, at least in the absence of TcR alpha beta-bearing cells, do not contribute to allograft rejection in vivo. PMID

  1. Egg rejection behavior in a population exposed to parasitism: Village Weavers on Hispaniola

    USGS Publications Warehouse

    Cruz, A.; Prather, J.W.; Wiley, J.W.; Weaver, P.F.

    2008-01-01

    In contrast to African Village Weavers (Ploceus cucullatus) that are parasitized by Diederik Cuckoos (Chrysococcyx caprius), introduced weavers on Hispaniola existed without parasitism for at least 2 centuries until the arrival of the Shiny Cowbird (Molothrus bonariensis) in the 1970s. Cruz and Wiley (1989) found that Hispaniolan weavers had a lower rejection rate of foreign eggs than African populations. Subsequently, Robert and Sorci (1999) and Lahti (2005, 2006) found that acceptance of dissimilar eggs is not characteristic of the species throughout its Hispaniolan range. In 1999-2002, we studied egg rejection in Hispaniolan weavers on a broad regional scale. Rejection increased as experimental eggs became increasingly different from the host eggs. Rejection rates for mimetic eggs, different color eggs, different-spotting eggs, and cowbird eggs was 23.2%, 33.3%, 61.5%, and 85.3%, respectively, with higher rejection of cowbird eggs in areas where cowbirds were observed. Although rejection is likely to have a genetic component, the differences could be due to phenotypic plasticity. Plasticity in egg rejection may be expected, given the potential cost of rejection and the spatiotemporal distribution of cowbirds. Thus, egg rejection has not necessarily decreased in Hispaniolan weavers, but it may act in a plastic manner, increasing where cowbirds are present. ?? The Author 2008. Published by Oxford University Press on behalf of the International Society for Behavioral Ecology. All rights reserved.

  2. Parental alignments and rejection: an empirical study of alienation in children of divorce.

    PubMed

    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.

  3. 7 CFR 54.1013 - When an application may be rejected.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... (CONTINUED) MEATS, PREPARED MEATS, AND MEAT PRODUCTS (GRADING, CERTIFICATION, AND STANDARDS) Regulations..., and shall explain the reason(s) for the rejection. If such notification is made verbally,...

  4. Incidence, risk factors, and outcome of chronic rejection during antiviral therapy for posttransplant recurrent hepatitis C.

    PubMed

    Fernández, Inmaculada; Ulloa, Esperanza; Colina, Francisco; Abradelo, Manuel; Jiménez, Carlos; Gimeno, Alberto; Meneu, Juan Carlos; Lumbreras, Carlos; Solís-Herruzo, José Antonio; Moreno, Enrique

    2009-08-01

    Antiviral therapy for recurrent hepatitis C in liver transplantation has been associated with the development of chronic rejection. The aim of this study was to assess the incidence, evolution, and risk factors associated with the development of chronic rejection during posttransplant hepatitis C virus antiviral therapy. Seventy-nine patients with posttransplant recurrent hepatitis C who were treated with pegylated interferon and ribavirin were prospectively followed. Liver biopsy was performed before antiviral therapy was initiated and when liver tests worsened during therapy. Pretransplant and posttransplant factors were analyzed as potential risk factors for the development of chronic rejection. Seven of 79 patients (9%) developed chronic rejection during antiviral therapy. The mean time from the start of treatment to the development of chronic rejection was 5.8 months (3-12 months). An analysis of factors associated with the development of chronic rejection showed that the use of cyclosporine as immunosuppression therapy (6 of 19 patients who received cyclosporine developed chronic rejection in comparison with only 1 of 57 patients who received tacrolimus; P = 0.0013), achievement of sustained virological response (P = 0.043), and ribavirin discontinuation (P = 0.027) were associated with the development of chronic rejection. In conclusion, the development of chronic rejection during posttransplant pegylated interferon and ribavirin therapy is a severe complication. The use of cyclosporine, ribavirin discontinuation, and viral infection elimination seem to be associated with the development of this complication. Liver Transpl 15:948-955, 2009. (c) 2009 AASLD.

  5. Gay-Related Rejection Sensitivity as a Risk Factor for Condomless Sex.

    PubMed

    Wang, Katie; Pachankis, John E

    2016-04-01

    Gay-related rejection sensitivity has been linked to numerous adverse health outcomes, but its relationship to condomless sex remains unexamined. The present study investigated the role of gay-related rejection sensitivity as a predictor of condomless sex. Gay and bisexual men completed questionnaires measuring rejection sensitivity and condom use self-efficacy as well as a timeline followback interview regarding past 90-day sexual behaviors. Gay-related rejection sensitivity was positively associated with the number of condomless anal sex acts with casual partners, and condom use self-efficacy mediated this association. These findings have important implications for effective HIV prevention efforts among this at-risk population.

  6. Affect of parental rejection on negative attention-seeking class room behaviors.

    PubMed

    Peretti, P O; Clark, D; Johnson, P

    1983-07-01

    Of concern to teachers are students displaying classroom behaviors which are disruptive in attaining pupil success in learning and teacher success in teaching. The present study was conducted to determine the effect of parental rejection on negative attention-seeking classroom behaviors. It was also conducted to find out what particular parent might be more rejecting toward the respondents, and, what specific negative attention-seeking behaviors might be overtly demonstrated in the classroom by sex of subject. Results indicated a significant influence of parental rejection on negative attention-seeking classroom behaviors, the father as a more rejecting parent, and differences in observed behaviors by sex of subject.

  7. AFFECT OF PARENTAL REJECTION ON NEGATIVE ATTENTION-SEEKING CLASS ROOM BEHAVIORS

    PubMed Central

    Peretti, Peter O.; Clark, Denise; Johnson, Pat

    1983-01-01

    SUMMARY Of concern to teachers are students displaying classroom behaviors which are disruptive in attaining pupil success in learning and teacher success in teaching. The present study was conducted to determine the effect of parental rejection on negative attention-seeking classroom behaviors. It was also conducted to find out what particular parent might be more rejecting toward the respondents, and, what specific negative attention-seeking behaviors might be overtly demonstrated in the classroom by sex of subject. Results indicated a significant influence of parental rejection on negative attention-seeking classroom behaviors, the father as a more rejecting parent, and differences in observed behaviors by sex of subject. PMID:21847284

  8. [Lymphoid neogenesis and lymphangiogenesis: two newcomers in the pathophysiology of chronic rejection].

    PubMed

    Attuil-Audenis, Valérie; Duthey, Aurélie; Patey, Natacha; Gautreau, Chantal; McGregor, Brigitte; Morelon, Emmanuel; Michel, Jean-Baptiste; Nicoletti, Antonino; Thaunat, Olivier

    2009-04-01

    Chronic rejection is one of the main causes of late allograft failure and no therapy is currently available to prevent efficiently its development. Improving the comprehension of the mechanisms involved in the pathophysiology of chronic rejection is a mandatory step to propose innovative therapies that would prolong grafts' survival. Using the rat aortic interposition model of chronic vascular rejection, we have demonstrated that the intragraft inflammatory infiltrate progressively organized itself into a functional ectopic lymphoid tissue (tertiary lymphoid organ) supporting the local synthesis of alloantibody. Thus, during chronic rejection the graft is at the same time the target and the site of elaboration of the humoral allo-immune response. This hypothesis has been confirmed in the clinical setting by the analysis of human grafts (kidneys, hearts and lungs) removed for terminal failure due to chronic rejection. This lymphoid neogenesis process, previously identified in other chronic inflammatory diseases, occurs with a strikingly high frequency in chronically rejected grafts, suggesting that an additional mechanism synergizes to initiate the development of tertiary lymphoid organs during chronic rejection. We propose that the defective lymphatic drainage of chronically rejected organs triggers lymphoid neogenesis and we discuss the complex crosstalk between lymphoid neogenesis and lymphangiogenesis that takes place during chronic rejection.

  9. Management of acute pancreatitis (AP) – Polish Pancreatic Club recommendations

    PubMed Central

    Rosołowski, Mariusz; Lipiński, Michał; Dobosz, Marek; Durlik, Marek; Głuszek, Stanisław; Kuśnierz, Katarzyna; Lampe, Paweł; Małecka-Panas, Ewa; Nowakowska-Duława, Ewa; Nowak-Niezgoda, Magdalena; Radomańska, Barbara; Talar-Wojnarowska, Renata; Wereszczyńska-Siemiątkowska, Urszula

    2016-01-01

    The presented recommendations concern the current management of acute pancreatitis. The recommendations relate to the diagnostics and treatment of early and late phases of acute pancreatitis and complications of the disease taking into consideration surgical and endoscopic methods. All the recommendations were subjected to voting by the members of the Working Group of the Polish Pancreatic Club, who evaluated them every single time on a five-point scale, where A means full acceptance, B means acceptance with a certain reservation, C means acceptance with a serious reservation, D means rejection with a certain reservation and E means full rejection. The results of the vote, together with commentary, are provided for each recommendation. PMID:27350832

  10. Acute Vestibulopathy

    PubMed Central

    Cha, Yoon-Hee

    2011-01-01

    The presentation of acute vertigo may represent both a common benign disorder or a life threatening but rare one. Familiarity with the common peripheral vestibular disorders will allow the clinician to rapidly “rule-in” a benign disorder and recognize when further testing is required. Key features of vertigo required to make an accurate diagnosis are duration, chronicity, associated symptoms, and triggers. Bedside tests that are critical to the diagnosis of acute vertigo include the Dix-Hallpike maneuver and canalith repositioning manuever, occlusive ophthalmoscopy, and the head impulse test. The goal of this review is to provide the clinician with the clinical and pathophysiologic background of the most common disorders that present with vertigo to develop a logical differential diagnosis and management plan. PMID:23983835

  11. [Acute diarrhea].

    PubMed

    Burgmann, Konstantin; Schoepfer, Alain

    2014-09-01

    Diarrhea, defined as three or more loose or watery stools per day, represents a frequent problem in outpatients as well as inpatients. As most of the patients with acute diarrhea show a self-limiting disease course, the main challenge for the physician is to discriminate patients for whom symptomatic therapy is sufficient from those with severe disease course and threatening complications. This review aims to provide a practical guidance for such decisions.

  12. Medicare Part D Claims Rejections for Nursing Home Residents, 2006 to 2010

    PubMed Central

    Stevenson, David G.; Keohane, Laura M.; Mitchell, Susan L.; Zarowitz, Barbara J.; Huskamp, Haiden A.

    2013-01-01

    Objectives Much has been written about trends in Medicare Part D formulary design and consumers’ choice of plans, but little is known about the magnitude of claims rejections or their clinical and administrative implications. Our objective was to study the overall rate at which Part D claims are rejected, whether these rates differ across plans, drugs, and medication classes, and how these rejection rates and reasons have evolved over time. Study Design and Methods We performed descriptive analyses of data on paid and rejected Part D claims submitted by 1 large national long-term care pharmacy from 2006 to 2010. In each of the 5 study years, data included approximately 450,000 Medicare beneficiaries living in long-term care settings with approximately 4 million Part D drug claims. Claims rejection rates and reasons for rejection are tabulated for each study year at the plan, drug, and class levels. Results Nearly 1 in 6 drug claims was rejected during the first 5 years of the Medicare Part D program, and this rate has increased over time. Rejection rates and reasons for rejection varied substantially across drug products and Part D plans. Moreover, the reasons for denials evolved over our study period. Coverage has become less of a factor in claims rejections than it was initially and other formulary tools such as drug utilization review, quantity-related coverage limits, and prior authorization are increasingly used to deny claims. Conclusions Examining claims rejection rates can provide important supplemental information to assess plans’ generosity of coverage and to identify potential areas of concern. PMID:23145808

  13. Greater positive schizotypy relates to reduced N100 activity during rejection scenes.

    PubMed

    Premkumar, Preethi; Onwumere, Juliana; Wilson, Daniel; Sumich, Alexander; Castro, Antonio; Kumari, Veena; Kuipers, Elizabeth

    2014-08-01

    Social anxiety due to rejection sensitivity (RS) exacerbates psychosis-like experiences in the general population. While reduced dorsal anterior cingulate cortex (dACC) activity during social rejection in high schizotypy has suggested self-distancing from rejection, earlier stages of mental processing such as feature encoding could also contribute to psychosis-like experiences. This study aimed to determine the stage of mental processing of social rejection that relates to positive schizotypy. Forty-one healthy participants were assessed for schizotypy and RS. Event-related potential amplitudes (ERPs) were measured at frontal, temporal and parieto-occipital sites and their cortical sources (dACC, temporal pole and lingual gyrus) at early (N100) and late (P300 and late slow wave, LSW) timeframes during rejection, acceptance and neutral scenes. ERPs were compared between social interaction types. Correlations were performed between positive schizotypy (defined as the presence of perceptual aberrations, hallucinatory experiences and magical thinking), RS and ERPs during rejection. Amplitude was greater during rejection than acceptance or neutral conditions at the dACC-P300, parieto-occipital-P300, dACC-LSW and frontal-LSW. RS correlated positively with positive schizotypy. Reduced dACC N100 activity during rejection correlated with greater positive schizotypy and RS. Reduced dACC N100 activity and greater RS independently predicted positive schizotypy. An N100 deficit that indicates reduced feature encoding of rejection scenes increases with greater positive schizotypy and RS. Higher RS shows that a greater tendency to misattribute ambiguous social situations as rejecting also increases with positive schizotypy. These two processes, namely primary bottom-up sensory processing and secondary misattribution of rejection, combine to increase psychosis-like experiences. PMID:25010933

  14. Neural processing of social rejection: the role of schizotypal personality traits.

    PubMed

    Premkumar, Preethi; Ettinger, Ulrich; Inchley-Mort, Sophie; Sumich, Alexander; Williams, Steven C R; Kuipers, Elizabeth; Kumari, Veena

    2012-03-01

    A fear of being rejected can cause perceptions of more insecurity and stress in close relationships. Healthy individuals activate the dorsal anterior cingulate cortex (dACC) when experiencing social rejection, while those who are vulnerable to depression deactivate the dACC presumably to downregulate salience of rejection cues and minimize distress. Schizotypal individuals, characterized by unusual perceptual experiences and/or odd beliefs, are more rejection sensitive than normal. We tested the hypothesis, for the first time, that individuals with high schizotypy also have an altered dACC response to rejection stimuli. Twenty-six healthy individuals, 14 with low schizotypy (LS) and 12 with high schizotypy (HS), viewed depictions of rejection and acceptance and neutral scenes while undergoing functional MRI. Activation maps in LS and HS groups during each image type were compared using SPM5, and their relation to participant mood and subjective ratings of the images was examined. During rejection relative to neutral scenes, LS activated and HS deactivated the bilateral dACC, right superior frontal gyrus, and left ventral prefrontal cortex. Across both groups, a temporo-occipito-parieto-cerebellar network was active during rejection, and a left fronto-parietal network during acceptance, relative to neutral scenes, and the bilateral lingual gyrus during rejection relative to acceptance scenes. Our finding of dACC-dorso-ventral PFC activation in LS, but deactivation in HS individuals when perceiving social rejection scenes suggests that HS individuals attach less salience to and distance themselves from such stimuli. This may enable them to cope with their higher-than-normal sensitivity to rejection. PMID:21425394

  15. The Nature of Experimental Second-set Kidney Transplant Rejection

    PubMed Central

    Dempster, W. J.

    1971-01-01

    The second-set reaction can be mimiced from a haemodynamic point of view by pharmacological vasopressors, warm and cold ischaemic factors producing vasocontriction and by the Shwartzman reaction. The second-set kidney transplant reaction is assumed to be due to antibodies which, if so, are not dependent for their cytotoxicity on complement fixation and are uninfluenced by antihistamine drugs, steroids, immunosuppression, incoagulable blood, adequate hydration and rheomacrodex. Once started, the reaction continues until the vasoconstriction is so severe that no blood enters the kidney and complete disorganization of kidney function and structure ensues. The deposition of fibrin in the vessels and glomeruli follows the severe vasomotor upset which evokes afferent vasoconstriction. Fibrin is not prevented from being deposited when the recipient of a second-set kidney is fully Arvinized so that the blood is rendered incoagulable. The second-set kidney reaction is first heralded by vasoconstriction in the outer cortex associated with acute renal failure and, as such, fits into the general phenomenon of acute renal failure associated with underperfusion of the outer cortex. There is no evidence that underperfusion of the outer cortex is due to a hyperreactivity of special vessels with a different structure from the other vessels supplying this area. There is the fact, however, that the outer cortical vessels are highly reactive to stimuli of many kinds besides angiotensin. Certain unexplained features of acute renal failure in general may be reasonably explained by reference to the effects of underperfusion of the outer cortex. Acute renal failure associated with mild signs of tubule necrosis, for example, may be explained by the fact that although there is afferent underperfusion of the outer cortex there is generally maintained a good venular collateral nutrient supply (maintained capacitance) sufficient for the oxygen requirements of tubules which are not pumping

  16. Nano-mineralogy of suspended sediment during the beginning of coal rejects spill.

    PubMed

    Civeira, Matheus S; Ramos, Claudete G; Oliveira, Marcos L S; Kautzmann, Rubens M; Taffarel, Silvio R; Teixeira, Elba C; Silva, Luis F O

    2016-02-01

    Ultrafine and nanometric sediment inputs into river systems can be a major source of nutrients and hazardous elements and have a strong impact on water quality and ecosystem functions of rivers and lakes regions. However, little is known to date about the spatial distribution of sediment sources in most large scale river basins in South America. The objective of this work was to study the coal cleaning rejects (CCRs) spill that occurred from a CCRs impoundment pond into the Tubarão River, South Brazil, provided a unique occasion to study the importance and role of incidental nanoparticles associated with pollutant dispersal from a large-scale, acute aquatic pollution event. Multifaceted geochemical research by X-ray diffraction (XRD), High Resolution-Transmission Electron microscopy (HR-TEM)/(Energy Dispersive Spectroscopy) EDS/(selected-area diffraction pattern) SAED, Field Emission-Scanning Electron Microscopy (FE-SEM)/EDS, and Raman spectroscopy, provided an in-depth understanding of importance of a nano-mineralogy approach of Aqueous Pollution Scenarios. The electron beam studies showed the presence of a number of potentially hazardous elements (PHEs) in nanoparticles (amorphous and minerals). Some of the neoformed ultrafine/nanoparticles found in the contaminated sediments are the same as those commonly associated with oxidation/transformation of oxides, silicates, sulfides, and sulfates. These data of the secondary ultra/nanoparticles, puts in evidence their ability to control the mobility of PHEs, suggesting possible presentations in environmental technology, including recuperation of sensitive coal mine. The developed methodology facilitated the sediment transport of the catchment providing consistent results and suggesting its usefulness as a tool for temporary rivers management.

  17. Nano-mineralogy of suspended sediment during the beginning of coal rejects spill.

    PubMed

    Civeira, Matheus S; Ramos, Claudete G; Oliveira, Marcos L S; Kautzmann, Rubens M; Taffarel, Silvio R; Teixeira, Elba C; Silva, Luis F O

    2016-02-01

    Ultrafine and nanometric sediment inputs into river systems can be a major source of nutrients and hazardous elements and have a strong impact on water quality and ecosystem functions of rivers and lakes regions. However, little is known to date about the spatial distribution of sediment sources in most large scale river basins in South America. The objective of this work was to study the coal cleaning rejects (CCRs) spill that occurred from a CCRs impoundment pond into the Tubarão River, South Brazil, provided a unique occasion to study the importance and role of incidental nanoparticles associated with pollutant dispersal from a large-scale, acute aquatic pollution event. Multifaceted geochemical research by X-ray diffraction (XRD), High Resolution-Transmission Electron microscopy (HR-TEM)/(Energy Dispersive Spectroscopy) EDS/(selected-area diffraction pattern) SAED, Field Emission-Scanning Electron Microscopy (FE-SEM)/EDS, and Raman spectroscopy, provided an in-depth understanding of importance of a nano-mineralogy approach of Aqueous Pollution Scenarios. The electron beam studies showed the presence of a number of potentially hazardous elements (PHEs) in nanoparticles (amorphous and minerals). Some of the neoformed ultrafine/nanoparticles found in the contaminated sediments are the same as those commonly associated with oxidation/transformation of oxides, silicates, sulfides, and sulfates. These data of the secondary ultra/nanoparticles, puts in evidence their ability to control the mobility of PHEs, suggesting possible presentations in environmental technology, including recuperation of sensitive coal mine. The developed methodology facilitated the sediment transport of the catchment providing consistent results and suggesting its usefulness as a tool for temporary rivers management. PMID:26688250

  18. Host genotype and age have no effect on rejection of parasitic eggs.

    PubMed

    Procházka, Petr; Konvičková-Patzenhauerová, Hana; Požgayová, Milica; Trnka, Alfréd; Jelínek, Václav; Honza, Marcel

    2014-05-01

    Egg rejection belongs to a widely used host tactic to prevent the costs incurred by avian brood parasitism. However, the genetic basis of this behaviour and the effect of host age on the probability of rejecting the parasitic egg remain largely unknown. Here, we used a set of 15 polymorphic microsatellite loci, including a previously detected candidate locus (Ase64), to link genotypes of female great reed warblers (Acrocephalus arundinaceus), a known rejecter, with their egg rejection responses in two host populations. We also tested whether host female age, as a measure of the experience with own eggs, plays a role in rejection of common cuckoo (Cuculus canorus) eggs. We failed to find any consistent association of egg rejection responses with host female genotypes or age. It seems that host decisions on egg rejection show high levels of phenotypic plasticity and are likely to depend on the spatiotemporal variation in the parasitism pressure. Future studies exploring the repeatability of host responses towards parasitic eggs and the role of host individual experience with parasitic eggs would greatly improve our understanding of the variations in host behaviours considering the persistence of brood parasitism in host populations with rejecter phenotypes. PMID:24718778

  19. Mental Health in Marriage: The Roles of Need for Affiliation, Sensitivity to Rejection, and Other Factors.

    ERIC Educational Resources Information Center

    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,…

  20. 40 CFR 204.57-6 - Acceptance and rejection of batches.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Acceptance and rejection of batches... Acceptance and rejection of batches. (a) A failing compressor is one whose measured sound level is in excess of the applicable noise emission standard. (b) The batch from which a batch sample is selected...

  1. 40 CFR 204.57-6 - Acceptance and rejection of batches.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Acceptance and rejection of batches... Acceptance and rejection of batches. (a) A failing compressor is one whose measured sound level is in excess of the applicable noise emission standard. (b) The batch from which a batch sample is selected...

  2. 40 CFR 204.57-6 - Acceptance and rejection of batches.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Acceptance and rejection of batches... Acceptance and rejection of batches. (a) A failing compressor is one whose measured sound level is in excess of the applicable noise emission standard. (b) The batch from which a batch sample is selected...

  3. 40 CFR 204.57-6 - Acceptance and rejection of batches.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Acceptance and rejection of batches... Acceptance and rejection of batches. (a) A failing compressor is one whose measured sound level is in excess of the applicable noise emission standard. (b) The batch from which a batch sample is selected...

  4. 40 CFR 204.57-6 - Acceptance and rejection of batches.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Acceptance and rejection of batches... Acceptance and rejection of batches. (a) A failing compressor is one whose measured sound level is in excess of the applicable noise emission standard. (b) The batch from which a batch sample is selected...

  5. Effects of age and MAOA genotype on the neural processing of social rejection.

    PubMed

    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.

  6. Social Prominence and the Heterogeneity of Rejected Status in Late Elementary School

    ERIC Educational Resources Information Center

    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".…

  7. 21 CFR 111.370 - What requirements apply to rejected dietary supplements?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production and Process Control... disposition any dietary supplement that is rejected and unsuitable for use in manufacturing, packaging, or... 21 Food and Drugs 2 2014-04-01 2014-04-01 false What requirements apply to rejected...

  8. 21 CFR 111.370 - What requirements apply to rejected dietary supplements?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production and Process Control... disposition any dietary supplement that is rejected and unsuitable for use in manufacturing, packaging, or... 21 Food and Drugs 2 2011-04-01 2011-04-01 false What requirements apply to rejected...

  9. 21 CFR 111.370 - What requirements apply to rejected dietary supplements?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production and Process Control... disposition any dietary supplement that is rejected and unsuitable for use in manufacturing, packaging, or... 21 Food and Drugs 2 2012-04-01 2012-04-01 false What requirements apply to rejected...

  10. 21 CFR 111.370 - What requirements apply to rejected dietary supplements?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production and Process Control... disposition any dietary supplement that is rejected and unsuitable for use in manufacturing, packaging, or... 21 Food and Drugs 2 2013-04-01 2013-04-01 false What requirements apply to rejected...

  11. 21 CFR 111.370 - What requirements apply to rejected dietary supplements?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production and Process Control... disposition any dietary supplement that is rejected and unsuitable for use in manufacturing, packaging, or... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What requirements apply to rejected...

  12. Resilient Adolescent Adjustment among Girls: Buffers of Childhood Peer Rejection and Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    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…

  13. Rejected Youth in Residential Treatment: Social Affiliation and Peer Group Configuration.

    ERIC Educational Resources Information Center

    Hoff, Kathryn E.; DuPaul, George J.; Handwerk, Michael L.

    2003-01-01

    A study examined social relationships of 105 middle school children attending a residential facility and identified as rejected. The majority affiliated within a peer cluster and were well integrated within the broader social network. Students who affiliated in peer clusters with rejected students tended to be similar in sociometric status.…

  14. Relationship of perceived maternal acceptance-rejection in childhood and social support networks of pregnant adolescents.

    PubMed

    Sherman, B R; Donovan, B R

    1991-01-01

    In a sample of 53 at-risk pregnant adolescents, the relationship between their perceptions of maternal acceptance-rejection in childhood and the nature of their social supports was examined. Perception of acceptance-rejection was significantly correlated with both frequency of interaction with social network members and expectations of their future support. Implications for public health strategies are discussed.

  15. 40 CFR 86.322-79 - NDIR CO2 rejection ratio check.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) Record the CO2 calibration gas concentration in ppm. (d) Record the analyzers' response (AR) in ppm to... 40 Protection of Environment 18 2010-07-01 2010-07-01 false NDIR CO2 rejection ratio check. 86.322....322-79 NDIR CO2 rejection ratio check. (a) Zero and span the analyzer on the lowest range that will...

  16. 75 FR 35019 - Hampshire Paper Company; Notice Rejecting Application, Waiving Regulations, and Soliciting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  17. A Multivariate Model for the Study of Parental Acceptance-Rejection and Child Abuse.

    ERIC Educational Resources Information Center

    Rohner, Ronald P.; Rohner, Evelyn C.

    This paper proposes a multivariate strategy for the study of parental acceptance-rejection and child abuse and describes a research study on parental rejection and child abuse which illustrates the advantages of using a multivariate, (rather than a simple-model) approach. The multivariate model is a combination of three simple models used to study…

  18. Host genotype and age have no effect on rejection of parasitic eggs

    NASA Astrophysics Data System (ADS)

    Procházka, Petr; Konvičková-Patzenhauerová, Hana; Požgayová, Milica; Trnka, Alfréd; Jelínek, Václav; Honza, Marcel

    2014-05-01

    Egg rejection belongs to a widely used host tactic to prevent the costs incurred by avian brood parasitism. However, the genetic basis of this behaviour and the effect of host age on the probability of rejecting the parasitic egg remain largely unknown. Here, we used a set of 15 polymorphic microsatellite loci, including a previously detected candidate locus (Ase64), to link genotypes of female great reed warblers ( Acrocephalus arundinaceus), a known rejecter, with their egg rejection responses in two host populations. We also tested whether host female age, as a measure of the experience with own eggs, plays a role in rejection of common cuckoo ( Cuculus canorus) eggs. We failed to find any consistent association of egg rejection responses with host female genotypes or age. It seems that host decisions on egg rejection show high levels of phenotypic plasticity and are likely to depend on the spatiotemporal variation in the parasitism pressure. Future studies exploring the repeatability of host responses towards parasitic eggs and the role of host individual experience with parasitic eggs would greatly improve our understanding of the variations in host behaviours considering the persistence of brood parasitism in host populations with rejecter phenotypes.

  19. Interpersonal Rejection Sensitivity in Childhood Sexual Abuse Survivors: Mediator of Depressive Symptoms and Anger Suppression

    ERIC Educational Resources Information Center

    Luterek, Jane A.; Harb, Gerlinde C.; Heimberg, Richard G.; Marx, Brian P.

    2004-01-01

    This study investigated whether interpersonal rejection sensitivity serves a mediating role between childhood sexual abuse (CSA) and three long-term psychological correlates of CSA in adult female survivors: depressive symptoms, anger suppression, and attenuated emotional expression. Interpersonal rejection sensitivity has been shown to be a risk…

  20. 9 CFR 355.17 - Tagging equipment “U.S. rejected.”

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Tagging equipment âU.S. rejected.â 355.17 Section 355.17 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF....17 Tagging equipment “U.S. rejected.” When necessary, inspectors shall attach a “U.S. rejected”...

  1. Physiologic Responses to Racial Rejection Images among Young Adults from African-American Backgrounds

    ERIC Educational Resources Information Center

    Kiang, Lisa; Blumenthal, Terry D.; Carlson, Erika N.; Lawson, Yolanda N.; Shell, J. Clark

    2009-01-01

    Physiologic reactivity to racially rejecting images was assessed in 35 young adults (10 males, 25 female) from African-American backgrounds using the startle probe paradigm. In a laboratory setting, participants viewed 16 images depicting racial rejection, racial acceptance, nonracial negative, and nonracial positive themes. While viewing these…

  2. Pitfalls of the Peer World: How Children Cope with Common Rejection Experiences

    ERIC Educational Resources Information Center

    Sandstrom, Marlene J.

    2004-01-01

    This study examines the reliability and validity of a newly developed self-report measure designed to assess children's coping strategies in response to everyday rejection experiences. The Survey for Coping with Rejection Experiences (SCORE) was administered to 225 children and factor analysis of responses resulted in the conceptually meaningful…

  3. Currently available useful immunohistochemical markers of renal pathology for the diagnosis of renal allograft rejection.

    PubMed

    Kanzaki, Go; Shimizu, Akira

    2015-07-01

    Renal allograft dysfunction may be induced by various causes, including alloimmune rejection, viral infection, urinary tract obstruction, calcineurin inhibitor nephrotoxicity and/or recurrent renal disease. In order to determine the underlying cause, a renal biopsy is performed and the renal transplant pathology is diagnosed using the internationally consensus Banff classification. Although a progressive understanding of allograft rejection has provided numerous immunohistochemical markers, only the C4d is regarded to be a sufficiently useful marker for antibody-mediated allograft rejection according to the Banff classification. This review summarizes currently available useful immunohistochemical markers of renal transplant pathology, including C4d, with diagnostic implications for human renal allograft rejection. In particular, we discuss immunohistochemical markers in the following three categories: immunohistochemical markers of renal pathology used to (i) analyze the mechanisms of alloimmune rejection, (ii) monitor cell injury and/or inflammation associated with rejection and (iii) identify renal components in order to improve the diagnosis of rejection. In addition, recent progress in the field of renal transplant pathology includes the development of a new method for assessing molecular pathology using OMICS analyses. As the recent findings of various studies in patients undergoing renal transplantation are very encouraging, novel immunohistochemical markers must be also developed and combined with new technologies for the diagnosis of human renal allograft rejection.

  4. Peer Rejection in Middle School: Subgroup Differences in Behavior, Loneliness, and Interpersonal Concerns.

    ERIC Educational Resources Information Center

    Parkhurst, Jennifer T.; Asher, Steven R.

    1992-01-01

    Studied patterns of behavior and emotional response associated with peer rejection in early adolescence. Obtained data on seventh and eighth graders' loneliness, social dissatisfaction, and concerns. The combination of aggressiveness and submissiveness with low levels of prosocial behavior was associated with peer rejection. (GLR)

  5. The relation between schizotypy and early attention to rejecting interactions: The influence of neuroticism

    PubMed Central

    Premkumar, Preethi; Onwumere, Juliana; Albert, Jacobo; Kessel, Dominique; Kumari, Veena; Kuipers, Elizabeth; Carretié, Luis

    2015-01-01

    Abstract Objectives: Schizotypy relates to rejection sensitivity (anxiety reflecting an expectancy of social exclusion) and neuroticism (excessive evaluation of negative emotions). Positive schizotypy (e.g., perceptual aberrations and odd beliefs) and negative schizotypy (e.g., social and physical anhedonia) could relate to altered attention to rejection because of neuroticism. Methods: Forty-one healthy individuals were assessed on positive and negative schizotypy and neuroticism, and event-related potentials during rejecting, accepting and neutral scenes. Participants were categorised into high, moderate and low neuroticism groups. Using temporo-spatial principal components analyses, P200 (peak latency =290 ms) and P300 amplitudes (peak latency = 390 ms) were measured, reflecting mobilisation of attention and early attention, respectively. Results: Scalp-level and cortical source analysis revealed elevated fronto-parietal N300/P300 amplitude and P200-related dorsal anterior cingulate current density during rejection than acceptance/neutral scenes. Positive schizotypy related inversely to parietal P200 amplitude during rejection. Negative schizotypy related positively to P200 middle occipital current density. Negative schizotypy related positively to parietal P300, where the association was stronger in high and moderate, than low, neuroticism groups. Conclusions: Positive and negative schizotypy relate divergently to attention to rejection. Positive schizotypy attenuates, but negative schizotypy increases rejection-related mobilisation of attention. Negative schizotypy increases early attention to rejection partly due to elevated neuroticism. PMID:26452584

  6. 40 CFR 86.322-79 - NDIR CO2 rejection ratio check.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 19 2012-07-01 2012-07-01 false NDIR CO2 rejection ratio check. 86.322....322-79 NDIR CO2 rejection ratio check. (a) Zero and span the analyzer on the lowest range that will be used. (b) Introduce a CO2 calibration gas of at least 10 percent CO2 or greater to the analyzer....

  7. Mutual Best Friendship Involvement, Best Friends' Rejection Sensitivity, and Psychological Maladaptation

    ERIC Educational Resources Information Center

    Bowker, Julie C.; Thomas, Katelyn K.; Norman, Kelly E.; Spencer, Sarah V.

    2011-01-01

    Rejection sensitivity (RS) refers to the tendency to anxiously expect, readily perceive, and overreact to experiences of possible rejection. RS is a clear risk factor for psychological maladaptation during early adolescence. However, there is growing evidence of significant heterogeneity in the psychological correlates of RS. To investigate when…

  8. Total lymphoid irradiation in heart transplantation: Adjunctive treatment for recurrent rejection

    SciTech Connect

    Frist, W.H.; Winterland, A.W.; Gerhardt, E.B.; Merrill, W.H.; Atkinson, J.B.; Eastburn, T.E.; Stewart, J.R.; Eisert, D.R. )

    1989-12-01

    In the face of recurrent heart transplant graft rejection refractory to all conventional immunotherapy, retransplantation is customary treatment. The case of a heart transplant recipient unsuitable for retransplantation whose recurrent rejection was successfully treated with postoperative total lymphoid irradiation is described.

  9. 40 CFR 86.321-79 - NDIR water rejection ratio check.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....321-79 NDIR water rejection ratio check. (a) Zero and span the analyzer on the lowest range that will be used. (b) Introduce a saturated mixture of water and zero gas at room temperature directly to the... 40 Protection of Environment 18 2011-07-01 2011-07-01 false NDIR water rejection ratio check....

  10. 40 CFR 86.321-79 - NDIR water rejection ratio check.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....321-79 NDIR water rejection ratio check. (a) Zero and span the analyzer on the lowest range that will be used. (b) Introduce a saturated mixture of water and zero gas at room temperature directly to the... 40 Protection of Environment 19 2012-07-01 2012-07-01 false NDIR water rejection ratio check....

  11. 40 CFR 86.321-79 - NDIR water rejection ratio check.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....321-79 NDIR water rejection ratio check. (a) Zero and span the analyzer on the lowest range that will be used. (b) Introduce a saturated mixture of water and zero gas at room temperature directly to the... 40 Protection of Environment 18 2010-07-01 2010-07-01 false NDIR water rejection ratio check....

  12. 40 CFR 86.322-79 - NDIR CO2 rejection ratio check.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 18 2011-07-01 2011-07-01 false NDIR CO2 rejection ratio check. 86.322....322-79 NDIR CO2 rejection ratio check. (a) Zero and span the analyzer on the lowest range that will be used. (b) Introduce a CO2 calibration gas of at least 10 percent CO2 or greater to the analyzer....

  13. Solute rejection by porous glass membranes. I - Hyperfiltration of sodium chloride and urea feed solutions.

    NASA Technical Reports Server (NTRS)

    Ballou, E. V.; Wydeven, T.; Leban, M. I.

    1971-01-01

    Hyperfiltration of sodium chloride and urea was studied with porous glass membranes in closed-end capillary form, to determine the effect of pressure, temperature, and concentration variations, and lifetime rejection and flux characteristics. Rejection data for sodium chloride were consistent with the functioning of the porous glass as a low-capacity ion-exchange membrane.

  14. Flirtation Rejection Strategies: Toward an Understanding of Communicative Disinterest in Flirting

    ERIC Educational Resources Information Center

    Goodboy, Alan K.; Brann, Maria

    2010-01-01

    Single adults often seek successful flirtatious encounters; yet these encounters can sometimes be considered failures. However, little research has identified flirtation rejection strategies enacted by those not interested in reciprocal flirting. The purpose of this study was to examine behavioral and verbal flirtation rejection strategies among…

  15. The costs of avian brood parasitism explain variation in egg rejection behaviour in hosts.

    PubMed

    Medina, Iliana; Langmore, Naomi E

    2015-07-01

    Many bird species can reject foreign eggs from their nests. This behaviour is thought to have evolved in response to brood parasites, birds that lay their eggs in the nest of other species. However, not all hosts of brood parasites evict parasitic eggs. In this study, we collate data from egg rejection experiments on 198 species, and perform comparative analyses to understand the conditions under which egg rejection evolves. We found evidence, we believe for the first time in a large-scale comparative analysis, that (i) non-current host species have rejection rates as high as current hosts, (ii) egg rejection is more likely to evolve when the parasite is relatively large compared with its host and (iii) egg rejection is more likely to evolve when the parasite chick evicts all the host eggs from the nest, such as in cuckoos. Our results suggest that the interactions between brood parasites and their hosts have driven the evolution of egg rejection and that variation in the costs inflicted by parasites is fundamental to explaining why only some host species evolve egg rejection.

  16. Graphene Ambipolar Nanoelectronics for High Noise Rejection Amplification.

    PubMed

    Liu, Che-Hung; Chen, Qi; Liu, Chang-Hua; Zhong, Zhaohui

    2016-02-10

    In a modern wireless communication system, signal amplification is critical for overcoming losses during multiple data transformations/processes and long-distance transmission. Common mode and differential mode are two fundamental amplification mechanisms, and they utilize totally different circuit configurations. In this paper, we report a new type of dual-gate graphene ambipolar device with capability of operating under both common and differential modes to realize signal amplification. The signal goes through two stages of modulation where the phase of signal can be individually modulated to be either in-phase or out-of-phase at two stages by exploiting the ambipolarity of graphene. As a result, both common and differential mode amplifications can be achieved within one single device, which is not possible in the conventional circuit configuration. In addition, a common-mode rejection ratio as high as 80 dB can be achieved, making it possible for low noise circuit application. These results open up new directions of graphene-based ambipolar electronics that greatly simplify the RF circuit complexity and the design of multifunction device operation. PMID:26808093

  17. Controlling incipient oxidation of pyrite for improved rejection. Final report

    SciTech Connect

    Yoon, R.H.; Richardson, P.E.; Tao, D.P.

    1996-04-01

    It is well known that superficial oxidation of pyrite produces a hydrophobic sulfur-rich surface and creates problems in separating the mineral from coal using surface-based processes such as flotation and agglomeration. Numerous studies of pyrite oxidation have been conducted but most of them were concerned with the advanced stages of oxidation, and as a result it was not possible to establish a relationship between oxidation and flotation behavior. A better understanding of the mechanisms and kinetics of the incipient oxidation reactions, which may vary with the origin, morphology, texture, and solid state properties of pyrite, can lead to the development of new processes that can improve pyrite rejection from coal. This project is aimed at better understanding of the mechanisms involved during the initial stages of pyrite oxidation to foster the development of advanced coal cleaning technologies. Studies were conducted by fracturing pyrite electrodes in-situ in an electrochemical cell to create virgin surfaces. Electrochemical and photoelectrochemical techniques were employed to characterize the incipient oxidation of pyrite in aqueous solutions. Microflotation tests were conducted to obtain information on the hydrophobicity of pyrite under controlled E{sub h} and pH conditions, and the results were correlated with electrochemical studies.

  18. Why did Kant reject physiological explanations in his anthropology?

    PubMed

    Sturm, Thomas

    2008-12-01

    One of Kant's central tenets concerning the human sciences is the claim that one need not, and should not, use a physiological vocabulary if one studies human cognitions, feelings, desires, and actions from the point of view of his 'pragmatic' anthropology. The claim is well known, but the arguments Kant advances for it have not been closely discussed. I argue against misguided interpretations of the claim, and I present his actual reasons in favor of it. Contemporary critics of a 'physiological anthropology' reject physiological explanations of mental states as more or less epistemologically dubious. Kant does not favor such ignorance claims--and this is for the good, since none of these claims was sufficiently justified at that time. Instead, he develops an original irrelevance thesis concerning the empirical knowledge of the physiological basis of the mind. His arguments for this claim derive from his original and, up to now, little understood criticism of a certain conception of pragmatic history, related to his anthropological insights concerning our ability to create new rules of action, the social dynamics of human action, and the relative inconstancy of human nature. The irrelevance thesis also changes his views of the goal and methodology of anthropology. Kant thereby argues for a distinctive approach in quest for a general 'science of man'. PMID:19391367

  19. Sliding seal materials for low heat rejection engines

    NASA Technical Reports Server (NTRS)

    Beaty, Kevin; Lankford, James; Vinyard, Shannon

    1989-01-01

    Sliding friction coefficients and wear rates of promising piston seal materials were measured under temperature, environmental, velocity, and loading conditions that are representative of the low heat rejection (LHR) diesel engine environment. These materials included carbides, oxides, and nitrides. In addition, silicon nitride and partially stablized zirconia disks (cylinder liners) were ion-implanted with TiNi, Ni, Co, and Cr, and subsequently run against carbide pins (piston rings), with the objective of producing reduced friction via solid lubrication at elevated temperature. Friction and wear measurements were obtained using pin-on-disk laboratory experiments and a unique engine friction test rig. Unmodified ceramic sliding couples were characterized at all temperatures by friction coefficients of 0.24 and above during the pin-on-disk tests. The coefficient at 800 C in an oxidizing environment was reduced to below 0.1, for certain material combination, by the ion-implantation of TiNi or Co. This beneficial effect was found to derive from the lubricious Ti, Ni, and Co oxides. Similar results were demonstrated on the engine friction test rig at lower temperatures. The structural integrity and feasibility of engine application with the most promising material combination were demonstrated during a 30-hour single-cylinder, direct-injection diesel engine test.

  20. Immunocompetent cells requisite for graft rejection in Lineus (Invertebrata, Nemertea).

    PubMed

    Langlet, C; Bierne, J

    1984-01-01

    Antecerebral ends from donors of one Lineus species (L. sanguineus) were grafted onto bispecific recipients previously constructed from two other Lineus species (denoted L. ruber----L. lacteus because the anterior component of chimeras was from L. ruber and the posterior component was from L. lacteus) and onto monospecific controls. Histological examination of areas where the tissues from L. sanguineus and L. ruber had been brought into contact by grafting always showed, at early stages, (6 to 20 days postgrafting), a great deal of difference depending upon whether the recipients were monospecific L. ruber or bispecific L. ruber----L. lacteus: only in grafts onto the former was there lysis of gland cells, connective tissue, muscular fibers, and finally epidermis. We attribute this lytic process to a strongly and rapidly cytotoxic action of lymphocyte-like cells from the L. ruber intestinal segment and the absence of lysis during the same stage in grafts onto composite recipients and monospecific L. lacteus to weak, delayed actions of immunocytes from the L. lacteus intestinal segment. Subsequent phagocytosis of material from lysed cell of grafts in the process of being rejected was effected by wandering amebocytes usually involved in destruction of degenerating "self" components, as in oosorption and resorptive processes after fasting. This work supports the existence of immunocytes at an early phylogenetic level.