[The relationship between acute rejection and expression of sCD30 for the patients after kidney transplantation].

PubMed

Yang, Jian-Lin; Hao, Hong-Jun; Qin, Bin; Bang, Ling-Qing; Zhang, Zhi-Hong; Xin, Dian-Qi; Guo, Ying-Lu; Na, Yan-Qun

2005-03-16

To study the relationship between the sCD30 and acute rejection. We tested the sCD30 level in serum for 58 cases with kidney transplantation before and the 7th day and 28th day after operation by ELISA. 31 healthy individual for control group, and simultaneously recorded the incidence of rejection after kidney transplantation. The results showed that there is an obviously relation before kidney transplantation between the sCD30 level in serum and the incidence of acute rejection (chi = 4.843, P = 0.028, P < 0.05). There is a significantly relation at the 7th day after kidney transplantation between the sCD30 level in serum and the incidence of acute rejection (chi = 7.201, P = 0.007, P < 0.01). There is no obviously relation at 28th day after kidney transplantation between the sCD30 level in serum and the incidence of acute rejection (chi = 2.095, P = 0.148, P > 0.05). The results suggested that the expressions of sCD30 are related to acute rejection. We speculated that the expressions of sCD30 could play an important role in acute rejection.

HILDA/LIF urinary excretion during acute kidney rejection.

PubMed

Taupin, J L; Morel, D; Moreau, J F; Gualde, N; Potaux, L; Bezian, J H

1992-03-01

Recently, a new lymphokine called HILDA (human interleukin for DA cells) has been described and cloned. This cytokine, initially described to be produced by alloreactive T lymphocyte clones grown from a rejected human kidney allograft, is identical to other factors termed D-factor, differentiation-inducing factor, differentiation inhibitory activity, hepatocyte-stimulating factor III, and leukemia inhibitory factor. HILDA/LIF induces various effects on neural, hemopoietic, embryonic cells as well as on bone remodeling and acute phase protein synthesis in hepatocyte. In this study we demonstrate the presence of HILDA/LIF in the urine but not in the serum of kidney graft recipients during acute rejection episodes, whereas this lymphokine was detectable neither in the serum nor in the urine of kidney transplanted patients with stable renal function. These data reinforce the notion of a possible role for this lymphokine in the inflammatory and/or the immune response.

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

PubMed

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

2018-04-01

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

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

PubMed

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

2008-02-01

To study the value of detection of both preoperative soluble CD30 (sCD30) and hepatocyte growth factor (HGF) level 5 days after transplantation in the diagnosis of acute rejection of renal allograft. Preoperative serum sCD30 levels and HGF level 5 days after transplantation were determined in 65 renal-transplant recipients using enzyme-linked immunosorbent assay. The recipients were divided according to the sCD30 levels positivity. Receiver operating characteristic (ROC) curves were used to assess the value of HGF level on day 5 posttransplantation for diagnosis of acute renal allograft rejection, and the value of combined assay of the sCD30 and HGF levels was also estimated. After transplantation, 26 recipients developed graft rejection and 39 had uneventful recovery without rejection. With the cut-off value of sCD30 of 120 U/ml, the positivity rate of sCD30 was significantly higher in recipients with graft rejection than in those without (61.5% vs 17.9%, P<0.05). Recipients with acute rejection showed also significantly higher HGF levels on day 5 posttransplantation than those without rejection (P<0.05). ROC curve analysis indicated that HGF levels on day 5 posttransplantation was a good marker for diagnosis of acute renal allograft rejection, and at the cut-off value of 90 ug/L, the diagnostic sensitivity was 84.6% and specificity 76.9%. Evaluation of both the sCD30 and HGF levels significantly enhanced the diagnostic accuracy of acute graft rejection. Combined assay of serum sCD30 and HGF levels offers a useful means for diagnosis of acute renal allograft rejection.

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

PubMed

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

2015-01-01

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

CMV driven CD8(+) T-cell activation is associated with acute rejection in lung transplantation.

PubMed

Roux, Antoine; Mourin, Gisèle; Fastenackels, Solène; Almeida, Jorge R; Iglesias, Maria Candela; Boyd, Anders; Gostick, Emma; Larsen, Martin; Price, David A; Sacre, Karim; Douek, Daniel C; Autran, Brigitte; Picard, Clément; Miranda, Sandra de; Sauce, Delphine; Stern, Marc; Appay, Victor

2013-07-01

Lung transplantation is the definitive treatment for terminal respiratory disease, but the associated mortality rate is high. Acute rejection of the transplanted lung is a key determinant of adverse prognosis. Furthermore, an epidemiological relationship has been established between the occurrence of acute lung rejection and cytomegalovirus infection. However, the reasons for this association remain unclear. Here, we performed a longitudinal characterization of CMV-specific T-cell responses and immune activation status in the peripheral blood and bronchoalveolar lavage fluid of forty-four lung transplant patients. Acute rejection was associated with high levels of cellular activation in the periphery, reflecting strong CMV-specific CD8(+) T-cell activity post-transplant. Peripheral and lung CMV-specific CD8(+) T-cell responses were very similar, and related to the presence of CMV in the transplanted organ. These findings support that activated CMV-specific CD8(+) T-cells in the lung may play a role in promoting acute rejection. Copyright © 2013 Elsevier Inc. All rights reserved.

Acute Rejection Increases Risk of Graft Failure and Death in Recent Liver Transplant Recipients.

PubMed

Levitsky, Josh; Goldberg, David; Smith, Abigail R; Mansfield, Sarah A; Gillespie, Brenda W; Merion, Robert M; Lok, Anna S F; Levy, Gary; Kulik, Laura; Abecassis, Michael; Shaked, Abraham

2017-04-01

Acute rejection is detrimental to most transplanted solid organs, but is considered to be less of a consequence for transplanted livers. We evaluated risk factors for and outcomes after biopsy-proven acute rejection (BPAR) based on an analysis of a more recent national sample of recipients of liver transplants from living and deceased donors. We analyzed data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) from 2003 through 2014 as the exploratory cohort and the Scientific Registry of Transplant Recipients (SRTR) from 2005 through 2013 as the validation cohort. We examined factors associated with time to first BPAR using multivariable Cox regression or discrete-survival analysis. Competing risks methods were used to compare causes of death and graft failure between recipients of living and deceased donors. At least 1 BPAR episode occurred in 239 of 890 recipients in A2ALL (26.9%) and 7066 of 45,423 recipients in SRTR (15.6%). In each database, risk of rejection was significantly lower when livers came from biologically related living donors (A2ALL hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.43-0.76; and SRTR HR, 0.78; 95% CI, 0.66-0.91) and higher in liver transplant recipients with primary biliary cirrhosis, of younger age, or with hepatitis C. In each database, BPAR was associated with significantly higher risks of graft failure and death. The risks were highest in the 12 month post-BPAR period in patients whose first episode occurred more than 1 year after liver transplantation: HRs for graft failure were 6.79 in A2ALL (95% CI, 2.64-17.45) and 4.41 in SRTR (95% CI, 3.71-5.23); HRs for death were 8.81 in A2ALL (95% CI, 3.37-23.04) and 3.94 in SRTR (95% CI, 3.22-4.83). In analyses of cause-specific mortality, associations were observed for liver-related (graft failure) causes of death but not for other causes. Contrary to previous data, acute rejection after liver transplant is associated with significantly increased

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Xiaoyou; Dong, Changgui; Jiang, Zhengyao

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, andmore » 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.« less

Altered Exosomal RNA Profiles in Bronchoalveolar Lavage from Lung Transplants with Acute Rejection.

PubMed

Gregson, Aric L; Hoji, Aki; Injean, Patil; Poynter, Steven T; Briones, Claudia; Palchevskiy, Vyacheslav; Weigt, S Sam; Shino, Michael Y; Derhovanessian, Ariss; Sayah, David; Saggar, Rajan; Ross, David; Ardehali, Abbas; Lynch, Joseph P; Belperio, John A

2015-12-15

The mechanism by which acute allograft rejection leads to chronic rejection remains poorly understood despite its common occurrence. Exosomes, membrane vesicles released from cells within the lung allograft, contain a diverse array of biomolecules that closely reflect the biologic state of the cell and tissue from which they are released. Exosome transcriptomes may provide a better understanding of the rejection process. Furthermore, biomarkers originating from this transcriptome could provide timely and sensitive detection of acute cellular rejection (AR), reducing the incidence of severe AR and chronic lung allograft dysfunction and improving outcomes. To provide an in-depth analysis of the bronchoalveolar lavage fluid exosomal shuttle RNA population after lung transplantation and evaluate for differential expression between acute AR and quiescence. Serial bronchoalveolar lavage specimens were ultracentrifuged to obtain the exosomal pellet for RNA extraction, on which RNA-Seq was performed. AR demonstrates an intense inflammatory environment, skewed toward both innate and adaptive immune responses. Novel, potential upstream regulators identified offer potential therapeutic targets. Our findings validate bronchoalveolar lavage fluid exosomal shuttle RNA as a source for understanding the pathophysiology of AR and for biomarker discovery in lung transplantation.

Altered Exosomal RNA Profiles in Bronchoalveolar Lavage from Lung Transplants with Acute Rejection

PubMed Central

Hoji, Aki; Injean, Patil; Poynter, Steven T.; Briones, Claudia; Palchevskiy, Vyacheslav; Sam Weigt, S.; Shino, Michael Y.; Derhovanessian, Ariss; Saggar, Rajan; Ross, David; Ardehali, Abbas; Lynch, Joseph P.; Belperio, John A.

2015-01-01

Rationale: The mechanism by which acute allograft rejection leads to chronic rejection remains poorly understood despite its common occurrence. Exosomes, membrane vesicles released from cells within the lung allograft, contain a diverse array of biomolecules that closely reflect the biologic state of the cell and tissue from which they are released. Exosome transcriptomes may provide a better understanding of the rejection process. Furthermore, biomarkers originating from this transcriptome could provide timely and sensitive detection of acute cellular rejection (AR), reducing the incidence of severe AR and chronic lung allograft dysfunction and improving outcomes. Objectives: To provide an in-depth analysis of the bronchoalveolar lavage fluid exosomal shuttle RNA population after lung transplantation and evaluate for differential expression between acute AR and quiescence. Methods: Serial bronchoalveolar lavage specimens were ultracentrifuged to obtain the exosomal pellet for RNA extraction, on which RNA-Seq was performed. Measurements and Main Results: AR demonstrates an intense inflammatory environment, skewed toward both innate and adaptive immune responses. Novel, potential upstream regulators identified offer potential therapeutic targets. Conclusions: Our findings validate bronchoalveolar lavage fluid exosomal shuttle RNA as a source for understanding the pathophysiology of AR and for biomarker discovery in lung transplantation. PMID:26308930

"Snowmelt Sign" and "Corkscrew Microvessels" Predicting Epithelium Regeneration After Acute Rejection of Small-Bowel Transplantation: A Case Report.

PubMed

Chung, C-S; Lee, T-H; Chiu, C-T; Chen, Y

2017-12-01

Intestinal failure characterized by inadequate maintenance of nutrition via normal intestinal function comprises a group of disorders with many different causes. If parenteral nutrition dependency develops, which is associated with higher mortality and complications, it is considered for intestine transplantation. However, the graft failure rate is not low, and acute cellular rejection is one of the most important reasons for graft failure. As a result, early identification of rejection and timely modification of anti-rejection medications have been considered to be associated with better graft and patient survival rates. The diagnostic gold standard for rejection is mainly based on histology, but hours of delay by pathology may occur. Some researchers investigated the association of endoscopic images with graft rejection to provide timely diagnosis. In this study, we present the first case report with characteristic features under magnifying endoscopy with a narrow-band imaging system to predict epithelial regeneration and improvement of graft rejection in a patient with small-bowel transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

Eotaxin/CCL11 expression by infiltrating macrophages in rat heart transplants during ongoing acute rejection.

PubMed

Zweifel, Martin; Mueller, Christoph; Schaffner, Thomas; Dahinden, Clemens; Matozan, Katja; Driscoll, Robert; Mohacsi, Paul

2009-10-01

Eotaxin/CCL11 chemokine is expressed in different organs, including the heart, but its precise cellular origin in the heart is unknown. Eotaxin is associated with Th2-like responses and exerts its chemotactic effect through the chemokine receptor-3 (CCR3), which is also expressed on mast cells (MC). The aim of our study was to find the cellular origin of eotaxin in the heart, and to assess whether expression is changing during ongoing acute heart transplant rejection, indicating a correlation with mast cell infiltration which we observed in a previous study. In a model of ongoing acute heart transplant rejection in the rat, we found eotaxin mRNA expression within infiltrating macrophages, but not in mast cells, by in situ-hybridization. A five-fold increase in eotaxin protein in rat heart transplants during ongoing acute rejection was measured on day 28 after transplantation, compared to native and isogeneic control hearts. Eotaxin concentrations in donor hearts on day 28 after transplantation were significantly higher compared to recipient hearts, corroborating an origin of eotaxin from cells within the heart, and not from the blood. The quantitative comparison of eotaxin mRNA expression between native hearts, isografts, and allografts, respectively, revealed no statistically significant difference after transplantation, probably due to an overall increase in the housekeeping gene's 18S rRNA during rejection. Quantitative RT-PCR showed an increase in mRNA expression of CCR3, the receptor for eotaxin, during ongoing acute rejection of rat heart allografts. Although a correlation between increasing eotaxin expression by macrophages and mast cell infiltration is suggestive, functional studies will elucidate the role of eotaxin in the process of ongoing acute heart transplant rejection.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1985-07-01

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

High serum soluble CD30 does not predict acute rejection in liver transplant patients.

PubMed

Matinlauri, I; Höckerstedt, K; Isoniemi, H

2006-12-01

Increased pre- and posttransplantation values of soluble CD30 (sCD30) have been shown to be associated with acute kidney transplant rejection. We sought to study whether high sCD30 could predict rejection early after liver transplantation. The study population included 54 consecutive liver transplant patients, whose samples were collected before liver transplantation and at discharge, which was at a mean time of 3 weeks after transplantation. During the first 6 months posttransplantation, 22 patients experienced an acute rejection episode. Serum sCD30 concentrations were measured by an enzyme-linked immunoassay; changes in serum sCD30 levels posttransplantation were also expressed as relative values compared with pretransplantation results. Liver patients before transplantation displayed higher serum sCD30 values compared with healthy controls: mean values +/- SD were 93 +/- 58 IU/mL vs 17 +/- 8 IU/mL, respectively. At 3 weeks after transplantation the mean sCD30 concentration in liver transplant patients decreased to 59 +/- 42 IU/mL (P = .005). The mean pretransplantation serum sCD30 value was slightly lower among rejecting vs nonrejecting patients: 78 +/- 43 IU/mL vs 104 +/- 65 IU/mL (P = NS). Posttransplantation values in both groups decreased significantly: 47 +/- 34 IU/mL in patients with rejection (P = .014) vs 69 +/- 45 IU/mL in patients without rejection (P = .012). The relative value at 3 weeks posttransplantation decreased slightly more among patients with vs without rejection (70% vs 88%; NS). No correlation was found between serum sCD30 and anti-HLA class I antibodies or crossmatch positivity. In conclusion, neither pre- nor posttransplantation sCD30 levels were associated with acute rejection in liver transplant patients.

Increased levels of circulating nitrates and impaired endothelium-mediated vasodilation suggest multiple roles of nitric oxide during acute rejection of pulmonary allografts.

PubMed

Wiklund, L; Lewis, D H; Sjöquist, P O; Nilsson, F; Tazelaar, H; Miller, V M; McGregor, C G

1997-05-01

Experiments were designed to determine whether changes in pulmonary artery function could be reduced by treatment with a lipid peroxidation inhibitor (H 290/51) during acute rejection of pulmonary allografts. Single lung transplantation was performed in three groups of dogs: group 1 was maintained on immunosuppression for 8 days after operation (immunosuppressed, n = 5); in group 2, immunosuppression was discontinued on postoperative day 5, so that rejection occurred on postoperative day 8 (rejecting, n = 6); in group 3, immunosuppression was discontinued after 5 days, and the lipid peroxidation inhibitor H 290/51 (25 mg/kg) was given perorally for 3 days (rejecting + H 290/51, n = 6). Plasma nitric oxide (NO(x)) was measured by use of chemoluminescence. On postoperative day 8 rejection was observed in groups 2 and 3. Contractions to angiotensin I and endothelium-dependent relaxations to adenosine diphosphate were reduced in pulmonary arteries from rejecting lungs. Responses of rings from dogs treated with H 290/51 were similar to those from rejecting lungs. Rejection did not alter relaxations to exogenous nitric oxide. However, plasma levels of NO(x) increased significantly during rejection independently of treatment with H 290/51. Results of this study confirm that endothelium-dependent relaxation of pulmonary arteries is reduced during acute rejection of lung allografts. The result extends these observations to suggest that treatment with a lipid peroxidation inhibitor neither protects the pulmonary artery function nor affects levels of circulating NO(x). Therefore mechanisms other than lipid peroxidation participate in vascular changes associated with allograft rejection.

Relation between pretransplant serum levels of soluble CD30 and acute rejection during the first 6 months after a kidney transplant.

PubMed

Shooshtarizadeh, Tina; Mohammadali, Ali; Ossareh, Shahrzad; Ataipour, Yousef

2013-06-01

The immunologic status of kidney allograft recipients affects transplant outcome. High levels of pretransplant serum soluble CD30 correlate with an increased risk of acute rejection. Studies show conflicting results. We evaluated the relation between pretransplant serum sCD30 levels with the risk of posttransplant acute kidney rejection in renal transplant recipients. This prospective cohort study was performed between March 2010 and March 2011 on 77 kidney transplant recipients (53 men [68.8%], 24 women [31.2%]; mean age, 41 ± 14 y). Serum samples were collected 24 hours before transplant and analyzed for soluble CD30 levels by enzyme-linked immunosorbent assay. Patients were followed for 6 months after transplant. Acute biopsy-proven rejection episodes were recorded, serum creatinine levels were measured, and glomerular filtration rates were calculated at the first and sixth months after transplant. Preoperative serum soluble CD30 levels were compared in patients with and without rejection. The mean pretransplant serum soluble CD30 level was 92.1 ± 47.3 ng/mL. At 6 months' follow-up, 10 patients experienced acute rejection. Mean pretransplant soluble CD30 levels were 128.5 ± 84 ng/mL versus 86.7 ± 37 ng/mL in patients with and without acute rejection episodes (P = .008). At 100 ng/mL, the sensitivity, specificity, and positive and negative predictive values of pretransplant serum soluble CD30 level to predict acute rejection were 70%, 73.6%, 29.1%, and 94.3%. We showed a significant relation between pretransplant serum soluble CD30 levels and acute allograft rejection. High pretransplant levels of serum soluble CD30 can be a risk factor for kidney transplant rejection, and its high negative predictive value at various cutoffs make it useful to find candidates with a low risk of acute rejection after transplant.

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

PubMed Central

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

2015-01-01

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. PMID:25529862

Acute liver allograft antibody-mediated rejection: an inter-institutional study of significant histopathological features.

PubMed

O'Leary, Jacqueline G; Michelle Shiller, S; Bellamy, Christopher; Nalesnik, Michael A; Kaneku, Hugo; Jennings, Linda W; Isse, Kumiko; Terasaki, Paul I; Klintmalm, Göran B; Demetris, Anthony J

2014-10-01

Acute antibody-mediated rejection (AMR) occurs in a small minority of sensitized liver transplant recipients. Although histopathological characteristics have been described, specific features that could be used (1) to make a generalizable scoring system and (2) to trigger a more in-depth analysis are needed to screen for this rare but important finding. Toward this goal, we created training and validation cohorts of putative acute AMR and control cases from 3 high-volume liver transplant programs; these cases were evaluated blindly by 4 independent transplant pathologists. Evaluations of hematoxylin and eosin (H&E) sections were performed alone without knowledge of either serum donor-specific human leukocyte antigen alloantibody (DSA) results or complement component 4d (C4d) stains. Routine histopathological features that strongly correlated with severe acute AMR included portal eosinophilia, portal vein endothelial cell hypertrophy, eosinophilic central venulitis, central venulitis severity, and cholestasis. Acute AMR inversely correlated with lymphocytic venulitis and lymphocytic portal inflammation. These and other characteristics were incorporated into models created from the training cohort alone. The final acute antibody-mediated rejection score (aAMR score)--the sum of portal vein endothelial cell hypertrophy, portal eosinophilia, and eosinophilic venulitis divided by the sum of lymphocytic portal inflammation and lymphocytic venulitis--exhibited a strong correlation with severe acute AMR in the training cohort [odds ratio (OR) = 2.86, P < 0.001] and the validation cohort (OR = 2.49, P < 0.001). SPSS tree classification was used to select 2 cutoffs: one that optimized specificity at a score > 1.75 (sensitivity = 34%, specificity = 86%) and another that optimized sensitivity at a score > 1.0 (sensitivity = 81%, specificity = 71%). In conclusion, the routine histopathological features of the aAMR score can be used to

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

PubMed

Kanitakis, Jean; Morelon, Emmanuel

2017-06-01

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

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

PubMed

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

2006-06-01

To evaluate the feasibility of serum sCD30 for prediction of acute graft rejection, we analyzed clinical data of 231 patients, whose serum levels of sCD30 were detected by ELISA before and after transplantation. They were divided into three groups: acute rejection group (AR, n = 49), uncomplicated course group (UC, n = 171) and delayed graft function group (DGF, n = 11). Preoperative sCD30 levels of three groups were 183 +/- 74, 177 +/- 82 and 168 +/- 53 U/ml, respectively (P = 0.82). Significant decrease of sCD30 was detected in three groups on day 5 and 10 post-transplantation respectively (52 +/- 30 and 9 +/- 5 U/ml respectively, P < 0.001). Compared with Group UC and DGF, patients of Group AR had higher sCD30 values on day 5 post-transplantation (92 +/- 27 U/ml vs. 41 +/- 20 U/ml and 48 +/- 18 U/ml, P < 0.001). However, sCD30 levels on day 10 post-transplantation were virtually similar in patients of three groups (P = 0.43). Receiver operating characteristic (ROC) curve demonstrated that sCD30 level on day 5 post-transplantation could differentiate patients who subsequently suffered acute allograft rejection from others (area under ROC curve 0.95). According to ROC curve, 65 U/ml may be the optimal operational cut-off level to predict impending graft rejection (specificity 91.8%, sensitivity 87.1%). Measurement of soluble CD30 on day 5 post-transplantation might offer a noninvasive means to recognize patients at risk of impending acute graft rejection during early post-transplantation period.

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

PubMed

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

2006-09-01

In renal transplant recipients elevated soluble serum CD30 levels are associated with increased rejection and graft loss. We sought to determine the sCD30 plasma levels before and after kidney transplantation and to assess whether sCD30 was a predictive factor of immunological risk. sCD30 plasma levels were determined by an enzyme-linked immunosorbent assay assay in 52 kidney graft recipients before as well as 7, 15, and 21 days after transplantation. Eighteen patients developed acute allograft rejection (group I) and 34 patients showed uneventful courses (group II). Before transplantation sCD30 plasma levels were elevated in both groups (mean: 162.6 +/- 89.5 U/mL). After transplantation, group I recipients with acute rejection showed higher relative levels of plasma sCD30 on days 7 and 15 (120.8 +/- 74.6 U/mL and 210.6 +/- 108.7 U/mL respectively) compared with group II patients without rejection (95 +/- 45 U/mL and 59.4 +/- 31.6 U/mL), a difference that was significant for group I (P = .0003) and not significant for group II (P = .09). On day 21, sCD30 decreased in the two groups but remained higher among group I patients (120.6 +/- 92.7 U/mL). HLA antibodies were positive in 18 patients (34.6%) with 9 (50%) experiencing at last one episode of acute rejection. Among 34 patients negative for anti-HLA antibodies, nine displayed acute rejection only (26.4%), a difference that was not significant (P > .05). If we consider 100 U/mL as the minimum predictive level for allograft rejection, our results suggested that levels of sCD30 should be taken into consideration with the presence of HLA-antibodies detectable before and after transplantation, especially in patients with more than three HLA mismatches [RR = 3.20 (0.94 < RR < 10.91)]. These data suggested that measurement of plasma sCD30 is a useful procedure for the recognition of rejection in its earliest stages.

Maintenance of airway epithelium in acutely rejected orthotopic vascularized mouse lung transplants.

PubMed

Okazaki, Mikio; Gelman, Andrew E; Tietjens, Jeremy R; Ibricevic, Aida; Kornfeld, Christopher G; Huang, Howard J; Richardson, Steven B; Lai, Jiaming; Garbow, Joel R; Patterson, G Alexander; Krupnick, Alexander S; Brody, Steven L; Kreisel, Daniel

2007-12-01

Lung transplantation remains the only therapeutic option for many patients suffering from end-stage pulmonary disease. Long-term success after lung transplantation is severely limited by the development of bronchiolitis obliterans. The murine heterotopic tracheal transplantation model has been widely used for studies investigating pathogenesis of obliterative airway disease and immunosuppressive strategies to prevent its development. Despite its utility, this model employs proximal airway that lacks airflow and is not vascularized. We have developed a novel model of orthotopic vascularized lung transplantation in the mouse, which leads to severe vascular rejection in allogeneic strain combinations. Here we characterize differences in the fate of airway epithelial cells in nonimmunosuppressed heterotopic tracheal and vascularized lung allograft models over 28 days. Up-regulation of growth factors that are thought to be critical for the development of airway fibrosis and interstitial collagen deposition were similar in both models. However, while loss of airway epithelial cells occurred in the tracheal model, airway epithelium remained intact and fully differentiated in lung allografts, despite profound vascular rejection. Moreover, we demonstrate expression of the anti-apoptotic protein Bcl-2 in airway epithelial cells of acutely rejected lung allografts. These findings suggest that in addition to alloimmune responses, other stimuli may be required for the destruction of airway epithelial cells. Thus, the model of vascularized mouse lung transplantation may provide a new and more physiologic experimental tool to study the interaction between immune and nonimmune mechanisms affecting airway pathology in lung allografts.

Lipoxygenase products in the urine correlate with renal function and body temperature but not with acute transplant rejection.

PubMed

Reinhold, Stephan W; Scherl, Thomas; Stölcker, Benjamin; Bergler, Tobias; Hoffmann, Ute; Weingart, Christian; Banas, Miriam C; Kollins, Dmitrij; Kammerl, Martin C; Krüger, Bernd; Kaess, Bernhard; Krämer, Bernhard K; Banas, Bernhard

2013-02-01

Acute transplant rejection is the leading cause of graft loss in the first months after kidney transplantation. Lipoxygenase products mediate pro- and anti-inflammatory actions and thus we aimed to correlate the histological reports of renal transplant biopsies with urinary lipoxygenase products concentrations to evaluate their role as a diagnostic marker. This study included a total of 34 kidney transplant recipients: 17 with an acute transplant rejection and 17 controls. LTE4, LTB4, 12-HETE and 15-HETE concentrations were measured by enzyme immunoassay. Urinary lipoxygenase product concentrations were not significantly changed during an acute allograft rejection. Nevertheless, LTB4 concentrations correlated significantly with the body temperature (P ≤ 0.05) 3 months after transplantation, and 12- and 15-HETE concentrations correlated significantly with renal function (P ≤ 0.05) 2 weeks after transplantation. In conclusion, our data show a correlation for LTB4 with the body temperature 3 months after transplantation and urinary 12- and 15-HETE concentrations correlate positively with elevated serum creatinine concentrations but do not predict acute allograft rejection.

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

PubMed

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

2014-01-01

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. 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. 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. 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 be related to acute renal allograft

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

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

PubMed

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

2018-01-01

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

Acute cellular rejection with isolated v-lesions is not associated with more favorable outcomes than vascular rejection with more tubulointerstitial inflammations.

PubMed

Wu, K Y; Budde, K; Schmidt, D; Neumayer, H H; Rudolph, B

2014-04-01

The impact of isolated v-lesions on clinical outcome in biopsies with acute cellular rejection (ACR) is unclear. Two hundred and sixty-five biopsies showing the highest ACR severity for each patient were recruited and classified into four groups: (i) acute interstitial rejection (AIR) I with minimal tubulointerstitial inflammation (TI), (ii) AIR II with intensive TI, (iii) acute vascular rejection (AVR) I with minimal TI, and (iv) AVR II with intensive TI. The complete reversal rates of AIR I and AIR II groups were marginally higher than AVR I and AVR II groups (p = 0.16). At eight yr of transplantation, the death-censored graft survival (DCGS) rate of AIR I group (93.3%) was significantly higher compared with the AVR I (72.7%) or AVR II (72.9%) group. AVR I group had a similar DCGS rate with AVR II group (72.7% vs. 74.1%), whereas AVR with v1-lesion showed significantly higher graft survival (GS) rate than those with v2-lesion (70.2% vs. 45.5%). The t-lesion of AIR and v-lesion of AVR group were associated with graft loss. The extent of TI is non-specifically associated with graft loss in biopsies with AVR; the higher grade v-lesion predicts the lower complete reversal rate and poorer long-term graft survival. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed

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

2011-01-01

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

Correlation of IMPDH1 gene polymorphisms with subclinical acute rejection and mycophenolic acid exposure parameters on day 28 after renal transplantation.

PubMed

Kagaya, Hideaki; Miura, Masatomo; Saito, Mitsuru; Habuchi, Tomonori; Satoh, Shigeru

2010-08-01

The risk of acute rejection in patients with higher exposure to mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), might be due to inosine 5'-monophosphate dehydrogenase (IMPDH) polymorphisms. The correlations with subclinical acute rejection, IMPDH1 polymorphisms and MPA exposure on day 28 post-transplantation were investigated in 82 Japanese recipients. Renal transplant recipients were given combination immunosuppressive therapy consisting of tacrolimus and 1.0, 1.5 or 2.0 g/day of MMF in equally divided doses every 12 hr at designated times. There were no significant differences in the incidence of subclinical acute rejection between IMPDH1 rs2278293 or rs2278294 polymorphisms (p = 0.243 and 0.735, respectively). However, in the high MPA night-time exposure range (AUC > 60 microg x h/ml and C(0 )> or = 1.9 microg/ml), there was a significant difference in the incidence of subclinical acute rejection between IMPDH1 rs2278293 A/A, A/G and G/G genotypes (each p = 0.019), but not the IMPDH1 rs2278294 genotype. In the higher daytime MPA exposure range, patients with the IMPDH1 rs2278293 G/G genotype also tended to develop subclinical acute rejection. In patients with the IMPDH rs2278293 A/A genotype, the risk of subclinical acute rejection episode tends to be low and the administration of MMF was effective. The risk of subclinical acute rejection for recipients who cannot adapt in therapeutic drug monitoring (TDM) of MPA seems to be influenced by IMPDH1 rs2278293 polymorphism. The prospective analysis of IMPDH1 rs2278293 polymorphism as well as monitoring of MPA plasma concentration after transplantation might help to improve MMF therapy.

Urine protein profiling identified alpha-1-microglobulin and haptoglobin as biomarkers for early diagnosis of acute allograft rejection following kidney transplantation.

PubMed

Stubendorff, Beatrice; Finke, Stephanie; Walter, Martina; Kniemeyer, Olaf; von Eggeling, Ferdinand; Gruschwitz, Torsten; Steiner, Thomas; Ott, Undine; Wolf, Gunter; Wunderlich, Heiko; Junker, Kerstin

2014-12-01

Early diagnosis of acute rejection and effective immunosuppressive therapy lead to improvement in graft survival following kidney transplantation. In this study, we aimed to establish a urinary protein profile suitable to distinguish between patients with rejection and stable graft function and to predict acute rejection based on postoperatively collected urine samples. A further objective was to identify candidate proteins for the use as biomarkers in clinical practice. Urine samples of 116 kidney recipients were included. Rejection was proven by biopsy (n = 58), and stable transplant function was monitored for at least 2 years (n = 58). Postoperative urine samples were collected between 3rd and 10th day following transplantation. Urinary protein profiles were obtained by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Protein identification and validation were performed using multiplex fluorescence 2DE, peptide mass fingerprinting and enzyme-linked immunosorbent assay. A protein profile including four mass peaks differentiated acute rejection from stable transplants at the time point of rejection and at the postoperative state with 73 % sensitivity and 88 % specificity. Alpha-1-microglobulin (A1MG) and Haptoglobin (Hp) were identified as putative rejection biomarkers. Protein levels were significantly higher in postoperative urine from patients with rejection (A1MG 29.13 vs. 22.06 μg/ml, p = 0.001; Hp 628.34 vs. 248.57 ng/ml, p = 0.003). The combination of both proteins enabled the diagnosis of early rejection with 85 % sensitivity and 80 % specificity. Protein profiling using mass spectrometry is suitable for noninvasive detection of rejection-specific changes following kidney transplantation. A specific protein profile enables the prediction of early acute allograft rejection in the immediate postoperative period. A1MG and Hp appear to be reliable rejection biomarkers.

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

PubMed

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

2017-01-01

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

Bone marrow mesenchymal stromal cells protect allograft lung transplants from acute rejection via the PD-L1/IL-17A axis.

PubMed

Ishibashi, Naoya; Watanabe, Tatsuaki; Kanehira, Masahiko; Watanabe, Yui; Hoshikawa, Yasushi; Notsuda, Hirotsugu; Noda, Masafumi; Sakurada, Akira; Ohkouchi, Shinya; Kondo, Takashi; Okada, Yoshinori

2018-03-15

Using a rat model of allograft lung transplantation, we investigated the effectiveness of mesenchymal stromal cells (MSCs) as prophylactic and therapeutic agents against the acute rejection of lung grafts. Lung grafts were harvested from donor rats and transplanted orthotopically into major histocompatibility complex-mismatched rats. MSCs were administered to the recipients once (on day 0) or twice (on days 0 and 3) after transplantation. The grade of acute rejection was evaluated both macroscopically and microscopically 6 days after transplantation. To elucidate the related mechanism, mRNA levels of inflammatory cytokines and immunomodulatory receptors in the transplanted grafts were measured using quantitative RT-PCR. The lung graft tissue from the rats that received MSCs post-surgically was protected from acute rejection significantly better than that from the untreated controls. Notably, the rats administered MSCs twice after surgery exhibited the least signs of rejection, with a markedly upregulated mRNA level of PD-L1 and a downregulated mRNA level of IL-17A. This study assessed MSC protection of lung allografts from acute rejection by modulating T cell activity via enforced expression of PD-L1 in transplants and downregulation of IL-17A.

Anti-IL-17 therapy restricts and reverses late-term corneal allo-rejection

PubMed Central

Yin, Xiao-Tang; Zobell, Stephanie; Jarosz, Jason G.; Stuart, Patrick M.

2015-01-01

Corneal allograft rejection has been described as a Th1-mediated process involving IFN-γ production. However, recent evidence has also implicated IL-17 as being involved during acute corneal allograft responses. Our data supports those that maintain that IL-17 is involved in early acute corneal allograft acceptance. However, we decided to extend these studies to include a later phase of rejection in which there is a peak of IL-17 production that is >15 fold higher than seen during acute rejection that occurs >45 days post-engraftment at the onset of late-term rejection. We demonstrate that neutralizing IL-17A at this time significantly reduced corneal graft rejection. Surprisingly, when corneal grafts that are undergoing this later phase of rejection are treated with anti-IL17A there is a reversal of both opacity and neovascularization. When compared to the early phase of rejection, the cellular infiltrate is significantly less with a greatly reduced presence of Gr-1+ neutrophils with a relative increase in CD4+ T cells and macrophages. We went on to identify that the cells expressing IL-17 were CD4+ IL-17+ T cells and somewhat surprisingly, IL-17+ F4/80+ macrophages within the rejecting corneal allografts. Taken together, these findings describe a distinct late phase of corneal allograft rejection which is likely mediated by Th17 cells and that therapeutic neutralization of IL-17A reverses this rejection. This further suggests that IL-17 might serve as an excellent therapeutic target to reduce this form of corneal allograft rejection. PMID:25754737

Proteomic signatures in plasma during early acute renal allograft rejection.

PubMed

Freue, Gabriela V Cohen; Sasaki, Mayu; Meredith, Anna; Günther, Oliver P; Bergman, Axel; Takhar, Mandeep; Mui, Alice; Balshaw, Robert F; Ng, Raymond T; Opushneva, Nina; Hollander, Zsuzsanna; Li, Guiyun; Borchers, Christoph H; Wilson-McManus, Janet; McManus, Bruce M; Keown, Paul A; McMaster, W Robert

2010-09-01

Acute graft rejection is an important clinical problem in renal transplantation and an adverse predictor for long term graft survival. Plasma biomarkers may offer an important option for post-transplant monitoring and permit timely and effective therapeutic intervention to minimize graft damage. This case-control discovery study (n = 32) used isobaric tagging for relative and absolute protein quantification (iTRAQ) technology to quantitate plasma protein relative concentrations in precise cohorts of patients with and without biopsy-confirmed acute rejection (BCAR). Plasma samples were depleted of the 14 most abundant plasma proteins to enhance detection sensitivity. A total of 18 plasma proteins that encompassed processes related to inflammation, complement activation, blood coagulation, and wound repair exhibited significantly different relative concentrations between patient cohorts with and without BCAR (p value <0.05). Twelve proteins with a fold-change >or=1.15 were selected for diagnostic purposes: seven were increased (titin, lipopolysaccharide-binding protein, peptidase inhibitor 16, complement factor D, mannose-binding lectin, protein Z-dependent protease and beta(2)-microglobulin) and five were decreased (kininogen-1, afamin, serine protease inhibitor, phosphatidylcholine-sterol acyltransferase, and sex hormone-binding globulin) in patients with BCAR. The first three principal components of these proteins showed clear separation of cohorts with and without BCAR. Performance improved with the inclusion of sequential proteins, reaching a primary asymptote after the first three (titin, kininogen-1, and lipopolysaccharide-binding protein). Longitudinal monitoring over the first 3 months post-transplant based on ratios of these three proteins showed clear discrimination between the two patient cohorts at time of rejection. The score then declined to baseline following treatment and resolution of the rejection episode and remained comparable between cases and

Proteomic Signatures in Plasma during Early Acute Renal Allograft Rejection*

PubMed Central

Freue, Gabriela V. Cohen; Sasaki, Mayu; Meredith, Anna; Günther, Oliver P.; Bergman, Axel; Takhar, Mandeep; Mui, Alice; Balshaw, Robert F.; Ng, Raymond T.; Opushneva, Nina; Hollander, Zsuzsanna; Li, Guiyun; Borchers, Christoph H.; Wilson-McManus, Janet; McManus, Bruce M.; Keown, Paul A.; McMaster, W. Robert

2010-01-01

Acute graft rejection is an important clinical problem in renal transplantation and an adverse predictor for long term graft survival. Plasma biomarkers may offer an important option for post-transplant monitoring and permit timely and effective therapeutic intervention to minimize graft damage. This case-control discovery study (n = 32) used isobaric tagging for relative and absolute protein quantification (iTRAQ) technology to quantitate plasma protein relative concentrations in precise cohorts of patients with and without biopsy-confirmed acute rejection (BCAR). Plasma samples were depleted of the 14 most abundant plasma proteins to enhance detection sensitivity. A total of 18 plasma proteins that encompassed processes related to inflammation, complement activation, blood coagulation, and wound repair exhibited significantly different relative concentrations between patient cohorts with and without BCAR (p value <0.05). Twelve proteins with a fold-change ≥1.15 were selected for diagnostic purposes: seven were increased (titin, lipopolysaccharide-binding protein, peptidase inhibitor 16, complement factor D, mannose-binding lectin, protein Z-dependent protease and β2-microglobulin) and five were decreased (kininogen-1, afamin, serine protease inhibitor, phosphatidylcholine-sterol acyltransferase, and sex hormone-binding globulin) in patients with BCAR. The first three principal components of these proteins showed clear separation of cohorts with and without BCAR. Performance improved with the inclusion of sequential proteins, reaching a primary asymptote after the first three (titin, kininogen-1, and lipopolysaccharide-binding protein). Longitudinal monitoring over the first 3 months post-transplant based on ratios of these three proteins showed clear discrimination between the two patient cohorts at time of rejection. The score then declined to baseline following treatment and resolution of the rejection episode and remained comparable between cases and

Structural shifts of fecal microbial communities in rats with acute rejection after liver transplantation.

PubMed

Xie, Yirui; Luo, Zhuanbo; Li, Zhengfeng; Deng, Min; Liu, Hao; Zhu, Biao; Ruan, Bing; Li, Lanjuan

2012-08-01

Bacterial translocation and the development of sepsis after orthotopic liver transplantation (OLT) may be promoted by immunological damage to the intestinal mucosa or by quantitative and qualitative changes in intestinal microbiota. This study monitored structural shifts of gut microbiota in rats with OLT using PCR-denaturing gradient gel electrophoresis (DGGE) and real-time quantitative PCR (RT-qPCR). RT-qPCR targets six major microorganisms (Domain Bacteria, Bacteroides, Bifidobacteria, Enterobacteriaceae, Lactobacillus and Clostridium leptum subgroup). Isograft, Allograft and Sham model were studied. Bacterial translocation to host organs and plasma endotoxin were determined. Alteration in gut microbiota was associated with the elevation of plasma endotoxin and a higher rate of bacterial translocation (BT) to liver in rats with acute rejection. Dynamic analysis of DGGE fingerprints showed that the gut microbiota structure of animals in the three groups was similar before the operation. But significant alterations in the composition of fecal microbiota in Allograft group were observed at 1 and 2 weeks after the OLT. The acute rejection was accompanied by the shifts of gut microbiota towards members of Bacteroides and Ruminococcus. Results from RT-qPCR indicated that Bacteroides significantly increased at 2 weeks after the OLT, whereas numbers of Bifidobacterium spp. decreased at 1 week and recovered at 2 weeks after the OLT. In summary, our data showed that rats with acute rejection after OLT exhibited significant structure shifts in the gut microbiota which dominant by overgrowth of Bacteroides and Ruminococcus, and these were associated with elevation of plasma endotoxin and higher rate of BT.

C4d-the witness of humoral rejection.

PubMed

de Gouveia, R H; Vitorino, E; Ramos, S; Rebocho, M J; Queirós E Melo, J; Martins, A P; Moura, M L C

2009-04-01

Acute antibody-mediated (humoral) rejection is a major cause of morbidity, graft loss, and mortality among heart transplant patients. Herein we have presented our experience using C4d to characterize humoral rejection. All nonformalin-fixed cardiac graft biopsies (protocol or emergency) received between May 2007 and May 2008 were examined by immunofluorescence for C4d. One hundred twelve endomyocardial biopsies from 25 transplanted patients included 20 males and 5 females of ages ranging from 3 to 71 years. The number of biopsies per subject varied from 1 to 11; the timespan between transplantation and the diagnostic biopsies ranged from days to 8 years. Thirteen biopsies showed acute humoral rejection (intramyocardial capillaries positive for C4d); 31, acute cellular rejection (grades 1R, 2R); 7, both humoral and cellular rejection; and 1, acute humoral rejection and allograft vasculopathy. Some of the positive biopsies belonged to the same person, and some to transplanted individuals with signs and symptoms suggestive of rejection, while others did not. The persistence of humoral rejection, despite the disappearance of a cellular component, correlated with slower clinicoechocardiographic improvement. C4d positivity is a morphologic sign of humoral rejection. It may hasten the appearance and/or worsening of allograft vasculopathy independent of patient age or posttransplantation time.

Pre-transplant and post-transplant soluble CD30 for prediction and diagnosis of acute kidney allograft rejection.

PubMed

Nafar, Mohsen; Farrokhi, Farhat; Vaezi, Mohammad; Entezari, Amir-Ebrahim; Pour-Reza-Gholi, Fatemeh; Firoozan, Ahmad; Eniollahi, Behzad

2009-01-01

Serum levels of soluble CD30 (sCD30) have been considered as a predictor of acute kidney allograft rejection. We have evaluated the pre-transplant and post-transplant levels of sCD30 with the aim of determining its value in predicting and diagnosing kidney rejection. We measured sCD30 serum levels before kidney transplantation, 5 days post-operatively, and at creatinine elevation episodes. The predictive value of sCD30 for diagnosing acute rejection (AR) within the first 6 post-operative months was assessed in 203 kidney recipients from living donors. Pre-transplant and post-operative levels of serum sCD30 were 58.10 +/- 52.55 and 51.55 +/- 49.65 U/ml, respectively (P = 0.12). Twenty-three patients experienced biopsy-proven acute rejection, and 28 had acute allograft dysfunction due to non-immunologic diseases. The pre-transplant sCD30 level was not different between patients with and without AR. However, post-transplant sCD30 was higher in the AR group. The median serum level of post-transplant sCD30 was 52 U/ml in the AR group and 26.3 U/ml in a control group (P < 0.001). The relative changes of sCD30 on day 5 were higher in patients with AR (P = 0.003). Based on post-transplant sCD30 levels, we were able to differentiate between kidney recipients who experienced an AR within 6 months post-surgery and those without an AR (cutoff value 41 U/ml; sensitivity 70%; specificity 71.7%). The level of sCD30 during periods of elevated serum creatinine was not independently associated with the diagnosis of AR. Post-transplant sCD30 levels and their relative changes are higher in patients experiencing AR. We propose further studies on the post-transplant trend of this marker for the prediction of AR.

Histopathology of spleen allograft rejection in miniature swine

PubMed Central

Dor, Frank J M F; Gollackner, Bernd; Kuwaki, Kenji; Ko, Dicken S C; Cooper, David K C; Houser, Stuart L

2005-01-01

Spleen transplantation (SpTx) has established donor-specific tolerance in rodents, but not in large animals or humans. We report the histopathology of rejection in an established model of SpTx in major histocompatibility complex (MHC)-defined miniature swine. Of the 17 SpTx, rejection was observed in two grafts transplanted into untreated, MHC-matched, minor antigen-disparate recipients (group 1, n = 4), but not in the two that received a 12-day course of cyclosporin A (CyA). Rejection also occurred in five grafts transplanted into fully MHC-disparate recipients (group 2, n = 12), one of which was untreated and four of which received some form of immunosuppressive therapy. One recipient of an MHC class-I-mismatched spleen treated with 12 days of CyA did not show rejection. Following biopsy and/or necropsy, fixed allograft tissue sections were treated with multiple stains, immunohistochemical markers and TUNEL assay. Common features of rejection occurred in grafts from both groups, but with varying time courses. Necrosis developed as early as day 8 in group 2 and day 27 in group 1, ranging from focal fibrinoid necrosis of arteriolar walls and sinusoids to diffuse liquefactive necrosis, usually associated with haemorrhage. Other features of rejection included white pulp expansion by atypical cells and decreased staining of basement membranes and reticular fibres. A doubling of the baseline TUNEL index preceded histologically identifiable rejection. This study establishes histologic guidelines for diagnosing and, perhaps, in future studies, predicting acute rejection of splenic allografts transplanted across known histocompatibility barriers in a large-animal model. PMID:15676033

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

PubMed

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

2014-09-01

Acute rejection (AR) remains a major cause for long-term kidney allograft failure. Reliable immunological parameters suitable to define the pre-transplant immune state and hence the individual risk of graft rejection are highly desired to preferably adapt the immunosuppressive regimen in advance. Donor and third party alloreactivities were determined by mixed lymphocyte cultures. Soluble forms of CD25, CD30, and CD44 were detected in patients' serum by ELISA. Various lymphocyte subpopulations were measured using flow cytometry. All patients received triple immunosuppression (tacrolimus/mycophenolate mofetil/steroids) and were grouped according to biopsy results within the first year: rejection-free (RF, n = 13), borderline (BL, n = 5), or acute rejection (AR, n = 7). Patients with AR showed the highest pre-transplant alloreactivities and serum levels (sCD25/sCD30/sCD44) according to the pattern RF < BL < AR. Relying on serum analysis only, multivariate logistic regression (logit link function) yielded a prognostic score for prediction of rejection with 75.0% sensitivity and 69.2% specificity. Patients with rejection showed markedly higher pre-transplant frequencies of CD4(+) /CD8(+) T cells lacking CD28, but lower numbers of CD8(+) CD161(bright) T cells and NK cells than RF individuals. Pre-transplant immune state defined by alloreactivity, serum markers, and particular lymphocyte subsets seems to correlate with occurrence of graft rejection after kidney transplantation. A prognostic score based on pre-transplant serum levels has shown great potential for prediction of rejection episodes and should be further evaluated. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed

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

2017-08-01

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

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

PubMed

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

2017-04-01

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

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

Increased intracellular adenosine triphosphate level as an index to predict acute rejection in kidney transplant recipients.

PubMed

Wang, Xu-Zhen; Jin, Zhan-Kui; Tian, Xiao-Hui; Xue, Wu-Jun; Tian, Pu-Xun; Ding, Xiao-Ming; Zheng, Jin; Li, Yang; Jing, Xin; Luo, Zi-Zhen

2014-01-01

Peripheral blood CD4+ T cell adenosine triphosphate (ATP) release has been reported to be an adjunct tool to evaluate global cellular immune response in solid-organ transplant recipients. However, the correlation between the ATP level and rejection was controversial. The aim of this prospective clinical study was to explore the association between the intracellular ATP level and the occurrence, progression, and treatment of acute rejection (AR) episodes, determine the predicting value of intracellular ATP level for AR in kidney transplant (KT) recipients. In the period of October 2011 to October 2012, 140 KT recipients were recruited and followed for six months after transplantation. Patients were categorized into stable group and AR group according to their clinical course. Whole blood samples were collected pretransplantation, and at 7, 14, 21, and 28days, and at 2, 3, 4, 5 and 6months post-transplantation. Additional blood samples were obtained from AR patients on the day AR occurred, on the day before and 3 and 7days after intravenous anti-rejection therapy started, and on the day when AR reversed. The intracellular ATP in CD4+ T cells was detected by ImmuKnow Immune Cell Function Assay according to the manufacturer's instruction. The absolute number of CD4+ T cells and the trough levels of tacrolimus and cyclosporine were also measured. The ATP level detected on the day AR occurred (627.07±149.85ng/ml) was obviously higher than that of the stable group (320.48±149.11ng/ml, P<0.05). ATP value decreased to 265.35±84.33ng/m at the end of anti-rejection therapy, which was obviously lower than that measured on the day before the anti-rejection therapy started (665.87±162.85ng/ml, P<0.05). ROC analysis revealed that increased intracellular adenosine triphosphate level showed better sensitivity and specificity than those obtained using single time point detection (89.5% vs 85.0%;95.0% vs 88.9%). The best cutoff value was 172.55ng/ml. A positive correlation

Re-Transplantation, Higher Creatinine Levels in Hepatitis C Virus Patients, and Donor Age Are Predictors of Mortality in Long-Term Analysis of Late Acute Rejection in Liver Transplantation.

PubMed

Nacif, Lucas Souto; Pinheiro, Rafael Soares; de Arruda Pécora, Rafael Antônio; Tanigawa, Ryan Yukimatsu; Rocha-Santos, Vinicius; Andraus, Wellington; Alves, Venancio Avancini Ferreira; D'Albuquerque, Luiz Carneiro

2017-01-10

BACKGROUND Late acute rejection (LAR) differs in its clinical and histological presentation and management from early acute rejection. This clinical entity is not completely understood; thus, we aimed to identify significant prognostic factors that can influence post-transplant survival in LAR patients. The purpose of this study was to evaluate the incidence and post-transplant survival of patients from a single center with a focus on late acute rejection. MATERIAL AND METHODS From January 2002 to June 2013, all liver biopsies from patients with rejection were scored using the Banff criteria. The groups were compared, and simple and multiple logistic regression and survival curves were created. RESULTS A total of 779 liver transplants were performed; 585 patients with no rejections and 194 patients with rejections were analyzed. The overall incidence of LAR was 6.7%, and there was a higher prevalence of early acute cellular rejection than LAR. The mean time to LAR was 564 days (median 214 days, range 91-2642). LAR had a more severe grade (35.3%) than early acute rejection (23.5%). The survival rates were similar between both modalities for the long-term period. Worse mortality rates were observed in liver re-transplantation (HR 4.77; p<0.0001); in hepatitis C virus patients with increased creatinine levels (HR 22.48; p=0.016); and in donors >41 years of age (OR 2.1; p=0.047) in a long-term analysis of LAR. CONCLUSIONS Liver re-transplantation, higher creatinine levels in hepatitis C virus patients, and donor age were predictors of mortality in this long-term analysis of late acute rejection in liver transplantation.

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

PubMed

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

2009-12-01

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

The role of FDG-PET in detecting rejection after liver transplantation.

PubMed

Watson, Ashley M; Bhutiani, Neal; Philips, Prejesh; Davis, Eric G; Eng, Mary; Cannon, Robert M; Jones, Christopher M

2018-05-15

The activation and increased metabolic activity of T cells in acute cellular rejection could allow fluoro-2-deoxyglucose positron emission tomography to be utilized for detection of acute cellular rejection. The objective of this study was to evaluate the effectiveness of fluoro-2-deoxyglucose positron emission tomography in detecting acute cellular rejection in the clinical setting. Fluoro-2-deoxyglucose positron emission tomography studies were performed on 88 orthotopic liver transplant patients at 7 and 17 days postoperatively (first positron emission tomography and second positron emission tomography, respectively). Additional studies were performed if patients had suspicion of rejection and at resolution of rejection (third positron emission tomography and fourth positron emission tomography, respectively). A circular region of interest was placed over the liver for semiquantitative evaluation of fluoro-2-deoxyglucose positron emission tomography images by means of standard uptake values. Eighteen of 88 patients in our study (20.5%) had histologically proven acute cellular rejection during a 16 ± 11 day follow-up. There was no significant difference between the standard uptake values of first positron emission tomography among non-rejecters versus rejecters (2.05 ±0.46 non-rejecters versus 1.82 ± 0.40 rejecters, P = .127). Within the rejection cohort, the standard uptake values from the third positron emission tomography (rejection) were higher compared to the first positron emission tomography (baseline) (2.41 ± 0.48 third positron emission tomography versus 1.82 ± 0.41 first positron emission tomography, P < .001). Increased signal on fluoro-2-deoxyglucose positron emission tomography over baseline is associated with acute cellular rejection in liver transplant recipients. Additional prospective validation studies are essential to define the role of fluoro-2-deoxyglucose positron emission tomography scan as an early marker for acute cellular

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

PubMed

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

2017-08-01

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

Existence of circulating anti-endothelial cell antibodies after heart transplantation is associated with post-transplant acute allograft rejection.

PubMed

Lehle, Karla; Kroher, Johannes; Kolat, Philipp; von Süßkind-Schwendi, Marietta; Schmid, Christof; Haneya, Assad; Rupprecht, Leopold; Hirt, Stephan

2016-05-01

Anti-endothelial cell antibodies (AECA) may be involved in the development of heart allograft rejection. Its detection might be a cheap and noninvasive method to identify high-risk patients. An indirect immunofluorescence method on human umbilical vein endothelial cells was used to investigate the presence of AECAs in 260 pre- and post-transplant serum samples sequentially collected from 34 patients within the first year after heart transplantation (HTX). The presence of AECAs before (23.5 %) and early after HTX (14.7 %) was associated with a significantly increased risk of early acute rejection (75 and 60 %, respectively) compared to 33 % in AECA-negative patients (p = 0.049). Moreover, rejections from AECA-positive patients were more severe (p = 0.057) with a significantly increased incidence of multiple (p = 0.025). The mean number of the sum of rejection episodes was significantly higher in AECA-positive patients (p ≤ 0.05). Patients free of AECAs mainly received mycophenolate mofetil as primary immunosuppression (p = 0.067). Nevertheless, the presence of AECAs did not affect long-term outcome and mortality of HTX patients. Despite a low number of patient samples, the detection of AECAs before and early after HTX could be used as a biomarker for an increased risk of early acute rejection in high-risk patients. This easy method might be a valuable tool to support screening procedures to improve individualized immunosuppressive therapy.

Antibody-Mediated Rejection of the Kidney after Simultaneous Pancreas-Kidney Transplantation

PubMed Central

Pascual, Julio; Samaniego, Milagros D.; Torrealba, José R.; Odorico, Jon S.; Djamali, Arjang; Becker, Yolanda T.; Voss, Barbara; Leverson, Glen E.; Knechtle, Stuart J.; Sollinger, Hans W.; Pirsch, John D.

2008-01-01

The prevalence, risk factors, and outcome of antibody-mediated rejection (AMR) of the kidney after simultaneous pancreas-kidney transplantation are unknown. In 136 simultaneous pancreas-kidney recipients who were followed for an average of 3.1 yr, 21 episodes of AMR of the kidney allograft were identified. Eight episodes occurred early (≤90 d) after transplantation, and 13 occurred later. Histologic evidence of concomitant acute cellular rejection was noted in 12 cases; the other nine had evidence only of humoral rejection. In 13 cases, clinical rejection of the pancreas was diagnosed simultaneously, and two of these were biopsy proven and were positive for C4d immunostaining. Multivariate analysis identified only one significant risk factor: Female patients were three times more likely to experience AMR. Nearly all early episodes resolved with treatment and did not predict graft loss, but multivariate Cox models revealed that late AMR episodes more than tripled the risk for kidney and pancreas graft loss; therefore, new strategies are needed to prevent and to treat late AMR in simultaneous pancreas-kidney transplant recipients. PMID:18235091

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

PubMed Central

Khatri, Purvesh; Roedder, Silke; Kimura, Naoyuki; De Vusser, Katrien; Morgan, Alexander A.; Gong, Yongquan; Fischbein, Michael P.; Robbins, Robert C.; Naesens, Maarten

2013-01-01

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. PMID:24127489

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.

Immunosuppressive therapies after intestinal transplant modulate the expression of Th1 signature genes during acute cellular rejection. Implications in the search for rejection biomarkers.

PubMed

Zambernardi, Agustina; Chiodetti, Ana; Meier, Dominik; Cabanne, Ana; Nachman, Fabio; Solar, Héctor; Rumbo, Carolina; Gondolesi, Gabriel E; Rumbo, Martin

2014-12-01

Acute cellular rejection (ACR) and infections are leading causes of graft loss and death in intestinal transplant patients. Our aim was to evaluate the impact of maintenance immunosuppressive therapies on the expression of pro-inflammatory mediators in small bowel at ACR diagnosis. We analyzed expression levels of Th1-associated genes, IFNG, CXCL10, and CXCL11 by qPCR in 46 selected graft biopsies unequivocally assigned to mild ACR (n = 14) or normal histopathology and clinical condition (n = 32) from 15 patients receiving two different immunosuppressive (IS) schemes. Double treatment: corticosteroids and tacrolimus (n = 17) and triple treatment: sirolimus or mycophenolate mofetil in addition to the basal therapy (n = 29). IFNG, CXCL10, and CXCL11 were induced during rejection (p < 0.05; p < 0.005, and p < 0.05, respectively). However, when rejection and control groups were classified according to immunosuppressive treatment, in the rejection group, significant differences of IFNG, CXCL10, and CXCL11 expression (p < 0.001; p < 0.005, and 0.01, respectively) were detected, whereas no differences were observed in the control group. Gene expression of Th1 response mediators is higher during ACR. Triple IS group showed significantly lower expression of pro-inflammatory Th1 mediators during mild ACR indicating that use of these markers to monitor rejection can be affected by the IS treatment used. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Perturbations in the Urinary Exosome in Transplant Rejection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sigdel, Tara K.; NG, Yolanda; Lee, Sangho

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. Themore » 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

T1 Mapping by Cardiac Magnetic Resonance and Multidimensional Speckle-Tracking Strain by Echocardiography for the Detection of Acute Cellular Rejection in Cardiac Allograft Recipients.

PubMed

Sade, Leyla Elif; Hazirolan, Tuncay; Kozan, Hatice; Ozdemir, Handan; Hayran, Mutlu; Eroglu, Serpil; Pirat, Bahar; Sezgin, Atilla; Muderrisoglu, Haldun

2018-04-14

The aim of this study was to test the hypothesis that echocardiographic strain imaging, by tracking subtle alterations in myocardial function, and cardiac magnetic resonance T1 mapping, by quantifying tissue properties, are useful and complement each other to detect acute cellular rejection in heart transplant recipients. Noninvasive alternatives to endomyocardial biopsy are highly desirable to monitor acute cellular rejection. Surveillance endomyocardial biopsies, catheterizations, and echocardiograms performed serially according to institutional protocol since transplantation were retrospectively reviewed. Sixteen-segment global longitudinal strain (GLS) and circumferential strain were measured before, during, and after the first rejection and at 2 time points for patients without rejection using Velocity Vector Imaging for the first part of the study. The second part, with cardiac magnetic resonance added to the protocol, served to validate previously derived strain cutoffs, examine the progression of strain over time, and to determine the accuracy of strain and T1 measurements to define acute cellular rejection. All tests were performed within 48 h. Median time to first rejection (16 grade 1 rejection, 15 grade ≥2 rejection) was 3 months (interquartile range: 3 to 36 months) in 49 patients. GLS and global circumferential strain worsened significantly during grade 1 rejection and ≥2 rejection and were independent predictors of any rejection. In the second part of the study, T1 time ≥1,090 ms, extracellular volume ≥32%, GLS >-14%, and global circumferential strain ≥-24% had 100% sensitivity and 100% negative predictive value to define grade ≥2 rejection with 70%, 63%, 55%, and 35% positive predictive values, respectively. The combination of GLS >-16% and T1 time ≥1,060 ms defined grade 1 rejection with 91% sensitivity and 92% negative predictive value. After successful treatment, T1 times decreased significantly. T1 mapping and

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. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2015-08-01

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

Effects of Hypercapnia on Acute Cellular Rejection after Lung Transplantation in Rats.

PubMed

Tan, Jing; Liu, Yanhong; Jiang, Tao; Wang, Ling; Zhao, Can; Shen, Dongfang; Cui, Xiaoguang

2018-01-01

Hypercapnia alleviates pulmonary ischemia-reperfusion injury, regulates T lymphocytes, and inhibits immune reaction. This study aimed to evaluate the effect of hypercapnia on acute cellular rejection in a rat lung transplantation model. Recipient rats in sham-operated (Wistar), isograft (Wistar to Wistar), and allograft (Sprague-Dawley to Wistar) groups were ventilated with 50% oxygen, whereas rats in the hypercapnia (Sprague-Dawley to Wistar) group were administered 50% oxygen and 8% carbon dioxide for 90 min during reperfusion (n = 8). Recipients were euthanized 7 days after transplantation. The hypercapnia group showed a higher oxygenation index (413 ± 78 vs. 223 ± 24), lower wet weight-to-dry weight ratio (4.23 ± 0.54 vs. 7.04 ± 0.80), lower rejection scores (2 ± 1 vs. 4 ± 1), and lower apoptosis index (31 ± 6 vs. 57 ± 4) as compared with the allograft group. The hypercapnia group showed lower CD8 (17 ± 4 vs. 31 ± 3) and CD68 (24 ± 3 vs. 43 ± 2), lower CD8 T cells (12 ± 2 vs. 35 ± 6), and higher CD4/CD8 ratio (2.2 ± 0.6 vs. 1.1 ± 0.4) compared to the allograft group. Tumor necrosis factor-α (208 ± 40 vs. 292 ± 49), interleukin-2 (30.6 ± 6.7 vs. 52.7 ± 8.3), and interferon-γ (28.1 ± 4.9 vs. 62.7 ± 10.1) levels in the hypercapnia group were lower than those in allograft group. CD4, CD4 T cells, and interleukin-10 levels were similar between groups. Hypercapnia ameliorated acute cellular rejection in a rat lung transplantation model.

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

PubMed

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

2011-07-01

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

Preventing Rejection

MedlinePlus

... living donor Being a living donor Liver Heart Lung Pancreas Intestine VCA Common diseases Living with devices Before Before the transplant How ... At least one episode of acute rejection is common within the first year ... after transplantation. Therefore, organ recipients should be aware of the ...

Panel reactive HLA antibodies, soluble CD30 levels, and acute rejection six months following renal transplant.

PubMed

Domingues, Elizabeth M F L; Matuck, Teresa; Graciano, Miguel L; Souza, Edison; Rioja, Suzimar; Falci, Mônica C; Monteiro de Carvalho, Deise B; Porto, Luís Cristóvão

2010-01-01

Specific anti-human leukocyte antigen antibodies (HLA) in the post-transplant period may be present with acute rejection episodes (ARE), and high soluble CD30 (sCD30) serum levels may be a risk factor for ARE and graft loss. HLA cross-matching, panel reactive antibodies (PRA), and sCD30 levels were determined prior to transplantation in 72 patients. Soluble CD30 levels and PRA were re-assessed at day 7, 14, 21, and 28, and monthly up to the sixth.   Twenty-four subjects had a positive PRA and 17 experienced ARE. Nine of 17 ARE subjects demonstrated positive PRA and 16 had HLA mismatches. Positive PRA was more frequent in ARE subjects (p = 0.03). Eight subjects with ARE had donor-specific antibodies (DSA) in serum samples pre-transplantation, two subjects developed DSA. Three subjects without ARE had positive PRA only in post-transplantation samples. Soluble CD30 levels were higher in pre-transplant samples and ARE subjects than non-ARE subjects (p = 0.03). Post-transplant sCD30 levels were elevated in subjects who experienced rejection and were significantly higher at seven d (p = 0.0004) and six months (p = 0.03). Higher sCD30 levels following transplant were associated with ARE. Elevated sCD30 levels may represent a risk factor for acute rejection. © 2009 John Wiley & Sons A/S.

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

PubMed

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

2006-12-27

Serum soluble CD30 (sCD30) levels might be a useful marker of immunologic status in pre transplant (Tx) recipients. We retrospectively correlated preTx sCD30 levels (high versus low) on postTx graft survival, incidence of acute rejection, and graft function using stored preTx serum. Of 254 recipients who underwent kidney Tx, 120 recipients were enrolled under the uniform criteria (living donor, age >25 years, viral hepatitis free, diabetes free). The preTx sCD30 was not significantly associated with differences in graft survival rate during 47.5+/-11.4 months of follow-up (P = 0.5901). High sCD30 (> or =115 U/ml) was associated with a higher incidence of clinically or pathologically defined acute rejection than low sCD30, but the difference was not statistically significant (33.9% vs. 22.4%, P = 0.164). The response rate to antirejection therapy in patients with high sCD30 was inferior to those with low sCD30, but also was not statistically significant (33.3% vs. 7.7%, P = 0.087). However, mean serum creatinine levels in high sCD30 patients at one month, one year, and three years postTx were significantly different from those with low sCD30 (P < 0.05). In multiple regression analysis, acute rejection episodes, donor age, kidney weight/recipient body weight ratio, and preTx sCD30 levels were independent variables affecting the serum creatinine level three years postTx. PreTx sCD30 level has a limited effect on the incidence of acute rejection and response to antirejection treatment, but inversely and independently affects serum creatinine level after living donor kidney transplantation.

High-sensitivity cardiac troponin I assay to screen for acute rejection in patients with heart transplant.

PubMed

Patel, Parag C; Hill, Douglas A; Ayers, Colby R; Lavingia, Bhavna; Kaiser, Patricia; Dyer, Adrian K; Barnes, Aliessa P; Thibodeau, Jennifer T; Mishkin, Joseph D; Mammen, Pradeep P A; Markham, David W; Stastny, Peter; Ring, W Steves; de Lemos, James A; Drazner, Mark H

2014-05-01

A noninvasive biomarker that could accurately diagnose acute rejection (AR) in heart transplant recipients could obviate the need for surveillance endomyocardial biopsies. We assessed the performance metrics of a novel high-sensitivity cardiac troponin I (cTnI) assay for this purpose. Stored serum samples were retrospectively matched to endomyocardial biopsies in 98 cardiac transplant recipients, who survived ≥3 months after transplant. AR was defined as International Society for Heart and Lung Transplantation grade 2R or higher cellular rejection, acellular rejection, or allograft dysfunction of uncertain pathogenesis, leading to treatment for presumed rejection. cTnI was measured with a high-sensitivity assay (Abbott Diagnostics, Abbott Park, IL). Cross-sectional analyses determined the association of cTnI concentrations with rejection and International Society for Heart and Lung Transplantation grade and the performance metrics of cTnI for the detection of AR. Among 98 subjects, 37% had ≥1 rejection episode. cTnI was measured in 418 serum samples, including 35 paired to a rejection episode. cTnI concentrations were significantly higher in rejection versus nonrejection samples (median, 57.1 versus 10.2 ng/L; P<0.0001) and increased in a graded manner with higher biopsy scores (P(trend)<0.0001). The c-statistic to discriminate AR was 0.82 (95% confidence interval, 0.76-0.88). Using a cut point of 15 ng/L, sensitivity was 94%, specificity 60%, positive predictive value 18%, and negative predictive value 99%. A high-sensitivity cTnI assay seems useful to rule out AR in cardiac transplant recipients. If validated in prospective studies, a strategy of serial monitoring with a high-sensitivity cTnI assay may offer a low-cost noninvasive strategy for rejection surveillance. © 2014 American Heart Association, Inc.

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

PubMed

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

2015-07-01

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

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

DTIC Science & Technology

2016-10-01

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

Molecular Classifiers for Acute Kidney Transplant Rejection in Peripheral Blood by Whole Genome Gene Expression Profiling

PubMed Central

Kurian, S. M.; Williams, A. N.; Gelbart, T.; Campbell, D.; Mondala, T. S.; Head, S. R.; Horvath, S.; Gaber, L.; Thompson, R.; Whisenant, T.; Lin, W.; Langfelder, P.; Robison, E. H.; Schaffer, R. L.; Fisher, J. S.; Friedewald, J.; Flechner, S. M.; Chan, L. K.; Wiseman, A. C.; Shidban, H.; Mendez, R.; Heilman, R.; Abecassis, M. M.; Marsh, C. L.; Salomon, D. R.

2015-01-01

There are no minimally invasive diagnostic metrics for acute kidney transplant rejection (AR), especially in the setting of the common confounding diagnosis, acute dysfunction with no rejection (ADNR). Thus, though kidney transplant biopsies remain the gold standard, they are invasive, have substantial risks, sampling error issues and significant costs and are not suitable for serial monitoring. Global gene expression profiles of 148 peripheral blood samples from transplant patients with excellent function and normal histology (TX; n = 46), AR (n = 63) and ADNR (n = 39), from two independent cohorts were analyzed with DNA microarrays. We applied a new normalization tool, frozen robust multi-array analysis, particularly suitable for clinical diagnostics, multiple prediction tools to discover, refine and validate robust molecular classifiers and we tested a novel one-by-one analysis strategy to model the real clinical application of this test. Multiple three-way classifier tools identified 200 highest value probesets with sensitivity, specificity, positive predictive value, negative predictive value and area under the curve for the validation cohort ranging from 82% to 100%, 76% to 95%, 76% to 95%, 79% to 100%, 84% to 100% and 0.817 to 0.968, respectively. We conclude that peripheral blood gene expression profiling can be used as a minimally invasive tool to accurately reveal TX, AR and ADNR in the setting of acute kidney transplant dysfunction. PMID:24725967

Recipient Myd88 Deficiency Promotes Spontaneous Resolution of Kidney Allograft Rejection

PubMed Central

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

2015-01-01

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. PMID:25788530

Non-invasive diagnosis of acute rejection in renal transplant patients using mass spectrometry of urine samples - a multicentre phase 3 diagnostic accuracy study.

PubMed

Zapf, Antonia; Gwinner, Wilfried; Karch, Annika; Metzger, Jochen; Haller, Hermann; Koch, Armin

2015-09-15

Reliable and timely detection of acute rejection in renal transplant patients is important to preserve the allograft function and to prevent premature allograft failure. The current gold standard for the rejection diagnosis is an allograft biopsy which is usually performed upon an unexplained decline in allograft function. Because of the invasiveness of the biopsy, non-invasive tests have been suggested to diagnose acute rejection including mass spectrometry analysis of urine samples. The aim of this study is to examine the diagnostic accuracy of mass spectrometry analysis in urine for the diagnosis of acute rejections using the biopsy as gold-standard. The study is an ongoing prospective, single-arm, multicentre, phase 3 diagnostic accuracy study. It started in October 2011 and will be concluded in December 2015. Patient within the first year after transplantation who are scheduled for a biopsy to clarify unexplained impairment of the allograft are consecutively recruited into the study. The overall sample size (n = 600) was calculated to demonstrate a sensitivity of 83 % and a specificity of 70 % for a one-sided type one error of 2.5 % and a power of 80 % per hypothesis. Biopsy evaluation and mass spectrometry analysis of urine samples (obtained immediately before biopsy) are performed independently by different readers without knowledge from the respective other assessment. The follow-up observation period is 6 months. For the primary analysis, the lower limits of the two-sided 95 % Wald confidence intervals for sensitivity and specificity will be compared with the pre-specified thresholds (83 % for sensitivity and 70 % for specificity). In secondary analyses the predictive values, the diagnostic measures in subgroups, and the clinical course will be assessed. Previous phase 2 diagnostic accuracy studies (in small selected study populations) provided sufficient evidence to suggest mass spectrometry on urine samples as a promising approach to detect

Lower incidence of CMV infection and acute rejections with valganciclovir prophylaxis in lung transplant recipients

PubMed Central

2013-01-01

Background Cytomegalovirus (CMV) is the most common opportunistic infection following lung transplantation. CMV replication in the lung allograft is described as accelerating the development of bronchiolitis obliterans syndrome (BOS). Finding a strategy to prevent CMV infection is an important issue. Methods We performed a retrospective, single-centre study of 114 lung transplant recipients (LTRs) who underwent lung transplantation from January 2001 to December 2006. In a smaller cohort of 88 CMV seropositive (R+) LTRs, three months of valganciclovir prophylaxis (2004-2006) was compared to three months of oral ganciclovir (2001-2003) with respect to the incidence of CMV infection/disease, the severity of CMV disease, acute rejection, BOS-free 4 year survival and 4 year survival. In the whole group of 114 LTRs the impact of CMV infection on long-term survival (BOS free 4 year survival and 6 year survival) was assessed. Results For the cohort of 88 CMV seropositive LTRs, the incidence of CMV infection/disease at one year was lower in the valganciclovir group compared to the ganciclovir group (24% vs. 54%, p = 0.003). There was a tendency towards reduced CMV disease, from 33% to 20% and a significant lower incidence of asymptomatic CMV infection (22% vs. 4%, p = 0.005). A lower incidence of acute rejection was observed in the valganciclovir group. However, there was no significant difference between the two groups in BOS free 4 year survival and 4 year survival. For the entire group of 114 LTRs, BOS-free 4 year survival for recipients with CMV disease was (32%, p = 0.005) and among those with asymptomatic CMV infection (36%, p = 0.061) as compared with patients without CMV infection (69%). Six year survival was lower among patients with CMV disease, (64%, p = 0.042) and asymptomatic CMV infection (55%, p = 0.018) than patients without CMV infection (84%). Conclusions A lower incidence of CMV infection/disease and acute rejections was

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

PubMed

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

2017-04-01

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

OKT3 treatment for steroid-resistant acute rejection in kidney transplantation.

PubMed

Sevmis, S; Emiroglu, R; Karakayali, F; Yagmurdur, M C; Dalgic, A; Moray, G; Haberal, M

2005-09-01

Orthoclone (OKT3, Ortho Biotech Inc, USA) monoclonal antilymphocyte antibody is a powerful T-cell-specific immunosuppressive agent. OKT3 has been used for induction therapy in kidney and liver transplantation, as well as to treat acute or steroid-resistant acute rejection episodes (ARE). This study was a retrospective analysis of 43 renal transplant recipients who developed steroid-resistant ARE and were treated with OKT3 between September 1994 and June 2004. The recipients were 36 men and 7 women of mean age 32.7 +/- 11.6 years (range, 19 to 48 years). The mean time from transplantation to OKT3 treatment was 7.2 +/- 6.7 months. Thirty-four episodes (79.1%) responded to OKT3 therapy with improved graft function, but the remaining 9 (20.9%) grafts did not respond. Among the 34 OKT3 responders, the mean serum creatinine decreased from 3.96 +/- 2.5 mg/dL to 2.45 +/- 1.77 mg/dL after treatment. Eleven (25.6%) of the 43 patients experienced minor side effects: fever, dyspnea, tachycardia, bradycardia. One patient (2.3%) developed acute pulmonary edema; one (2.3%), cytomegalovirus infection; and eight (18.6%), bacterial infections. The 1-, 3-, and 5-year graft survival rates for the 34 patients who responded to OKT3 therapy were 96%, 93%, and 85%, respectively. All patients are currently alive. The results indicate that OKT3 is a safe, effective treatment choice for steroid-resistant ARE in kidney transplantation.

Outcome of Acute Pancreatic and Peripancreatic Collections Occurring in Patients With Acute Pancreatitis.

PubMed

Manrai, Manish; Kochhar, Rakesh; Gupta, Vikas; Yadav, Thakur Deen; Dhaka, Narendra; Kalra, Naveen; Sinha, Saroj K; Khandelwal, Niranjan

2018-02-01

To study the outcome of acute collections occurring in patients with acute pancreatitis BACKGROUND:: There are limited data on natural history of acute collections arising after acute pancreatitis (AP). Consecutive patients of AP admitted between July 2011 and December 2012 were evaluated by imaging for development of acute collections as defined by revised Atlanta classification. Imaging was repeated at 1 and 3 months. Spontaneous resolution, evolution, and need for intervention were assessed. Of the 189 patients, 151 patients (79.9%) had acute collections with severe disease and delayed hospitalization being predictors of acute collections. Thirty-six patients had acute interstitial edematous pancreatitis, 8 of whom developed acute peripancreatic fluid collections, of which 1 evolved into pseudocyst. Among the 153 patients with acute necrotizing pancreatitis, 143 (93.4%) developed acute necrotic collection (ANC). Twenty-three of 143 ANC patients died, 21 had resolved collections, whereas 84 developed walled-off necrosis (WON), with necrosis >30% (P = 0.010) and Computed Tomographic Severity Index score ≥7 (P = 0.048) predicting development of WON. Of the 84 patients with WON, 8 expired, 53 patients required an intervention, and 23 were managed conservatively. Independent predictors of any intervention among all patients were Computed Tomographic Severity Index score ≥7 (P < 0.001) and interval between onset of pain to hospitalization >7 days (P = 0.04). Patients with severe AP and delayed hospitalization more often develop acute collections. Pancreatic pseudocysts are a rarity in acute interstitial pancreatitis. A majority of patients with necrotising pancreatitis will develop ANC, more than half of whom will develop WON. Delay in hospitalization and higher baseline necrosis score predict need for intervention.

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

PubMed

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

2012-09-01

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

HLA-DQ Mismatches and Rejection in Kidney Transplant Recipients

PubMed Central

Chapman, Jeremy R.; Coates, Patrick T.; Lewis, Joshua R.; Russ, Graeme R.; Watson, Narelle; Holdsworth, Rhonda; Wong, Germaine

2016-01-01

Background and objectives The current allocation algorithm for deceased donor kidney transplantation takes into consideration HLA mismatches at the ABDR loci but not HLA mismatches at other loci, including HLA-DQ. However, the independent effects of incompatibilities for the closely linked HLA-DQ antigens in the context of HLA-DR antigen matched and mismatched allografts are uncertain. We aimed to determine the effect of HLA-DQ mismatches on renal allograft outcomes. Design, setting, participants, & measurements Using data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the association between HLA-DQ mismatches and acute rejections in primary live and deceased donor kidney transplant recipients between 2004 and 2012 using adjusted Cox regression models. Results Of the 788 recipients followed for a median of 2.8 years (resulting in 2891 person-years), 321 (40.7%) and 467 (59.3%) received zero and one or two HLA-DQ mismatched kidneys, respectively. Compared with recipients who have received zero HLA-DQ mismatched kidneys, those who have received one or two HLA-DQ mismatched kidneys experienced greater numbers of any rejection (50 of 321 versus 117 of 467; P<0.01), late rejections (occurring >6 months post-transplant; 8 of 321 versus 27 of 467; P=0.03), and antibody-mediated rejections (AMRs; 12 of 321 versus 38 of 467; P=0.01). Compared with recipients of zero HLA-DQ mismatched kidneys, the adjusted hazard ratios for any and late rejections in recipients who had received one or two HLA-DQ mismatched kidneys were 1.54 (95% confidence interval [95% CI], 1.08 to 2.19) and 2.85 (95% CI, 1.05 to 7.75), respectively. HLA-DR was an effect modifier between HLA-DQ mismatches and AMR (P value for interaction =0.02), such that the association between HLA-DQ mismatches and AMR was statistically significant in those who have received one or two HLA-DR mismatched kidneys, with adjusted hazard ratio of 2.50 (95% CI, 1.05 to 5.94). Conclusions HLA

Use of capecitabine to prevent acute renal allograft rejection in dog erythrocyte antigen-mismatched mongrel dogs.

PubMed

Milovancev, Milan; Schmiedt, Chad W; Bentley, Ellison; Schwab, Michelle; Dubielzig, Richard R; Gendron-Fitzpatrick, Annette P; McAnulty, Jonathan F

2007-01-01

To assess efficacy and toxicity of a capecitabine (CAP)-based regimen for preventing rejection of renal allografts in dog erythrocyte antigen (DEA)-mismatched mongrel dogs. Prospective, pilot study. Eight healthy, unrelated, DEA mismatched, adult mongrel dogs. All dogs received CAP, starting at 50 mg/m2 PO b.i.d. 4 days preoperatively, increasing to 200 mg/m2 PO b.i.d. by the day of surgery. All dogs received cyclosporine-A (CsA) and prednisolone starting 2 days preoperatively. Standard heterotopic renal transplantation with native nephrectomy was performed. After 90 days, surviving dogs were euthanatized and histopathologic examination was performed. Two of 8 dogs developed acute neurotoxicity leading to death or euthanasia within 5 days of surgery. For the 6 remaining dogs, there were no statistically significant changes in complete blood count or serum biochemical values. No opportunistic infections developed during the study period. Five of 6 dogs had no to minimal evidence of graft rejection. Two of 6 dogs developed superficial and pigmentary keratitis. Significant histopathologic findings in all dogs included mild lymphoplasmacytic gastroenteritis, steroid hepatopathy, and corneal epithelial thinning. One dog had moderate interstitial nephritis and pyelitis. In this experimental model, a CAP-CsA-prednisolone immunosuppressive regimen was effective in preventing rejection of allografts in DEA-mismatched dogs. Severe, unpredictable neurotoxicity and variable ocular toxicity significantly limit clinical applications at this time. A CAP-CsA-prednisolone protocol is an effective, oral immunosuppressive regimen for prevention of allograft rejection in DEA-mismatched mongrel dogs. For clinical application, identification of patients susceptible to toxic side effects would be necessary.

Triple therapy in cadaveric renal transplantation: role of induction cyclosporine and targeted levels to avoid rejection.

PubMed

Khauli, R B; Wilson, J M; Baker, S P; Valliere, S A; Lovewell, T D; Stoff, J S

1995-06-01

The updated data on 61 consecutive cadaveric transplants performed at our institution from 1987 to 1990 (followup 31 to 82 months, median 54 months) were analyzed with emphasis on cyclosporine monitoring and long-term results. All patients received triple therapy with cyclosporine induction, azathioprine and prednisone regardless of graft function, and they were preferentially placed on the calcium blocker nifedipine. We monitored 12-hour cyclosporine trough levels in whole blood using high performance liquid chromatography and the dose was adjusted to maintain levels at 150 ng./ml. or greater for the first 3 months. In 17 of 61 patients (28%) 22 rejection episodes occurred and 20 nephrotoxicity episodes occurred in 17 of 61 patients (28%). There was no significant difference in the mean cyclosporine levels among 32 rejection, nonrejection, nephrotoxic and nonnephrotoxic cases at any interval. Rejection occurred by 1 month in 13 (76%) and by 3 months in 15 (88%) of 17 patients. Comparisons were made in the first month to define the desirable cyclosporine levels by calculating the mean cyclosporine only within 10 to 14 days of rejection or nephrotoxicity events. The mean cyclosporine level before rejection was significantly lower than that for nephrotoxicity (188 +/- 113 versus 304 +/- 62 ng./ml., p < 0.01). The median cyclosporine level for first month rejection was also significantly lower than that for nonrejection (156 versus 218 ng./ml., p < 0.05) and it was significantly greater for nephrotoxicity versus nonnephrotoxicity (272 versus 218 ng./ml., p < 0.05). Of 13 rejections in the first month 10 (77%) were associated with mean levels of less than 210 ng./ml. Actuarial graft survival at 1, 3 and 5 years was 93.4%, 87.8% and 78.5%, respectively. The 3-year graft survival was significantly worse for patients who experienced acute rejection episodes versus those who did not (68.8% versus 96.7%, p < 0.05) but it was not different for nephrotoxic versus

The severity of acute cellular rejection defined by Banff classification is associated with kidney allograft outcomes.

PubMed

Wu, Kaiyin; Budde, Klemens; Lu, Huber; Schmidt, Danilo; Liefeldt, Lutz; Glander, Petra; Neumayer, Hans Helmut; Rudolph, Birgit

2014-06-15

It is unclear if the severity or the timing of acute cellular rejection (ACR) defined by Banff classification 2009 is associated with graft survival. Borderline changes, TCMR I (interstitial rejection), and TCMR II/III (vascular rejection) were defined as low, moderate, and high ACR severity, respectively. Approximately 270 patients who had at least one episode of ACR were enrolled, 270 biopsies were chosen which showed the highest ACR severity of each patient and were negative for donor-specific antibodies (DSA), C4d, and microcirculation changes (MC). Six months were used as the cutoff to define early and late ACR; 370 patients without biopsy posttransplantation were recruited in the control group. Up to 8-year posttransplantation, death-censored graft survival (DCGS) rates of control, borderline, TCMR I, and TCMR II/III groups were 97.6%, 93.3%, 79.6%, and 73.6% (log rank test, P<0.001); the control group had significantly higher DCGS rate than the three ACR groups (each pairwise comparison yields P<0.05). The DCGS rate of late ACR was significantly lower compared with early ACR (63.6% vs. 87.4%, P<0.001). Intimal arteritis (Banff v-lesion) was an independent histologic risk factor correlated with long-term graft loss regardless of the timing of ACR. The v-lesions with minimal or high-grade tubulitis displayed similar graft survival (72.7% vs. 72.9%, P=0.96). All types of ACR affect long-term graft survival. Vascular or late ACR predict poorer graft survival; the extent of tubulointerstitial inflammation (TI) is of no prognostic significance for vascular rejection.

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

PubMed

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

2010-01-01

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

Acute Cellular Rejection in ABO-Incompatible Renal Transplant Recipients Receiving Rituximab Is Associated with Delayed-Onset Neutropenia.

PubMed

Uchida, Junji; Iwai, Tomoaki; Nishide, Shunji; Kabei, Kazuya; Kuwabara, Nobuyuki; Yamasaki, Takeshi; Naganuma, Toshihide; Kumada, Norihiko; Takemoto, Yoshiaki; Nakatani, Tatsuya

2017-07-25

BACKGROUND Rituximab induces long-lasting B cell depletion in the peripheral blood and increases the levels of proinflammatory cytokines associated with regulatory B cell depletion. Previous reports showed that B cell-related cytokine release after administration of rituximab may induce acute cellular rejection (ACR) and delayed-onset neutropenia. The present study was conducted to investigate the correlation between acute rejection and delayed-onset neutropenia in ABO-incompatible renal transplant recipients who underwent administration of rituximab for 1 year after transplantation. MATERIAL AND METHODS From June 2006 to July 2015, 47 patients with chronic renal failure received ABO-incompatible renal transplant with rituximab induction at Osaka City University Hospital. All 47 patients underwent plasmapheresis due to removal of anti-A/B antibodies and administration of rituximab, and their transplants were carried out successfully. We investigated the correlation between ACR and delayed-onset neutropenia in ABO-incompatible renal transplant recipients who underwent administration of rituximab for 1 year after transplantation. RESULTS Fourteen patients (29.8%) experienced ACR (group A), and 33 recipients did not develop ACR (group B). The frequency of delayed-onset neutropenia was higher in group A than in group B (p=0.0503). Multivariate logistic regression analysis revealed that the frequency of ACR correlated significantly with the prevalence of delayed-onset neutropenia. CONCLUSIONS Our results indicated that ACR in ABO-incompatible renal transplant recipients receiving rituximab was associated with delayed-onset neutropenia.

Identification of patients at risk of acute rejection by pretransplantation and posttransplantation monitoring of soluble CD30 levels in kidney transplantation.

PubMed

Sengul, Sule; Keven, Kenan; Gormez, Ulku; Kutlay, Sim; Erturk, Sehsuvar; Erbay, Bulent

2006-04-27

In this study, we investigated the impact of pre- and posttransplantation sCD30 monitoring on early (<6 months) acute rejection (AR) risk and analyzed the effect of different immunosuppressive regimens on posttransplantation sCD30 levels in kidney recipients. Fifty patients receiving kidney allograft and 10 healthy donors were included in this retrospective cohort study. Eight patients developed biopsy-proven AR (19%). In pretransplantation samples, patients showed a significantly higher sCD30 than healthy controls. The pretransplantation and posttransplantation (day-15) sCD30 levels were significantly elevated in rejecting patients compared to non-rejecting patients. No significant differences among immunosuppressive regimens were found in posttransplantation sCD30 levels. High pretransplantation and posttransplantation (day 15) sCD30 levels are associated with increased risk of early AR, and sCD30 can be another tool to evaluate immunological risk prior to kidney transplantation. There was no difference in immunosuppressive regimens used in this study on posttransplantation sCD30 levels at the first month.

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

PubMed

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

2005-06-01

Recent literary data suggest that high pre- and post-transplant serum levels of the soluble CD30 (sCD30) molecule may be a risk factor for acute rejection and worse prognosis of the transplanted kidney. The aim of our study was to correlate the concentrations of sCD30 and the presence of HLA antibodies as defined by flow cytometry and ELISA with the clinical course and graft prognosis after transplantation. One hundred and seventeen kidney transplant patients were included into the study. The incidence of rejection episodes, graft function and graft survival for up to 1 year post-transplant were evaluated. Soluble CD30 levels before transplantation were virtually the same in patients who experienced rejection and in non-rejecting patients. In both patient groups, a significant decrease of sCD30 was detected 2 weeks after transplantation (104.4 U/ml before vs. 37.0 U/ml post-transplant, P < 0.001). However, there was a substantial difference in the level of decrease of sCD30 between rejecting and non-rejecting patients. Patients without rejection had lower sCD30 values (31.2 U/ml post-transplant) compared to patients who experienced rejection episodes (62.9 U/ml), P < 0.04. Multifactorial analysis showed that antibodies to HLA class II antigens and elevated concentrations of sCD30 shortly after transplantation were associated with increased risk for acute rejection in the first post-transplant year. Measurement of soluble CD30 after transplantation, taken into consideration with the presence of HLA class II antibodies, might be helpful for evaluating the potential risk for acute rejection.

Kidney Transplant Rejection and Tissue Injury by Gene Profiling of Biopsies and Peripheral Blood Lymphocytes

PubMed Central

Flechner, Stuart M.; Kurian, Sunil M.; Head, Steven R.; Sharp, Starlette M.; Whisenant, Thomas C.; Zhang, Jie; Chismar, Jeffrey D.; Horvath, Steve; Mondala, Tony; Gilmartin, Timothy; Cook, Daniel J.; Kay, Steven A.; Walker, John R.; Salomon, Daniel R.

2007-01-01

A major challenge for kidney transplantation is balancing the need for immunosuppression to prevent rejection, while minimizing drug-induced toxicities. We used DNA microarrays (HG-U95Av2 GeneChips, Affymetrix) to determine gene expression profiles for kidney biopsies and peripheral blood lymphocytes (PBLs) in transplant patients including normal donor kidneys, well-functioning transplants without rejection, kidneys undergoing acute rejection, and transplants with renal dysfunction without rejection. We developed a data analysis schema based on expression signal determination, class comparison and prediction, hierarchical clustering, statistical power analysis and real-time quantitative PCR validation. We identified distinct gene expression signatures for both biopsies and PBLs that correlated significantly with each of the different classes of transplant patients. This is the most complete report to date using commercial arrays to identify unique expression signatures in transplant biopsies distinguishing acute rejection, acute dysfunction without rejection and well-functioning transplants with no rejection history. We demonstrate for the first time the successful application of high density DNA chip analysis of PBL as a diagnostic tool for transplantation. The significance of these results, if validated in a multicenter prospective trial, would be the establishment of a metric based on gene expression signatures for monitoring the immune status and immunosuppression of transplanted patients. PMID:15307835

Immune function surveillance: association with rejection, infection and cardiac allograft vasculopathy.

PubMed

Heikal, N M; Bader, F M; Martins, T B; Pavlov, I Y; Wilson, A R; Barakat, M; Stehlik, J; Kfoury, A G; Gilbert, E M; Delgado, J C; Hill, H R

2013-01-01

Rejection, cardiac allograft vasculopathy (CAV), and infection are significant causes of mortality in heart transplantation recipients. Assessing the immune status of a particular patient remains challenging. Although endomyocardial biopsy (EMB) and angiography are effective for the identification of rejection and CAV, respectively, these are expensive, invasive, and may have numerous complications. The aim of this study was to evaluate the immune function and assess its utility in predicting rejection, CAV, and infection in heart transplantation recipients. We prospectively obtained samples at the time of routine EMB and when clinically indicated for measurement of the ImmuKnow assay (IM), 12 cytokines and soluble CD30 (sCD30). EMB specimens were evaluated for acute cellular rejection, and antibody-mediated rejection (AMR). CAV was diagnosed by the development of angiographic coronary artery disease. Infectious episodes occurring during the next 30 days after testing were identified by the presence of positive bacterial or fungal cultures and/or viremia that prompted treatment with antimicrobials. We collected 162 samples from 56 cardiac transplant recipients. There were 31 infection episodes, 7 AMR, and 4 CAV cases. The average IM value was significantly lower during infection, (P = .04). Soluble CD30 concentrations showed significantly positive correlation with infection episodes, (P = .001). Significant positive correlation was observed between interleukin-5(IL-5) and AMR episodes (P = .008). Tumor necrosis factor-α and IL-8 showed significant positive correlation with CAV (P = .001). Immune function monitoring appears promising in predicting rejection, CAV, and infection in cardiac transplantation recipients. This approach may help in more individualized immunosuppression and it may also minimize unnecessary EMBs and cardiac angiographies. Published by Elsevier Inc.

Peripheral blood sampling for the detection of allograft rejection: biomarker identification and validation.

PubMed

Heidt, Sebastiaan; San Segundo, David; Shankar, Sushma; Mittal, Shruti; Muthusamy, Anand S R; Friend, Peter J; Fuggle, Susan V; Wood, Kathryn J

2011-07-15

Currently, acute allograft rejection can only be detected reliably by deterioration of graft function confirmed by allograft biopsy. A huge drawback of this method of diagnosis is that substantial organ damage has already taken place at the time that rejection is diagnosed. Discovering and validating noninvasive biomarkers that predict acute rejection, and chronic allograft dysfunction, is of great importance. Many studies have investigated changes in the peripheral blood in an attempt to find biomarkers that reflect changes in the graft directly or indirectly. Herein, we will review the promises and limitations of the peripheral blood biomarkers that have been described in the literature so far.

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

The cellular lesion of humoral rejection: predominant recruitment of monocytes to peritubular and glomerular capillaries.

PubMed

Fahim, T; Böhmig, G A; Exner, M; Huttary, N; Kerschner, H; Kandutsch, S; Kerjaschki, D; Bramböck, A; Nagy-Bojarszky, K; Regele, H

2007-02-01

Accumulation of inflammatory cells within capillaries is a common morphologic feature of humoral renal allograft rejection and is most easily appreciated if it occurs in glomeruli. The aim of our study was to determine the amount and composition of immune cells within glomeruli and peritubular capillaries (PTC) in cellular and humoral allograft rejection. Immunofluorescent double-labeling for CD31 and CD3 or CD68 was used for phenotyping and enumerating immune cells within glomeruli and PTC. The major findings are: (1) accumulation of immune cells in PTC is far more common than it would be anticipated based on the assessment by conventional histology; (2) it is not the absolute number of immune cells accumulating within capillaries, but rather the composition of the intracapillary cell population that distinguishes humoral rejection from cellular rejection and (3) in C4d positive biopsies a predominantly monocytic cell population accumulates not only within glomeruli but also within PTC. The median value of monocyte/T-cell ratio within PTC was 2.3 in C4d positive biopsies but only 1 (p = 0.0008) in C4d negative biopsies. Given their prominent presence within capillaries and their extensive biological versatility monocytes might contribute to the capillary damage observed in acute and chronic allograft rejection.

Rejection is less common in children undergoing liver transplantation for hepatoblastoma.

PubMed

Ruth, N D; Kelly, D; Sharif, K; Morland, B; Lloyd, C; McKiernan, P J

2014-02-01

To compare the incidence of acute histologically proven rejection in children who have had a liver transplant for hepatoblastoma with a control group of children transplanted for biliary atresia (EHBA). A retrospective case notes based study was performed. Twenty patients were identified with hepatoblastoma who were transplanted at a single unit between 1991 and 2008. These were matched as closely as possible for age, gender, year of transplant and type of immunosuppression used to the control group transplanted for biliary atresia (n = 60). There was a significant decrease in rate of acute rejection as assessed by the rejection activity index (RAI) in the hepatoblastoma group (75% vs. 50%, respectively, p < 0.04). Chronic rejection was rare in both groups, but twice as common in the biliary atresia group. Equal levels of immunosuppression were achieved in both groups. Renal function was noted to be reduced one yr post-transplant in both groups, as previously reported. A modified immunosuppression regimen could be considered in children with hepatoblastoma undergoing liver transplantation. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Level of soluble CD30 after kidney transplantation correlates with acute rejection episodes.

PubMed

Yang, J L; Hao, H J; Zhang, B; Liu, Y X; Chen, S; Na, Y Q

2008-12-01

Measurement of soluble CD30 (sCD30) levels may predict acute rejection episodes (ARE). To explore the value of sCD30 after transplantation, we tested serum sCD30 levels in 58 kidney transplant cases at 1 day before and 7 and 28 days after transplantation by enzyme-linked immunosorbent assay (ELISA). The incidences of ARE after kidney transplantation were recorded simultaneously. Meanwhile, 31 healthy individuals were selected as a control group. The results showed a relationship between sCD30 level in serum before kidney transplantation and the incidence of ARE. However, the relationship was more significant between serum sCD30 levels at day 7 after kidney transplantation and the incidence of ARE. There was no obvious relationship between serum sCD30 levels at day 28 after kidney transplantation and the incidence of ARE. These results suggested that the level of sCD30 at day 7 posttransplantation provides valuable data to predict ARE.

Loss of CD28 on Peripheral T Cells Decreases the Risk for Early Acute Rejection after Kidney Transplantation

PubMed Central

Dedeoglu, Burç; Meijers, Ruud W. J.; Klepper, Mariska; Hesselink, Dennis A.; Baan, Carla C.; Litjens, Nicolle H. R.; Betjes, Michiel G. H.

2016-01-01

Background End-stage renal disease patients have a dysfunctional, prematurely aged peripheral T-cell system. Here we hypothesized that the degree of premature T-cell ageing before kidney transplantation predicts the risk for early acute allograft rejection (EAR). Methods 222 living donor kidney transplant recipients were prospectively analyzed. EAR was defined as biopsy proven acute allograft rejection within 3 months after kidney transplantation. The differentiation status of circulating T cells, the relative telomere length and the number of CD31+ naive T cells were determined as T-cell ageing parameters. Results Of the 222 patients analyzed, 30 (14%) developed an EAR. The donor age and the historical panel reactive antibody score were significantly higher (p = 0.024 and p = 0.039 respectively) and the number of related donor kidney transplantation was significantly lower (p = 0.018) in the EAR group. EAR-patients showed lower CD4+CD28null T-cell numbers (p<0.01) and the same trend was observed for CD8+CD28null T-cell numbers (p = 0.08). No differences regarding the other ageing parameters were found. A multivariate Cox regression analysis showed that higher CD4+CD28null T-cell numbers was associated with a lower risk for EAR (HR: 0.65, p = 0.028). In vitro, a significant lower percentage of alloreactive T cells was observed within CD28null T cells (p<0.001). Conclusion Immunological ageing-related expansion of highly differentiated CD28null T cells is associated with a lower risk for EAR. PMID:26950734

Intestinal microbial variation may predict early acute rejection after liver transplantation in rats.

PubMed

Ren, Zhigang; Jiang, Jianwen; Lu, Haifeng; Chen, Xinhua; He, Yong; Zhang, Hua; Xie, Haiyang; Wang, Weilin; Zheng, Shusen; Zhou, Lin

2014-10-27

Acute rejection (AR) remains a life-threatening complication after orthotopic liver transplantation (OLT) and there are few available diagnostic biomarkers clinically for AR. This study aims to identify intestinal microbial profile and explore potential application of microbial profile as a biomarker for AR after OLT. The OLT models in rats were established. Hepatic graft histology, ultrastructure, function, and intestinal barrier function were tested. Ileocecal contents were collected for intestinal microbial analysis. Hepatic graft suffered from the ischemia-reperfusion (I/R) injury on day 1, initial AR on day 3, and severe AR on day 7 after OLT. Real-time quantitative polymerase chain reaction results showed that genus Faecalibacterium prausnitzii and Lactobacillus were decreased, whereas Clostridium bolteae was increased during AR. Notably, cluster analysis of denaturing gradient gel electrophoresis (DGGE) profiles showed the 7AR and 3AR groups clustered together with 73.4% similarity, suggesting that intestinal microbiota was more sensitive than hepatic function in responding to AR. Microbial diversity and species richness were decreased during AR. Phylogenetic tree analysis showed that most of the decreased key bacteria belonged to phylum Firmicutes, whereas increased key bacteria belonged to phylum Bacteroidetes. Moreover, intestinal microvilli loss and tight junction damage were noted, and intestinal barrier dysfunction during AR presented a decrease of fecal secretory immunoglobulin A (sIgA) and increase of blood bacteremia, endotoxin, and tumor necrosis factor-α. We dynamically detail intestinal microbial characterization and find a high sensitivity of microbial change during AR after OLT, suggesting that intestinal microbial variation may predict AR in early phase and become an assistant therapeutic target to improve rejection after OLT.

Intestinal Microbial Variation May Predict Early Acute Rejection after Liver Transplantation in Rats

PubMed Central

Ren, Zhigang; Jiang, Jianwen; Lu, Haifeng; Chen, Xinhua; He, Yong; Zhang, Hua; Xie, Haiyang; Wang, Weilin; Zheng, Shusen; Zhou, Lin

2014-01-01

Background Acute rejection (AR) remains a life-threatening complication after orthotopic liver transplantation (OLT) and there are few available diagnostic biomarkers clinically for AR. This study aims to identify intestinal microbial profile and explore potential application of microbial profile as a biomarker for AR after OLT. Methods The OLT models in rats were established. Hepatic graft histology, ultrastructure, function, and intestinal barrier function were tested. Ileocecal contents were collected for intestinal microbial analysis. Results Hepatic graft suffered from the ischemia-reperfusion (I/R) injury on day 1, initial AR on day 3, and severe AR on day 7 after OLT. Real-time quantitative polymerase chain reaction results showed that genus Faecalibacterium prausnitzii and Lactobacillus were decreased, whereas Clostridium bolteae was increased during AR. Notably, cluster analysis of denaturing gradient gel electrophoresis (DGGE) profiles showed the 7AR and 3AR groups clustered together with 73.4% similarity, suggesting that intestinal microbiota was more sensitive than hepatic function in responding to AR. Microbial diversity and species richness were decreased during AR. Phylogenetic tree analysis showed that most of the decreased key bacteria belonged to phylum Firmicutes, whereas increased key bacteria belonged to phylum Bacteroidetes. Moreover, intestinal microvilli loss and tight junction damage were noted, and intestinal barrier dysfunction during AR presented a decrease of fecal secretory immunoglobulin A (sIgA) and increase of blood bacteremia, endotoxin, and tumor necrosis factor-α. Conclusion We dynamically detail intestinal microbial characterization and find a high sensitivity of microbial change during AR after OLT, suggesting that intestinal microbial variation may predict AR in early phase and become an assistant therapeutic target to improve rejection after OLT. PMID:25321166

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

PubMed

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

2010-10-01

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

Donor age and delayed graft function as predictors of renal allograft survival in rejection-free patients.

PubMed

Moreso, F; Serón, D; Gil-Vernet, S; Riera, L; Fulladosa, X; Ramos, R; Alsina, J; Grinyó, J M

1999-04-01

Transplant recipients of kidneys harvested from old donors have a high incidence of delayed graft function (DGF) and a poor graft outcome. This result is partly explained by the increased incidence of acute rejection in patients suffering from DGF. However, the long-term impact of donor age and DGF in rejection free renal transplants is not well established. The aim of the present work is to evaluate the impact of donor age and DGF on long-term outcome in renal transplants with or without acute rejection. We review all cadaveric kidney transplants performed in our centre between April 1984 and December 1995 treated with a cyclosporin-based immunosuppression. Five hundred and ninety-five patients were included. The overall incidence of DGF was 29.1%, and this event was associated with an increased donor age and cold ischaemia time. Univariate and multivariate analysis showed that graft loss was associated with acute rejection (relative risk (RR) 2.24, 95% confidence interval (CI) 1.62-3.01); DGF (RR 1.83, 95% CI 1.32-2.54); donors >50 years (RR 1.65, 95% CI 1.13-2.38); and retransplantation (RR 1.52, 95% CI 1.01-2.31). In rejection-free patients there were two independent predictors of graft failure: donor >50 years (RR 2.40, 95% CI 1.45-4.01); and DGF (RR 2.42, 95% CI 1.53-3.84). Regardless of the presence of acute rejection, delayed graft function amplifies the detrimental effect of advanced donor age on long-term graft outcome.

Incidence and Severity of Acute Cellular Rejection in Recipients Undergoing Adult Living Donor or Deceased Donor Liver Transplantation123

PubMed Central

Shaked, Abraham; Ghobrial, R. Mark; Merion, Robert M.; Shearon, Tempie H.; Emond, Jean C.; Fair, Jeffrey H.; Fisher, Robert A.; Kulik, Laura M.; Pruett, Timothy L.; Terrault, Norah A.

2013-01-01

Living donor liver transplantation (LDLT) may have better immunological outcomes compared to deceased donor liver transplantation (DDLT). The aim of this study was to analyze the incidence of acute cellular rejection (ACR) after LDLT and DDLT. Data from the Adult-to-Adult Living Donor Liver Transplantation (A2ALL) Retrospective Cohort Study on 593 liver transplants done between May 1998 and March 2004 were studied (380 LDLT; 213 DDLT). Median LDLT and DDLT follow-up was 778 and 713 days, respectively. Rates of clinically treated and biopsy-proven ACR were compared. There were 174 (46%) LDLT and 80 (38%) DDLT recipients with ≥1 clinically treated episodes of ACR, whereas 103 (27%) LDLT and 58 (27%) DDLT recipients had ≥1 biopsy-proven ACR episode. A higher proportion of LDLT recipients had clinically treated ACR (P=0.052), but this difference was largely attributable to one center. There were similar proportions of biopsy-proven rejection (P=0.97) and graft loss due to rejection (P=0.16). Longer cold ischemia time was associated with a higher rate of ACR in both groups despite much shorter median cold ischemia time in LDLT. These data do not show an immunological advantage for LDLT, and therefore do not support the application of unique post-transplant immunosuppression protocols for LDLT recipients. PMID:19120082

Augmenter of liver regeneration attenuates acute rejection after rat liver transplantation.

PubMed

Chen, Yong; Liang, Shaoyong; Long, Feiwu; Li, Jinzheng; Gong, Jianping

2016-07-01

The role of augmenter of liver regeneration (ALR) on liver transplantation immune regulation remains unknown. Male Lewis and Brown-Norway (BN) rats were assigned to allograft group (Lewis-to-BN liver transplantation), isograft group (BN-to-BN), and ALR group (Lewis-to-BN, ALR, 100 μg/kg/d, intramuscular injection postoperatively). Rats were sacrificed at indicated times for assessment of cytokines production, T-cell (TC) activation and apoptosis. Kupffer cells (KCs) and TCs were isolated from grafts to assess cytokine expression. Effect of ALR and KCs on TCs was monitored by co-culture of (3)H-thymidine TCs. (1) Treatment with ALR significantly decreased interleukin-2 and interferon-γ expression, promoted TC apoptosis, and prolonged the survival of allografts; (2) KCs in ALR group and isograft group that had significantly increased interleukin-10 and decreased tumor necrosis factor-α expression were able to inhibit TC proliferation and induce their apoptosis relative to KCs in the allograft group; (3) ALR and KCs directly inhibited TC proliferation and activation and induced TC apoptosis. ALR could inhibit TC proliferation and function both in vivo and in vitro and attenuate acute rejection after liver transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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

PubMed

Lee, Hyeseon; Park, Young-Mi; We, Yu-Mee; Han, Duck Jong; Seo, Jung-Woo; Moon, Haena; Lee, Yu-Ho; Kim, Yang-Gyun; Moon, Ju-Young; Lee, Sang-Ho; Lee, Jong-Keuk

2017-03-01

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

Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms.

PubMed

Skelly, Donal T; Griffin, Éadaoin W; Murray, Carol L; Harney, Sarah; O'Boyle, Conor; Hennessy, Edel; Dansereau, Marc-Andre; Nazmi, Arshed; Tortorelli, Lucas; Rawlins, J Nicholas; Bannerman, David M; Cunningham, Colm

2018-06-06

Systemic inflammation can impair cognition with relevance to dementia, delirium and post-operative cognitive dysfunction. Episodes of delirium also contribute to rates of long-term cognitive decline, implying that these acute events induce injury. Whether systemic inflammation-induced acute dysfunction and acute brain injury occur by overlapping or discrete mechanisms remains unexplored. Here we show that systemic inflammation, induced by bacterial LPS, produces both working-memory deficits and acute brain injury in the degenerating brain and that these occur by dissociable IL-1-dependent processes. In normal C57BL/6 mice, LPS (100 µg/kg) did not affect working memory but impaired long-term memory consoliodation. However prior hippocampal synaptic loss left mice selectively vulnerable to LPS-induced working memory deficits. Systemically administered IL-1 receptor antagonist (IL-1RA) was protective against, and systemic IL-1β replicated, these working memory deficits. Dexamethasone abolished systemic cytokine synthesis and was protective against working memory deficits, without blocking brain IL-1β synthesis. Direct application of IL-1β to ex vivo hippocampal slices induced non-synaptic depolarisation and irrevesible loss of membrane potential in CA1 neurons from diseased animals and systemic LPS increased apoptosis in the degenerating brain, in an IL-1RI -/- -dependent fashion. The data suggest that LPS induces working memory dysfunction via circulating IL-1β but direct hippocampal action of IL-1β causes neuronal dysfunction and may drive neuronal death. The data suggest that acute systemic inflammation produces both reversible cognitive deficits, resembling delirium, and acute brain injury contributing to long-term cognitive impairment but that these events are mechanistically dissociable. These data have significant implications for management of cognitive dysfunction during acute illness.

Immunological and inflammatory mapping of vascularized composite allograft rejection processes in a rat model

PubMed Central

Friedman, Or; Carmel, Narin; Sela, Meirav; Abu Jabal, Ameen; Inbal, Amir; Ben Hamou, Moshe; Krelin, Yakov; Gur, Eyal

2017-01-01

Background Hand and face vascularized composite allotransplantation (VCA) is an evolving and challenging field with great opportunities. During VCA, massive surgical damage is inflicted on both donor and recipient tissues, which may contribute to the high VCA rejection rates. To segregate between the damage-induced and rejection phase of post-VCA responses, we compared responses occurring up to 5 days following syngeneic versus allogeneic vascularized groin flap transplantations, culminating in transplant acceptance or rejection, respectively. Methods The immune response elicited upon transplantation of a syngeneic versus allogeneic vascularized groin flap was compared at Post-operative days 2 or 5 by histology, immunohistochemistry and by broad-scope gene and protein analyses using quantitative real-time PCR and Multiplex respectively. Results Immune cell infiltration began at the donor-recipient interface and paralleled expression of a large group of wound healing-associated genes in both allografts and syngrafts. By day 5 post-transplantation, cell infiltration spread over the entire allograft but remained confined to the wound site in the syngraft. This shift correlated with upregulation of IL-18, INFg, CXCL9, 10 and 11, CCL2, CCL5, CX3CL1 and IL-10 in the allograft only, suggesting their role in the induction of the anti-alloantigen adaptive immune response. Conclusions High resemblance between the cues governing VCA and solid organ rejection was observed. Despite this high resemblance we describe also, for the first time, a damage induced inflammatory component in VCA rejection as immune cell infiltration into the graft initiated at the surgical damage site spreading to the entire allograft only at late stage rejection. We speculate that the highly inflammatory setting created by the unique surgical damage during VCA may enhance acute allograft rejection. PMID:28746417

Combined use of rapamycin and leflunomide in prevention of acute cardiac allografts rejection in rats.

PubMed

Sun, Yan; Chen, Xi; Zhao, Jiabin; Zou, Xiaoming; Li, Gang; Li, Xiaolin; Shen, Bin; Sun, Shibo

2012-08-01

This study aimed to evaluate the role of combined use of rapamycin and leflunomide(Lef) on the prevention of acute allograft rejection in rats. After cardiac transplantations, rats were randomly divided into untreated group, rapamycin group, Lef group and rapamycin+Lef group. The drugs were given by gavage from day 0 to day 9 after transplantations. Graft survival time was observed. Some grafts were harvested for histopathological investigation on day 10 after transplantations. The levels of CD(4)(+) and CD(8)(+) T lymphocytes and the concentrations of interleukin 2(IL-2) and interferon (IFN)γ in peripheral blood were examined on day 10 after transplantations. At the same time, the body weight, the hepatic function, renal function and the haemoglobin of the recipients were also examined. The graft survival time of untreated group was 7.14 ± 1.07 days. Rapamycin group was 11.14 ± 1.35 days. Lef group was 11.29 ± 1.80 days. While in rapamycin+Lef group, the graft survival time was prolonged to 13.86 ± 1.57 days(P<0.05). Histological changes of the allografts in rapamycin+Lef group were much milder than either of the two single drug groups. The absolute number and the percentage of CD(4)(+) T lymphocytes in peripheral blood in rapamycin+Lef group were lower than those of rapamycin or Lef group on day 10 after transplantations(P<0.05), while the percentage of CD(8)(+) T lymphocytes in rapamycin+Lef group was higher than that of rapamycin or Lef group(P<0.05). The absolute number of CD(8)(+) T lymphocytes was not significantly different among rapamycin group, Lef group and rapamycin+Lef group. The levels of IL-2 and IFN-γ in rapamycin+Lef group were significantly lower than that of rapamycin group or Lef group(P<0.05). The body weight, the hepatic function, renal function and the haemoglobin were not significantly different among rapamycin group, Lef group and rapamycin+Lef group (P>0.05). Combined use of rapamycin and Lef had better effect on the prevention of

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. © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

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

PubMed

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

2017-03-29

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

Soluble CD30 correlates with clinical but not subclinical renal allograft rejection.

PubMed

Hirt-Minkowski, Patricia; Roth, Michèle; Hönger, Gideon; Amico, Patrizia; Hopfer, Helmut; Schaub, Stefan

2013-01-01

Soluble CD30 (sCD30) has been proposed as a promising noninvasive biomarker for clinical renal allograft rejection, but its diagnostic characteristics regarding detection of subclinical rejection have not been assessed. We investigated sCD30 in 146 consecutive kidney allograft recipients under tacrolimus-mycophenolate-based immunosuppression having 250 surveillance biopsies at 3 and 6 months as well as 52 indication biopsies within the first year post-transplant. Allograft histology results were classified as (i) acute Banff score zero or interstitial infiltrates only, (ii) tubulitis t1, (iii) tubulitis t2-3 and (iv) isolated vascular compartment inflammation. sCD30 correlated well with the extent of clinical (P < 0.0001), but not subclinical tubulointerstitial rejection (P = 0.06). To determine diagnostic characteristics of sCD30, histological groups were assigned to two categories: no relevant inflammation (i.e. acute Banff score zero and interstitial infiltrates only) versus all other pathologies (tubulitis t1-3 and isolated vascular compartment inflammation). For clinical allograft inflammation, AUC was 0.87 (sensitivity 89%, specificity 79%; P = 0.0006); however, for subclinical inflammation, AUC was only 0.59 (sensitivity 50%, specificity 69%; P = 0.47). In conclusion, sCD30 correlated with clinical, but not subclinical renal allograft rejection limiting its clinical utility as a noninvasive rejection screening biomarker in patients with stable allograft function receiving tacrolimus-mycophenolate-based immunosuppression. © 2012 The Authors Transplant International © 2012 European Society for Organ Transplantation.

Subclinical rejection in renal transplants is associated with low serum mannose-binding lectin levels.

PubMed

Ibernon, Meritxell; Moreso, Francesc; Serón, Daniel

2011-08-01

Surveillance biopsies have contributed to the understanding of the natural history of renal allograft lesions. Subclinical rejection, defined as the presence of histological lesions, indistinguishable from acute rejection in stable grafts, is associated with progression of interstitial fibrosis and tubular atrophy. The prevalence of subclinical rejection has decreased as more powerful immunosuppressive treatments have been introduced, suggesting that subclinical rejection represents the degree of control of the alloimmune response. However, non-immune factors such as donor age are also associated with the prevalence of subclinical rejection, suggesting that kidneys from older donors are more susceptible to insult and have a reduced capacity for tissue regeneration. Innate immunity has a crucial role in the modulation of the inflammatory response during infection and tissue damage. Mannose-binding lectin (MBL) is an innate immune protein, the polymorphisms of which are associated with infection, low-grade inflammation, diabetes, and cardiovascular disease. However, the relationship between MBL and disease is complex. For example, low MBL level is associated with higher risk for diabetes, whereas in patients with diabetes, high MBL level is associated with more severe renal damage. In renal transplant patients, low MBL levels are associated with an increased prevalence of infection and diabetes, whereas high MBL levels are associated with shortened graft survival. Although MBL is not clearly associated with prevalence of acute rejection, surveillance biopsy studies have shown that low MBL levels are associated with subclinical rejection in kidney and the heart, suggesting that MBL modulates the injury-repair process of the allograft.

Subclinical rejection in renal transplants is associated with low serum mannose-binding lectin levels

PubMed Central

Ibernon, Meritxell; Moreso, Francesc; Serón, Daniel

2011-01-01

Surveillance biopsies have contributed to the understanding of the natural history of renal allograft lesions. Subclinical rejection, defined as the presence of histological lesions, indistinguishable from acute rejection in stable grafts, is associated with progression of interstitial fibrosis and tubular atrophy. The prevalence of subclinical rejection has decreased as more powerful immunosuppressive treatments have been introduced, suggesting that subclinical rejection represents the degree of control of the alloimmune response. However, non-immune factors such as donor age are also associated with the prevalence of subclinical rejection, suggesting that kidneys from older donors are more susceptible to insult and have a reduced capacity for tissue regeneration. Innate immunity has a crucial role in the modulation of the inflammatory response during infection and tissue damage. Mannose-binding lectin (MBL) is an innate immune protein, the polymorphisms of which are associated with infection, low-grade inflammation, diabetes, and cardiovascular disease. However, the relationship between MBL and disease is complex. For example, low MBL level is associated with higher risk for diabetes, whereas in patients with diabetes, high MBL level is associated with more severe renal damage. In renal transplant patients, low MBL levels are associated with an increased prevalence of infection and diabetes, whereas high MBL levels are associated with shortened graft survival. Although MBL is not clearly associated with prevalence of acute rejection, surveillance biopsy studies have shown that low MBL levels are associated with subclinical rejection in kidney and the heart, suggesting that MBL modulates the injury–repair process of the allograft. PMID:25018901

Capillary Thrombosis in the Skin: A Pathologic Hallmark of Severe/Chronic Rejection of Human Vascularized Composite Tissue Allografts?

PubMed

Kanitakis, Jean; Petruzzo, Palmina; Gazarian, Aram; Karayannopoulou, Georgia; Buron, Fannie; Dubois, Valérie; Thaunat, Olivier; Badet, Lionel; Morelon, Emmanuel

2016-04-01

Vascularized composite tissue allografts (VCA) can undergo rejection, manifesting pathologically with skin changes that form the basis of the Banff 2007 classification of VCA rejection. We have followed 10 human VCA recipients (7 with hand allografts, 3 with face allografts) for pathological signs of rejection. All of them developed episodes of acute rejection. Two patients with hand allografts presented in some of their skin biopsies an as yet unreported pathological finding in human VCA, consisting of capillary thromboses (CT) in the upper dermis. Capillary thrombosis was associated with other typical changes of grade II to III VCA rejection, namely, perivascular T cell infiltrates, but not with vascular C4d deposits (in formalin-fixed tissue). Clinically, the lesions presented as red or violaceous (lichenoid) cutaneous maculopapules. The first patient had several episodes of acute rejection during the 7-year follow-up. The second patient developed donor-specific antibodies; some months after CT were first observed, he developed chronic rejection leading to partial amputation of the allograft. Pathological examination of the skin showed graft vasculopathy and occasional C4d deposits in cutaneous capillaries. Capillary thrombosis seems to be a novel pathologic finding associated with human VCA rejection. Although its mechanism (immunologic vs nonimmunologic) remains unclear, this finding could carry an unfavorable prognostic significance, prompting close monitoring of the patients for severe/chronic rejection.

PRINS Long Noncoding RNA Involved in IP-10-Mediated Allograft Rejection in Rat Kidney Transplant.

PubMed

Zou, X-F; Song, B; Duan, J-H; Hu, Z-D; Cui, Z-L; Yang, T

2018-06-01

Previously, high levels of CXCR3+ T-cell recruitment was demonstrated in the prolonged ischemia-accelerated acute allograft rejection in rat kidney transplant. In the present study, the effect of chemokine IP-10 was investigated and the expression of chemokine-related PRINS (Psoriasis susceptibility-related RNA gene induced by stress) lncRNA determined in the allografts subjected to ischemia. F344-to-Lewis rat kidney transplantation was performed, and renal grafts were stored for 2 hours or 16 hours. Samples were removed at 24 hours and 7 days after operation. Cellular infiltration was determined with the use of immunohistochemistry, and messenger RNA expression was assessed with the use of real-time polymerase chain reaction. The 16-hour-ischemia kidney displayed acute tubule damage and up-regulation of PRINS lncRNA expression. On day 7, IP-10 expression and CD3-positive T cells were increased in allografts compared with control samples, which were inhibited by the IP-10 antibody treatment accompanied by reduced serum creatinine. These observations provide evidence for IP-10 in a regulatory role in cold ischemia-elicited acute allograft rejection and in PRINS lncRNA expression. Our data enhance the understanding of the mechanism underlying between prolonged ischemia and acute rejection. Copyright © 2018 Elsevier Inc. All rights reserved.

Co-Occurrence and Predictors of Three Commonly Occurring Behavioral Symptoms in Dementia: Agitation, Aggression, and Rejection of Care.

PubMed

Choi, Scott Seung W; Budhathoki, Chakra; Gitlin, Laura N

2017-05-01

To investigate co-occurrences of agitation, aggression, and rejection of care in community-dwelling families living with dementia. Cross-sectional, secondary analysis from a randomized controlled trial testing a nonpharmacological intervention to reduce behavioral symptoms. We examined frequency of occurrence of presenting behaviors at baseline and their combination. Omnibus tests compared those exhibiting combinations of behaviors on contributory factors. Multinomial logistic regression analyses examined relationships of contributory factors to combinations of behaviors. Of 272 persons with dementia (PwDs), 41 (15%) had agitation alone (Agi), 3 (1%) had aggression alone, 5 (2%) had rejection of care alone. For behavioral combinations, 65 (24%) had agitation and aggression (Agi+Aggr), 35 (13%) had agitation and rejection (Agi+Rej), 1 (0%) had aggression and rejection, and 106 (39%) had all three behaviors (All). Four behavioral subgroups (Agi, Agi+Aggr, Agi+Rej, and All) were examined. Kruskal-Wallis tests showed that there were significant group differences in PwD cognition, functional dependence, and caregiver frustration. PwDs in Agi+Rej and All were more cognitively impaired than those in Agi and Agi+Aggr. Also, caregivers in All were more frustrated than those in Agi. In logistic regression analyses, compared with Agi, greater cognitive impairment was a significant predictor of Agi+Rej and All, but not Agi+Aggr. In contrast, greater caregiver frustration was a significant predictor of Agi+Aggr and All, but not Agi+Rej. We found that agitation, aggression, and rejection are common but distinct behaviors. Combinations of these behaviors have different relationships with contributory factors, suggesting the need for targeting treatment approaches to clusters. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Isolated v-lesion represents a benign phenotype of vascular rejection of the kidney allograft- a retrospective study.

PubMed

Novotny, Marek; Hruba, Petra; Vichova, Petra; Maluskova, Jana; Honsova, Eva; Viklicky, Ondrej; Wohlfahrtova, Mariana

2018-05-31

While the detrimental impact of the humoral acute vascular rejection (AVR) phenotype is recognized, the prognostic significance of isolated v-lesion (IV) remains unclear. In this retrospective single-centre study, AVR was found in 98 out of 1015 patients (9.7%) who had undergone kidney transplantation in 2010-2014, with donor-specific antibodies (DSA) evaluated in all of them. The outcome of four AVR phenotypes was evaluated during median follow-up of 59 months; in 25 patients with IV, 18 with T cell-mediated vascular rejection (TCMRV), 19 with antibody-mediated vascular rejection (AMRV) and 36 with suspected antibody-mediated rejection (sAMRV). AVR was diagnosed mainly by for-cause biopsy (81%) early after transplantation (median 19 POD) and appeared as mild grade intimal arteritis. IV occurred in low sensitized patients after the first transplantation (96%) in the absence of DSA. IV responded satisfactorily to treatment (88%), showed no persistence of rejection in surveillance biopsy, had stable graft function, minimal proteinuria and excellent DCGS (96%). Contrary to that, Kaplan-Meier estimate of 3-year DCGS of AMRV was 66% (log rank=0.0004). Early IV represents a benign phenotype of AVR with a favourable outcome. This study prompts further research to evaluate the nature of IV before considering any change in the classification and management. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Acute leukemia occurring after radiotherapy and chemotherapy with a nitrosourea, PCNU.

PubMed

Shepard, K V; Larson, R; Le Beau, M M; Leichman, L; Levin, B

1988-06-01

Secondary acute leukemias can occur in patients who have been treated with chemotherapy. Several reports have shown that treatment with nitrosoureas can result in secondary leukemia, but this is the first report implicating the investigational drug PCNU as a cause. This case is unique because of the cytogenetic findings, the short latency period between the chemotherapy and the diagnosis of leukemia, and the successful treatment of the leukemia with high-dose cytarabine (ara-C).

MDMA DECREASES THE EFFECTS OF SIMULATED SOCIAL REJECTION

PubMed Central

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

2014-01-01

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. PMID

Impact of Banff borderline acute rejection among renal allograft recipients.

PubMed

Matoza, J R A; Danguilan, R A; Chicano, S

2008-09-01

This study was performed to determine the incidence, treatment, and outcomes of Banff borderline acute rejection (AR) among renal transplant recipients. We reviewed the courses of adult kidney transplant recipients with borderline AR on clinically indicated biopsies performed at our center from January 2003 to July 2006. Patients with complete transplant records and serum creatinine values at 6 and 12 months were included in this study. The primary outcome measures were serum creatinine values at 1 to 2 weeks after treatment, and at 6 and 12 months after graft biopsy. Among 428 renal graft biopsies, borderline AR was observed in 100 cases (23%). Patients were maintained on the same immunosuppression. The 86 who had complete data were included in the study. Seventy-eight percent of the patients received treatment with 3 days of methylprednisolone, while 22% were untreated. Mean serum creatinine values in the treated group were 2.9 +/- 1.0, 2.6 +/- 2.5, and 3.0 +/- 2.9 mg/dL at the time of biopsy, and at 6 and 12 months thereafter, respectively. In the untreated group, mean serum creatinine values were 2.2 +/- 1.0, 1.9 +/- 0.8, and 2.3 +/- 1.2 mg/dL during biopsy, and at 6 and 12 months thereafter, respectively. There was no significant difference in the serum creatinine at any of the measured time points between the 2 groups. Twelve patients had repeat renal graft biopsies which showed AR (6%), chronic allograft nephropathy (2.4%), and borderline changes (3.8%). Nine of the patients in the treated group eventually developed graft loss. Patients with borderline AR showed a progressive increase in serum creatinine over time. They should be followed closely; immunosuppression may need to be intensified.

Evaluation of serum sCD30 in renal transplantation patients with and without acute rejection.

PubMed

Cervelli, C; Fontecchio, G; Scimitarra, M; Azzarone, R; Famulari, A; Pisani, F; Battistoni, C; Di Iulio, B; Fracassi, D; Scarnecchia, M A; Papola, F

2009-05-01

Despite new immunosuppressive approaches, acute rejection episodes (ARE) are still a major cause of early kidney dysfunction with a negative impact on long-term allograft survival. Noninvasive markers able to identify renal ARE earlier than creatinine measurement include sCD30. We sought to establish whether circulating levels of sCD30 in pretransplantation and posttransplantation periods were of clinical relevance to avoid graft damage. Quantitative detection of serum sCD30 was performed using an enzyme-linked immunosorbent assay. Our results demonstrated that the mean concentrations of sCD30 were significantly higher in the sera of renal transplant recipients with ARE (30.04 U/mL) and in uremic patients on the waiting list (37.7 U/mL) compared with healthy controls (HC; 9.44 U/mL), but not nonrejecting patients (12.01 U/mL). Statistical analysis revealed a strong association between high sCD30 levels in posttransplantation sera and ARE risk. This study suggested that sCD30 levels were a reliable predictor of ARE among deceased-donor kidney recipients.

Significant reduction of acute cardiac allograft rejection by selective janus kinase-1/3 inhibition using R507 and R545.

PubMed

Deuse, Tobias; Hua, Xiaoqin; Taylor, Vanessa; Stubbendorff, Mandy; Baluom, Muhammad; Chen, Yan; Park, Gary; Velden, Joachim; Streichert, Thomas; Reichenspurner, Hermann; Robbins, Robert C; Schrepfer, Sonja

2012-10-15

Selective inhibition of lymphocyte activation through abrogation of signal 3-cytokine transduction emerges as a new strategy for immunosuppression. This is the first report on the novel Janus kinase (JAK)1/3 inhibitors R507 and R545 for prevention of acute allograft rejection. Pharmacokinetic and in vitro enzyme inhibition assays were performed to characterize the drugs. Heterotopic Brown Norway-Lewis heart transplantations were performed to study acute cardiac allograft rejection, graft survival, suppression of cellular host responsiveness, and antibody production. Therapeutic and subtherapeutic doses of R507 (60 and 15 mg/kg 2 times per day) and R545 (20 and 5 mg/kg 2 times per day) were compared with those of tacrolimus (Tac; 4 and 1 mg/kg once per day). Plasma levels of R507 and R545 were sustained high for several hours. Cell-based enzyme assays showed selective inhibition of JAK1/3-dependent pathways with 20-fold or greater selectivity over JAK2 and Tyrosine kinase 2 kinases. After heart transplantation, both JAK1/3 inhibitors reduced early mononuclear graft infiltration, even significantly more potent than Tac. Intragraft interferon-γ release was significantly reduced by R507 and R545, and for interleukin-10 suppression, they were even significantly more potent than Tac. Both JAK1/3 inhibitors and Tac were similarly effective in reducing the host Th1 and Th2, but not Th17, responsiveness and similarly prevented donor-specific immunoglobulin M antibody production. Subtherapeutic and therapeutic R507 and R545 doses prolonged the mean graft survival and were similarly effective as 1 and 4 mg/kg Tac, respectively. In combination regimens, however, only R507 showed highly beneficial synergistic drug interactions with Tac. Both R507 and R545 are potent novel immunosuppressants with favorable pharmacokinetics and high JAK1/3 selectivity, but only R507 synergistically interacts with Tac.

Contralateral acute interdural haematoma occurring after burr hole drainage of chronic subdural haematoma.

PubMed

Eom, Ki Seong; Kim, Tae Young; Park, Jong Tae

2009-04-01

We report the case of a 78-year-old man with chronic subdural haematoma (CSDH) who presented with impairment in recent memory and gait disturbance. He underwent burr-hole craniostomy with a closed-drainage system. A computed tomography scan conducted on postoperative day 3 demonstrated an acute epidural haematoma over the contralateral frontoparietal convexity. Craniotomy and haematoma evacuation were immediately performed. The haematoma was located between the outer and inner dura mater that each comprise a single layer. To our knowledge, this is the first reported case of an acute haematoma located between the separated dura mater that occurred following drainage of a contralateral CSDH, and it is the second reported case of interdural haematoma over the cerebral convexity.

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

Acute respiratory alkalosis occurring after endoscopic third ventriculostomy -A case report-.

PubMed

Sung, Hui-Jin; Sohn, Ju-Tae; Kim, Jae-Gak; Shin, Il-Woo; Ok, Seong-Ho; Lee, Heon-Keun; Chung, Young-Kyun

2010-12-01

An endoscopic third ventriculostomy was performed in a 55-year-old man with an obstructive hydrocephalus due to aqueductal stenosis. The vital signs and laboratory studies upon admission were within the normal limits. Anesthesia was maintained with nitrous oxide in oxygen and 6% desflurane. The patient received irrigation with approximately 3,000 ml normal saline during the procedure. Anesthesia and operation were uneventful. However, he developed postoperative hyperventilation in the recovery room, and arterial blood gas analysis revealed acute respiratory alkalosis. We report a rare respiratory alkalosis that occurred after an endoscopic third ventriculostomy.

Did You Reject Me for Someone Else? Rejections That Are Comparative Feel Worse.

PubMed

Deri, Sebastian; Zitek, Emily M

2017-12-01

Rejections differ. For those who are rejected, one important difference is whether they are rejected for someone else (comparative rejection) or no one at all (noncomparative rejection). We examined the effect of this distinction on emotional reactions to a rejection in four studies ( N = 608), one of which was fully preregistered. Our results show that comparative rejections feel worse than noncomparative rejections and that this may be because such rejections lead to an increased sense of exclusion and decreased belonging. Furthermore, we found evidence that, by default, people react to a rejection as though it were comparative-that is, in the absence of any information about whether they have been rejected for someone or no one, they react as negatively as if they were rejected for someone. Our discussion focuses on the implications of these findings, including why people often seek out information in the wake of a rejection.

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

PubMed

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

2006-06-01

The aim of the present study was to identify whether the serum interferon-gamma (IFNgamma), a Th1 cytokine, or soluble CD30 (sCD30), a marker for activation of Th2 cytokine-producing T cells, predict acute cellular rejection episodes among liver graft patients. Pretransplant and posttransplant sera from 32 living donor liver transplant recipients obtained on days 1, 3, and 7 after surgery were tested for serum IFNgamma and sCD30 concentrations using commercial enzyme-linked immunosorbent assay kits. Recipients with an acute rejection episode (ARE) (n=14) displayed significantly higher IFNgamma concentrations pretransplant than did the patients with no ARE (n=18) (P<.05). The pretransplant serum levels of sCD30 were not different between the non-ARE and ARE groups. However, in comparison with the non-ARE group, who showed steadily decreasing serum sCD30 levels after transplantation, 12 among the 14 patients in the ARE group showed increasing sCD30 levels from day 1 to day 3 after transplantation (P<.05). These results suggest that the sCD30 increment during the early period after liver transplantation affects the immune response of rejection. This observation emphasizes the clinical relevance of serum sCD30, in addition to serum IFNgamma, as predictive markers for acute liver graft rejection.

C1 Inhibitor in Acute Antibody-Mediated Rejection Nonresponsive to Conventional Therapy in Kidney Transplant Recipients: A Pilot Study.

PubMed

Viglietti, D; Gosset, C; Loupy, A; Deville, L; Verine, J; Zeevi, A; Glotz, D; Lefaucheur, C

2016-05-01

Complement inhibitors have not been thoroughly evaluated in the treatment of acute antibody-mediated rejection (ABMR). We performed a prospective, single-arm pilot study to investigate the potential effects and safety of C1 inhibitor (C1-INH) Berinert added to high-dose intravenous immunoglobulin (IVIG) for the treatment of acute ABMR that is nonresponsive to conventional therapy. Kidney recipients with nonresponsive active ABMR and acute allograft dysfunction were enrolled between April 2013 and July 2014 and received C1-INH and IVIG for 6 months (six patients). The primary end point was the change in eGFR at 6 months after inclusion (M+6). Secondary end points included the changes in histology and DSA characteristics and adverse events as evaluated at M+6. All patients showed an improvement in eGFR between inclusion and M+6: from 38.7 ± 17.9 to 45.2 ± 21.3 mL/min/1.73 m(2) (p = 0.0277). There was no change in histological features, except a decrease in the C4d deposition rate from 5/6 to 1/6 (p = 0.0455). There was a change in DSA C1q status from 6/6 to 1/6 positive (p = 0.0253). One deep venous thrombosis was observed. In a secondary analysis, C1-INH patients were compared with a similar historical control group (21 patients). C1-INH added to IVIG is safe and may improve allograft function in kidney recipients with nonresponsive acute ABMR. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Paneth and intestinal stem cells preserve their functional integrity during worsening of acute cellular rejection in small bowel transplantation.

PubMed

Pucci Molineris, M; Gonzalez Polo, V; Perez, F; Ramisch, D; Rumbo, M; Gondolesi, G E; Meier, D

2018-04-01

Graft survival after small bowel transplantation remains impaired due to acute cellular rejection (ACR), the leading cause of graft loss. Although it was shown that the number of enteroendocrine progenitor cells in intestinal crypts was reduced during mild ACR, no results of Paneth and intestinal stem cells localized at the crypt bottom have been shown so far. Therefore, we wanted to elucidate integrity and functionality of the Paneth and stem cells during different degrees of ACR, and to assess whether these cells are the primary targets of the rejection process. We compared biopsies from ITx patients with no, mild, or moderate ACR by immunohistochemistry and quantitative PCR. Our results show that numbers of Paneth and stem cells remain constant in all study groups, whereas the transit-amplifying zone is the most impaired zone during ACR. We detected an unchanged level of antimicrobial peptides in Paneth cells and similar numbers of Ki-67 + IL-22R + stem cells revealing cell functionality in moderate ACR samples. We conclude that Paneth and stem cells are not primary target cells during ACR. IL-22R + Ki-67 + stem cells might be an interesting target cell population for protection and regeneration of the epithelial monolayer during/after a severe ACR in ITx patients. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Two-Stage, In Silico Deconvolution of the Lymphocyte Compartment of the Peripheral Whole Blood Transcriptome in the Context of Acute Kidney Allograft Rejection

PubMed Central

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

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

PubMed

Arjona, Alvaro

2009-09-01

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

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.

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

PubMed

Bowman, Caitlin R; Dennis, Nancy A

2016-08-01

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

Recurrent AA Amyloidosis Combined With Chronic Active Antibody-mediated Rejection After Kidney Transplantation.

PubMed

Yeo, Min-Kyung; Ham, Young Rok; Choi, Song-Yi; Lee, Yong-Moon; Park, Moon Hyang; Suh, Kwang-Sun

2017-07-01

Kidney transplantation for amyloidosis remains a contentious issue. Recurrence of amyloidosis is one of the risks of transplantation. Chronic active antibody-mediated rejection is an important cause of chronic allograft dysfunction. A 47-year-old woman underwent kidney transplantation due to renal AA amyloidosis with unknown etiology. Six years posttransplantation, a kidney biopsy showed AA amyloidosis with chronic active antibody-mediated rejection. Donor-specific antibody class II was positive. The patient underwent intravenous plasmapheresis and treatment with rituximab and colchicine. The relationship between recurrence of amyloidosis and rejection was not obvious. Clinical characteristics of kidney transplantation for AA amyloidosis were subjected to literature review and 315 cases were identified. The incidence of amyloidosis recurrence and acute and chronic rejection rates were 15%, 15%, and 8%, respectively. Five-year patient and graft survival rates were 77% and 82%, respectively. Clinical courses of kidney transplantation in AA amyloidosis were, thus, identified.

The Relationship of the Severity and Category of Acute Rejection With Intimal Arteritis Defined in Banff Classification to Clinical Outcomes.

PubMed

Wu, Kaiyin; Budde, Klemens; Schmidt, Danilo; Neumayer, Hans-Helmut; Rudolph, Birgit

2015-08-01

It is unclear if the category of acute rejection with intimal arteritis (ARV) is relevant to short- and long-term clinical outcomes and if the graft outcomes are affected by the severity of intimal arteritis. One hundred forty-eight ARV episodes were reviewed and categorized according to the 2013 Banff criteria of AMR: T cell-mediated rejection with intimal arteritis (v) lesion (TCMRV; n = 78), total antibody-mediated rejection with v lesion (AMRV), which were further divided into suspicious AMRV (n = 37) and AMRV (n = 33). The Banff scores of intimal arteritis (v1, v2 and v3) represented low, moderate, and high ARV severity. The grafts with TCMRV, suspicious AMRV (sAMRV), and AMRV showed similar responses to antirejection therapy, whereas the grafts with v2- or v3-ARV responded significantly poorer compared to those with v1-ARV. The 8-year death-censored graft survival (DCGS) rate was 56.8% of TCMRV versus 34.1% of total AMRV (Log rank, P = 0.03), but the 1- and 5-year DCGS rates were comparable between the 2 groups; moreover, the 1-, 5-, and 8-year DCGS rates of v1-ARV were evidently higher than v2- and v3-ARV (each pairwise comparison to v1-AVR yields P < 0.01); in contrast, the DCGS rates were similar between sAMRV and AMRV. The existing donor-specific antibodies or moderate microvascular inflammation or C4d-positive staining or intensive tubulointerstitial inflammation played a less significant role on the long-term graft survival. Compared to the category, the ARV severity is more closely associated with the initial response to antirejection therapy and long-term graft failure. The sAMRV and AMRV might represent a spectrum of the same disorder.

Soluble CD30 and ELISA-detected human leukocyte antigen antibodies for the prediction of acute rejection in pediatric renal transplant recipients.

PubMed

Billing, Heiko; Sander, Anja; Süsal, Caner; Ovens, Jörg; Feneberg, Reinhard; Höcker, Britta; Vondrak, Karel; Grenda, Ryszard; Friman, Stybjorn; Milford, David V; Lucan, Mihai; Opelz, Gerhard; Tönshoff, Burkhard

2013-03-01

Biomarker-based post-transplant immune monitoring for the prediction of impending graft rejection requires validation in specific patient populations. Serum of 28 pediatric renal transplant recipients within the framework of a well-controlled prospective randomized trial was analyzed pre- and post-transplant for soluble CD30 (sCD30), a biomarker reflecting mainly T-cell reactivity, and anti-human leukocyte antigen (anti-HLA) antibody reactivity, a biomarker for B-cell activation. A sCD30 concentration ≥40.3 U/ml on day 14 was able to discriminate between patients with or without biopsy-proven acute rejection (BPAR) with a sensitivity of 100% and a specificity of 76%. Six of seven patients (86%) with BPAR showed a sCD30 above this cut-off, whereas only 3/21 patients (14%) without BPAR had a sCD30 above this cut-off (P = 0.004). For pre- and post-transplant anti-HLA class II reactivities by enzyme-linked immunosorbent assay, a cut-off value of 140 optical density was able to discriminate rejecters from nonrejecters with a sensitivity of 86% or 71% and a specificity of 81% or 90%, respectively. Withdrawal of steroids was associated with a approximately twofold higher serum sCD30 compared to controls, but did not affect anti-HLA reactivities. An increased post-transplant sCD30 serum concentration and positive pre- and post-transplant anti-HLA class II reactivities are informative biomarkers for impending BPAR in pediatric renal transplant recipients. (TWIST, Clinical Trial No: FG-506-02-43). © 2012 The Authors Transplant International © 2012 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.

Pretransplantation soluble CD30 level as a predictor of acute rejection in kidney transplantation: a meta-analysis.

PubMed

Chen, Yile; Tai, Qiang; Hong, Shaodong; Kong, Yuan; Shang, Yushu; Liang, Wenhua; Guo, Zhiyong; He, Xiaoshun

2012-11-15

The question of whether high pretransplantation soluble CD30 (sCD30) level can be a predictor of kidney transplant acute rejection (AR) is under debate. Herein, we performed a meta-analysis on the predictive efficacy of sCD30 for AR in renal transplantation. PubMed (1966-2012), EMBASE (1988-2012), and Web of Science (1986-2012) databases were searched for studies concerning the predictive efficacy of sCD30 for AR after kidney transplantation. After a careful review of eligible studies, sensitivity, specificity, and other measures of the accuracy of sCD30 were pooled. A summary receiver operating characteristic curve was used to represent the overall test performance. Twelve studies enrolling 2507 patients met the inclusion criteria. The pooled estimates for pretransplantation sCD30 in prediction of allograft rejection risk were poor, with a sensitivity of 0.70 (95% confidence interval (CI), 0.66-0.74), a specificity of 0.48 (95% CI, 0.46-0.50), a positive likelihood ratio of 1.35 (95% CI, 1.20-1.53), a negative likelihood ratio of 0.68 (95% CI, 0.55-0.84), and a diagnostic odds ratio of 2.07 (95% CI, 1.54-2.80). The area under curve of the summary receiver operating characteristic curve was 0.60, indicating poor overall accuracy of the serum sCD30 level in the prediction of patients at risk for AR. The results of the meta-analysis show that the accuracy of pretransplantation sCD30 for predicting posttransplantation AR was poor. Prospective studies are needed to clarify the usefulness of this test for identifying risks of AR in transplant recipients.

Digital radiography reject analysis: data collection methodology, results, and recommendations from an in-depth investigation at two hospitals.

PubMed

Foos, David H; Sehnert, W James; Reiner, Bruce; Siegel, Eliot L; Segal, Arthur; Waldman, David L

2009-03-01

Reject analysis was performed on 288,000 computed radiography (CR) image records collected from a university hospital (UH) and a large community hospital (CH). Each record contains image information, such as body part and view position, exposure level, technologist identifier, and--if the image was rejected--the reason for rejection. Extensive database filtering was required to ensure the integrity of the reject-rate calculations. The reject rate for CR across all departments and across all exam types was 4.4% at UH and 4.9% at CH. The most frequently occurring exam types with reject rates of 8% or greater were found to be common to both institutions (skull/facial bones, shoulder, hip, spines, in-department chest, pelvis). Positioning errors and anatomy cutoff were the most frequently occurring reasons for rejection, accounting for 45% of rejects at CH and 56% at UH. Improper exposure was the next most frequently occurring reject reason (14% of rejects at CH and 13% at UH), followed by patient motion (11% of rejects at CH and 7% at UH). Chest exams were the most frequently performed exam at both institutions (26% at UH and 45% at CH) with half captured in-department and half captured using portable x-ray equipment. A ninefold greater reject rate was found for in-department (9%) versus portable chest exams (1%). Problems identified with the integrity of the data used for reject analysis can be mitigated in the future by objectifying quality assurance (QA) procedures and by standardizing the nomenclature and definitions for QA deficiencies.

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

Urinary C‑X‑C motif chemokine 13 is a noninvasive biomarker of antibody‑mediated renal allograft rejection.

PubMed

Chen, Dajin; Zhang, Jian; Peng, Wenhan; Weng, Chunhua; Chen, Jianghua

2018-06-22

Noninvasive monitoring methods of immune status are preferred by transplant recipients. The present study investigated whether urinary C‑X‑C motif chemokine 13 (CXCL13) had the potential to reflect ongoing immune processes within renal allografts. Using an ELISA assay, the level of urinary CXCL13 was quantified in a total of 146 renal allograft recipients and 40 healthy controls at scheduled intervals and at the time of the indicated or protocol biopsy. The results of the present study revealed that urinary CXCL13/creatinine (Cr) was lower in normal transplants compared with in those with acute tubular necrosis (ATN; P=0.001), chronic allograft nephropathy (CAN; P=0.01), and acute rejection (AR; P<0.0001), which was associated with a good diagnostic performance for AR [area under the curve (AUC)=0.818, P<0.0001). In addition, urinary CXCL13/Cr levels in patients with AR were also higher than that of patients with graft dysfunction but no rejection, including ATN and CAN (P=0.034). Notably, urinary CXCL13 distinguished between acute antibody‑mediated rejection (ABMR) and acute cellular rejection, with an AUC of 0.856. Furthermore, patients with steroid‑resistant AR exhibited significantly increased urinary CXCL13/Cr levels than patients with reversible AR (P=0.001). Additionally, elevated levels of urinary CXCL13/Cr within the first month of transplant were predictive of graft function at 3 and 6 months (P=0.044 and P=0.04, respectively). Collectively, the findings of the present study indicated that the noninvasive investigation of urinary CXCL13/Cr may be valuable for the detection of AR, particularly ABMR. In addition, high urinary CXCL13/Cr levels predicted a poor response to steroid treatment and compromised graft function.

Imaging mouse lung allograft rejection with 1H MRI

PubMed Central

Guo, Jinbang; Huang, Howard J.; Wang, Xingan; Wang, Wei; Ellison, Henry; Thomen, Robert P.; Gelman, Andrew E.; Woods, Jason C.

2014-01-01

Purpose To demonstrate that longitudinal, non-invasive monitoring via MRI can characterize acute cellular rejection (ACR) in mouse orthotopic lung allografts. Methods Nineteen Balb/c donor to C57BL/6 recipient orthotopic left lung transplants were performed, further divided into control-Ig vs anti-CD4/anti-CD8 treated groups. A two-dimensional multi-slice gradient-echo pulse sequence synchronized with ventilation was used on a small-animal MR scanner to acquire proton images of lung at post-operative days 3, 7 and 14, just before sacrifice. Lung volume and parenchymal signal were measured, and lung compliance was calculated as volume change per pressure difference between high and low pressures. Results Normalized parenchymal signal in the control-Ig allograft increased over time, with statistical significance between day 14 and day 3 post transplantation (0.046→0.789, P < 0.05), despite large inter-mouse variations; this was consistent with histopathologic evidence of rejection. Compliance of the control-Ig allograft decreased significantly over time (0.013→0.003, P < 0.05), but remained constant in mice treated with anti-CD4/anti-CD8 antibodies. Conclusion Lung allograft rejection in individual mice can be monitored by lung parenchymal signal changes and by lung compliance through MRI. Longitudinal imaging can help us better understand the time course of individual lung allograft rejection and response to treatment. PMID:24954886

Imaging mouse lung allograft rejection with (1)H MRI.

PubMed

Guo, Jinbang; Huang, Howard J; Wang, Xingan; Wang, Wei; Ellison, Henry; Thomen, Robert P; Gelman, Andrew E; Woods, Jason C

2015-05-01

To demonstrate that longitudinal, noninvasive monitoring via MRI can characterize acute cellular rejection in mouse orthotopic lung allografts. Nineteen Balb/c donor to C57BL/6 recipient orthotopic left lung transplants were performed, further divided into control-Ig versus anti-CD4/anti-CD8 treated groups. A two-dimensional multislice gradient-echo pulse sequence synchronized with ventilation was used on a small-animal MR scanner to acquire proton images of lung at postoperative days 3, 7, and 14, just before sacrifice. Lung volume and parenchymal signal were measured, and lung compliance was calculated as volume change per pressure difference between high and low pressures. Normalized parenchymal signal in the control-Ig allograft increased over time, with statistical significance between day 14 and day 3 posttransplantation (0.046→0.789; P < 0.05), despite large intermouse variations; this was consistent with histopathologic evidence of rejection. Compliance of the control-Ig allograft decreased significantly over time (0.013→0.003; P < 0.05), but remained constant in mice treated with anti-CD4/anti-CD8 antibodies. Lung allograft rejection in individual mice can be monitored by lung parenchymal signal changes and by lung compliance through MRI. Longitudinal imaging can help us better understand the time course of individual lung allograft rejection and response to treatment. © 2014 Wiley Periodicals, Inc.

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.

Immune response and histology of humoral rejection in kidney transplantation.

PubMed

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

2016-01-01

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

Interleukin-10-1082 G/a polymorphism and acute renal graft rejection: a meta-analysis.

PubMed

Hu, Qiongwen; Tian, Hua; Wu, Qing; Li, Jun; Cheng, Xiaocheng; Liao, Pu

2016-01-01

The aim of this study was to investigate the association between interleukin (IL)-10-1082 (G/A) promoter polymorphism and acute rejection (AR) in renal transplant recipients. We searched MEDLINE, EMBASE, Web of Science, and Cochrane Central Register from the inception to March 2015 for relevant studies. Data concerning publication information, population characteristics, and transplant information were extracted. Odds ratios (ORs) was calculated for the association between IL-10-1082 GG genotype (or IL-10-1082 G allele) and AR risk. This meta-analysis included 22 case-control studies including 2779 cases of renal transplant recipients. The pooled estimate showed that the IL-10-1082 GG genotype was not significantly associated with AR risk (ORrandom=1.07, 95% CI 0.80-1.43, p = 0.64). Similarly, the pooled estimate showed that the IL-10-1082 G allele was not significantly associated with AR risk (ORfixed=1.02, 95% CI 0.90-1.16, p = 0.74). None of subgroup analyses yielded significant results in the association between IL-10-1082 GG genotype (or IL-10-1082 G allele) and AR risk. Meta-regression confirmed that there was no significant correlation between the pre-selected trial characteristics and our study results. This meta-analysis suggests that IL-10-1082 G/A polymorphism is not significantly associated with AR risk in renal transplant recipients.

Rejection sensitivity moderates the impact of rejection on self-concept clarity.

PubMed

Ayduk, Ozlem; Gyurak, Anett; Luerssen, Anna

2009-11-01

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.

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.

RNaseI from Escherichia coli cannot substitute for S-RNase in rejection of Nicotiana plumbaginifolia pollen.

PubMed

Beecher, B; Murfett, J; McClure, B A

1998-03-01

Unilateral incompatibility often occurs between self-incompatible (SI) species and their self-compatible (SC) relatives. For example, SI Nicotiana alata rejects pollen from SC N. plumbaginifolia, but the reciprocal pollination is compatible. This interspecific pollen rejection system closely resembles intraspecific S-allele-specific pollen rejection. However, the two systems differ in degree of specificity. In SI, rejection is S-allele-specific, meaning that only a single S-RNase causes rejection of pollen with a specific S genotype. Rejection of N. plumbaginifolia pollen is less specific, occurring in response to almost any S-RNase. Here, we have tested whether a non-S-RNase can cause rejection of N. plumbaginifolia pollen. The Escherichia coli rna gene encoding RNAseI was engineered for expression in transgenic (N. plumbaginifolia x SC N. alata) hybrids. Expression levels and pollination behavior of hybrids expressing E. coli RNaseI were compared to controls expressing SA2-RNase from N. alata. Immunoblot analysis and RNase activity assays showed that RNaseI and SA2-RNase were expressed at comparable levels. However, expression of SA2-RNase caused rejection of N. plumbaginifolia pollen, whereas expression of RNaseI did not. Thus, in this system, RNase activity alone is not sufficient for rejection of N. plumbaginifolia pollen. The results suggest that S-RNases may be specially adapted to function in pollen rejection.

Intermediate-term graft loss after renal transplantation is associated with both donor-specific antibody and acute rejection.

PubMed

Devos, Jennifer M; Gaber, Ahmed Osama; Teeter, Larry D; Graviss, Edward A; Patel, Samir J; Land, Geoffrey A; Moore, Linda W; Knight, Richard J

2014-03-15

Renal transplant recipients with de novo DSA (dDSA) experience higher rates of rejection and worse graft survival than dDSA-free recipients. This study presents a single-center review of dDSA monitoring in a large, multi-ethnic cohort of renal transplant recipients. The authors performed a nested case-control study of adult kidney and kidney-pancreas recipients from July 2007 through July 2011. Cases were defined as dDSA-positive whereas controls were all DSA-negative transplant recipients. DSA were determined at 1, 3, 6, 9, and 12 months posttransplant, and every 6 months thereafter. Of 503 recipients in the analysis, 24% developed a dDSA, of whom 73% had dDSA against DQ antigen. Median time to dDSA was 6.1 months (range 0.2-44.6 months). After multivariate analysis, African American race, kidney-pancreas recipient, and increasing numbers of human leukocyte antigen mismatches were independent risk factors for dDSA. Recipients with dDSA were more likely to suffer an acute rejection (AR) (35% vs. 10%, P<0.001), an antibody-mediated AR (16% vs. 0.3%, P<0.001), an AR ascribed to noncompliance (8% vs. 2%, P=0.001), and a recurrent AR (6% vs. 1%, P=0.002) than dDSA-negative recipients. At a median follow-up of 31 months, the death-censored actuarial graft survival of dDSA recipients was worse than the DSA-free cohort (P=0.002). Yet, for AR-free recipients, there was no difference in graft survival between cohorts (P=0.66). Development of dDSA was associated with an increased incidence of graft loss, yet the detrimental effect of dDSA was limited in the intermediate term to recipients with AR.

Enhanced B Cell Alloantigen Presentation and Its Epigenetic Dysregulation in Liver Transplant Rejection.

PubMed

Ningappa, M; Ashokkumar, C; Higgs, B W; Sun, Q; Jaffe, R; Mazariegos, G; Li, D; Weeks, D E; Subramaniam, S; Ferrell, R; Hakonarson, H; Sindhi, R

2016-02-01

T cell suppression prevents acute cellular rejection but causes life-threatening infections and malignancies. Previously, liver transplant (LTx) rejection in children was associated with the single-nucleotide polymorphism (SNP) rs9296068 upstream of the HLA-DOA gene. HLA-DOA inhibits B cell presentation of antigen, a potentially novel antirejection drug target. Using archived samples from 122 white pediatric LTx patients (including 77 described previously), we confirmed the association between rs9296068 and LTx rejection (p = 0.001, odds ratio [OR] 2.55). Next-generation sequencing revealed that the putative transcription factor (CCCTC binding factor [CTCF]) binding SNP locus rs2395304, in linkage disequilibrium with rs9296068 (D' 0.578, r(2) = 0.4), is also associated with LTx rejection (p = 0.008, OR 2.34). Furthermore, LTx rejection is associated with enhanced B cell presentation of donor antigen relative to HLA-nonidentical antigen in a novel cell-based assay and with a downregulated HLA-DOA gene in a subset of these children. In lymphoblastoid B (Raji) cells, rs2395304 coimmunoprecipitates with CTCF, and CTCF knockdown with morpholino antisense oligonucleotides enhances alloantigen presentation and downregulates the HLA-DOA gene, reproducing observations made with HLA-DOA knockdown and clinical rejection. Alloantigen presentation is suppressed by inhibitors of methylation and histone deacetylation, reproducing observations made during resolution of rejection. Enhanced donor antigen presentation by B cells and its epigenetic dysregulation via the HLA-DOA gene represent novel opportunities for surveillance and treatment of transplant rejection. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Combating the sting of rejection with the pleasure of revenge: A new look at how emotion shapes aggression.

PubMed

Chester, David S; DeWall, C Nathan

2017-03-01

How does emotion explain the relationship between social rejection and aggression? Rejection reliably damages mood, leaving individuals motivated to repair their negatively valenced affective state. Retaliatory aggression is often a pleasant experience. Rejected individuals may then harness revenge's associated positive affect to repair their mood. Across 6 studies (total N = 1,516), we tested the prediction that the rejection-aggression link is motivated by expected and actual mood repair. Further, we predicted that this mood repair would occur through the positive affect of retaliatory aggression. Supporting these predictions, naturally occurring (Studies 1 and 2) and experimentally manipulated (Studies 3 and 4) motives to repair mood via aggression moderated the rejection-aggression link. These effects were mediated by sadistic impulses toward finding aggression pleasant (Studies 2 and 4). Suggesting the occurrence of actual mood repair, rejected participants' affective states were equivalent to their accepted counterparts after an act of aggression (Studies 5 and 6). This mood repair occurred through a dynamic interplay between preaggression affect and aggression itself, and was driven by increases in positive affect (Studies 5 and 6). Together, these findings suggest that the rejection-aggression link is driven, in part, by the desire to return to affective homeostasis. Additionally, these findings implicate aggression's rewarding nature as an incentive for rejected individuals' violent tendencies. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Acute aortic dissection occurring during the butterfly stroke in a 12-year-old boy.

PubMed

Uchida, Keiji; Imoto, Kiyotaka; Yanagi, Hiromasa; Date, Koichiro

2009-08-01

A 12-year-old boy had severe chest and back pain of sudden onset while practicing the butterfly stroke in a swimming class. Computed tomography revealed an intimal flap in the descending thoracic aorta with massive right hemothorax. A ruptured type B acute aortic dissection was diagnosed, and then he collapsed. We totally replaced the descending aorta with a woven polyester prosthetic graft during deep hypothermic circulatory arrest. Hemostasis was achieved, but consciousness was not regained after operation, and multiple organ failure occurred. He died on the fifth postoperative day. He and his family had no history of cardiovascular disease. It seems that the swimming provoked a severe Valsalva maneuver, raising blood pressure acutely and thereby leading to dissection. This is then analogous to the propensity for dissection during intense isometic exercise such as weightlifting.

Delayed xenograft rejection.

PubMed

Hancock, W W

1997-01-01

The triumph of genetic engineering in overcoming hyperacute rejection (HAR) of a discordant organ xenograft is clear, but the promise of clinical application of xenotransplantation remains unfulfilled as further immunologic barriers are defined that lead to rejection of a vascularized xenograft within days of transplantation. This report describes the features of this second set of immunologic responses, collectively termed delayed xenograft rejection (DXR). DXR is a syndrome seen in xenograft recipients in which HAR has been avoided or suppressed by antibody depletion or blockade of complement activation. DXR may result, at least in part, from the persisting activation of those pathways first encountered during the HAR phase. Serial studies over several days after transplant show that, histologically, xenografts undergoing DXR demonstrate varying combinations of (1) progressive infiltration by activated macrophages and natural killer (NK) cells, (2) platelet aggregation and fibrin deposition throughout the microvasculature, and (3) endothelial activation. In various experimental models, DXR is T cell-independent and can occur in the absence of demonstrable xenoreactive antibodies. Hence DXR is probably best regarded as arising from the activation of innate host defense mechanisms coupled with failure of normal regulatory mechanisms due to manifold molecular incompatibilities. Although DXR-like features can be seen in concordant models, T cell involvement in the latter is probably requisite. Similarly, in a much muted form, aspects of a DXR-like process may contribute to numerous inflammatory processes, including allograft rejection. The importance of DXR in xenotransplantation is that its development appears resistant to all but the most dense and toxic forms of immunosuppression, which prolong xenograft survival at the expense of inducing host leukopenia, thrombocytopenia, and coagulopathies. It is likely that until the basis of DXR is more clearly understood

Purtscher's retinopathy that occurred 6 months before acute pancreatitis.

PubMed

Sharma, Ashish G; Kazim, Nadia A; Eliott, Dean; Houghton, Odette; Abrams, Gary W

2006-01-01

To report Purtscher's retinopathy in a patient with chronic pancreatitis 6 months before the development of fulminant acute pancreatitis. Observational case report. Review of clinical chart, photographs, fluorescein angiography, and optical coherence tomography. A 45-year-old man with a history of alcohol abuse with a 3-day history of decreased vision in both eyes was examined. Diffuse retinal whitening and intraretinal hemorrhages that were consistent with Purtscher's retinopathy were present in both eyes. Serum amylase and lipase levels were normal. Six months later, he experienced intractable abdominal pain. Serum amylase and lipase levels were elevated markedly. Abdominal computed tomography and endoscopic retrograde cholangiopancreatography confirmed acute pancreatitis, with evidence of coexisting chronic pancreatitis. His funduscopic examination after the development of acute pancreatitis was improved, with almost complete resolution of retinal whitening and hemorrhages. Visual acuity remained poor because of retinal ischemia. Purtscher's retinopathy can be associated with chronic pancreatitis and can precede the development of fulminant acute pancreatitis.

Interleukin-10-1082G/A polymorphism and acute liver graft rejection: A meta-analysis

PubMed Central

Liu, Fei; Li, Bo; Wang, Wen-Tao; Wei, Yong-Gang; Yan, Lv-Nan; Wen, Tian-Fu; Xu, Ming-Qing; Yang, Jia-Yin

2012-01-01

AIM: To investigate the association between interleukin (IL)-10-1082 (G/A) promoter polymorphism and acute rejection (AR) in liver transplant (LT) recipients. METHODS: Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Databases. Summary odds ratios (ORs) and 95% CIs for IL-10-1082 G/A polymorphism and AR were calculated in a fixed- and a random-effects model as appropriate. RESULTS: This meta-analysis included seven case-control studies, which comprised 652 cases of LT recipients in which 241 cases developed AR and 411 cases did not develop AR. Overall, the variant A allele was not associated with AR risk when compared with the wild-type G allele (OR = 0.94, 95% CI: 0.64-1.39). Moreover, similar results were observed when the AA genotype was compared with the AG/GG genotype (OR = 1.05, 95% CI: 0.55-2.02). When stratifying for ethnicity, no significant association was observed among either Caucasians or Asians. Because only one study was performed in Asian patients, the result of subgroup analysis by ethnicity would not be reliable for Asians. Limiting the analysis to the studies with controls in the Hardy-Weinberg equilibrium, the results were persistent and robust. No publication bias was found in the present study. CONCLUSION: This meta-analysis suggests that IL-10-1082 G/A polymorphism may be not associated with AR risk in LT recipients among Caucasians. PMID:22371646

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

PubMed

Bergler, Tobias; Jung, Bettina; Bourier, Felix; Kühne, Louisa; Banas, Miriam C; Rümmele, Petra; Wurm, Simone; Banas, Bernhard

2016-01-01

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

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

Use of OKT3 with Ciclosporin and Steroids for Reversal of Acute Kidney and Liver Allograft Rejection 1

PubMed Central

Fung, John J.; Demetris, A. Jake; Porter, Kendrick A.; Iwatsuki, Shunzaburo; Gordon, Robert D.; Esquivel, Carlos O.; Jaffe, Ronald; Tzakis, Andreas; Shaw, Byers W.; Starzl, Thomas E.

2010-01-01

OKT3 monoclonal antibody therapy was added to preexisting baseline immunosuppressive treatment with ciclosporin and steroids to treat rejection in 52 recipients of cadaveric livers and 10 recipients of cadaveric kidneys. Rejection was controlled in 75% of patients treated, often after high-dose steroid therapy had failed. Rejection recurred during the 17-month follow-up period, after completion of OKT3, in only 25% of the patients who had responded. The safety and effectiveness of this monoclonal therapy, added to ciclosporin and steroids, has been established in this study. PMID:3306422

How to handle a rejection. Teaching course presentation at the 21st European Stroke Conference, Lisboa, May 2012.

PubMed

Venketasubramanian, Narayanaswamy; Hennerici, Michael G

2013-01-01

The rejection rate by scientific journals may be rather high, sometimes up to 70-90%. On receipt of notification of rejection, one may experience various stages of the Kübler-Ross grief cycle--denial, anger, bargaining, depression and acceptance, with an initial shock and an intermediate 'testing' stage. A paper may be rejected because of several reasons, such as the following: (1) it was submitted to an inappropriate journal, (2) journal format was not followed, (3) reading was not interesting or scientific/clinically sound, (4) topic was not current, (5) research was not novel, (6) low publication priority despite the absence of major flaws, (7) poor En-glish/writing style, (8) poor methods and statistics, (9) unbelievable results that were not properly discussed and (10) 'recycled' paper. Plagiarism is not tolerated. Simultaneous submission to 2 or more journals is not allowed. Outright rejection sometimes occurs in 70-80%; for 10-15%, the editor rejects without sending the paper to reviewers for obvious reasons as mentioned. For the majority, reviewers give feedback that leads to the editor rejecting the paper. On receiving notification of rejection, one should read the feedback and consider its contents prior to rewriting and submitting the paper to another journal (sometimes reviewers may see the same manuscript several times if asked by different editors). An invitation to resubmit 'de novo' occurs in only 1-5% of submissions; it requires substantial revision before resubmission. Being rejected but invited to resubmit a revised version occurs in 5-20% of submissions--it indicates a good chance of acceptance; one should carefully read the feedback and respond/comply with all suggestions. Papers rejected repeatedly may have 'fatal flaws' and are best abandoned. Copyright © 2013 S. Karger AG, Basel.

Banff schema for grading pancreas allograft rejection: working proposal by a multi-disciplinary international consensus panel.

PubMed

Drachenberg, C B; Odorico, J; Demetris, A J; Arend, L; Bajema, I M; Bruijn, J A; Cantarovich, D; Cathro, H P; Chapman, J; Dimosthenous, K; Fyfe-Kirschner, B; Gaber, L; Gaber, O; Goldberg, J; Honsová, E; Iskandar, S S; Klassen, D K; Nankivell, B; Papadimitriou, J C; Racusen, L C; Randhawa, P; Reinholt, F P; Renaudin, K; Revelo, P P; Ruiz, P; Torrealba, J R; Vazquez-Martul, E; Voska, L; Stratta, R; Bartlett, S T; Sutherland, D E R

2008-06-01

Accurate diagnosis and grading of rejection and other pathological processes are of paramount importance to guide therapeutic interventions in patients with pancreas allograft dysfunction. A multi-disciplinary panel of pathologists, surgeons and nephrologists was convened for the purpose of developing a consensus document delineating the histopathological features for diagnosis and grading of rejection in pancreas transplant biopsies. Based on the available published data and the collective experience, criteria for the diagnosis of acute cell-mediated allograft rejection (ACMR) were established. Three severity grades (I/mild, II/moderate and III/severe) were defined based on lesions known to be more or less responsive to treatment and associated with better- or worse-graft outcomes, respectively. The features of chronic rejection/graft sclerosis were reassessed, and three histological stages were established. Tentative criteria for the diagnosis of antibody-mediated rejection were also characterized, in anticipation of future studies that ought to provide more information on this process. Criteria for needle core biopsy adequacy and guidelines for pathology reporting were also defined. The availability of a simple, reproducible, clinically relevant and internationally accepted schema for grading rejection should improve the level of diagnostic accuracy and facilitate communication between all parties involved in the care of pancreas transplant recipients.

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. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Innate NK cells and macrophages recognize and reject allogeneic nonself in vivo via different mechanisms.

PubMed

Liu, Wentao; Xiao, Xiang; Demirci, Gulcin; Madsen, Joren; Li, Xian C

2012-03-15

Both innate and adaptive immune cells are involved in the allograft response. But how the innate immune cells respond to allotransplants remains poorly defined. In the current study, we examined the roles of NK cells and macrophages in recognizing and rejecting allogeneic cells in vivo. We found that in naive mice NK cells are the primary effector cells in the killing of allogeneic cells via "missing self" recognition. However, in alloantigen-presensitized mice, NK cells are dispensable. Instead, macrophages become alloreactive and readily recognize and reject allogeneic nonself. This effect requires help from activated CD4(+) T cells and involves CD40/CD40L engagement, because blocking CD40/CD40L interactions prevents macrophage-mediated rejection of allogeneic cells. Conversely, actively stimulating CD40 triggers macrophage-mediated rejection in the absence of CD4(+) T cells. Importantly, alloantigen-primed and CD4(+) T cell-helped macrophages (licensed macrophages) exhibit potent regulatory function in vivo in an acute graft-versus-host disease model. Together, our data uncover an important role for macrophages in the alloimmune response and may have important clinical implications.

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

PubMed

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

2010-02-01

Pre-transplant sera of 586 renal graft recipients were tested to investigate whether soluble CD30 (sCD30) is a useful predictor of some severe clinical episodes post-transplant. Correlation analysis showed sCD30 level was significantly correlated with acute rejection (AR) (r=0.242, P<0.001), graft loss (r=0.162, P<0.001), and pneumonia (r=-0.147, P<0.001). Higher sCD30 levels were observed in patients with AR than the others (180.0+/-89.1 vs. 135.3+/-72.7U/ml, P<0.001). And patients with pneumonia had significantly lower pre-transplant sCD30 level than the others (123.2+/-75.5 vs. 150.7+/-79.6U/ml, P=0.003). Based on statistical results, 120 and 240U/ml were selected as the optimal couple of cut-off value to divide patients into three groups: Group High (H), Group Intermedial (I) and Group Low (L). The lowest AR rate of 17.4% was observed in Group L (P<0.001). Significant difference of AR rate was also observed between Group I (29.2%) and H (42.9%) (P<0.001). There were much more patients suffering pneumonia in Group L (P=0.001). Significantly lower 5-year patient survival rate (79.4%) was observed in Group H (P=0.016). These data showed that elevated pre-transplant sCD30 level of renal allograft recipients may reflect an immune state detrimental for renal allograft survival. But sCD30 level lower than <120U/ml may be associated with a high risk of pneumonia. Pre-transplant sCD30 level is an independent predictor of acute rejection, lung infection, even graft survival. Suitable immunosuppression protocol should be selected according to pre-transplant sCD30 level in an attempt to promote patient and graft survival. Copyright 2010 Elsevier B.V. All rights reserved.

Counter-regulation of rejection activity against human liver grafts by donor PD-L1 and recipient PD-1 interaction.

PubMed

Shi, Xiao-Lei; Mancham, Shanta; Hansen, Bettina E; de Knegt, Robert J; de Jonge, Jeroen; van der Laan, Luc J W; Rivadeneira, Fernando; Metselaar, Herold J; Kwekkeboom, Jaap

2016-06-01

Co-inhibitory receptor-ligand interactions fine-tune immune responses by negatively regulating T cell functions. Our aim is to examine the involvement of co-inhibitory receptor-ligand pair PD-1/PD-L1 in regulating rejection after liver transplantation (LT) in humans. PD-L1/PD-1 expression in liver allograft was determined by immunohistochemistry or flow cytometry, and the effect of blockade was studied using graft-infiltrating T cells ex vivo. Five single nucleotide polymorphisms within PD-1 and PD-L1 genes were genotyped in 528 LT recipients and 410 donors, and associations with both early (⩽6months) and late (>6months) acute rejection were analyzed using Cox proportional-hazards regression model. The effect of PD-L1 rs4143815 on PD-L1 expression was analyzed using donor hepatic leukocytes. PD-L1 was expressed by hepatocytes, cholangiocytes and along the sinusoids in post-transplant liver allografts, and PD-1 was abundantly expressed on allograft-infiltrating T cells. PD-L1 blockade enhanced allogeneic proliferative responses of graft-infiltrating T cells. In the genetic association analysis, donor PD-L1 rs4143815 (CC/CG vs. GG; HR=0.230; p=0.002) and recipient PD-1 rs11568821 (AA/AG vs. GG; HR=3.739; p=0.004) were associated with acute rejection late after LT in multivariate analysis. Recipients carrying the PD-1 rs11568821 A allele who were transplanted with liver grafts of PD-L1 rs4143815 GG homozygous donors showed the highest risk for late acute rejection. PD-L1 rs4143815 is associated with differential PD-L1 expression on donor hepatic dendritic cells upon IFN-γ stimulation. Our data suggest that interplay between donor PD-L1 and recipient PD-1 counter-regulates rejection activity against liver grafts in humans. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The stylar 120 kDa glycoprotein is required for S-specific pollen rejection in Nicotiana.

PubMed

Hancock, C Nathan; Kent, Lia; McClure, Bruce A

2005-09-01

S-RNase participates in at least three mechanisms of pollen rejection. It functions in S-specific pollen rejection (self-incompatibility) and in at least two distinct interspecific mechanisms of pollen rejection in Nicotiana. S-specific pollen rejection and rejection of pollen from Nicotiana plumbaginifolia also require additional stylar proteins. Transmitting-tract-specific (TTS) protein, 120 kDa glycoprotein (120K) and pistil extensin-like protein III (PELP III) are stylar glycoproteins that bind S-RNase in vitro and are also known to interact with pollen. Here we tested whether these glycoproteins have a direct role in pollen rejection. 120K shows the most polymorphism in size between Nicotiana species. Larger 120K-like proteins are often correlated with S-specific pollen rejection. Sequencing results suggest that the polymorphism primarily reflects differences in glycosylation, although indels also occur in the predicted polypeptides. Using RNA interference (RNAi), we suppressed expression of 120K to determine if it is required for S-specific pollen rejection. Transgenic SC N. plumbaginifolia x SI Nicotiana alata (S105S105 or SC10SC10) hybrids with no detectable 120K were unable to perform S-specific pollen rejection. Thus, 120K has a direct role in S-specific pollen rejection. However, suppression of 120K had no effect on rejection of N. plumbaginifolia pollen. In contrast, suppression of HT-B, a factor previously implicated in S-specific pollen rejection, disrupts rejection of N. plumbaginifolia pollen. Thus, S-specific pollen rejection and rejection of N. plumbaginifolia pollen are mechanistically distinct, because they require different non-S-RNase factors.

Why do people reject unintended inequity? Responders' rejection in a truncated ultimatum game.

PubMed

Ohmura, Yu; Yamagishi, Toshio

2005-04-01

Rejection of an inequitable and yet unintended outcome in a truncated ultimatum game was examined in an experiment with 46 undergraduate students (27 men and 19 women) from a large national university in Japan. In an ultimatum game, one of two players, the proposer, makes an offer to divide a fixed-sum of money. The other player, the responder, decides whether to accept or reject the offer. When the responder rejects the proposer's offer, neither of the two players receives a reward. Previous work examining the behavior of participants in the truncated ultimatum game employed strategy method in their experimental design. We examined whether these previous findings would be replicated in an experimental design that did not use the strategy method and instead used the standard one-shot game. Seven out of 46 responders given an inequitable offer rejected it, replicating prior results with the strategy method. We further found that subjects who rejected an offer that was involuntary and yet inequitable did not over-attribute intentions to the proposer's involuntary behavior more strongly than did acceptors. These findings strongly suggest that aversion to inequity is the explanation for the subjects' rejection of the inequitable offer.

Artificial intelligence techniques: predicting necessity for biopsy in renal transplant recipients suspected of acute cellular rejection or nephrotoxicity.

PubMed

Hummel, A D; Maciel, R F; Sousa, F S; Cohrs, F M; Falcão, A E J; Teixeira, F; Baptista, R; Mancini, F; da Costa, T M; Alves, D; Rodrigues, R G D S; Miranda, R; Pisa, I T

2011-05-01

The gold standard for nephrotoxicity and acute cellular rejection (ACR) is a biopsy, an invasive and expensive procedure. More efficient strategies to screen patients for biopsy are important from the clinical and financial points of view. The aim of this study was to evaluate various artificial intelligence techniques to screen for the need for a biopsy among patients suspected of nephrotoxicity or ACR during the first year after renal transplantation. We used classifiers like artificial neural networks (ANN), support vector machines (SVM), and Bayesian inference (BI) to indicate if the clinical course of the event suggestive of the need for a biopsy. Each classifier was evaluated by values of sensitivity and area under the ROC curve (AUC) for each of the classifiers. The technique that showed the best sensitivity value as an indicator for biopsy was SVM with an AUC of 0.79 and an accuracy rate of 79.86%. The results were better than those described in previous works. The accuracy for an indication of biopsy screening was efficient enough to become useful in clinical practice. Copyright © 2011 Elsevier Inc. All rights reserved.

Abbreviated AUC monitoring of cyclosporine more adequately identified patients at risk for acute rejection during induction of immunosuppressive therapy after kidney transplantation than recommended C2 concentration values.

PubMed

Troncoso, P; Ortiz, A M; Jara, A; Vilches, S

2009-01-01

Monitoring of cyclosporine (CsA) is critical during the induction of immunosuppressive therapy. Although most centers have incorporated C2 levels, our unit still uses an abbreviated AUC model which includes concentrations at C1, C2, and C6 post-dose (AUC(1-6)). The objective of this study was to compare both strategies of CsA monitoring during the first 30 days after kidney transplantation. The study included 89 recipients induced with CsA microemulsion and steroids. AUC(1-6) profiles were performed around days 3, 10, and 30 after transplantation with a target of 5500 to 6000 ng*h/mL considered therapeutic. For comparison purposes, a value of C2 >/= 1500 ng/mL was also considered therapeutic. Mean C2 and AUC(1-6) values were low dated with biopsy-proven acute rejection episodes (BPAR) during the study period. Twenty patients received living donor kidneys and overall there were 46 females. During this period, 253 AUC(1-6) were performed including 44 (17.4%) below the therapeutic range. When the analysis included only C2, 171 (67.6%) were below the therapeutic target (P < .001). Five patients experience BPAR and only AUC(1-6) at day 10 discriminated rejectors versus nonrejectors (5645 +/- 1390 and 8221 +/- 2502, respectively; P = .008). C2 was not significantly different at any time in either group. In this study, abbreviated AUC monitoring more adequately identified patients at risk for acute rejection than C2. Recommended C2 concentration levels need to be redefined in our patients.

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

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

PubMed

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

2017-01-01

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

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

PubMed Central

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

2017-01-01

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

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 Central

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

2016-01-01

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+CD25highCD45RO+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. PMID:26270267

Early subclinical rejection as a risk factor for late chronic humoral rejection.

PubMed

Moreso, Francesc; Carrera, Marta; Goma, Montse; Hueso, Miguel; Sellares, Joana; Martorell, Jaume; Grinyó, Josep M; Serón, Daniel

2012-01-15

Subclinical rejection and interstitial fibrosis and tubular atrophy (IF/TA) in protocol biopsies are associated with outcome. We study the relationship between histologic lesions in early protocol biopsies and histologic diagnoses in late biopsies for cause. Renal transplants with a protocol biopsy performed within the first 6 months posttransplant between 1988 and 2006 were reviewed. Biopsies were evaluated according to Banff criteria, and C4d staining was available in biopsies for cause. Of the 517 renal transplants with a protocol biopsy, 109 had a subsequent biopsy for cause which showed the following histological diagnoses: chronic humoral rejection (CHR) (n=44), IF/TA (n=42), recurrence of the primary disease (n=11), de novo glomerulonephritis (n=7), T-cell-mediated rejection (n=4), and polyoma virus nephropathy (n=1). The proportion of retransplants (15.9% vs. 2.3%, P=0.058) and the prevalence of subclinical rejection were higher in patients with CHR than in patients with IF/TA (52.3% vs. 28.6%, P=0.0253). Demographic donor and recipient characteristics and clinical data at the time of protocol biopsy were not different between groups. Logistic regression analysis showed that subclinical rejection (relative risk, 2.52; 95% confidence interval, 1.1-6.3; P=0.047) but not retransplantation (relative risk, 6.7; 95% confidence interval, 0.8-58.8; P=0.085) was associated with CHR. Subclinical rejection in early protocol biopsies is associated with late appearance of CHR.

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

Defensive Physiological Reactions to Rejection

PubMed Central

Gyurak, Anett; Ayduk, Özlem

2014-01-01

We examined the hypothesis that rejection automatically elicits defensive physiological reactions in people with low self-esteem (SE) but that attentional control moderates this effect. Undergraduates (N = 67) completed questionnaire measures of SE and attentional control. Their eye-blink responses to startle probes were measured while they viewed paintings related to rejection and acceptance themes. The stimuli also included positive-, negative-, and neutral-valence control paintings unrelated to rejection. As predicted, compared with people high in SE, those low in SE showed stronger startle eye-blink responses to paintings related to rejection, but not to negative paintings. Paintings related to acceptance did not attenuate their physiological reactivity. Furthermore, attentional control moderated their sensitivity to rejection, such that low SE was related to greater eye-blink responses to rejection only among individuals who were low in attentional control. Implications of the role of attentional control as a top-down process regulating emotional reactivity in people with low SE are discussed. PMID:17894606

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.

Chemistry and haematology sample rejection and clinical impact in a tertiary laboratory in Cape Town.

PubMed

Jacobsz, Lourens A; Zemlin, Annalise E; Roos, Mark J; Erasmus, Rajiv T

2011-10-14

Recent publications report that up to 70% of total laboratory errors occur in the pre-analytical phase. Identification of specific problems highlights pre-analytic processes susceptible to errors. The rejection of unsuitable samples can lead to delayed turnaround time and affect patient care. A retrospective audit was conducted investigating the rejection rate of routine blood specimens received at chemistry and haematology laboratories over a 2-week period. The reasons for rejection and potential clinical impact of these rejections were investigated. Thirty patient files were randomly selected and examined to assess the impact of these rejections on clinical care. A total of 32,910 specimens were received during the study period, of which 481 were rejected, giving a rejection rate of 1.46%. The main reasons for rejection were inappropriate clotting (30%) and inadequate sample volume (22%). Only 51.7% of rejected samples were repeated and the average time for a repeat sample to reach the laboratory was about 5 days (121 h). Of the repeated samples, 5.1% had results within critical values. Examination of patient folders showed that in 40% of cases the rejection of samples had an impact on patient care. The evaluation of pre-analytical processes in the laboratory, with regard to sample rejection, allowed one to identify problem areas where improvement is necessary. Rejected samples due to factors out of the laboratory's control had a definite impact on patient care and can thus affect customer satisfaction. Clinicians should be aware of these factors to prevent such rejections.

Behavioral Response Generation and Selection of Rejected-Reactive Aggressive, Rejected-Nonaggressive, and Average Status Children.

ERIC Educational Resources Information Center

Wood, C. Nannette; Gross, Alan M.

2002-01-01

Examines response decision processes of rejected-reactive aggressive, rejected-nonaggressive and average children in terms of the presence or absence of behavioral response alternatives. Congruent with previous research, rejected-reactive aggressive children made significantly more hostile attributions and generated a higher number of aggressive…

Antibody-Mediated Rejection of Human Orthotopic Liver Allografts

PubMed Central

Demetris, A. Jake; Jaffe, Ron; Tzakis, A.; Ramsey, Glenn; Todo, S.; Belle, Steven; Esquivel, Carlos; Shapiro, Ron; Markus, Bernd; Mroczek, Elizabeth; Van Thiel, D. H.; Sysyn, Greg; Gordon, Robert; Makowka, Leonard; Starzl, Tom

1988-01-01

A clinicopathologic analysis of liver transplantation across major ABO blood group barriers was carried out 1) to determine if antibody-mediated (humoral) rejection was a cause of graft failure and if humoral rejection can be identified, 2) to propose criteria for establishing the diagnosis, and 3) to describe the clinical and pathologic features of humoral rejection. A total of 51 (24 primary) ABO-incompatible (ABO-I) liver grafts were transplanted into 49 recipients. There was a 46% graft failure rate during the first 30 days for primary ABO-I grafts compared with an 11% graft failure rate for primary ABO compatible (ABO-C), crossmatch negative, age, sex and priority-matched control patients (P < 0.02). A similarly high early graft failure rate (60%) was seen for nonprimary ABO-I grafts during the first 30 days. Clinically, the patients experienced a relentless rise in serum transaminases, hepatic failure, and coagulopathy during the first weeks after transplant. Pathologic examination of ABO-I grafts that failed early demonstrated widespread areas of geographic hemorrhagic necrosis with diffuse intraorgan coagulation. Prominent arterial deposition of antibody and complement components was demonstrated by immunoflourescent staining. Elution studies confirmed the presence of tissue-bound, donor-specific isoagglutinins within the grafts. No such deposition was seen in control cases. These studies confirm that antibody mediated rejection of the liver occurs and allows for the development of criteria for establishing the diagnosis. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6 PMID:3046369

History of Abuse and Risky Sex among Substance Users: The Role of Rejection Sensitivity and the Need to Belong

PubMed Central

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

2016-01-01

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 = .124, SE = .040, p = .002), which was in turn associated with increased risky sex (B = .06, SE = .028, p = .03) (indirect effect = .0075, SE = .0043; 95% CI [.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

Antibody-Mediated Rejection of Single Class I MHC-Disparate Cardiac Allografts

PubMed Central

Hattori, Yusuke; Bucy, R. Pat; Kubota, Yoshinobu; Baldwin, William M.; Fairchild, Robert L.

2012-01-01

Murine CCR5−/− recipients produce high titers of antibody to complete MHC-mismatched heart and renal allografts. To study mechanisms of class I MHC antibody-mediated allograft injury, we tested the rejection of heart allografts transgenically expressing a single class I MHC disparity in wild-type C57BL/6 (H-2b) and B6.CCR5−/− recipients. Donor-specific antibody titers in CCR5−/− recipients were 30-fold higher than in wild-type recipients. B6.Kd allografts survived longer than 60 days in wild-type recipients whereas CCR5−/− recipients rejected all allografts within 14 days. Rejection was accompanied by infiltration of CD8 T cells, neutrophils, and macrophages and C4d deposition in the graft capillaries. B6.Kd allografts were rejected by CD8−/−/CCR5−/−, but not μMT−/−/CCR5−/−, recipients indicating the need for antibody but not CD8 T cells. Grafts retrieved at day 10 from CCR5−/− and CD8−/−/CCR5−/− recipients and from RAG-1−/− allograft recipients injected with anti-Kd antibodies expressed high levels of perforin, myeloperoxidase and CCL5 mRNA. These studies indicate that the continual production of anti-donor class I MHC antibody can mediate allograft rejection, that donor-reactive CD8 T cells synergize with the antibody to contribute to rejection, and that expression of three biomarkers during rejection can occur in the absence of this CD8 T cell activity. PMID:22578247

Proton Pump Inhibitors Independently Protect Against Early Allograft Injury or Chronic Rejection After Lung Transplantation.

PubMed

Lo, Wai-Kit; Goldberg, Hilary J; Boukedes, Steve; Burakoff, Robert; Chan, Walter W

2018-02-01

Acid reflux has been associated with poor outcomes following lung transplantation. Unlike surgical fundoplication, the role of noninvasive, pharmacologic acid suppression remains uncertain. To assess the relationship between post-transplant acid suppression with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) and onset of early allograft injury or chronic rejection following lung transplantation. This was a retrospective cohort study of lung transplant recipients at a tertiary center in 2007-2014. Patients with pre-transplant antireflux surgery were excluded. Time-to-event analysis using the Cox proportional hazards model was applied to assess acid suppression therapy and onset of acute or chronic rejection, defined histologically and clinically. Subgroup analyses were performed to assess PPI versus H2RA use. A total of 188 subjects (60% men, mean age 54, follow-up 554 person-years) met inclusion criteria. During follow-up, 115 subjects (61.5%) developed rejection, with all-cause mortality of 27.6%. On univariate analyses, acid suppression and BMI, but not other patient demographics, were associated with rejection. The Kaplan-Meier curve demonstrated decreased rejection with use of acid suppression therapy (log-rank p = 0.03). On multivariate analyses, acid suppression (HR 0.39, p = 0.04) and lower BMI (HR 0.67, p = 0.04) were independently predicted against rejection. Subgroup analyses demonstrated that persistent PPI use was more protective than H2RA or no antireflux medications. Post-lung transplant exposure to persistent PPI therapy results in the greatest protection against rejection in lung transplant recipients, independent of other clinical predictors including BMI, suggesting that PPI may have antireflux or anti-inflammatory effects in enhancing allograft protection.

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

PubMed

Plaisier, Xanthe S; Konijn, Elly A

2013-06-01

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

Rejection sensitivity prospectively predicts increased rumination.

PubMed

Pearson, Katherine A; Watkins, Edward R; Mullan, Eugene G

2011-10-01

Converging research findings indicate that rumination is correlated with a specific maladaptive interpersonal style encapsulating submissive (overly-accommodating, non-assertive and self-sacrificing) behaviours, and an attachment orientation characterised by rejection sensitivity. This study examined the prospective longitudinal relationship between rumination, the submissive interpersonal style, and rejection sensitivity by comparing two alternative hypotheses: (a) the submissive interpersonal style and rejection sensitivity prospectively predict increased rumination; (b) rumination prospectively predicts the submissive interpersonal style and rejection sensitivity. Currently depressed (n = 22), previously depressed (n = 42) and never depressed (n = 28) individuals completed self-report measures assessing depressive rumination and key psychosocial measures of interpersonal style and behaviours, at baseline and again six months later. Baseline rejection sensitivity prospectively predicted increased rumination six months later, after statistically controlling for baseline rumination, gender and depression. Baseline rumination did not predict the submissive interpersonal style or rejection sensitivity. The results provide a first step towards delineating a potential casual relationship between rejection sensitivity and rumination, and suggest the potential value of clinical assessment and intervention for both rejection sensitivity and rumination in individuals who present with either difficulty. Copyright © 2011 Elsevier Ltd. All rights reserved.

Individual differences in the rejection-aggression link in the hot sauce paradigm: The case of Rejection Sensitivity

PubMed Central

Ayduk, Özlem; Gyurak, Anett; Luerssen, Anna

2008-01-01

Prior research shows that social rejection elicits aggression. In this study, we investigated whether this is moderated by individual differences in Rejection Sensitivity (RS) – a processing disposition to anxiously expect, readily perceive and overreact to rejection. Participants (N = 129) took part in a purported web-based social interaction in which they were either rejected or not by a potential partner. Subsequently, they were given the opportunity to allocate hot sauce to the perpetrator, knowing that he/she disliked spicy food. Amount of hot sauce was used as a behavioral index of aggression. Participants in the rejection condition allocated more hot sauce to the perpetrator than those in the control condition. However, RS moderated this effect such that rejection elicited aggression in high but not in low RS people. These results held after controlling for trait neuroticism. Implications of these findings for understanding how and why rejection elicits aggression are discussed. PMID:20228947

Neural mechanisms of the rejection-aggression link.

PubMed

Chester, David S; Lynam, Donald R; Milich, Richard; DeWall, C Nathan

2018-05-01

Social rejection is a painful event that often increases aggression. However, the neural mechanisms of this rejection-aggression link remain unclear. A potential clue may be that rejected people often recruit the ventrolateral prefrontal cortex's (VLPFC) self-regulatory processes to manage the pain of rejection. Using functional MRI, we replicated previous links between rejection and activity in the brain's mentalizing network, social pain network and VLPFC. VLPFC recruitment during rejection was associated with greater activity in the brain's reward network (i.e. the ventral striatum) when individuals were given an opportunity to retaliate. This retaliation-related striatal response was associated with greater levels of retaliatory aggression. Dispositionally aggressive individuals exhibited less functional connectivity between the ventral striatum and the right VLPFC during aggression. This connectivity exerted a suppressing effect on dispositionally aggressive individuals' greater aggressive responses to rejection. These results help explain how the pain of rejection and reward of revenge motivate rejected people to behave aggressively.

Reward, addiction, and emotion regulation systems associated with rejection in love.

PubMed

Fisher, Helen E; Brown, Lucy L; Aron, Arthur; Strong, Greg; Mashek, Debra

2010-07-01

Romantic rejection causes a profound sense of loss and negative affect. It can induce clinical depression and in extreme cases lead to suicide and/or homicide. To begin to identify the neural systems associated with this natural loss state, we used functional magnetic resonance imaging to study 10 women and 5 men who had recently been rejected by a partner but reported they were still intensely "in love." Participants alternately viewed a photograph of their rejecting beloved and a photograph of a familiar, individual, interspersed with a distraction-attention task. Their responses while looking at their rejecter included love, despair, good, and bad memories, and wondering why this happened. Activation specific to the image of the beloved occurred in areas associated with gains and losses, craving and emotion regulation and included the ventral tegmental area (VTA) bilaterally, ventral striatum, medial and lateral orbitofrontal/prefrontal cortex, and cingulate gyrus. Compared with data from happily-in-love individuals, the regional VTA activation suggests that mesolimbic reward/survival systems are involved in romantic passion regardless of whether one is happily or unhappily in love. Forebrain activations associated with motivational relevance, gain/loss, cocaine craving, addiction, and emotion regulation suggest that higher-order systems subject to experience and learning also may mediate the rejection reaction. The results show activation of reward systems, previously identified by monetary stimuli, in a natural, endogenous, negative emotion state. Activation of areas involved in cocaine addiction may help explain the obsessive behaviors associated with rejection in love.

Practices for Identifying and Rejecting Hemolyzed Specimens Are Highly Variable in Clinical Laboratories.

PubMed

Howanitz, Peter J; Lehman, Christopher M; Jones, Bruce A; Meier, Frederick A; Horowitz, Gary L

2015-08-01

Hemolysis is an important clinical laboratory quality attribute that influences result reliability. To determine hemolysis identification and rejection practices occurring in clinical laboratories. We used the College of American Pathologists Survey program to distribute a Q-Probes-type questionnaire about hemolysis practices to Chemistry Survey participants. Of 3495 participants sent the questionnaire, 846 (24%) responded. In 71% of 772 laboratories, the hemolysis rate was less than 3.0%, whereas in 5%, it was 6.0% or greater. A visual scale, an instrument scale, and combination of visual and instrument scales were used to identify hemolysis in 48%, 11%, and 41% of laboratories, respectively. A picture of the hemolysis level was used as an aid to technologists' visual interpretation of hemolysis levels in 40% of laboratories. In 7.0% of laboratories, all hemolyzed specimens were rejected; in 4% of laboratories, no hemolyzed specimens were rejected; and in 88% of laboratories, some specimens were rejected depending on hemolysis levels. Participants used 69 different terms to describe hemolysis scales, with 21 terms used in more than 10 laboratories. Slight and moderate were the terms used most commonly. Of 16 different cutoffs used to reject hemolyzed specimens, moderate was the most common, occurring in 30% of laboratories. For whole blood electrolyte measurements performed in 86 laboratories, 57% did not evaluate the presence of hemolysis, but for those that did, the most common practice in 21 laboratories (24%) was centrifuging and visually determining the presence of hemolysis in all specimens. Hemolysis practices vary widely. Standard assessment and consistent reporting are the first steps in reducing interlaboratory variability among results.

Donor-specific HLA alloantibodies: Impact on cardiac allograft vasculopathy, rejection, and survival after pediatric heart transplantation.

PubMed

Tran, Andrew; Fixler, David; Huang, Rong; Meza, Tiffany; Lacelle, Chantale; Das, Bibhuti B

2016-01-01

There is increasing evidence that donor-specific anti-HLA antibodies (DSA) are associated with poor outcomes after cardiac transplantation in adults, but data are limited in children. The objective of this study was to examine the development and consequences of de novo DSA in pediatric recipients of heart transplants. We analyzed 105 pediatric patients who received heart transplants at our center from January 2002 to December 2012. All patients had negative T-cell and B-cell post-transplant crossmatches. Patients underwent HLA antibody screening at 1, 2, 3, 6, and 12 months post-transplant and annually thereafter unless there was suspicion for rejection. HLA class I and II antibodies were identified using Luminex assay. Coronary angiography was performed at 1 year and annually thereafter. Acute cellular rejection, antibody-mediated rejection, and treated clinical rejections were included together as rejection events. Of 105 patients, 45 (43%) developed de novo DSA. DSA-positive patients had significantly higher rates of coronary artery vasculopathy (CAV) compared with DSA-negative patients (36% vs 13%). CAV-free survival at 1 year and 5 years post-transplant for DSA-negative patients was 90% and 25%, respectively, compared with 70% and 0%, respectively, for DSA-positive patients (p < 0.01). DSA-positive patients had 2.5 times more rejection events per year than DSA-negative patients. The 5-year graft survival rate was 72.4% for DSA-negative patients and 21% for DSA-positive patients (p < 0.001). De novo DSA has a strong negative impact on CAV, rejection, and graft survival in pediatric recipients of heart transplants. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

Song, Alice Tung Wan; de Mello, Evandro Sobroza; Alves, Venâncio Avancini Ferreira; Cavalheiro, Norma de Paula; Melo, Carlos Eduardo; Bonazzi, Patricia Rodrigues; Tengan, Fatima Mitiko; Freire, Maristela Pinheiro; Barone, Antonio Alci; D'Albuquerque, Luiz Augusto Carneiro; Abdala, Edson

2015-01-01

Histology is the gold standard for diagnosing acute rejection and hepatitis C recurrence after liver transplantation. However, differential diagnosis between the two can be difficult. We evaluated the role of C4d staining and quantification of hepatitis C virus (HCV) RNA levels in liver tissue. This was a retrospective study of 98 liver biopsy samples divided into four groups by histological diagnosis: acute rejection in patients undergoing liver transplant for hepatitis C (RejHCV+), HCV recurrence in patients undergoing liver transplant for hepatitis C (HCVTx+), acute rejection in patients undergoing liver transplant for reasons other than hepatitis C and chronic hepatitis C not transplanted (HCVTx-). All samples were submitted for immunohistochemical staining for C4d and HCV RNA quantification. Immunoexpression of C4d was observed in the portal vessels and was highest in the HCVTx- group. There was no difference in C4d expression between the RejHCV+ and HCVTx+ groups. However, tissue HCV RNA levels were higher in the HCVTx+ group samples than in the RejHCV+ group samples. Additionally, there was a significant correlation between tissue and serum levels of HCV RNA. The quantification of HCV RNA in liver tissue might prove to be an efficient diagnostic test for the recurrence of HCV infection. PMID:25742264

Subclinical rejection associated with chronic allograft nephropathy in protocol biopsies as a risk factor for late graft loss.

PubMed

Moreso, F; Ibernon, M; Gomà, M; Carrera, M; Fulladosa, X; Hueso, M; Gil-Vernet, S; Cruzado, J M; Torras, J; Grinyó, J M; Serón, D

2006-04-01

Chronic allograft nephropathy (CAN) in protocol biopsies is associated with graft loss while the association between subclinical rejection (SCR) and outcome has yielded contradictory results. We analyze the predictive value of SCR and/or CAN in protocol biopsies on death-censored graft survival. Since 1988, a protocol biopsy was done during the first 6 months in stable grafts with serum creatinine <300 micromol/L and proteinuria <1 g/day. Biopsies were evaluated according to Banff criteria. Borderline changes and acute rejection were grouped as SCR. CAN was defined as presence of interstitial fibrosis and tubular atrophy. Mean follow-up was 91 +/- 46 months. Sufficient tissue was obtained in 435 transplants. Biopsies were classified as normal (n = 186), SCR (n = 74), CAN (n = 110) and SCR with CAN (n = 65). Presence of SCR with CAN was associated with old donors, percentage of panel reactive antibodies and presence of acute rejection before protocol biopsy. Cox regression analysis showed that SCR with CAN (relative risk [RR]: 1.86, 95% confidence interval [CI]: 1.11-3.12; p = 0.02) and hepatitis C virus (RR: 2.27, 95% CI: 1.38-3.75; p = 0.01) were independent predictors of graft survival. In protocol biopsies, the detrimental effect of interstitial fibrosis/tubular atrophy on long-term graft survival is modulated by SCR.

Effect of intestinal microbiota alteration on hepatic damage in rats with acute rejection after liver transplantation.

PubMed

Xie, Yirui; Chen, Huazhong; Zhu, Biao; Qin, Nan; Chen, Yunbo; Li, Zhengfeng; Deng, Min; Jiang, Haiyin; Xu, Xiangfei; Yang, Jiezuan; Ruan, Bing; Li, Lanjuan

2014-11-01

The previous studies all focus on the effect of probiotics and antibiotics on infection after liver transplantation. Here, we focus on the effect of gut microbiota alteration caused by probiotics and antibiotics on hepatic damage after allograft liver transplantation. Brown-Norway rats received saline, probiotics, or antibiotics via daily gavage for 3 weeks. Orthotopic liver transplantation (OLT) was carried out after 1 week of gavage. Alteration of the intestinal microbiota, liver function and histopathology, serum and liver cytokines, and T cells in peripheral blood and Peyer's patch were evaluated. Distinct segregation of fecal bacterial diversity was observed in the probiotic group and antibiotic group when compared with the allograft group. As for diversity of intestinal mucosal microbiota and pathology of intestine at 2 weeks after OLT, antibiotics and probiotics had a significant effect on ileum and colon. The population of Lactobacillus and Bifidobacterium in the probiotic group was significantly greater than the antibiotic group and the allograft group. The liver injury was significantly reduced in the antibiotic group and the probiotic group compared with the allograft group. The CD4/CD8 and Treg cells in Peyer's patch were decreased in the antibiotic group. The intestinal Treg cell and serum and liver TGF-β were increased markedly while CD4/CD8 ratio was significantly decreased in the probiotic group. It suggested that probiotics mediate their beneficial effects through increase of Treg cells and TGF-β and deduction of CD4/CD8 in rats with acute rejection (AR) after OLT.

Ultrasound molecular imaging of acute cellular cardiac allograft rejection in rat with T-cell-specific nanobubbles.

PubMed

Wu, Wei; Zhang, Zhe; Zhuo, Lisha; Zhou, Lina; Liu, Ping; He, Yun; Gao, Yunhua; Li, Rui; Chen, Qinghai; Hua, Xing

2013-09-01

Acute rejection (AR) is one of the main obstacles of cardiac transplantation; however, a noninvasive diagnostic method, which reflects its pathologic nature, has not been developed yet. In this study, we prepared a specific nanobubbles targeting to the activated T cells and applied it in the ultrasound molecular imaging of AR in heart transplantation by myocardial contrast echocardiography (MCE). Nanobubbles loading anti-CD25 antibody (NB(specific)) or isotype control antibody (NB(nonspecific)) were prepared and then applied in the ultrasound molecular imaging by MCE in a rat model. MCE was performed in 24 allografts and 18 isografts that were divided into three groups, including days 2, 4, and 6 after transplantation. Confocal laser scanning microscopy was used to evaluate the binding of nanobubbles and T cells in four allografts and four isografts. MCE with NB(specific) in allograft showed a "delayed enhancement," and the time-intensity curve presented a second peak. The intensity and time of second peak were both positively correlated with the transplant time (P<0.01) and the pathologic grade of AR (P<0.01). Confocal laser scanning microscopy demonstrated the binding of nanobubbles and lymphocytes in myocardium post-MCE with NB(specific). Ultrasound molecular imaging of AR after heart transplantation can be achieved by using MCE with the nanobubbles targeted to T cells. The appearance of delayed enhancement indicates the occurrence of AR, and the intensity and time of the second peak in time-intensity curve provide potential quantitative indications for diagnosis and severity of AR.

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 to...

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 to...

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

PubMed

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

1995-06-15

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

Rejecting salient distractors: Generalization from experience.

PubMed

Vatterott, Daniel B; Mozer, Michael C; Vecera, Shaun P

2018-02-01

Distraction impairs performance of many important, everyday tasks. Attentional control limits distraction by preferentially selecting important items for limited-capacity cognitive operations. Research in attentional control has typically investigated the degree to which selection of items is stimulus-driven versus goal-driven. Recent work finds that when observers initially learn a task, the selection is based on stimulus-driven factors, but through experience, goal-driven factors have an increasing influence. The modulation of selection by goals has been studied within the paradigm of learned distractor rejection, in which experience over a sequence of trials enables individuals eventually to ignore a perceptually salient distractor. The experiments presented examine whether observers can generalize learned distractor rejection to novel distractors. Observers searched for a target and ignored a salient color-singleton distractor that appeared in half of the trials. In Experiment 1, observers who learned distractor rejection in a variable environment rejected a novel distractor more effectively than observers who learned distractor rejection in a less variable, homogeneous environment, demonstrating that variable, heterogeneous stimulus environments encourage generalizable learned distractor rejection. Experiments 2 and 3 investigated the time course of learned distractor rejection across the experiment and found that after experiencing four color-singleton distractors in different blocks, observers could effectively reject subsequent novel color-singleton distractors. These results suggest that the optimization of attentional control to the task environment can be interpreted as a form of learning, demonstrating experience's critical role in attentional control.

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

PubMed

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

2009-03-01

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

Interstitial pneumonitis and the risk of chronic allograft rejection in lung transplant recipients.

PubMed

Mihalek, Andrew D; Rosas, Ivan O; Padera, Robert F; Fuhlbrigge, Anne L; Hunninghake, Gary M; DeMeo, Dawn L; Camp, Phillip C; Goldberg, Hilary J

2013-05-01

The presence of interstitial pneumonitis (IP) on surveillance lung biopsy specimens in lung transplant recipients is poorly described, and its impact on posttransplant outcomes is not established. The following study assessed the association of posttransplant IP with the development of bronchiolitis obliterans syndrome (BOS). We examined all recipients of primary cadaveric lung transplants at our institution between January 1, 2000, and December 31, 2007 (N = 145). Patients had bronchoscopies with BAL, and transbronchial biopsies performed for surveillance during posttransplant months 1, 3, 6, and 12 as well as when clinically indicated. Patients were given a diagnosis of IP if, in the absence of active infection and organizing pneumonia, they showed evidence of interstitial inflammation and fibrosis on two or more biopsy specimens. IP was a significant predictor of BOS (OR, 7.84; 95% CI, 2.84-21.67; P < .0001) and was significantly associated with time to development of BOS (hazard ratio, 3.8; 95% CI, 1.93-7.39; P = .0001) within the first 6 years posttransplant. The presence of IP did not correlate with a significantly higher risk of mortality or time to death. There was no association between the presence of IP and the development of or time to acute rejection. The presence of IP on lung transplant biopsy specimens suggests an increased risk for BOS, which is independent of the presence of acute cellular rejection.

Social Rejection and Alcohol Use in Daily Life

PubMed Central

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

2017-01-01

Background Prior studies have found that social rejection is associated with increases in negative affect, distress, and hostility. Fewer studies, however, have examined the impact of social rejection on alcohol use, and no known studies have tested whether the impact of social rejection by close others differs from social rejection by acquaintances in its association with subsequent drinking. Methods Participants completed event-contingent reports of their social interactions and alcohol use for 14 consecutive days on smartphones. Multilevel negative binomial regression models tested whether experiencing more social rejection than usual was associated with increased drinking, and whether this association was stronger when participants were rejected by close others (e.g. friends, spouses, family members) versus strangers or acquaintances. Results Results showed a significant interaction between social rejection and relationship closeness. On days characterized by rejection by close others, the likelihood of drinking significantly increased. On days characterized by rejection by acquaintances, by contrast, there was no increase in the likelihood of drinking. There was no main effect of rejection on likelihood of drinking. Conclusions These results suggest that relationship type is a key factor in whether social rejection translates to potentially harmful behaviors, such as increased alcohol use. This finding is in contrast to many laboratory paradigms of rejection, which emphasize rejection and ostracism by strangers rather than known others. In the more naturalistic setting of measuring social interactions on smartphone in daily life, however, our findings suggest that only social rejection delivered by close others, and not strangers, led to subsequent drinking. PMID:28253539

An Evolutionary Perspective on Mate Rejection.

PubMed

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

2016-01-01

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

Synchronous Occurance of Acute Myeloid Leukemia and Rhabdomyosarcoma.

PubMed

Jayasudha, A V; Nair, Rekha A; Renu, S; Binitha, R; Reghu, K S; Kusumakumary, P

2015-09-01

Metachronous primary distinct tumors are frequently and increasingly encountered in oncology clinical practice of recent times, but synchronous tumours are still a rarity. We report an unusual case of a 2 year old male child who had synchronous occurrence of rhabdomyosarcoma of pelvis and acute myeloid leukemia.Our search of literature suggests that this may be the first reported case of simultaneous occurrence of these two malignancies.

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. © 2015 by the Society for Personality and Social Psychology, Inc.

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. © 2014 Steunstichting ESOT.

Infections and reduced functioning kidney mass induce chronic rejection in rat kidney allografts.

PubMed

Heemann, U W; Azuma, H; Tullius, S G; Schmid, C; Philipp, T; Tilney, N L

1996-07-01

The etiology of chronic rejection of kidney allografts is unknown, although hyperfiltration, acute rejection, viral infection and initial graft ischemia have been implicated. To test whether endothelial activation may be the link between these factors and chronic rejection, the endotoxin (lipopolysaccharide-LPS), a potent activator of endothelial cells, was evaluated in an established chronic rejection model. Bilaterally nephrectomized Lewis recipients of orthotopically transplanted Fisher 344 kidneys were treated briefly with low dose cyclosporine (1.5 mg/kg/day x 10). Recipients were given a non-lethal dose of LPS (2 mg) i.p. at 8 weeks and compared to allografted controls treated with vehicle. Urine protein was measured every 4 weeks. Rats in the treated group were sacrificed at 12 and 16 weeks, control animals at 12, 16 and 24 weeks (20/group) and examined histologically. In the chronically rejecting control allografts, progressive interstitial and glomerular sclerosis and vascular intimal proliferation had become apparent by 12 weeks. Infiltration of glomeruli, particularly by macrophages (M phi), and the coincident presence of cytokines were prominent, peaking at 16 weeks. LPS treatment accelerated and intensified these changes; proteinuria was more pronounced (16 weeks: 79 mg/24 h vs. 49 mg/24 h, p < 0.05). Numbers of infiltrating M phi peaked at 12 weeks in LPS treated hosts (69 c/FV vs. 27 c/FV in untreated controls, p < 0.01), accompanied by an increased upregulation of MHC class II and cytokine expression, particularly TNF alpha and PDGF around arteries and areas of infiltration. BY 16 weeks, 35 +/- 3% of glomeruli in LPS treated recipients had become sclerotic vs. 15 +/- 6% (p < 0.05) in controls, again associated with increased expression of cytokines (PDGF, TNF alpha, TGF beta), adhesion molecules (ICAM-1) and extracellular matrix proteins. Overall, the extent of chronic rejection of grafts in LPS treated rats at 16 weeks was similar to that

Pretransplant soluble CD30 is a better predictor of posttransplant development of donor-specific antibodies and acute vascular rejection than panel reactive antibodies.

PubMed

Vaidya, Smita; Partlow, David; Barnes, Titus; Gugliuzza, Kristine

2006-12-27

This study tests a hypothesis that pretransplant concentration of soluble CD30 (sCD30) is a better predictor of posttransplant development of donor-specific HLA antibodies (DSA) and acute vascular rejection (AVR) than panel reactive HLA antibodies (PRA). Pretransplant sera from 115 patients were evaluated for their PRA and sCD30 concentrations. All patients received calcineurin-inhibitor based immunosuppressive therapy. Objective measurements for rejection were biopsy-proven AVR episodes within first 6 months of the transplant. Posttransplant sera of patients with or without AVR were tested for the presence of DSA. AVR rate was 16% (18/115). Patients positive for PRA and sCD30 tests were at significantly higher risk for AVR compared to those patients negative for both tests (36% versus 5%, p = 0.01). Among negative PRA patients risk for AR was significantly elevated if they were also tested positive for sCD30 concentrations (21% versus 5%, p = 0.04). Of the 18 patients with AVR, 14 were positive for sCD30, and 13 of them (93%) developed DSA posttransplant (p = 0.001) Nineteen patients without AVR were tested for DSA and sCD30 concentrations. Only two of these 19 patients were positive for sCD30 and DSA. AVR was strongly associated with the patients tested positive for both the tests: DSA and sCD30 (p = 0.00007). Furthermore, patients with AVR are more likely to produce DSA than those without AVR (p = 0.02). These data support our hypothesis that patients positive for sCD30 contents are at high risk the development of DSA and AVR posttransplant regardless of their pretransplant PRA.

A New Pulse Pileup Rejection Method Based on Position Shift Identification

NASA Astrophysics Data System (ADS)

Gu, Z.; Prout, D. L.; Taschereau, R.; Bai, B.; Chatziioannou, A. F.

2016-02-01

Pulse pileup events degrade the signal-to-noise ratio (SNR) of nuclear medicine data. When such events occur in multiplexed detectors, they cause spatial misposition, energy spectrum distortion and degraded timing resolution, which leads to image artifacts. Pulse pileup is pronounced in PETbox4, a bench top PET scanner dedicated to high sensitivity and high resolution imaging of mice. In that system, the combination of high absolute sensitivity, long scintillator decay time (BGO) and highly multiplexed electronics lead to a significant fraction of pulse pileup, reached at lower total activity than for comparable instruments. In this manuscript, a new pulse pileup rejection method named position shift rejection (PSR) is introduced. The performance of PSR is compared with a conventional leading edge rejection (LER) method and with no pileup rejection implemented (NoPR). A comprehensive digital pulse library was developed for objective evaluation and optimization of the PSR and LER, in which pulse waveforms were directly recorded from real measurements exactly representing the signals to be processed. Physical measurements including singles event acquisition, peak system sensitivity and NEMA NU-4 image quality phantom were also performed in the PETbox4 system to validate and compare the different pulse pile-up rejection methods. The evaluation of both physical measurements and model pulse trains demonstrated that the new PSR performs more accurate pileup event identification and avoids erroneous rejection of valid events. For the PETbox4 system, this improvement leads to a significant recovery of sensitivity at low count rates, amounting to about 1/4th of the expected true coincidence events, compared to the LER method. Furthermore, with the implementation of PSR, optimal image quality can be achieved near the peak noise equivalent count rate (NECR).

Batting 300 is Good: Perspectives of Faculty Researchers and their Mentors on Rejection, Resilience, and Persistence in Academic Medical Careers

PubMed Central

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

2013-01-01

Purpose Professional rejection is a frequent experience in an academic medical career. The authors sought to understand how rejection affects those pursuing such careers and why some individuals may be more resilient than others in a population of individuals with demonstrated ability and interest in research careers. Method Between February 2010 and August 2011, the authors conducted semi-structured, in-depth telephone interviews with 100 former recipients of National Institutes of Health mentored career development awards and 28 of their mentors. Purposive sampling ensured a diverse range of viewpoints. Multiple analysts thematically coded verbatim transcripts using qualitative data analysis software. Results Participants described a variety of experiences with criticism and rejection in their careers, as well as an acute need for persistence and resilience in the face of such challenges. Through their narratives, participants also vividly described a range of emotional and behavioral responses to their experiences of professional rejection. Their responses illuminated the important roles that various factors, including mentoring and gender, play in shaping the ultimate influence of rejection on their own careers and on the careers of those they have mentored. Conclusions Responses to rejection vary considerably, and negative responses can lead promising individuals to abandon careers in academic medicine. Resilience does not, however, appear to be immutable—it can be learned. Given the frequency of experiences with rejection in academic medicine, strategies such as training mentors to foster resilience may be particularly helpful in improving faculty retention in academic medicine. PMID:23425991

Adenovirus-mediated HIF-1α gene transfer promotes repair of mouse airway allograft microvasculature and attenuates chronic rejection

PubMed Central

Jiang, Xinguo; Khan, Mohammad A.; Tian, Wen; Beilke, Joshua; Natarajan, Ramesh; Kosek, Jon; Yoder, Mervin C.; Semenza, Gregg L.; Nicolls, Mark R.

2011-01-01

Chronic rejection, manifested as small airway fibrosis (obliterative bronchiolitis [OB]), is the main obstacle to long-term survival in lung transplantation. Recent studies demonstrate that the airways involved in a lung transplant are relatively hypoxic at baseline and that OB pathogenesis may be linked to ischemia induced by a transient loss of airway microvasculature. Here, we show that HIF-1α mediates airway microvascular repair in a model of orthotopic tracheal transplantation. Grafts with a conditional knockout of Hif1a demonstrated diminished recruitment of recipient-derived Tie2+ angiogenic cells to the allograft, impaired repair of damaged microvasculature, accelerated loss of microvascular perfusion, and hastened denudation of epithelial cells. In contrast, graft HIF-1α overexpression induced via an adenoviral vector prolonged airway microvascular perfusion, preserved epithelial integrity, extended the time window for the graft to be rescued from chronic rejection, and attenuated airway fibrotic remodeling. HIF-1α overexpression induced the expression of proangiogenic factors such as Sdf1, Plgf, and Vegf, and promoted the recruitment of vasoreparative Tie2+ cells. This study demonstrates that a therapy that enhances vascular integrity during acute rejection may promote graft health and prevent chronic rejection. PMID:21606594

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

PubMed

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

2003-11-01

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

From Rejected to Accepted: Part 2--Preparing a Rejected Manuscript for a New Journal

ERIC Educational Resources Information Center

Stivers, Jan; Cramer, Sharon F.

2017-01-01

Manuscript rejection is a fact of life for academics, and should be seen as just one step in a process of revision and resubmission that typically results in publication. This manuscript is the second in a two-part series offering suggestions to help authors take action on their rejected manuscripts, including analyzing reviewer feedback, revising…

When Rejection by One Fosters Aggression Against Many: Multiple-Victim Aggression as a Consequence of Social Rejection and Perceived Groupness

PubMed Central

Gaertner, Lowell; Iuzzini, Jonathan; O’Mara, Erin M.

2008-01-01

Two experiments examined the hypothesis that social rejection and perceived groupness function together to produce multiple-victim incidents of aggression. When a rejecter’s group membership is salient during an act of rejection, the rejectee ostensibly associates the rejecter’s group with rejection and retaliates against the group. Both experiments manipulated whether an aggregate of three persons appeared as separate individuals or members of an entity-like group and whether one of those persons rejected the participant. Consistent with the hypothesis, participants who experienced both rejection and perceived groupness behaved more aggressively against the aggregate (Experiment 1) and evidenced less favorable affective associations toward the aggregate (Experiment 2) than did participants who did not experience both rejection and perceived groupness. PMID:19079568

Validation of a Simple Score to Determine Risk of Early Rejection After Pediatric Heart Transplantation.

PubMed

Butts, Ryan J; Savage, Andrew J; Atz, Andrew M; Heal, Elisabeth M; Burnette, Ali L; Kavarana, Minoo M; Bradley, Scott M; Chowdhury, Shahryar M

2015-09-01

This study aimed to develop a reliable and feasible score to assess the risk of rejection in pediatric heart transplantation recipients during the first post-transplant year. The first post-transplant year is the most likely time for rejection to occur in pediatric heart transplantation. Rejection during this period is associated with worse outcomes. The United Network for Organ Sharing database was queried for pediatric patients (age <18 years) who underwent isolated orthotopic heart transplantation from January 1, 2000 to December 31, 2012. Transplantations were divided into a derivation cohort (n = 2,686) and a validation (n = 509) cohort. The validation cohort was randomly selected from 20% of transplantations from 2005 to 2012. Covariates found to be associated with rejection (p < 0.2) were included in the initial multivariable logistic regression model. The final model was derived by including only variables independently associated with rejection. A risk score was then developed using relative magnitudes of the covariates' odds ratio. The score was then tested in the validation cohort. A 9-point risk score using 3 variables (age, cardiac diagnosis, and panel reactive antibody) was developed. Mean score in the derivation and validation cohorts were 4.5 ± 2.6 and 4.8 ± 2.7, respectively. A higher score was associated with an increased rate of rejection (score = 0, 10.6% in the validation cohort vs. score = 9, 40%; p < 0.01). In weighted regression analysis, the model-predicted risk of rejection correlated closely with the actual rates of rejection in the validation cohort (R(2) = 0.86; p < 0.01). The rejection score is accurate in determining the risk of early rejection in pediatric heart transplantation recipients. The score has the potential to be used in clinical practice to aid in determining the immunosuppressant regimen and the frequency of rejection surveillance in the first post-transplant year. Copyright © 2015 American College of Cardiology

Questionnaire investigation to clarify the occurrence rate and characteristics of maternal rejection behavior in Japanese black cattle (Bos taurus).

PubMed

Kohari, Daisuke; Takakura, Azusa

2017-12-01

We conducted a questionnaire investigation among breeding farmers to clarify the actual conditions of maternal rejection in Japanese Black cattle. We asked keeping experience of maternal rejective cows and compared occurrence patterns, rejective behavior manners, birth assistance methods, colostrum feeding method for calves, parity and rearing conditions of the cows. We found that 24% of the farms had kept rejective cows and 6% of the cows in these farms indicated maternal rejections. The most common occurrence pattern was 'Occurred from the first birth (65.6%)' and behavior manner was performing no maternal grooming with aggressive behavior (75%). Almost all the farmers assisted in each parturition (P < 0.05). There was not a significant difference among the colostrum feeding methods, but a significant difference in the rearing conditions of the cows, except for the cows with no data (P < 0.005). The parity of the rejective cows did not significantly differ in association with rejective behavior manners, birth assistance methods, colostrum feeding methods or rearing conditions. These results suggest that the occurrence rate of maternal rejection in Japanese Black cattle was approximately 6% and many of the rejective cows continuously performed no maternal grooming with aggressive behavior. © 2017 Japanese Society of Animal Science.

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. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

Molecular analysis of transplant rejection: marching onward

PubMed Central

Lakkis, Fadi G.

2013-01-01

Transcriptional profiling of organ transplants is increasingly defining the biological pathways responsible for graft rejection at the molecular level and identifying gene transcripts that diagnose or predict rejection. These advances hold significant promise for the treatment of organ rejection and for improving clinical outcomes after transplantation, but hurdles remain. PMID:24145950

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…

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…

Does perceived parental rejection make adolescents sad and mad? The association of perceived parental rejection with adolescent depression and aggression.

PubMed

Hale, William W; Van Der Valk, Inge; Engels, Rutger; Meeus, Wim

2005-06-01

To research the association of perceived parental rejection to adolescent depression and aggression. This study focused on 1329 Dutch junior high and high school students (47.9% males and 52.1% females; age range 10-19 years) that completed depression, aggression and perceived parental rejection questionnaires. The data were analyzed by structural equation modeling that assumed a relationship between perceived parental rejection and adolescent aggression, as mediated by adolescent depression. Perceived parental rejection, mediated through adolescent depression, explains aggressive behaviors of adolescents, as tested by a mediation model. Additionally, the fit of this mediation model is somewhat enhanced when direct paths from perceived parental rejection to aggression are included. Further analysis demonstrates that these effects are also somewhat dependent on the gender and the age of the adolescents, as would be expected in light of previous studies of these cohorts. The study of perceived parental rejection should receive the same attention in the research of the development of both adolescent depression and aggression, as has been the case for adolescent peer rejection.

Rejection of unfair offers can be driven by negative emotions, evidence from modified ultimatum games with anonymity.

PubMed

Ma, Ning; Li, Nan; He, Xiao-Song; Sun, De-Lin; Zhang, Xiaochu; Zhang, Da-Ren

2012-01-01

The rejection of unfair offers can be affected by both negative emotions (e.g. anger and moral disgust) and deliberate cognitive processing of behavioral consequences (e.g. concerns of maintaining social fairness and protecting personal reputation). However, whether negative emotions are sufficient to motivate this behavior is still controversial. With modified ultimatum games, a recent study (Yamagishi T, et al. (2009) Proc Natl Acad Sci USA 106:11520-11523) found that people reject unfair offers even when this behavior increases inequity, and even when they could not communicate to the proposers. Yamagishi suggested that rejection of unfair offers could occur without people's concerning of maintaining social fairness, and could be driven by negative emotions. However, as anonymity was not sufficiently guaranteed in Yamagishi's study, the rejection rates in their experiments may have been influenced by people's concerns of protecting personal reputation (reputational concerns) in addition to negative emotions; thus, it was unclear whether the rejection was driven by negative emotions, or by reputational concerns, or both. In the present study, with specific methods to ensure anonymity, the effect of reputational concerns was successfully ruled out. We found that in a private situation in which rejection could not be driven by reputational concerns, the rejection rates of unfair offers were significantly larger than zero, and in public situations in which rejection rates could be influenced by both negative emotions and reputational concerns, rejection rates were significantly higher than that in the private situation. These results, together with Yamagishi's findings, provided more complete evidence suggesting (a) that the rejection of unfair offers can be driven by negative emotions and (b) that deliberate cognitive processing of the consequences of the behavior can increase the rejection rate, which may benefit social cooperation.

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

PubMed

Bagley, Jessamyn; Tian, Chaorui; Iacomini, John

2007-07-15

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

On fiber rejection loss in flotation deinking

Treesearch

J.Y. Zhu; Freya Tan

2005-04-01

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

Disappearance of T Cell-Mediated Rejection Despite Continued Antibody-Mediated Rejection in Late Kidney Transplant Recipients

PubMed Central

Chang, Jessica; Famulski, Konrad; Hidalgo, Luis G.; Salazar, Israel D.R.; Merino Lopez, Maribel; Matas, Arthur; Picton, Michael; de Freitas, Declan; Bromberg, Jonathan; Serón, Daniel; Sellarés, Joana; Einecke, Gunilla; Reeve, Jeff

2015-01-01

The prevalent renal transplant population presents an opportunity to observe the adaptive changes in the alloimmune response over time, but such studies have been limited by uncertainties in the conventional biopsy diagnosis of T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR). To circumvent these limitations, we used microarrays and conventional methods to investigate rejection in 703 unselected biopsies taken 3 days to 35 years post-transplant from North American and European centers. Using conventional methods, we diagnosed rejection in 205 biopsy specimens (28%): 67 pure TCMR, 110 pure ABMR, and 28 mixed (89 designated borderline). Using microarrays, we diagnosed rejection in 228 biopsy specimens (32%): 76 pure TCMR, 124 pure ABMR, and 28 mixed (no borderline). Molecular assessment confirmed most conventional diagnoses (agreement was 90% for TCMR and 83% for ABMR) but revealed some errors, particularly in mixed rejection, and improved prediction of failure. ABMR was strongly associated with increased graft loss, but TCMR was not. ABMR became common in biopsy specimens obtained >1 year post-transplant and continued to appear in all subsequent intervals. TCMR was common early but progressively disappeared over time. In 108 biopsy specimens obtained 10.2–35 years post-transplant, TCMR defined by molecular and conventional features was never observed. We conclude that the main cause of kidney transplant failure is ABMR, which can present even decades after transplantation. In contrast, TCMR disappears by 10 years post-transplant, implying that a state of partial adaptive tolerance emerges over time in the kidney transplant population. PMID:25377077

Prevention and treatment of corneal graft rejection: current practice patterns of the Cornea Society (2011).

PubMed

Kharod-Dholakia, Bhairavi; Randleman, J Bradley; Bromley, Jennifer G; Stulting, R Doyle

2015-06-01

To analyze current practice patterns in the prevention and treatment of corneal graft rejection for both penetrating keratoplasty (PK) and endothelial keratoplasty (EK) and to compare these patterns with previously reported practices. In 2011, an electronic survey was sent to 670 members of the Cornea Society worldwide addressing the routine postoperative management of corneal transplants at different time points, treatment of various manifestations of corneal graft rejection, and preferred surgical techniques. A total of 204 of 670 surveys (30%) were returned and evaluated. All respondents used topical corticosteroids for routine postoperative management and treatment of endothelial graft rejection. Prednisolone was the topical steroid of choice in all clinical scenarios, similar to previous surveys from 1989 to 2004. Use of subconjunctival and systemic steroids increased for many scenarios of probable and definite graft rejection. Routine use of prednisolone decreased by approximately 10% from previous surveys, whereas difluprednate was used in 13% of high-risk eyes during the first 6 months. Dexamethasone, fluorometholone, and loteprednol use remained stable. Adjunctive topical cyclosporine use increased significantly for PK and EK. EK was the preferred technique for endothelial dysfunction, whereas PK and deep anterior lamellar keratoplasty were both used for keratoconus and anterior scars. Most respondents (75%) felt that graft rejection occurs more frequently after PK than after EK. Prednisolone remains the treatment of choice for management and treatment of graft rejection; however, since the introduction of difluprednate, its use has declined slightly since the introduction of difluprednate. Despite perceived differences in rejection rates, there were no differences in prophylactic steroid treatment for PK and EK.

Neural responses to witnessing peer rejection after being socially excluded: fMRI as a window into adolescents’ emotional processing

PubMed Central

Masten, Carrie L.; Eisenberger, Naomi I.; Pfeifer, Jennifer H.; Dapretto, Mirella

2013-01-01

During adolescence, concerns about peer rejection and acceptance become increasingly common. Adolescents regularly experience peer rejection firsthand and witness these behaviors among their peers. In the current study, neuroimaging techniques were employed to conduct a preliminary investigation of the affective and cognitive processes involved in witnessing peer acceptance and rejection—specifically when these witnessed events occur in the immediate aftermath of a firsthand experience with rejection. During an fMRI scan, twenty-three adolescents underwent a simulated experience of firsthand peer rejection. Then, immediately following this experience they watched as another adolescent was ostensibly first accepted and then rejected. Findings indicated that in the immediate aftermath of being rejected by peers, adolescents displayed neural activity consistent with distress when they saw another peer being accepted, and neural activity consistent with emotion regulation and mentalizing (e.g., perspective-taking) processes when they saw another peer being rejected. Furthermore, individuals displaying a heightened sensitivity to firsthand rejection were more likely to show neural activity consistent with distress when observing a peer being accepted. Findings are discussed in terms of how witnessing others being accepted or rejected relates to adolescents’ interpretations of both firsthand and observed experiences with peers. Additionally, the potential impact that witnessed events might have on the broader perpetuation of bullying at this age is also considered. PMID:24033579

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

PubMed

Murphy, Anna M; Russell, Gemma

2018-07-01

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

Rituximab Therapy for Rejection in Pediatric Heart Transplant.

PubMed

Erdogan, Ilkay; Varan, Birgul; Sezgin, Atilla; Pirat, Arash; Zeyneloglu, Pinar

2018-04-01

Humoral rejection is the B-cell-mediated production of immunoglobulin G antibody against the transplanted heart. Antibody-mediated rejection may be resistant to standard immunosuppressive therapy and is associated with high mortality and graft loss. Rituximab can be used to treat antibody-mediated rejection in heart transplant recipients. This retrospective study describes our experience with rituximab treatment in children with heart transplants. We present 7 pediatric patients with antibody-mediated rejection who were treated with plasma exchange and rituximab therapy. Rituximab was given at a dose of 375 mg/m2 by slow infusion in the intensive care unit after 5 days of plasmapheresis, in addition to a conventional regimen consisting of steroids, mycophenolate mofetil, and tacrolimus. The peripheral blood count and sodium, potassium, serum urea nitrogen, creatinine, aspartate aminotransferase, and alanine aminotransferase levels were measured in all patients before and after treatment. Seven patients were treated with plasma exchange and rituximab. We repeated this therapy in 5 patients because of refractoriness or recurrent rejection. After diagnoses of antibody-mediated rejection, 4 patients died within 6 months (mortality rate of 57.1%). We did not observe any adverse effects or complications related to rituximab. Rituximab can be used in humoral rejection after pediatric heart transplant. However, the success of the treatment is controversial, and further study is needed to find an effective treatment for antibody-mediated rejection and steroid-resistant cellular rejection in children.

Pre- and post-transplant monitoring of soluble CD30 levels as predictor of acute renal allograft rejection.

PubMed

Wang, Dong; Wu, Guo-Jun; Wu, Wei-Zhen; Yang, Shun-Liang; Chen, Jin-Hua; Wang, He; Lin, Wen-Hong; Wang, Qing-Hua; Zeng, Zhang-Xin; Tan, Jian-Ming

2007-06-01

Identification of renal graft candidates at high risk of impending acute rejection (AR) and graft loss may be helpful for patient-tailored immunosuppressive regimens and renal graft survival. To investigate the feasibility with soluble CD30 (sCD30) as predictor of AR, sCD30 levels of 70 patients were detected on day 0 pre-transplant and day 1, 3, 5, 7, 10, 14, 21, and 30 post-transplant. AR episodes in 6 months were recorded and then patients were divided into Group AR (n=11) and Group UC (n=59). Results showed that the patients had higher pre-transplant sCD30 levels than healthy people. A significant decrease of sCD30 was observed on the first day post-transplant and continued until day 14 post-transplant. Soluble CD30 presented a stable level from day 14 to 30 post-transplant. Pre-transplant sCD30 levels of Group AR were much higher than those of Group UC (P<0.001). Patients of Group AR also had higher sCD30 levels than those of Group UC on day 1, 3, 5, 7, 10 and 14 (P<0.001). The sCD30 level presented a significantly delayed decrease in the patients of Group AR. Statistical results showed that the highest value of area under ROC curve (0.95) was obtained on day 5 post-transplant, suggesting that sCD30 levels on day 5 are of high predictive value. Therefore, sCD30 level may be a good marker of increased alloreactivity and of significant predictive value. It's necessary to monitor the variation of sCD30 in the early period post-transplant.

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.

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

PubMed

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

2015-03-01

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

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…

C4d Deposition and Cellular Infiltrates as Markers of Acute Rejection in Rat Models of Orthotopic Lung Transplantation

PubMed Central

Murata, Kazunori; Iwata, Takekazu; Nakashima, Shinji; Fox-Talbot, Karen; Qian, Zhiping; Wilkes, David S.; Baldwin, William M.

2008-01-01

Background C4d is a useful marker of antibody-mediated rejection in cardiac and renal transplants, but clinical studies examining correlations between circulating alloantibodies, C4d deposition, and rejection in lung transplants have yielded conflicting results. Methods We studied circulating alloantibody levels and C4d deposition in two rat models of lung transplantation: Brown Norway (BN) to Wistar-Kyoto (WKY) and PVG.R8 to PVG.1U lung allografts. The availability of C6 deficient (C6−) and C6 sufficient (C6+) PVG 1U rats allowed evaluation of the effects of the terminal complement components on graft injury and C4d deposition. Results The lung allografts had histologic features resembling human posttransplant capillaritis, characterized by neutrophilic infiltration of alveoli, edema, and hemorrhage. Immunoperoxidase stains on cross sections of allografts showed intense, diffuse, C4d deposition in a continuous linear pattern on the vascular endothelium. C4d deposits were found in both BN to WKY and PVG R8 to 1U allografts, whereas no staining was detectable in WKY to WKY isografts or native lungs. Complement deposition was associated with vascular disruption in C6−, but not in C6+ recipients. The presence of circulating donor-specific alloantibodies was verified by flow cytometry. Cell-specific staining revealed perivascular accumulation of macrophages and T lymphocytes whereas neutrophils were sequestered in the intravascular and alveolar capillary compartments. Conclusions The deposition of C4d on vascular endothelium as well as the coincident presence of alloantibodies is consistent with previous findings in antibody-mediated rejection of renal and cardiac transplants. Furthermore, the histological features of our allografts support the concept that posttransplant capillaritis is a form of humoral rejection. PMID:18622289

Disparate rates of acute rejection and donor-specific antibodies among high-immunologic risk renal transplant subgroups receiving antithymocyte globulin induction.

PubMed

Patel, Samir J; Suki, Wadi N; Loucks-DeVos, Jennifer; Graviss, Edward A; Nguyen, Duc T; Knight, Richard J; Kuten, Samantha A; Moore, Linda W; Teeter, Larry D; Gaber, Lillian W; Gaber, A Osama

2016-08-01

Lymphocyte-depleting induction lowers acute rejection (AR) rates among high-immunologic risk (HIR) renal transplant recipients, including African Americans (AAs), retransplants, and the sensitized. It is unclear whether different HIR subgroups experience similarly low rates of AR. We aimed to describe the incidence of AR and de novo donor-specific antibody (dnDSA) among HIR recipients categorized by age, race, or donor type. All received antithymocyte globulin (ATG) induction and triple maintenance immunosuppression. A total of 464 HIR recipients from 2007 to 2014 were reviewed. AR and dnDSA rates at 1 year for the entire population were 14% and 27%, respectively. AR ranged from 6.7% among living donor (LD) recipients to 30% in younger AA deceased donor (DD) recipients. De novo donor-specific antibody at 1 year ranged from 7% in older non-AA LD recipients to 32% in AAs. AA race remained as an independent risk factor for AR among DD recipients and for dnDSA among all HIR recipients. Development of both AR and dnDSA within the first year was associated with a 54% graft survival at 5 years and was an independent risk factor for graft loss. Despite utilization of recommended immunosuppression for HIR recipients, substantial disparities exist among subgroups, warranting further consideration of individualized immunosuppression in certain HIR subgroups. © 2016 Steunstichting ESOT.

Peer victimization and peer rejection during early childhood.

PubMed

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

2015-01-01

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

Peer victimization and peer rejection during early childhood

PubMed Central

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

2014-01-01

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

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. Copyright © 2010 Elsevier Ltd. All rights reserved.

Incidence, etiology, and significance of acute kidney injury in the early post-kidney transplant period.

PubMed

Panek, Romuald; Tennankore, Karthik K; Kiberd, Bryce A

2016-01-01

Little is known about the incidence, causes, and significance of acute kidney injury (AKI) in the early transplant period. This study used a definition as >26 μmol/L increase in creatinine within 48 h or >50% increase over a period >48 h. In 326 adult consecutive recipients of a solitary kidney transplant from 2006 to 2014 followed at this center, 21% developed AKI within the first six months. Most etiologies were CNI toxicity (33%) or unknown (26%), whereas acute rejection accounted for 17% and urinary tract obstruction for 10%. Those with AKI had a significantly lower glomerular filtration rate (GFR) at one-yr post-transplant (adjusted beta coefficient -5.5 mL/min/1.73 m(2) , 95% CI: -10.4, -0.7, p = 0.025) in a multivariable linear regression model. However, the AKI definition missed 6 of 19 episodes of acute rejection and 4 of 10 episodes of urinary tract obstruction. When acute rejection (including those that did not satisfy AKI criteria) was included in the model, other causes of AKI were not significantly associated with GFR at year 1. Although AKI, using current criteria, is likely to be a significant predictor of later outcomes, important causes are missed and the criteria are not sensitive for clinical decision-making. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hiv-associated nephropathy occurring before HIV antibody seroconversion.

PubMed

Levin, M L; Palella, F; Shah, S; Lerma, E; Butter, J; Kanwar, Y S

2001-05-01

It currently is thought that human immunodeficiency virus-associated nephropathy (HIVAN) occurs late in the course of HIV infection. Although HIVAN may be the presenting manifestation of acquired immunodeficiency syndrome (AIDS), it usually occurs after a prolonged period of viral infection often associated with high levels of HIV viremia. The patient described here developed HIVAN as a manifestation of acute retroviral syndrome. A 41-year-old black man presented with nephrotic range proteinuria, renal insufficiency, and acute gastrointestinal and pulmonary symptoms. He recently had been treated for primary syphilis. Two HIV serologic tests, performed 3 months apart, were negative. Renal biopsy was consistent with HIVAN. After the biopsy, the patient was discovered to have more than 700,000 viral copies per mL in his blood. CD4(+) count was greater than 500/mm(3). Six weeks later, enzyme-linked immunosorbent assay and Western blot analyses for HIV antibody became positive. HIVAN can occur early in the course of HIV infection, even during acute infection before seroconversion, and prolonged exposure to virus is not necessary for this renal involvement to occur in the susceptible host.

Understanding maladaptive responses to rejection: Aggression with an audience.

PubMed

DeBono, Amber; Layton, Rebekah L; Freeman, Nicholas; Muraven, Mark

2017-01-01

Logically, responding aggressively to rejection is maladaptive because one is unlikely to seek a relationship with an aggressor. We predict that when concealed, the illogical aggressive response to rejection is more likely, whereas when the rejected individuals' aggressive responses are perceived as public, the aggressive acts may be reduced. Participants were rejected by others (Experiment 1) or were either accepted or rejected during an online ball-tossing game (Experiment 2) and were then given an opportunity to aggress publicly or privately. Across experiments, when the opportunity to aggress was made public, rejected participants exhibited less aggressive behavior. When concerned about the perception of their public aggressive responses by others, rejected individuals' aggressive responses diminished compared with those whose actions were private. Crucially, this extended to aggression visible only to neutral others, suggesting that effects cannot solely be due to fear of retribution.

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

PubMed

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

2004-12-01

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

Parental Acceptance-Rejection Theory and the Phylogenetic Model.

ERIC Educational Resources Information Center

Rohner, Ronald P.

Guided by specific theoretical and methodological points of view--the phylogenetic perspective and the universalistic approach respectively--this paper reports on a worldwide study of the antecedents and effects of parental acceptance and rejection. Parental acceptance-rejection theory postulates that rejected children throughout our species share…

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 rejected...

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 rejected...

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 rejected...

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 rejected...

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 rejected...

Prevalence and characteristics of foal rejection in Arabian mares.

PubMed

Juarbe-Díaz, S V; Houpt, K A; Kusunose, R

1998-09-01

Separate surveys of Thoroughbred, Paint, and Arabian mare owners revealed a higher than expected rate of foal rejection in Arabian mares. A behavioural history form was submitted by owners of foal rejecting and nonrejecting Arabian mares, and maternal behaviour and management practices compared. Four generation pedigrees of rejecting and nonrejecting Arabian mares were also examined. Foal rejecting mares were more likely to avoid, threaten, squeal at, chase, bite, and kick their foals post partum than nonrejecting mares. Nonrejecting mares were more likely to lick, nicker and defend their foals post partum than rejecting mares. No statistically significant relationship was found between foal rejection and the type of breeding method (natural vs. artificial insemination), the presence of people at birth, the presence of nearby horses at birth, or assistance of the first nursing bout. The presence at least once of 1 of 2 related sires was statistically higher in the pedigrees of rejecting vs. nonrejecting mares. Inherited and learned or environmental factors are likely to affect the expression of foal rejection behaviour.

Stomaching rejection: Self-compassion and self-esteem moderate the impact of daily social rejection on restrictive eating behaviours among college women.

PubMed

Beekman, Janine B; Stock, Michelle L; Howe, George W

2017-11-01

The present study examined whether having high self-esteem or a self-compassionate perspective help mitigate the impact of daily social rejection on negative affect and restrictive eating behaviours. Following a baseline survey assessing self-esteem and self-compassion, 121 college women completed online daily diaries for one week. Negative affect and restrictive eating behaviours. On days when women reported more rejection, they also reported higher restrictive eating behaviours and greater negative affect. Effects were moderated by self-esteem and self-compassion, such that the lower participants were in self-esteem or self-compassion, the stronger the positive relation between rejection and negative affect and restrictive eating. However, only the common humanity/isolation dimension of self-compassion significantly moderated daily effects of rejection when controlling for self-esteem. Mediated moderation results reveal different mechanisms by which self-esteem and self-compassion buffer against rejections' effects on affect and restrictive eating. Self-compassion and self-esteem influence the complex impact that social rejection has on affect and restrictive eating. More than other dimensions of self-compassion or self-esteem, remembering one's common humanity can result in a healthier response to social rejection.

Longitudinal Associations between Parental Rejection and Bullying/Victimization

ERIC Educational Resources Information Center

Stavrinides, Panayiotis; Tantaros, Spyridon; Georgiou, Stelios; Tricha, Loukia

2018-01-01

The present study investigated the direction of the relationship between parental rejection and children's engagement in bullying and victimization. Using a cross-lagged design, we examined whether (a) bullying and victimization predict an increase in parental rejection six months later, (b) parental rejection predicts an increase in bullying and…

Reactions to Discrimination, Stigmatization, Ostracism, and Other Forms of Interpersonal Rejection: A Multimotive Model

ERIC Educational Resources Information Center

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…

[Comparison of clinical and histological diagnosis in kidney post-transplantation period].

PubMed

de Castro, M C; Chocair, P R; Saldanha, L B; Nahas, W; Arap, S; Sabbaga, E; Ianhez, L E

1998-01-01

To assess the agreement between clinical and histopathological diagnosis in a renal transplantation center, 40 episodes of acute renal failure were studied. Kidney biopsies were performed at the moment that a clinical diagnosis was made by the staff. Nineteen episodes of acute tubular necrosis (ATN), eighteen episodes of acute cellular rejection (ACR), 2 humoral rejections and 1 acute cyclosporin nephrotoxicity episodes were diagnosed. ATN episodes were confirmed by renal biopsy in 84.21%, ACR episodes in 83.33%, humoral rejections in 100%. Renal biopsy showed ATN in the occurrence of clinical cyclosporin nephrotoxicity. Total agreement was 82.5%. There is a good relationship between clinical and histopathological diagnosis in the post-transplantation period. Diagnostic mistakes occurred mainly when oliguria was present.

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

Late Graft Rejection in Association With T-Large Granular Lymphocyte Expansion of Recipient Origin After Human Leukocyte Antigen-Haploidentical Stem Cell Transplantation: A Case Report.

PubMed

Nakagawa, N; Yamazaki, H; Aoki, G; Kondo, Y; Nakao, S

2016-11-01

Large granular lymphocyte (LGL) expansion occasionally occurs after allogeneic stem cell transplantation (allo-SCT), and is thought to be a good prognostic sign that is associated with a lower relapse rate. However, there have been no reports of late graft failure (LGF) due to graft rejection in association with oligoclonal LGL expansion. We herein report a case of LGF associated with the transient expansion of recipient-derived T-LGL after allo-SCT. A 65-year-old man underwent peripheral blood stem cell transplantation (PBSCT) from his human leukocyte antigen (HLA)-haploidentical son for the treatment of acute myeloid leukemia, which had evolved from a myelodysplastic syndrome (MDS). Neutrophil engraftment occurred on day 20. A chimerism analysis on day 29 showed both granulocytes and mononuclear cells in the peripheral blood to be completely of donor origin. However, his neutrophil count gradually decreased and a chimerism analysis on day 61 showed that 84% of the patient's T cells were of recipient origin while the granulocytes were 100% donor-derived. His LGLs rapidly increased to 4.01 × 10 9 /L on day 113 and decreased thereafter. The percentage of donor cells in his granulocytes gradually decreased, and the patient's leukocytes were completely replaced by recipient cells on day 177. The clinical course suggests that the expansion of recipient-derived T-LGLs after allo-SCT can be a sign of graft rejection. Early intervention may be needed if the LGL expansion is recipient-derived. Copyright © 2016 Elsevier Inc. All rights reserved.

Laughter as a social rejection cue: Influence of prior explicit experience of social rejection on cardiac signs of "freezing".

PubMed

Lackner, Helmut K; Reiter-Scheidl, Katharina; Aydin, Nilüfer; Perchtold, Corinna M; Weiss, Elisabeth M; Papousek, Ilona

2018-06-01

The study aimed at investigating the immediate cardiac effect of the sudden perception of other people's laughter after experimentally manipulating healthy participants' proneness to experience laughter as a cue of social threat. We expected that participants would show cardiac signs of freezing (i.e., sustained heart rate deceleration immediately after perception of the laughter) after prior social rejection but not or less so after prior acceptance, due to an increased bias to perceive the ambiguous social signal as a cue of social threat and rejection after rejection had been primed. Contrary to expectations, the perception of other people's laughter elicited a decelerative (freezing) response regardless of whether it was preceded by the experience of social rejection or acceptance. The response was prolonged in participants who had been accepted beforehand compared to those who had been rejected. The findings indicate that, given a relevant social context, other people's laughter can be a powerful cue of social threat and rejection also in healthy individuals. Prolonged heart rate deceleration after an ambiguous social signal may facilitate the processing of significant social information in the socially threatening situation. The study adds to the literature rendering the course of the immediate transient heart rate response a useful tool in social rejection research. Additionally, the findings suggested that in some cases the further progress of transient heart rate changes in more extended time-windows (about 30 s) may provide additional relevant information about the processing of social cues. Copyright © 2018 Elsevier B.V. All rights reserved.

Urine biomarkers informative of human kidney allograft rejection and tolerance.

PubMed

Nissaisorakarn, Voravech; Lee, John Richard; Lubetzky, Michelle; Suthanthiran, Manikkam

2018-05-01

We developed urinary cell messenger RNA (mRNA) profiling to monitor in vivo status of human kidney allografts based on our conceptualization that the kidney allograft may function as an in vivo flow cell sorter allowing access of graft infiltrating cells to the glomerular ultrafiltrate and that interrogation of urinary cells is informative of allograft status. For the profiling urinary cells, we developed a two-step preamplification enhanced real-time quantitative PCR (RT-QPCR) assays with a customized amplicon; preamplification compensating for the low RNA yield from urine and the customized amplicon facilitating absolute quantification of mRNA and overcoming the inherent limitations of relative quantification widely used in RT-QPCR assays. Herein, we review our discovery and validation of urinary cell mRNAs as noninvasive biomarkers prognostic and diagnostic of acute cellular rejection (ACR) in kidney allografts. We summarize our results reflecting the utility of urinary cell mRNA profiling for predicting reversal of ACR with anti-rejection therapy; differential diagnosis of kidney allograft dysfunction; and noninvasive diagnosis and prognosis of BK virus nephropathy. Messenger RNA profiles associated with human kidney allograft tolerance are also summarized in this review. Altogether, data supporting the idea that urinary cell mRNA profiles are informative of kidney allograft status and tolerance are reviewed in this report. Copyright © 2018. Published by Elsevier Inc.

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection.

PubMed

Ong, Michael; Ibrahim, Andrea Marie; Bourassa-Blanchette, Samuel; Canil, Christina; Fairhead, Todd; Knoll, Greg

2016-01-01

Nivolumab (Opdivo™) is a novel IgG4 subclass programmed death-1 (PD-1) inhibiting antibody that has demonstrated breakthrough-designation anti-tumor activity. To date, clinical trials of nivolumab and other checkpoint inhibitors have generally excluded patients with solid organ transplantation and patients with concurrent immunosuppression. However, organ transplant recipients are at high-risk of development of malignancy as a result of suppressed immune surveillance of cancer. We illustrate the outcomes of a 63 year-old type I diabetic female patient who developed pulmonary metastatic, BRAF wild-type cutaneous melanoma 10 years after renal transplantation. After downward titration of the patient's immunosuppressive medications and extensive multidisciplinary review, she was treated with nivolumab in the first-line setting. Within 1 week of administration, the patient experienced acute renal allograft rejection, renal failure and concurrent diabetic ketoacidosis due to steroid therapy. Allograft function did not return, but patient made a full clinical recovery after being placed on hemodialysis. Subsequently, the patient had clinical disease progression off therapy and required re-challenge with nivolumab on hemodialysis, resulting in ongoing clinical and radiographic response. This case illustrates multiple practical challenges and dangers of administering anti-PD1 immune checkpoint inhibitors to patients with solid-organ transplantation including need for titration of immunosuppressive medications, risks of allograft rejection, and treatment during hemodialysis.

Shortcut nitrification/partial nitritation start-up for reject water treatment in a SBR

NASA Astrophysics Data System (ADS)

Muszyński-Huhajło, Mateusz; Miodoński, Stanisław

2017-11-01

For many wastewater treatment plants (WWTPs), side-stream treatment of reject water from digested sludge dewatering is a feasible opportunity to improve N-removal efficiency without costly plant expansion. Biological nitrogen removal over nitrite or combined partial nitritation (PN)-Anammox process has recently become a popular treatment method for such ammonium-rich streams. Shortcut nitrification and PN start-ups were successfully performed in a pilot-scale SBR treating real reject water. In all performed experiments, effective nitrate production inhibition occurred in less than 20 days due to operational conditions selection and without advanced control system. pH adjustment in the PN reactor allowed to achieve NO2-N /NH4-N ratio suitable for Anammox process (1.24±0.07).

High-testosterone men reject low ultimatum game offers.

PubMed

Burnham, Terence C

2007-09-22

The ultimatum game is a simple negotiation with the interesting property that people frequently reject offers of 'free' money. These rejections contradict the standard view of economic rationality. This divergence between economic theory and human behaviour is important and has no broadly accepted cause. This study examines the relationship between ultimatum game rejections and testosterone. In a variety of species, testosterone is associated with male seeking dominance. If low ultimatum game offers are interpreted as challenges, then high-testosterone men may be more likely to reject such offers. In this experiment, men who reject low offers ($5 out of $40) have significantly higher testosterone levels than those who accept. In addition, high testosterone levels are associated with higher ultimatum game offers, but this second finding is not statistically significant.

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 months...

Phenotypes of antibody-mediated rejection in organ transplants.

PubMed

Mengel, Michael; Husain, Sufia; Hidalgo, Luis; Sis, Banu

2012-06-01

Antibody-mediated hyperacute rejection was the first rejection phenotype observed in human organ transplants. This devastating phenotype was eliminated by reliable crossmatch technologies. Since then, the focus was on T-cell-mediated rejection and de novo donor-specific antibodies were considered an epiphenomenon of cognate T-cell activation. The immune theory was that controlling the T-cell response would entail elimination of antibody-mediated rejection (ABMR). With modern immunosuppressive drugs, T-cell-mediated rejection is essentially treatable. However, this did not prevent ABMR from emerging as a significant phenotype in all types of organ transplants. It became obvious that both rejection types require distinct treatment and thus reliable diagnosis. This is the current challenge. ABMR, depending on stage, grade, time course, organ type or prior treatment, can present with a wide spectrum of phenotypes. This review summarizes the current diagnostic consensus for ABMR, describes unmet needs and challenges in diagnostics, and proposes new approaches for consideration. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.

Specimen rejection in laboratory medicine: Necessary for patient safety?

PubMed

Dikmen, Zeliha Gunnur; Pinar, Asli; Akbiyik, Filiz

2015-01-01

The emergency laboratory in Hacettepe University Hospitals receives specimens from emergency departments (EDs), inpatient services and intensive care units (ICUs). The samples are accepted according to the rejection criteria of the laboratory. In this study, we aimed to evaluate the sample rejection ratios according to the types of pre-preanalytical errors and collection areas. The samples sent to the emergency laboratory were recorded during 12 months between January to December, 2013 in which 453,171 samples were received and 27,067 specimens were rejected. Rejection ratios was 2.5% for biochemistry tests, 3.2% for complete blood count (CBC), 9.8% for blood gases, 9.2% for urine analysis, 13.3% for coagulation tests, 12.8% for therapeutic drug monitoring, 3.5% for cardiac markers and 12% for hormone tests. The most frequent rejection reasons were fibrin clots (28%) and inadequate volume (9%) for biochemical tests. Clotted samples (35%) and inadequate volume (13%) were the major causes for coagulation tests, blood gas analyses and CBC. The ratio of rejected specimens was higher in the EDs (40%) compared to ICUs (30%) and inpatient services (28%). The highest rejection ratio was observed in neurology ICU (14%) among the ICUs and internal medicine inpatient service (10%) within inpatient clinics. We detected an overall specimen rejection rate of 6% in emergency laboratory. By documentation of rejected samples and periodic training of healthcare personnel, we expect to decrease sample rejection ratios below 2%, improve total quality management of the emergency laboratory and promote patient safety.

Specimen rejection in laboratory medicine: Necessary for patient safety?

PubMed Central

Dikmen, Zeliha Gunnur; Pinar, Asli; Akbiyik, Filiz

2015-01-01

Introduction The emergency laboratory in Hacettepe University Hospitals receives specimens from emergency departments (EDs), inpatient services and intensive care units (ICUs). The samples are accepted according to the rejection criteria of the laboratory. In this study, we aimed to evaluate the sample rejection ratios according to the types of pre-preanalytical errors and collection areas. Materials and methods The samples sent to the emergency laboratory were recorded during 12 months between January to December, 2013 in which 453,171 samples were received and 27,067 specimens were rejected. Results Rejection ratios was 2.5% for biochemistry tests, 3.2% for complete blood count (CBC), 9.8% for blood gases, 9.2% for urine analysis, 13.3% for coagulation tests, 12.8% for therapeutic drug monitoring, 3.5% for cardiac markers and 12% for hormone tests. The most frequent rejection reasons were fibrin clots (28%) and inadequate volume (9%) for biochemical tests. Clotted samples (35%) and inadequate volume (13%) were the major causes for coagulation tests, blood gas analyses and CBC. The ratio of rejected specimens was higher in the EDs (40%) compared to ICUs (30%) and inpatient services (28%). The highest rejection ratio was observed in neurology ICU (14%) among the ICUs and internal medicine inpatient service (10%) within inpatient clinics. Conclusions We detected an overall specimen rejection rate of 6% in emergency laboratory. By documentation of rejected samples and periodic training of healthcare personnel, we expect to decrease sample rejection ratios below 2%, improve total quality management of the emergency laboratory and promote patient safety. PMID:26527231

Neural Responses to Partner Rejection Cues

PubMed Central

Zayas, Vivian; Shoda, Yuichi; Mischel, Walter; Osterhout, Lee; Takahashi, Melissa

2009-01-01

Little is known about neural responses in the early automatic-stage processing of rejection cues from a partner. Event-related potentials (ERPs) offer a window to study processes that may be difficult to detect via behavioral methods. We focused on the N400 ERP component, which reflects the amount of semantic processing prompted by a target. When participants were primed by attachment-related contexts (“If I need help from my partner, my partner will be …”), rejection-related words (e.g., dismissing) elicited greater N400 amplitudes than acceptance-related words (e.g., supporting). Analyses of results for nonattachment primes suggest that these findings were not simply caused by target valence; the brain responds differentially to cues of partner rejection versus acceptance in under 300 ms. Moreover, these early-stage neurophysiological responses were heightened or dampened as a function of individuals’ adult attachment; women characterized by high anxiety and low avoidance showed the greatest N400 responses to cues of partner rejection (vs. acceptance). PMID:19493321

Lack of Association between Interleukin-10 Gene Polymorphisms and Graft Rejection Risk in Kidney Transplantation Recipients: A Meta-Analysis

PubMed Central

Xiong, Jiachuan; Wang, Yiqin; Zhang, Ying; Nie, Ling; Wang, Daihong; Huang, Yunjian; Feng, Bing; Zhang, Jingbo; Zhao, Jinghong

2015-01-01

Background Interleukin-10 (IL-10) is an important immunomodulatory cytokine. Several studies focused the association between IL-10 promoter gene polymorphisms and graft rejection risk in kidney transplantation recipients. However, the results of these studies remain inconclusive. The aim of this study was to conduct a meta-analysis to further assess the associations. Methods The PubMed, Embase, and Ovid Medline databases were searched. Two independent authors extracted data, and the effects were estimated from an odds ratio (OR) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses identified sources of heterogeneity. Results A total of 16 studies including 595 rejection patients and 1239 stable graft patients were included in order to study the IL-10 -1082 (rs1800896 G/A), -819 (rs1800871 C/T), -592 (rs1800872 C/A) and IL-10 (-1082,-819,-592) polymorphisms. The -1082 G/A polymorphism was not associated with an increased graft rejection risk (OR = 1.03; 95%CI, 0.85–1.25, P = 0.74 for GA+AA vs. GG model). Moreover, all of the -819 C/T (OR = 1.06, 95%CI, 0.79–1.42, P = 0.70 for TA+TT vs. CC model), -592 C/A (OR = 1.10, 95% CI, 0.85–1.42, P = 0.47 for AC+AA vs. CC model) and IL-10 (-1082,-819,-592) polymorphisms (OR = 1.00, 95%CI, 0.79–1.27, P = 0.98 for I+L vs. H model) did not increase the graft rejection risk. In addition, we also performed subgroup analysis by ethnic group (mainly in Europeans or Asians) and rejection type (acute or chronic). There was also lack of evidence of a significant association between the IL-10 gene polymorphism and graft rejection risk. The present meta-analysis indicated that the IL-10 gene polymorphism was not associated with graft rejection risk in kidney transplantation recipients. Conclusion This meta-analysis found evidence that the IL-10 polymorphism does not increase the risk of graft rejection in kidney transplantation recipients. Further chronic rejection and other ethnic population studies are needed

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.

Does gender impact upon application rejection rate among Canadian radiology residency applicants?

PubMed

Baerlocher, Mark O; Walker, Michelle

2005-10-01

To determine if and how gender ratios have changed within Canadian radiology, and to determine if gender discrimination occurs at the level of the radiology resident selection committee. The Canadian Medical Association, Canadian Association of Radiologists, Canadian Institute for Health Information, Royal College of Physicians and Surgeons of Canada, and Canadian Residency Matching Service provided gender-specific data. We compared the proportion of female applicants who ranked a radiology program as their top choice and were rejected from any radiology program with the corresponding proportion for male applicants. The numbers of women and men being awarded an MD from a Canadian university equalized nearly a decade ago. Women continue to be numerically underrepresented among practicing radiologists; however, the proportion of women continues to increase so that there is 1 female radiologist in practice to every 3 male radiologists in practice in 2005. More male medical students ranked a radiology residency training program as their top choice in the residency match; however, of those who did, they were as likely as women to be rejected from a radiology residency training program. Grouping all female and male graduating medical students participating in the residency match and ranking a radiology residency as their top choice between 1993 and 2004, the odds of men being rejected were 1.4 times (95% CI 0.99-1.9, p = 0.07) greater than for women. There continues to be more men than women radiologists in practice; however, the female-to-male ratio continues to increase. Our data suggest that discrimination against female applicants at the level of radiology residency selection does not occur.

Soluble donor HLA class I and beta 2m-free heavy chain in serum of lung transplant recipients: steady-state levels and increases in patients with recurrent CMV infection, acute rejection episodes, and poor outcome.

PubMed

DeVito-Haynes, L D; Jankowska-Gan, E; Meyer, K C; Cornwell, R D; Zeevi, A; Griffith, B; Dauber, J; Iacono, A; Burlingham, W J; Love, R B

2000-12-01

We determined the concentration of donor sHLA/beta(2)m and total beta(2)m-free heavy chain (HC) in the serum of lung transplant recipients with ELISA assays. While we were unable to detect specific donor beta(2)m-free HCs due to a lack of available antibodies, we could determine if events that led to an increase in the release of beta(2)m-free HC also led to an increase in the release of donor sHLA/beta(2)m, particularly the 36 kDa, proteolytically cleaved form. We found that lung transplants constituitively release donor sHLA/beta(2)m at ng/ml levels. The levels (both of donor sHLA/beta(2)m and total beta(2)m-free HC) were significantly increased in CMV-sero-negative recipients (but not in CMV-sero-positive recipients) at the onset of post-transplant CMV disease. Acute rejection episodes were also associated with an increased release of donor sHLA/beta(2)m, but not of beta(2)m-free HC. However, in patients with particularly poor outcome (i.e., graft loss within 1 year) there was a significant release of beta(2)m-free HC. Analysis of one such patient showed a predominance of 36 kDa forms of donor-sHLA/beta(2)m. Our data are consistent with the hypothesis that the metalloproteinase that cleaves beta(2)m-free HC is active during uncontrolled CMV infection and acute rejection. However, recall responses to CMV and controlled immune responses to donor may result in little or no activation of sHLA class I release.

The fate of triaged and rejected manuscripts.

PubMed

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

2015-12-01

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

The Parental "Acceptance-Rejection Syndrome": Universal Correlates of Perceived Rejection

ERIC Educational Resources Information Center

Rohner, Ronald P.

2004-01-01

This article reviews theory, methods, and evidence supporting the concept of a relational diagnosis here called the parental acceptance-rejection syndrome. This syndrome is composed of 2 complementary sets of factors. First, 4 classes of behaviors appear universally to convey the symbolic message that "my parent (or other attachment…

Diagnosis of Acute Cellular Rejection Using Probe-Based Confocal Laser Endomicroscopy in Lung Transplant Recipients: a Prospective, Multicenter Trial.

PubMed

Keller, Cesar A; Khoor, Andras; Arenberg, Douglas A; Smith, Michael A; Islam, Shaheen U

2018-05-29

Acute cellular rejection (ACR) in lung transplant recipients requires demonstration of perivascular lymphocytic infiltration in alveolar tissue samples from transbronchial biopsies (TBBs). Probe-based confocal laser endomicroscopy (pCLE) allows in vivo observation of alveolar, vascular, and cellular microstructures in the lung with potential to identify ACR. The objective of our prospective, blinded, multicenter observational study was to identify pCLE findings in patients with ACR diagnosed histopathologically by TBB. Lung transplant recipients undergoing diagnostic bronchoscopies within 1 year posttransplant for suspected ACR had pCLE video imaging obtained immediately prior to tissue sampling via TBB. Findings of 2 pCLE criteria, abundant alveolar cellularity and perivascular cellularity (PVC), were assessed by 4 investigators familiar with pCLE and compared to histopathologic criteria of ACR to derive sensitivity, specificity, area under the receiver operating characteristic curve, and accuracy. Interobserver agreement was assessed by calculating intraclass coefficient and Fleiss κ. Findings were analyzed before and after a consensus meeting of investigators on interpreting images. Thirty pCLE procedures were performed on 24 patients, 8 showing ACR in TBB. Diagnostic performance and interobserver agreement using pCLE to identify PVC were significantly higher than those of abundant alveolar cellularity (P<.01). The number of blood vessels identified with PVC on pCLE was significantly correlated with histopathologic activity grading of ACR (P<.01). PVC agreement among investigators significantly improved after consensus meeting (P<.01) CONCLUSIONS: When found on pCLE, PVC is a feasible and reproducible criterion for assessment of ACR in vivo, but there is a learning curve for image interpretation.

Rejection of Bromide and Bromate Ions by a Ceramic Membrane.

PubMed

Moslemi, Mohammadreza; Davies, Simon H; Masten, Susan J

2012-12-01

Effects of pH and the addition of calcium chloride (CaCl(2)) on bromate (BrO(3) (-)) and bromide (Br(-)) rejection by a ceramic membrane were investigated. Rejection of both ions increased with pH. At pH 8, the rejection of BrO(3) (-) and Br(-) was 68% and 63%, respectively. Donnan exclusion appears to play an important role in determining rejection of BrO(3) (-) and Br(-). In the presence of CaCl(2), rejection of BrO(3) (-) and Br(-) ions was greatly reduced, confirming the importance of electrostatic interactions in determining rejection of BrO(3) (-) and Br(-). The effect of Ca(2+) is so pronounced that in most natural waters, rejection of both BrO(3) (-) and Br(-) by the membrane would be extremely small.

48 CFR 19.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Rejecting Small Business... REGULATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Set-Asides for Small Business 19.505 Rejecting Small Business Administration recommendations. (a) If the contracting officer rejects a recommendation...

48 CFR 19.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Rejecting Small Business... REGULATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Set-Asides for Small Business 19.505 Rejecting Small Business Administration recommendations. (a) If the contracting officer rejects a recommendation...

48 CFR 19.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Rejecting Small Business... REGULATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Set-Asides for Small Business 19.505 Rejecting Small Business Administration recommendations. (a) If the contracting officer rejects a recommendation...

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

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.

Review: The transcripts associated with organ allograft rejection.

PubMed

Halloran, Philip F; Venner, Jeffery M; Madill-Thomsen, Katelynn S; Einecke, Gunilla; Parkes, Michael D; Hidalgo, Luis G; Famulski, Konrad S

2018-04-01

The molecular mechanisms operating in human organ transplant rejection are best inferred from the mRNAs expressed in biopsies because the corresponding proteins often have low expression and short half-lives, while small non-coding RNAs lack specificity. Associations should be characterized in a population that rigorously identifies T cell-mediated (TCMR) and antibody-mediated rejection (ABMR). This is best achieved in kidney transplant biopsies, but the results are generalizable to heart, lung, or liver transplants. Associations can be universal (all rejection), TCMR-selective, or ABMR-selective, with universal being strongest and ABMR-selective weakest. Top universal transcripts are IFNG-inducible (eg, CXCL11 IDO1, WARS) or shared by effector T cells (ETCs) and NK cells (eg, KLRD1, CCL4). TCMR-selective transcripts are expressed in activated ETCs (eg, CTLA4, IFNG), activated (eg, ADAMDEC1), or IFNG-induced macrophages (eg, ANKRD22). ABMR-selective transcripts are expressed in NK cells (eg, FGFBP2, GNLY) and endothelial cells (eg, ROBO4, DARC). Transcript associations are highly reproducible between biopsy sets when the same rejection definitions, case mix, algorithm, and technology are applied, but exact ranks will vary. Previously published rejection-associated transcripts resemble universal and TCMR-selective transcripts due to incomplete representation of ABMR. Rejection-associated transcripts are never completely rejection-specific because they are shared with the stereotyped response-to-injury and innate immunity. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Impulsivity, Rejection Sensitivity, and Reactions to Stressors in Borderline Personality Disorder

PubMed Central

Berenson, Kathy R.; Gregory, Wesley Ellen; Glaser, Erin; Romirowsky, Aliza; Rafaeli, Eshkol; Yang, Xiao; Downey, Geraldine

2016-01-01

This research investigated baseline impulsivity, rejection sensitivity, and reactions to stressors in individuals with borderline personality disorder compared to healthy individuals and those with avoidant personality disorder. The borderline group showed greater impulsivity than the avoidant and healthy groups both in a delay-discounting task with real monetary rewards and in self-reported reactions to stressors; moreover, these findings could not be explained by co-occurring substance use disorders. Distress reactions to stressors were equally elevated in both personality disorder groups (relative to the healthy group). The borderline and avoidant groups also reported more maladaptive reactions to a stressor of an interpersonal vs. non-interpersonal nature, whereas the healthy group did not. Finally, self-reported impulsive reactions to stressors were associated with baseline impulsivity in the delay-discounting task, and greater self-reported reactivity to interpersonal than non-interpersonal stressors was associated with rejection sensitivity. This research highlights distinct vulnerabilities contributing to impulsive behavior in borderline personality disorder. PMID:27616800

Rejection of Bromide and Bromate Ions by a Ceramic Membrane

PubMed Central

Moslemi, Mohammadreza; Davies, Simon H.; Masten, Susan J.

2012-01-01

Abstract Effects of pH and the addition of calcium chloride (CaCl2) on bromate (BrO3−) and bromide (Br−) rejection by a ceramic membrane were investigated. Rejection of both ions increased with pH. At pH 8, the rejection of BrO3− and Br− was 68% and 63%, respectively. Donnan exclusion appears to play an important role in determining rejection of BrO3− and Br−. In the presence of CaCl2, rejection of BrO3− and Br− ions was greatly reduced, confirming the importance of electrostatic interactions in determining rejection of BrO3− and Br−. The effect of Ca2+ is so pronounced that in most natural waters, rejection of both BrO3− and Br− by the membrane would be extremely small. PMID:23236251

28 CFR 540.13 - Notification of rejections.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Notification of rejections. 540.13 Section 540.13 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT CONTACT WITH PERSONS IN THE COMMUNITY Correspondence § 540.13 Notification of rejections. When...

Electronically controlled rejections of spoof surface plasmons polaritons

NASA Astrophysics Data System (ADS)

Zhou, Yong Jin; Xiao, Qian Xun

2017-03-01

We have proposed and experimentally demonstrated a band-notched surface plasmonic filter, which is composed of an ultra-wide passband plasmonic filter with a simple C-shaped ring on the back of the substrate. Enhanced narrowband or broadband rejections of spoof surface plasmon polaritons (SPPs) can be achieved with double C-shaped rings in the propagation or transverse direction. By mounting active components across the slit cut in the C-shaped ring, dynamic control of rejection of spoof SPPs can be accomplished. Both the rejection of spoof SPPs and the rejection bandwidth can be controlled when the Schottky barrier diode is forward-biased or reverse-biased. The frequency spectrum of the rejection band can be electronically adjusted by tuning the applied bias voltage across the varactor diode. Both simulated and measured results agree well and demonstrate dynamic control of propagation of spoof SPPs at the microwave frequencies. Such electronically controllable devices could find more applications in advanced plasmonic integrated functional circuits in microwave and terahertz frequencies.

Detection and measurement of tubulitis in renal allograft rejection

NASA Astrophysics Data System (ADS)

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

1997-04-01

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

Rejection of isolated pancreatic allografts in patients with with diabetes.

PubMed

Groth, C G; Lundgren, G; Arner, P; Collste, H; Hårdstedt, C; Lewander, R; Ostman, J

1976-12-01

Four patients with diabetes mellitus of juvenile onset but without uremia have been treated with segmental transplantation of the body and tail of pancreas. The indications were hyperlabile diabetes or progressive loss of vision. The grafts were procured from cadaveric donors four to 16 minutes after circulary arrest and were subsequently stored in the cold for approximately four hours. In one patient, the pancreatic duct was ligated, while in the other three, drainage was attained by suturing the transected end of the pancreas into a jejunal Roux-en-Y loop. Three of the grafts failed within six weeks as a result of irreversible refection, and one graft failed because of the early onset of venous thrombosis. The first sign of graft rejection was an increase in the postprandial blood sugar level, an increase in the fasting blood sugar level occurring several days later. Neither hyperamylasemia nor fever was observed. Radioisotope scans and angiograms were of great value in establishing the diagnosis of graft rejection. All of the patients survived after graft removal.

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

PubMed

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

2014-01-01

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

Allorecognition pathways in transplant rejection and tolerance.

PubMed

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

2013-10-27

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

"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…

Human Xenografts Are Not Rejected in a Naturally Occurring Immunodeficient Porcine Line: A Human Tumor Model in Pigs

PubMed Central

Basel, Matthew T.; Balivada, Sivasai; Beck, Amanda P.; Kerrigan, Maureen A.; Pyle, Marla M.; Dekkers, Jack C.M.; Wyatt, Carol R.; Rowland, Robert R.R.; Anderson, David E.; Bossmann, Stefan H.

2012-01-01

Abstract Animal models for cancer therapy are invaluable for preclinical testing of potential cancer treatments; however, therapies tested in such models often fail to translate into clinical settings. Therefore, a better preclinical model for cancer treatment testing is needed. Here we demonstrate that an immunodeficient line of pigs can host and support the growth of xenografted human tumors and has the potential to be an effective animal model for cancer therapy. Wild-type and immunodeficient pigs were injected subcutaneously in the left ear with human melanoma cells (A375SM cells) and in the right ear with human pancreatic carcinoma cells (PANC-1). All immunodeficient pigs developed tumors that were verified by histology and immunohistochemistry. Nonaffected littermates did not develop tumors. Immunodeficient pigs, which do not reject xenografted human tumors, have the potential to become an extremely useful animal model for cancer therapy because of their similarity in size, anatomy, and physiology to humans. PMID:23514746

7 CFR 1956.84 - Approval or rejection.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 14 2010-01-01 2009-01-01 true Approval or rejection. 1956.84 Section 1956.84 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS... Housing § 1956.84 Approval or rejection. (a)-(d) [Reserved] (e) Appeal rights. A debtor whose debt...

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

PubMed

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

2015-09-03

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.

Influence of delayed graft function and acute rejection on outcomes after kidney transplantation from donors after cardiac death.

PubMed

Nagaraja, Pramod; Roberts, Gareth W; Stephens, Michael; Horvath, Szabolcs; Fialova, Jana; Chavez, Rafael; Asderakis, Argiris; Kaposztas, Zsolt

2012-12-27

Delayed graft function (DGF) and acute rejection (AR) exert an adverse impact on graft outcomes after kidney transplantation using organs from donation after brain-stem death (DBD) donors. Here, we examine the impact of DGF and AR on graft survival in kidney transplants using organs from donation after cardiac death (DCD) donors. We conducted a single-center retrospective study of DCD and DBD donor kidney transplants. We compared 1- and 4-year graft and patient survival rates, as well as death-censored graft survival (DCGS) rates, between the two groups using univariate analysis, and the impact of DGF and AR on graft function was compared using multivariate analysis. Eighty DCD and 206 DBD donor transplants were analyzed. Median follow-up was 4.5 years. The incidence of DGF was higher among DCD recipients (73% vs. 27%, P<0.001), and AR was higher among DBD recipients (23% vs. 9%, P<0.001). One-year and 4-year graft survival rates were similar (DCD 94% and 79% vs. DBD 90% and 82%). Among recipients with DGF, the 4-year DCGS rate was better for DCD recipients compared with DBD recipients (100% vs. 92%, P=0.04). Neither DGF nor AR affected the 1-year graft survival rate in DCD recipients, whereas in DBD recipients, the 1-year graft survival rate was worse in the presence of DGF (88% vs. 96%, P=0.04) and the 4-year DCGS rate was worse in the presence of AR (88% vs. 96%, P=0.04). Despite the high incidence of DGF, medium-term outcomes of DCD kidney transplants are comparable to those from DBD transplants. Short-term graft survival from DCD transplants is not adversely influenced by DGF and AR, unlike in DBD transplants.

The private rejection of unfair offers and emotional commitment.

PubMed

Yamagishi, Toshio; Horita, Yutaka; Takagishi, Haruto; Shinada, Mizuho; Tanida, Shigehito; Cook, Karen S

2009-07-14

In a series of experiments, we demonstrate that certain players of an economic game reject unfair offers even when this behavior increases rather than decreases inequity. A substantial proportion (30-40%, compared with 60-70% in the standard ultimatum game) of those who responded rejected unfair offers even when rejection reduced only their own earnings to 0, while not affecting the earnings of the person who proposed the unfair split (in an impunity game). Furthermore, even when the responders were not able to communicate their anger to the proposers by rejecting unfair offers in a private impunity game, a similar rate of rejection was observed. The rejection of unfair offers that increases inequity cannot be explained by the social preference for inequity aversion or reciprocity; however, it does provide support for the model of emotion as a commitment device. In this view, emotions such as anger or moral disgust lead people to disregard the immediate consequences of their behavior, committing them to behave consistently to preserve integrity and maintain a reputation over time as someone who is reliably committed to this behavior.

Relationship between subclinical rejection and genotype, renal messenger RNA, and plasma protein transforming growth factor-beta1 levels.

PubMed

Hueso, Miguel; Navarro, Estanis; Moreso, Francesc; Beltrán-Sastre, Violeta; Ventura, Francesc; Grinyó, Josep M; Serón, Daniel

2006-05-27

Transforming growth factor (TGF)-beta(1) is increased in allograft rejection and its production is associated with single nucleotide polymorphisms (SNPs). The contribution of SNPs at codons 10 and 25 of the TGF-beta(1) gene to renal allograft damage was assessed in 6-month protocol biopsies and their association with TGF-beta(1) production. TGF-beta(1) genotypes were evaluated by polymerase chain reaction (PCR)/restriction fragment length polymorphism. Intragraft TGF-beta(1) messenger RNA (mRNA) was measured by real-time PCR and TGF-beta(1) plasma levels were assessed by enzyme-linked immunosorbent assay. Eighty consecutive patients were included. Allele T at codon 10 (risk ratio, 6.7; P = 0.02) and an episode of acute rejection before protocol biopsy (risk ratio, 6.2; P = 0.01) were independent predictors of subclinical rejection (SCR). TGF-beta(1) plasma levels, but not those of TGF-beta(1) mRNA, were increased in patients with SCR (2.59 ng/mL +/- 0.91 [n = 22] vs. 2.05 ng/mL +/- 0.76 [n = 43]; P = 0.01). There was no association between allele T and TGF-beta(1) plasma or intragraft levels. Allele T at codon 10 of the TGF-beta(1) gene is associated with a higher incidence of SCR.

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

PubMed

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

2014-07-01

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

Presence of FoxP3+ regulatory T Cells predicts outcome of subclinical rejection of renal allografts.

PubMed

Bestard, Oriol; Cruzado, Josep M; Rama, Inés; Torras, Joan; Gomà, Montse; Serón, Daniel; Moreso, Francesc; Gil-Vernet, Salvador; Grinyó, Josep M

2008-10-01

Subclinical rejection (SCR) of renal allografts refers to histologic patterns of acute rejection despite stable renal function. The clinical approach to SCR is controversial; it would be helpful to identify biomarkers that could determine whether the identified cellular infiltrates were detrimental. For investigation of whether the presence of FoxP3+ regulatory T cells (Treg) could help determine the functional importance of tubulointerstitial infiltrates observed in 6-mo protocol biopsies, 37 cases of SCR were evaluated. The presence of FoxP3+ Treg discriminated harmless from injurious infiltrates, evidenced by independently predicting better graft function 2 and 3 yr after transplantation. Furthermore, the FoxP3+ Treg/CD3+ T cell ratio positively correlated with graft function at 2 yr after transplantation, suggesting that an increasing proportion of Treg within the global T cell infiltrate may facilitate renal engraftment; therefore, immunostaining for FoxP3+ Treg in patients with SCR on protocol biopsies may ultimately be useful to identify patients who may require alterations in their immunosuppressive regimens.

Presence of FoxP3+ Regulatory T Cells Predicts Outcome of Subclinical Rejection of Renal Allografts

PubMed Central

Bestard, Oriol; Cruzado, Josep M.; Rama, Inés; Torras, Joan; Gomà, Montse; Serón, Daniel; Moreso, Francesc; Gil-Vernet, Salvador; Grinyó, Josep M.

2008-01-01

Subclinical rejection (SCR) of renal allografts refers to histologic patterns of acute rejection despite stable renal function. The clinical approach to SCR is controversial; it would be helpful to identify biomarkers that could determine whether the identified cellular infiltrates were detrimental. For investigation of whether the presence of FoxP3+ regulatory T cells (Treg) could help determine the functional importance of tubulointerstitial infiltrates observed in 6-mo protocol biopsies, 37 cases of SCR were evaluated. The presence of FoxP3+ Treg discriminated harmless from injurious infiltrates, evidenced by independently predicting better graft function 2 and 3 yr after transplantation. Furthermore, the FoxP3+ Treg/CD3+ T cell ratio positively correlated with graft function at 2 yr after transplantation, suggesting that an increasing proportion of Treg within the global T cell infiltrate may facilitate renal engraftment; therefore, immunostaining for FoxP3+ Treg in patients with SCR on protocol biopsies may ultimately be useful to identify patients who may require alterations in their immunosuppressive regimens. PMID:18495961

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.

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.

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

ERIC Educational Resources Information Center

Park, Yoonjung; Killen, Melanie

2010-01-01

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

Films reject analysis for conventional radiography in Iranian main hospitals.

PubMed

Roohi Shalemaei, R

2011-09-01

The purpose of this study was to evaluate image quality, to determine the reject film rate in conventional radiology procedures and to determine the causes of defects on the films. Rejected films were collected in four main hospitals in Iran and five routine examinations were considered. The rejected films were analysed and assigned to five different categories. There was a significant reduction in the overall film reject rate for all examinations investigated from 17.6 to 11.4 % when a quality assurance (QA) programme was implemented. The major reasons for rejection of films were over- or under-exposure and processing problems. The study showed the importance of a QA programme in order to deliver high-quality health service to patients.

Effect of Donor and Recipient Factors on Corneal Graft Rejection

PubMed Central

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

2014-01-01

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

Developmental Pathways from Child Maltreatment to Peer Rejection.

ERIC Educational Resources Information Center

Bolger, Kerry E.; Patterson, Charlotte J.

2001-01-01

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

Balancing rejection and infection with respect to age, race, and gender: clues acquired from 17 years of cardiac transplantation data.

PubMed

George, James F; Pamboukian, Salpy V; Tallaj, José A; Naftel, David C; Myers, Susan L; Foushee, Margaret T; Brown, Robert N; Pajaro, Octavio E; McGiffin, David C; Kirklin, James K

2010-09-01

Donor and recipient risk factors for rejection and infection have been well characterized. The contribution of demographic factors, especially age at the time of transplantation to morbidity and mortality due to rejection and infection, is much less well understood. Using parametric hazard analysis and multivariate risk-factor equations for infection and rejection events, we quantitatively determined the relationship of fundamental demographic variables (age, race and gender) to infection and rejection. These analyses were conducted with respect to date of transplant and age at the time of transplantation. The patient group consisted of all primary heart transplants performed at the University of Alabama at Birmingham during the years 1990 to 2007 (n = 526). Risk factors for rejection within 12 months post-transplantation were date of transplant (p < 0.0001) and age at the time of transplantation (young adults 10 to 30 years of age, p < 0.0001). Risk factors for infection were date of transplant (p < 0.0001) and age at the time of transplantation (young children and older adults, p < 0.0001). There were three immunosuppressive eras in 1990 to 2007. Notably, although the proportion of patients experiencing rejection and infection events decreased during each successive immunosuppressive era, the relative relationship of infection to rejection, as well as age at the time of transplantation, remained similar into the most recent era. The maximal frequency of rejection events and rejection death occurred among patients transplanted at ages 10 to 30 years. Conversely, the frequency of infection events was minimal within the same group. In the oldest and youngest patients receiving transplants, infection was the predominant cause of death and rates of rejection events decreased. These data show that evolving immunosuppressive strategies have successfully reduced rejection and infection frequencies, and those patients transplanted at 30 to 60 years of age have the lowest

Modeling the rejection probability in plant imports.

PubMed

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

2008-06-01

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

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. PsycINFO Database Record (c) 2013 APA, all rights reserved.

The STScI STIS Pipeline V: Cosmic Ray Rejection

NASA Astrophysics Data System (ADS)

Baum, Stefi; Hsu, J. C.; Hodge, Phil; Ferguson, Harry

1996-07-01

In this ISR we describe calstis-2, the calstis calibration module which combines CRSPLIT exposures to produce a single cosmic ray rejected image. Cosmic ray rejection in the STIS pipeline will follow the same basic philosophy as does the STSDAS task crrej - a series of separate CRSPLIT exposures are combined to produce a single summed image, where discrepant (different by some number of sigma from the guess value) are discarded in forming the output image. The calstis pipeline is able to perform this cosmic ray rejection because the individually commanded exposures are associated together into a single dataset by TRANS and generic conversion. The crrej will also exist as a task in STSDAS to allow users to reperform the cosmic ray rejection, altering the input parameters.

Fate of Manuscripts Rejected From the Red Journal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holliday, Emma B., E-mail: emmaholliday@gmail.com; Yang, George; Jagsi, Reshma

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 publishedmore » 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

Influence of naturally occurring dissolved organic matter, colloids, and cations on nanofiltration of pharmaceutically active and endocrine disrupting compounds.

PubMed

Sadmani, A H M Anwar; Andrews, Robert C; Bagley, David M

2014-12-01

This study examined the rejection of selected pharmaceutically active (PhAC) and endocrine disrupting compounds (EDCs) when using nanofiltration as a function of naturally occurring dissolved organic matter (DOM), colloidal particles, cations and their interactions. Lake Ontario water served as a source of natural DOM and colloidal particles. PhAC/EDC rejection experiments were conducted using raw Lake Ontario water and Lake Ontario water that was pre-treated with either ultrafiltration to remove colloidal particles, or fluidized ion exchange resins to remove DOM. Additionally, the concentration of cations (Ca(2+), Mg(2+), and Na(+)) in the raw and pre-treated water matrices was varied. While ionic PhACs and EDCs exhibited high rejections from all the water matrices examined, neutral compounds were most effectively rejected in water containing DOM and no colloids, and least effectively rejected from colloid-containing water with increased cations but no DOM. The presence of DOM significantly improved compound rejection and the increase in cation concentration significantly decreased rejection. The presence of colloids had comparatively little effect except to mitigate the impact of increased cation concentration, apparently providing some cation-buffering capacity. The sequence in which constituents are removed from waters during treatment may significantly impact PhAC and EDC removal, especially of neutral compounds. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.…

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.…

Examining ethnic differences in parental rejection of LGB youth sexual identity.

PubMed

Richter, Brian E J; Lindahl, Kristin M; Malik, Neena M

2017-03-01

Upward of 70% of lesbian, gay, and bisexual (LGB) youth experience some degree of parental rejection of their sexual identity, which is problematic in light of research documenting links between parental rejection and psychological difficulties in LGB youth. Additionally, emerging research suggests that ethnic minority LGB youth may be at greater risk to experience parental rejection than ethnic majority LGB youth. However, this research is inconclusive and has significant gaps. The current study is one of the first to include a multiethnic sample of LGB youth and their parents to investigate how ethnicity may be related to parental rejection. Specifically, the current study examined ethnic differences in parental rejection as well as in intrapersonal variables (i.e., homonegativity and traditional gender role beliefs), which are thought to be related both to ethnicity and parental rejection. Additionally, indirect effects of ethnicity on parental rejection through homonegativity and traditional gender role beliefs were examined. Participants included 90 parents (ages 32-63) and their 90 LGB children (ages 15-24). Fifty-nine percent of the sample were ethnic minority. Significant ethnic differences were found in parental rejection and homonegativity, but not in traditional gender role beliefs. Homonegativity was found to fully mediate the relation between ethnicity and parental rejection. These results provide important information on why ethnic minority parents, in general, may have a more difficult time accepting their LGB children than ethnic majority parents. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Examining Ethnic Differences in Parental Rejection of LGB Youth Sexual Identity

PubMed Central

Richter, Brian E. J.; Lindahl, Kristin M.; Malik, Neena M.

2016-01-01

Upward of 70% of lesbian, gay, and bisexual (LGB) youth experience some degree of parental rejection of their sexual identity, which is problematic in light of research documenting links between parental rejection and psychological difficulties in LGB youth. Additionally, emerging research suggests that ethnic minority LGB youth may be at greater risk to experience parental rejection than ethnic majority LGB youth. However, this research is inconclusive and has significant gaps. The current study is one of the first to include a multiethnic sample of LGB youth and their parents to investigate how ethnicity may be related to parental rejection. Specifically, the current study examined ethnic differences in parental rejection as well as in intrapersonal variables (i.e., homonegativity and traditional gender role beliefs), which are thought to be related both to ethnicity and parental rejection. Additionally, indirect effects of ethnicity on parental rejection through homonegativity and traditional gender role beliefs were examined. Participants included 90 parents (ages 32-63) and their 90 LGB children (ages 15-24). Fifty-nine percent of the sample was ethnic minority. Significant ethnic differences were found in parental rejection and homonegativity, but not in traditional gender role beliefs. Homonegativity was found to fully mediate the relation between ethnicity and parental rejection. These results provide important information on why ethnic minority parents, in general, may have a more difficult time accepting their LGB children than ethnic majority parents. PMID:27571323

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…

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

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

Protective function of pirfenidone and everolimus on the development of chronic allograft rejection after experimental lung transplantation.

PubMed

von Suesskind-Schwendi, M; Heigel, E; Pfaehler, S; Haneya, A; Schmid, C; Hirt, S W; Lehle, K

2016-07-01

Long-term survival of lung allografts is limited by chronic rejection (CR). Oxidative stress (OxS) plays a central role in the development of CR. We investigated the influence of pirfenidone (alone or in combination with everolimus) on OxS and CR. A rat model of left lung allo-transplantation (F344-to-WKY) was used to evaluate the effects of pirfenidone alone [0,85% in chow from postoperative day (POD) -3 to 20/60] and in combination with everolimus [2,5 mg/kg bw daily from POD 7 to 20/60]. Allografts of non-treated animals, everolimus treated animals and right, non-transplanted lungs were used as references. Immunohistology of myeloperoxidase (MPO), haemoxygenase-1 (HO-1), iron and platelet-derived-growth-factor-receptor-alpha (PDGFR-a) were performed. On POD 20, all groups showed severe acute rejection (ISHLT A3-4/B1R-B2R). Groups treated with pirfenidone showed a lower interstitial inflammatory infiltration and a lower participation of highly fibrotic degenerated vessels (ISHLT-D2R). In the long term follow up (POD 60), pirfenidone alone significantly reduced chronic airway rejection (ISHLT-C; p≤0.05), interstitial fibrosis (IF; p≤0.05), content of collagen (p≤0.05), expression of PDGFR-a (p≤0.05) and the deposition of iron (p≤0.05). All groups treated with pirfenidone showed a high expression of the cytoprotective enzyme HO-1 (p≤0.05). The additional application of everolimus resulted in a significant decrease of chronic airway rejection (ISHLT-C; p≤0.05), vasculopathy (ISHLT; p≤0.05) and IF (p≤0.05). In conclusion, early application of pirfenidone inhibited the progression of CR by its anti-fibrotic and anti-oxidative properties. The additional application of an m-TOR-inhibitor increased the anti-fibrotic effects of pirfenidone which resulted in a reduction of CR after experimental LTx.

Indirect Effects of Emotion Regulation on Peer Acceptance and Rejection: The Roles of Positive and Negative Social Behaviors

ERIC Educational Resources Information Center

Blair, Bethany L.; Gangel, Meghan J.; Perry, Nicole B.; O'Brien, Marion; Calkins, Susan D.; Keane, Susan P.; Shanahan, Lilly

2016-01-01

A growing body of literature indicates that childhood emotion regulation predicts later success with peers, yet little is known about the processes through which this association occurs. The current study examined mechanisms through which emotion regulation was associated with later peer acceptance and peer rejection, controlling for earlier…

Experimental Evaluation of Load Rejection Over-Voltage from Grid-Tied Solar Inverters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, Austin; Hoke, Andy, Chakraborty, Sudipta; Ropp, Michael

This paper investigates the impact of load rejection over-voltage (LRO) from commercially available grid-tied photovoltaic (PV) solar inverters. LRO can occur when a local feeder or breaker opens and the power output from a distributed energy resource exceeds the load power. Simplified models of current controlled inverters can over-predict over-voltage magnitudes, thus it is useful to quantify testing. The load rejection event was replicated using a hardware testbed at the National Renewable Energy Laboratory (NREL), and a set of commercially available PV inverters was tested to quantify the impact of LRO for a range of generation-to-load ratios. The magnitude andmore » duration of the over-voltage events are reported in this paper along with a discussion of characteristic inverter output behavior. The results for the inverters under test showed that maximum over-voltage magnitudes were less than 200 percent of nominal voltage, and much lower in many test cases. These research results are important because utilities that interconnect inverter-based DER need to understand their characteristics under abnormal grid conditions.« less

Immunosuppressant dose reduction and long-term rejection risk in renal transplant recipients with severe bacterial pneumonia.

PubMed

Shih, Chia-Jen; Tarng, Der-Cherng; Yang, Wu-Chang; Yang, Chih-Yu

2014-07-01

Due to lifelong immunosuppression, renal transplant recipients (RTRs) are at risk of infectious complications such as pneumonia. Severe pneumonia results in respiratory failure and is life‑threatening. We aimed to examine the influence of immunosuppressant dose reduction on RTRs with bacterial pneumonia and respiratory failure. From January 2001 to January 2011, 33 of 1,146 RTRs at a single centre developed bacterial pneumonia with respiratory failure. All patients were treated using mechanical ventilation and aggressive therapies in the intensive care unit. Average time from kidney transplantation to pneumonia with respiratory failure was 6.8 years. In-hospital mortality rate was 45.5% despite intensive care and aggressive therapies. Logistic regression analysis indicated that a high serum creatinine level at the time of admission to the intensive care unit (odds ratio 1.77 per mg/dL, 95% confidence interval 1.01-3.09; p = 0.045) was a mortality determinant. Out of the 33 patients, immunosuppressive agents were reduced in 17 (51.5%). We found that although immunosuppressant dose reduction tended to improve in-hospital mortality, this was not statistically significant. Nevertheless, during a mean follow-up period of two years, none of the survivors (n = 18) developed acute rejection or allograft necrosis. In RTRs with bacterial pneumonia and respiratory failure, higher serum creatinine levels were a mortality determinant. Although temporary immunosuppressant dose reduction might not reduce mortality, it was associated with a minimal risk of acute rejection during the two-year follow-up. Our results suggest that early immunosuppressant reduction in RTRs with severe pneumonia of indeterminate microbiology may be safe even when pathogens are bacterial in nature.

Prosthesis rejection in acquired major upper-limb amputees: a population-based survey.

PubMed

Østlie, Kristin; Lesjø, Ingrid Marie; Franklin, Rosemary Joy; Garfelt, Beate; Skjeldal, Ola Hunsbeth; Magnus, Per

2012-07-01

To estimate the rates of primary and secondary prosthesis rejection in acquired major upper-limb amputees (ULAs), to describe the most frequently reported reasons for rejection and to estimate the influence of background factors on the risk of rejection. Cross-sectional study analysing population-based questionnaire data (n = 224). Effects were analysed by logistic regression analyses and Cox regression analyses. Primary prosthesis rejection was found in 4.5% whereas 13.4% had discontinued prosthesis use. The main reasons reported for primary non-wear were a perceived lack of need and discrepancies between perceived need and the prostheses available. The main reasons reported for secondary prosthesis rejection were dissatisfaction with prosthetic comfort, function and control. Primary prosthesis rejection was more likely in ULAs amputated at high age and in ULAs with proximal amputations. Secondary prosthesis rejection was more likely in proximal ULAs and in women. Clinicians should be aware of the increased risk of rejection in proximal ULAs, elderly ULAs and in women. Emphasising individual needs will probably facilitate successful prosthetic fitting. Improved prosthesis quality and individualised prosthetic training may increase long-term prosthesis use. Further studies of the effect of prosthetic training and of the reasons for rejection of different prosthetic types are suggested.

When Saying Sorry May Not Help: The Impact of Apologies on Social Rejections

PubMed Central

Freedman, Gili; Burgoon, Erin M.; Ferrell, Jason D.; Pennebaker, James W.; Beer, Jennifer S.

2017-01-01

If you have to socially reject someone, will it help to apologize? Social rejection is a painful emotional experience for targets, yet research has been silent on recommendations for rejectors. Across three sets of studies, apologies increased hurt feelings and the need to express forgiveness but did not increase feelings of forgiveness. The investigation of hurt feelings arising from a social rejection is challenging because previous research has shown that participants are reluctant to admit they felt hurt by the rejection. The present research addressed the self-report issue in two ways. First, participants rated how much social rejections would hurt someone’s feelings as a function of whether an apology was included across various social rejection scenarios (Studies 1a–e). Second, aggressive behavior was measured in response to face-to-face social rejections that were manipulated to include or exclude apologies (Studies 2a–c). More specifically, Studies 1a–e (N = 1096) found that although individuals sometimes use apologies in social rejections, social rejections with apologies are associated with higher levels of explicit hurt feelings. Studies 2a–c (N = 355) manipulated the presence of an apology in face-to-face social rejections and found that social rejections with apologies cause more aggressive behavior. As in previous research, participants are reluctant to admit to feeling hurt. Finally, Study 3 (N = 426) found that in response to social rejections with apologies, individuals feel more compelled to express forgiveness despite not actually feeling more forgiveness. Implications for the role of language in social rejections are discussed. PMID:28848484

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

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. © 2011 The British Psychological Society.

Unified Database for Rejected Image Analysis Across Multiple Vendors in Radiography.

PubMed

Little, Kevin J; Reiser, Ingrid; Liu, Lili; Kinsey, Tiffany; Sánchez, Adrian A; Haas, Kateland; Mallory, Florence; Froman, Carmen; Lu, Zheng Feng

2017-02-01

Reject rate analysis has been part of radiography departments' quality control since the days of screen-film radiography. In the era of digital radiography, one might expect that reject rate analysis is easily facilitated because of readily available information produced by the modality during the examination procedure. Unfortunately, this is not always the case. The lack of an industry standard and the wide variety of system log entries and formats have made it difficult to implement a robust multivendor reject analysis program, and logs do not always include all relevant information. The increased use of digital detectors exacerbates this problem because of higher reject rates associated with digital radiography compared with computed radiography. In this article, the authors report on the development of a unified database for vendor-neutral reject analysis across multiple sites within an academic institution and share their experience from a team-based approach to reduce reject rates. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

48 CFR 219.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Rejecting Small Business Administration recommendations. 219.505 Section 219.505 Federal Acquisition Regulations System DEFENSE...-Asides for Small Business 219.505 Rejecting Small Business Administration recommendations. (b) The...

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 Administration recommendations. 2919.505 Section 2919.505 Federal Acquisition Regulations System DEPARTMENT OF... Small Business 2919.505 Rejecting Small Business Administration recommendations. When the SBA...

48 CFR 219.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Rejecting Small Business... ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Set-Asides for Small Business 219.505 Rejecting Small Business Administration recommendations. (b) The...

48 CFR 219.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Rejecting Small Business... ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Set-Asides for Small Business 219.505 Rejecting Small Business Administration recommendations. (b) The...

48 CFR 2919.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true 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 SBA...

48 CFR 219.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Rejecting Small Business... ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Set-Asides for Small Business 219.505 Rejecting Small Business Administration recommendations. (b) The...

48 CFR 2919.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 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 SBA...

48 CFR 2919.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 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 SBA...

Loss of Myeloid Related Protein-8/14 Exacerbates Cardiac Allograft Rejection

PubMed Central

Shimizu, Koichi; Libby, Peter; Rocha, Viviane Z.; Folco, Eduardo J.; Shubiki, Rica; Grabie, Nir; Jang, Sunyoung; Lichtman, Andrew H.; Shimizu, Ayako; Hogg, Nancy; Simon, Daniel I.; Mitchell, Richard N.; Croce, Kevin

2011-01-01

Background The calcium-binding proteins myeloid-related protein (MRP)-8 (S100A8) and MRP-14 (S100A9) form MRP-8/14 heterodimers (S100A8/A9, calprotectin) that regulate myeloid cell function and inflammatory responses, and serve as early serum markers for monitoring acute allograft rejection. Despite functioning as a pro-inflammatory mediator, the pathophysiological role of MRP-8/14 complexes in cardiovascular disease is incompletely defined. This study investigated the role of MRP-8/14 in cardiac allograft rejection using MRP-14-deficient mice (MRP14-/-) that lack MRP-8/14 complexes. Methods and Results We examined parenchymal rejection (PR) after major histocompatibility complex (MHC) class II allomismatched cardiac transplantation (bm12 donor heart and B6 recipients) in wild-type (WT) and MRP14-/- recipients. Allograft survival averaged 5.9 ± 2.9 weeks (n=10) in MRP14-/- recipients, compared to > 12 weeks (n = 15, p < 0.0001) in WT recipients. Two weeks after transplantation, allografts in MRP14-/- recipients had significantly higher PR scores (2.8 ± 0.8, n=8) than did WT recipients (0.8 ± 0.8, n=12, p<0.0001). Compared to WT recipients, allografts in MRP14-/- recipients had significantly increased T-cell and macrophage infiltration, as well as increased mRNA levels of IFN-γ and IFN-γ–associated chemokines (CXCL9, CXCL10, and CXCL11), IL-6, and IL-17, with significantly higher levels of Th17 cells. MRP14-/- recipients also had significantly more lymphocytes in the adjacent paraaortic lymph nodes than did WT recipients (cell number per lymph node: 23.7 ± 0.7 × 105 for MRP14-/- vs. 6.0 ± 0.2 × 105 for WT, p < 0.0001). The dendritic cells (DCs) of the MRP14-/- recipients of bm12 hearts expressed significantly higher levels of the co-stimulatory molecules CD80 and CD86 than did those of WT recipients 2 weeks after transplantation. Mixed leukocyte reactions using allo-EC-primed MRP14-/- DCs resulted in significantly higher antigen-presenting function than

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

Failure of ganciclovir prophylaxis to completely eradicate CMV disease in renal transplant recipients treated with intense anti-rejection immunotherapy.

PubMed

Isenberg, A L; Shen, G K; Singh, T P; Hahn, A; Conti, D J

2000-06-01

Ganciclovir prophylactic regimens have been shown to be effective in renal transplant recipients at risk for primary (donor seropositive/recipient seronegative) and secondary (recipient seropositive) cytomegalovirus (CMV) disease. However, in addition to serologic factors, the type and intensity of the administered immunosuppression is a strong risk factor for CMV disease. Since January 1995, we have utilized a potent immunosuppressive protocol selectively in recipients at high risk for immunologic graft loss, defined as retransplant recipients, recipients with delayed graft function, non-Caucasian recipients, and recipients suffering from acute rejection. Between January 1995 and December 1996, 110 consecutive renal transplants were performed in recipients who were either CMV seropositive or received an allograft from a CMV-seropositive donor. All recipients received ganciclovir prophylactic therapy for 3 months post-transplant. Group I (N = 43) consisted of recipients at high-immunologic risk for graft loss as defined above. These recipients were treated with an intense anti-rejection immunotherapeutic regimen consisting of Cellcept, Neoral, and prednisone, with the frequent addition of antilymphocyte antibody therapies and intravenous methylprednisolone. The remaining 67 recipients (group II) were treated with a less intense immunotherapeutic regimen consisting of azathioprine, Neoral, and prednisone. The incidence and severity of CMV disease and the patient and allograft survival were compared. The incidence of CMV syndrome was greater in group I (28%) compared with group II (7%), and was statistically significant (p < 0.05). The 1-yr patient and graft survival were similar, 95 and 91%, respectively, for group I compared with 97 and 97%, respectively, for group II. These data suggest that 3 months of ganciclovir prophylactic therapy is significantly less effective for the prevention of CMV disease in renal transplant recipients at high risk for acute rejection

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival.

PubMed

Trailin, Andriy V; Ostapenko, Tetyana I; Nykonenko, Tamara N; Nesterenko, Svitlana N; Nykonenko, Olexandr S

2017-01-01

We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day-6 months), late AR (>6 months), and early pyelonephritis (the 8th day-2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes.

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival

PubMed Central

Ostapenko, Tetyana I.; Nykonenko, Tamara N.; Nesterenko, Svitlana N.; Nykonenko, Olexandr S.

2017-01-01

Background We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. Methods Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. Results We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day–6 months), late AR (>6 months), and early pyelonephritis (the 8th day–2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. Conclusions Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes. PMID:28694560

Causes and impact of specimen rejection in a clinical chemistry laboratory.

PubMed

Cao, Liyun; Chen, Meng; Phipps, Ron A; Del Guidice, Robert E; Handy, Beverly C; Wagar, Elizabeth A; Meng, Qing H

2016-07-01

Pre-analytical errors necessitate specimen rejection and negatively affect patient safety. Our purpose was to investigate the factors leading to specimen rejection and its impact. Specimen rejections in a clinical chemistry laboratory during a 1-year period were reviewed retrospectively and analyzed for frequency, cause, circumstances, and impact. Of the 837,862 specimens received, 2178 (0.26%) were rejected. The most common reasons for specimen rejection were contamination (n=764, 35.1%), inappropriate collection container/tube (n=330, 15.2%), quantity not sufficient (QNS) (n=329, 15.1%), labeling errors (n=321, 14.7%), hemolyzed specimen (n=205, 9.4%), and clotted specimen (n=203, 9.3%). The analytes most often affected were glucose (n=192, 8.8%); calcium (n=152, 7.0%), magnesium (n=148, 6.8%), potassium (n=137, 6.3%), creatinine (n=100, 4.6%), and blood urea nitrogen (n=97, 4.4%). Outpatient service and blood draw by phlebotomists were associated with low rejection rates (536/493,501 or 0.11% and 368/586,503 or 0.06%, respectively). Recollection due to specimen rejection increased the turnaround time by an average of 108min. The total cost for the recollection was around $43,210 USD with an average cost around $21.9 USD. The factors associated with rejection are remediable by improved training and quality assurance measures. Policies and procedures specific to specimen collection, transportation, and preparation should be strictly followed. Copyright © 2016 Elsevier B.V. All rights reserved.

48 CFR 2919.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Administration recommendations. 2919.505 Section 2919.505 Federal Acquisition Regulations System DEPARTMENT OF... Small Business 2919.505 Rejecting Small Business Administration recommendations. When the SBA Procurement Center Representative appeals a “rejection of an SBA recommendation” as referenced in FAR 19.505(b...

48 CFR 1419.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Rejecting Small Business Administration recommendations. 1419.505 Section 1419.505 Federal Acquisition Regulations System DEPARTMENT OF... Rejecting Small Business Administration recommendations. (a) A written justification in support of the CO's...

48 CFR 619.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Rejecting Small Business... STATE SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Set-Asides for Small Business 619.505 Rejecting Small Business Administration recommendations. The Procurement Executive is the agency head for the...

48 CFR 619.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Rejecting Small Business... STATE SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Set-Asides for Small Business 619.505 Rejecting Small Business Administration recommendations. The Procurement Executive is the agency head for the...

48 CFR 619.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Rejecting Small Business... STATE SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Set-Asides for Small Business 619.505 Rejecting Small Business Administration recommendations. The Procurement Executive is the agency head for the...

Recollections of parental rejection, self-criticism and depression in suicidality.

PubMed

Campos, Rui C; Besser, Avi; Blatt, Sidney J

2013-01-01

The present study examines whether self-criticism and depressive symptoms mediate the relationship between recollections of parental rejection and suicidality. A community sample of 200 Portuguese adults completed, in counterbalanced order, a socio-demographic questionnaire, the short form of the Inventory for Assessing Memories of Parental Rearing Behaviour (EMBU), the Depressive Experiences Questionnaire (DEQ), the Center for Epidemiologic Studies Depression Scale (CES-D), and reports of any suicide intention and/or ideation and suicide attempts. Structural Equation Modeling (SEM) indicated that recollections of parental rejection are significantly associated with depressive symptoms and suicidality. Recollections of parental rejection are indirectly associated with depressive symptoms and suicidality through self-criticism. The association between self-criticism and suicidality is mediated by depressive symptoms. In addition to a significant direct association between recollections of parental rejection and suicidality, the final model indicated that recollections of parental rejection are significantly associated with self-criticism. That same self-criticism is significantly associated with depressive symptoms which, in turn, are significantly associated with suicidality. Individuals with recollections of parental rejection are at greater risk for suicide ideation and behavior, possibly because such experiences predispose them to intense self-criticism which is a risk factor for depression associated with suicidal ideation and behavior.

[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.

Rejection with hemodynamic compromise in the current era of pediatric heart transplantation: a multi-institutional study.

PubMed

Everitt, Melanie D; Pahl, Elfriede; Schechtman, Kenneth B; Zheng, Jie; Ringewald, Jeremy M; L'ecuyer, Thomas; Naftel, David C; Kirklin, James K; Blume, Elizabeth D; Bullock, Emily A; Canter, Charles E

2011-03-01

Survival after pediatric heart transplant has improved over time, as has the incidence of overall rejection. We studied the effect of era on the occurrence and outcome of rejection with hemodynamic compromise (HC). Data from 2227 patients who received allografts between 1993 and 2006 at 36 centers in the Pediatric Heart Transplant Study were analyzed to determine incidence, outcome, and risk factors for rejection with HC in early (1993-1999) and recent (2000-2006) eras. Rejection with HC was classified as severe (RSHC) when inotropes were used for circulatory support and mild (RMHC) when inotropes were not used. Of 1217 patients with any episode of rejection, 541 had rejection with HC. Freedom from RMHC improved at 1 year (81% vs 90%, p < 0.001) and at 5 years (74% vs 85%, p < 0.001) in the early vs recent eras, but freedom from RSHC was similar between eras (93% vs 95% at 1 year and 85% vs 87% at 5 years, p = 0.24). Survival after RSHC (63% at 1 year and 49% at 5 years) was worse than after RMHC (87% at 1 year and 72% at 5 years, p < 0.001) and did not change over time. Risk factors for RSHC were non-white race (hazard ratio [HR], 1.73; 95% confidence interval [CI], 1.29-2.32, p < 0.01), older age (HR, 2.85; 95% CI, 1.24-6.53; p = 0.01), and non-A blood type (HR, 1.51;, 95% CI, 1.11-2.04,; p = 0.01), but the only risk factor for RMHC was earlier era of transplant (HR, 1.94; 95% CI, 1.56-2.41; p < 0.001). The incidence of RMHC has declined over time but the same era effect has not occurred with RSHC. Close follow-up after RSHC is crucial because mortality is so high. Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Acute allograft failure in thoracic organ transplantation.

PubMed

Jahania, M S; Mullett, T W; Sanchez, J A; Narayan, P; Lasley, R D; Mentzer, R M

2000-01-01

Thoracic organ transplantation is an effective form of treatment for end-stage heart and lung disease. Despite major advances in the field, transplant patients remain at risk for acute allograft dysfunction, a major cause of early and late mortality. The most common causes of allograft failure include primary graft failure secondary to inadequate heart and lung preservation during cold storage, cellular rejection, and various donor-recipient-related factors. During cold storage and early reperfusion, heart and lung allografts are vulnerable to intracellular calcium overload, acidosis, cell swelling, injury mediated by reactive oxygen species, and the inflammatory response. Brain death itself is associated with a reduction in myocardial contractility, and recipient-related factors such as preexisting pulmonary hypertension can lead to acute right heart failure and the pulmonary reimplantation response. The development of new methods to prevent or treat these various causes of acute graft failure could lead to a marked improvement in short- and long-term survival of patients undergoing thoracic organ transplantation.

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

NASA Astrophysics Data System (ADS)

Kadota, Michio; Sannomiya, Toshio; Tanaka, Shuji

2017-07-01

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

48 CFR 1419.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Administration recommendations. 1419.505 Section 1419.505 Federal Acquisition Regulations System DEPARTMENT OF... Rejecting Small Business Administration recommendations. (a) A written justification in support of the CO's decision to reject the set-aside recommendation shall be approved by the HCA. It shall then be forwarded...

48 CFR 1319.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Rejecting Small Business... COMMERCE SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Set-Asides for Small Business 1319.505 Rejecting Small Business Administration recommendations. (a) The designee authorized to render a decision on the...

48 CFR 1419.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Rejecting Small Business... THE INTERIOR SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Set-Asides for Small Business 1419.505 Rejecting Small Business Administration recommendations. (a) A written justification in support of the CO's...

48 CFR 1319.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Rejecting Small Business... COMMERCE SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Set-Asides for Small Business 1319.505 Rejecting Small Business Administration recommendations. (a) The designee authorized to render a decision on the...

48 CFR 1319.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Rejecting Small Business... COMMERCE SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Set-Asides for Small Business 1319.505 Rejecting Small Business Administration recommendations. (a) The designee authorized to render a decision on the...

48 CFR 1419.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Rejecting Small Business... THE INTERIOR SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Set-Asides for Small Business 1419.505 Rejecting Small Business Administration recommendations. (a) A written justification in support of the CO's...

48 CFR 1419.505 - Rejecting Small Business Administration recommendations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Rejecting Small Business... THE INTERIOR SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Set-Asides for Small Business 1419.505 Rejecting Small Business Administration recommendations. (a) A written justification in support of the CO's...

Redox-Dependent Inflammation in Islet Transplantation Rejection

PubMed Central

Barra, Jessie M.; Tse, Hubert M.

2018-01-01

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

Anxious and angry rejection sensitivity, social withdrawal, and retribution in high and low ambiguous situations.

PubMed

Zimmer-Gembeck, Melanie J; Nesdale, Drew

2013-02-01

Rejection sensitivity (RS) is a tendency to expect, perceive, and overreact to rejection. Our objective was to examine whether anxious and angry RS have specific associations with negative social reactions, and whether responses are intensified in situations of high rejection ambiguity. In two studies, youth (N = 464 and N = 371) reported their RS and anticipated responses to social scenarios. In Study 1, all scenarios portrayed overt rejection events. In Study 2, participants were randomly assigned to conditions portraying overt or ambiguous rejection. Greater rejection expectation was associated with more negative reactions to rejection. Moreover, as expected, anxiety about rejection was uniquely associated with withdrawal, and anger about rejection was uniquely associated with retribution (i.e., reactive aggression). In the second study, RS persons responded more negatively than others to both overt and high ambiguous rejections, but retribution was intensified among participants high in rejection expectation when rejection was ambiguous, and withdrawal was intensified among participants high in anxious RS in overt rejection situations. Consistent with the revised RS model, there are different patterns of emotions, cognitions, and behaviors in response to high and low ambiguous rejection events, which are heightened in youth sensitive to rejection. © 2012, Wiley Periodicals, Inc.

Peer Rejection and Aggression and Early Starter Models of Conduct Disorder

PubMed Central

Miller-Johnson, Shari; Coie, John D.; Maumary-Gremaud, Anne; Bierman, Karen

2009-01-01

Peer rejection and aggression in the early school years were examined for their relevance to early starting conduct problems. The sample of 657 boys and girls from 4 geographical locations was followed from 1st through 4th grades. Peer rejection in 1st grade added incrementally to the prediction of early starting conduct problems in 3rd and 4th grades, over and above the effects of aggression. Peer rejection and aggression in 1st grade were also associated with the impulsive and emotionally reactive behaviors found in older samples. Being rejected by peers subsequent to 1st grade marginally added to the prediction of early starting conduct problems in 3rd and 4th grades, controlling for 1st grade ADHD symptoms and aggression. Furthermore, peer rejection partially mediated the predictive relation between early ADHD symptoms and subsequent conduct problems. These results support the hypothesis that the experience of peer rejection in the early school years adds to the risk for early starting conduct problems. PMID:12041708

A recognition-free mechanism for reliable rejection of brood parasites.

PubMed

Anderson, Michael G; Hauber, Mark E

2007-06-01

Hosts often discard eggs of avian brood parasites, whereas parasitic chicks are typically accepted. This can be explained theoretically by fitness losses associated with adults learning to recognize parasitic young and mistakenly rejecting their own young. A new experimental study confirms that rejection of parasitic chicks, without relying on memory to discriminate between foreign and own young, is a feasible and potentially cost-free mechanism used by reed warblers to reject common cuckoo chicks. By abandoning broods that are in the nest longer than is typical for their own young, parents can reliably reject parasite nestlings and reduce fitness losses owing to having to care for demanding parasitic young. Discrimination without recognition has important implications for the realized trajectories of host-parasite coevolutionary arms races.

Impact of Tacrolimus Compared With Cyclosporin on the Incidence of Acute Allograft Rejection in Human Immunodeficiency Virus-Positive Kidney Transplant Recipients.

PubMed

Gathogo, Esther; Harber, Mark; Bhagani, Sanjay; Levy, Jeremy; Jones, Rachael; Hilton, Rachel; Davies, Graham; Post, Frank A

2016-04-01

Kidney transplantation (KT) of human immunodeficiency virus (HIV)-positive patients has transformed the management of end-stage kidney disease in this population. Although favourable outcomes have been reported, patients experience high rates of acute allograft rejection (AR). We examined factors associated with AR in the first year after KT, with particular emphasis on the choice of calcineurin inhibitor (CNI) immunosuppressive therapy. We conducted a national observational cohort study of HIV/KT in the United Kingdom. Patients were included if HIV positive at KT, transplanted in the United Kingdom between January 2005 and December 2013, and did not experience primary graft failure. Kaplan-Meier methods were used to estimate host/graft survival and cumulative incidence of biopsy proven AR. Logrank tests were used to compare survival, and Cox proportional hazard models to examine factors associated with AR. Our study analyzed the incidence of AR in the first year after KT in 78 HIV-positive patients of whom 31 initiated cyclosporin (CsA) and 47 tacrolimus (Tac) based immunosuppression. AR was observed in 28 patients (36%) after a median of 2.6 (interquartile range, 0.5-5.9) months. The cumulative incidence of AR at 1 year was 58% and 21% among patients on CsA and Tac, respectively (P =0.003). Choice of CNI was the only factor significantly associated with AR (hazard ratio for Tac vs CsA 0.25 [95% confidence interval, 0.11-0.57], P = 0.001). Subtherapeutic CNI concentrations were common in the first 12 weeks after KT. Our data suggest that Tac may be the preferred CNI for use in KT in people living with HIV.

Rejection Thresholds in Solid Chocolate-Flavored Compound Coating

PubMed Central

Harwood, Meriel L.; Ziegler, Gregory R.; Hayes, John E.

2012-01-01

Classical detection thresholds do not predict liking, as they focus on the presence or absence of a sensation. Recently however, Prescott and colleagues described a new method, the rejection threshold, where a series of forced choice preference tasks are used to generate a dose-response function to determine hedonically acceptable concentrations. That is, how much is too much? To date, this approach has been used exclusively in liquid foods. Here, we determined group rejection thresholds in solid chocolate-flavored compound coating for bitterness. The influences of self-identified preferences for milk or dark chocolate, as well as eating style (chewers versus melters) on rejection thresholds were investigated. Stimuli included milk chocolate-flavored compound coating spiked with increasing amounts of sucrose octaacetate (SOA), a bitter GRAS additive. Paired preference tests (blank vs. spike) were used to determine the proportion of the group that preferred the blank. Across pairs, spiked samples were presented in ascending concentration. We were able to quantify and compare differences between two self-identified market segments. The rejection threshold for the dark chocolate preferring group was significantly higher than the milk chocolate preferring group (p = 0.01). Conversely, eating style did not affect group rejection thresholds (p = 0.14), although this may reflect the amount of chocolate given to participants. Additionally, there was no association between chocolate preference and eating style (p = 0.36). Present work supports the contention that this method can be used to examine preferences within specific market segments and potentially individual differences as they relate to ingestive behavior. PMID:22924788

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.

Self-Silencing and Rejection Sensitivity in Adolescent Romantic Relationships

ERIC Educational Resources Information Center

Harper, Melinda S.; Dickson, Joseph W.; Welsh, Deborah P.

2006-01-01

This study examined the link between rejection sensitivity, self-silencing behaviors, and depressive symptomatology among adolescent dating couples. Self-silencing was hypothesized to be the process mediating the association between rejection sensitivity and depressive symptoms. Our sample included 211 couples between 14 and 21 who were dating at…

15 CFR 700.13 - Acceptance and rejection of rated orders.

Code of Federal Regulations, 2010 CFR

2010-01-01

... order and transmit the acceptance or rejection in writing (hard copy), or in electronic format, within... rejection, pursuant to paragraphs (b) and (c) of this section, in writing (hard copy) or electronic format...

Raman Spectroscopy Detects Cardiac Allograft Rejection with Molecular Specificity

PubMed Central

Chung, Yoon Gi; Tu, Qiang; Cao, Dianjun; Harada, Shuko; Eisen, Howard J; Chang, Chang

2009-01-01

Abstract Spatially resolved Raman spectroscopy is shown here to be capable of molecular‐specific detection without exogenous labeling. This molecular specificity is achieved by detecting the strong and characteristic Raman spectral signature of an indole derivative, serotonin, whose selective existence in rejected heart transplants serves as the biomarker. The study also corroborates the increasingly recognized role of serotonin receptors in various immune responses, including cardiac allograft rejection. Combining both medical and physical sciences, this work demonstrates the potential use of Raman spectroscopy in replacing the invasive endomyocardial biopsy as the standard for post‐transplantation rejection surveillance and presents a new paradigm in advancing clinical care through interdisciplinary studies. PMID:20443894

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, since...

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…

Expecting Rejection: Understanding the Minority Stress Experiences of Transgender and Gender-Nonconforming Individuals

PubMed Central

Rood, Brian A.; Reisner, Sari L.; Surace, Francisco I.; Puckett, Jae A.; Maroney, Meredith R.; Pantalone, David W.

2016-01-01

Abstract Purpose: Transgender and gender-nonconforming (TGNC) individuals often are the target of enacted or external (i.e., distal) experiences of stigma, discrimination, and violence, which are linked to adverse health, particularly psychological distress. There is limited research, however, examining felt or internal (i.e., proximal) stressors faced by TGNC individuals. This study sought to examine one type of internal stressor, expecting rejection, and aimed to (1) identify how and to what extent rejection expectations operate day-to-day for TGNC individuals and (2) explore how TGNC individuals respond to expectations of rejection. Methods: In-depth interviews were conducted with 30 participants from 2014 to 2015 who identified as TGNC (mean age=30.4; 60% people of color); data were analyzed using a consensual qualitative research method. Results: Four thematic categories emerged about expecting rejection: (1) where to expect rejection; (2) thoughts and feelings associated with expectations of rejection; (3) coping strategies used to manage the expectation of rejection; and (4) the intersection of race and ethnicity with rejection expectations. Conclusion: Findings from this study suggest that expecting rejection is a frequent and salient internal stressor for TGNC individuals. We discuss the psychological and cumulative potential health impact of minority stress, and the applicability of Meyer's Minority Stress Model. Therapeutic interventions are needed to address the specific cognitive, emotional, and behavioral responses TGNC individuals experience as a result of the stress associated with expecting rejection, including fear, anxiety, and situational avoidance. PMID:29159306

Course of illness after the onset of chronic rejection in lung transplant recipients.

PubMed

Song, Mi-Kyung; De Vito Dabbs, Annette; Studer, Sean M; Zangle, Sarah E

2008-05-01

Despite the overall negative impact of chronic rejection on quality of life and survival after lung transplant, the specific clinical indicators of deterioration have not been identified. To describe the course of illness after the onset of chronic rejection, including demographic and transplant variables, morbidity, mortality, health resource utilization, and end-of-life care, and to identify clinical indicators of deterioration in health and limited survival after the onset of chronic rejection. The medical records of 311 recipients of lung transplants between 1998 and 2004 were reviewed retrospectively to identify 60 recipients who experienced chronic rejection. Median survival after chronic rejection was 31.34 months. Time to rejection (mean, 26.05 months; SD, 16.85) was significantly correlated with overall survival without need of a retransplant (r = 0.64; P < .001). The earlier the onset of chronic rejection or the need for oxygen at home, the shorter was the period of survival after chronic rejection and the more frequent were hospital and intensive care unit admissions and prolonged stays. Of the 26 recipients who died, 65% died at the transplant center, and all but 1 died in the intensive care unit; 3 died after multiple attempts of cardiopulmonary resuscitation; life support was ultimately withdrawn in 69%. Lung transplant recipients who experience chronic graft rejection have high rates of morbidity, mortality, and health resource utilization; however, the course of illness after chronic rejection is highly variable.

Family and community rejection and a Congolese led mediation intervention to reintegrate rejected survivors of sexual violence in Eastern Democratic Republic of Congo.

PubMed

Kohli, Anjalee; Tosha, Maphie; Ramazani, Paul; Safari, Octave; Bachunguye, Richard; Zahiga, Isaya; Iragi, Aline; Glass, Nancy

2013-01-01

Our purpose in this study is to describe the multiple and inter-related health, economic, and social reasons for rejection and to provide an example of a Congolese-led family mediation program to reintegrate survivors into their families. We conducted this study in Eastern Democratic Republic of Congo (DRC) and included two focus group discussions and twenty-seven interviews. Rejection extends beyond physical dislocation to include economic and social aspects. Family mediation is a process requiring knowledge of traditions and norms. Understanding the context of rejection and supporting promising local reintegration efforts will likely improve health, economic, and social outcomes for the survivor, her family, and her community.

Refusals and Rejections: Designing Messages to Serve Multiple Goals.

ERIC Educational Resources Information Center

Saeki, Mimako; O'Keefe, Barbara J.

1994-01-01

Tests a rational model of the elaboration of themes found in rejection messages, using Japanese and American participants. Finds partial support for the initial rational model but notes two key revisions: identifies two new themes in rejection messages and suggests substantial differences in the way Americans and Japanese elaborate themes to serve…

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transient blockade of Delta-like Notch ligands prevents allograft rejection mediated by cellular and humoral mechanisms in a mouse model of heart transplantation

PubMed Central

Wood, Sherri; Feng, Jiane; Chung, Jooho; Radojcic, Vedran; Sandy, Ashley R.; Friedman, Ann; Shelton, Amy; Yan, Minhong; Siebel, Christian W.; Bishop, D. Keith; Maillard, Ivan

2015-01-01

Rejection remains a major clinical challenge limiting allograft survival after solid organ transplantation. Both cellular and humoral immunity contribute to this complication, with increased recognition of antibody-mediated damage during acute and chronic rejection. Using a mouse model of MHC-mismatched heart transplantation, we report markedly protective effects of Notch inhibition, dampening both T cell and antibody-driven rejection. T cell-specific pan-Notch blockade prolonged heart allograft survival and decreased IFNγ and IL-4 production by alloreactive T cells, especially when combined with depletion of recipient CD8+ T cells. These effects were associated with decreased infiltration by conventional T cells and an increased proportion of regulatory T cells in the graft. Transient administration of neutralizing antibodies specific for Delta-like1/4 (Dll1/4) Notch ligands in the peri-transplant period led to prolonged acceptance of allogeneic hearts, with superior outcome over Notch inhibition only in T cells. Systemic Dll1/4 inhibition decreased T cell cytokines and graft infiltration, but also germinal center B cell and plasmablast numbers as well as production of donor-specific alloantibodies and complement deposition in the transplanted hearts. Dll1 or Dll4 inhibition alone provided partial protection. Thus, pathogenic signals delivered by Dll1/4 Notch ligands early after transplantation promote organ rejection through several complementary mechanisms. Transient interruption of theses signals represents a new attractive therapeutic strategy to enhance long-term allograft survival. PMID:25687759

Modeling the interplay between sea ice formation and the oceanic mixed layer: Limitations of simple brine rejection parameterizations

NASA Astrophysics Data System (ADS)

Barthélemy, Antoine; Fichefet, Thierry; Goosse, Hugues; Madec, Gurvan

2015-02-01

The subtle interplay between sea ice formation and ocean vertical mixing is hardly represented in current large-scale models designed for climate studies. Convective mixing caused by the brine release when ice forms is likely to prevail in leads and thin ice areas, while it occurs in models at the much larger horizontal grid cell scale. Subgrid-scale parameterizations have hence been developed to mimic the effects of small-scale convection using a vertical distribution of the salt rejected by sea ice within the mixed layer, instead of releasing it in the top ocean layer. Such a brine rejection parameterization is included in the global ocean-sea ice model NEMO-LIM3. Impacts on the simulated mixed layers and ocean temperature and salinity profiles, along with feedbacks on the sea ice cover, are then investigated in both hemispheres. The changes are overall relatively weak, except for mixed layer depths, which are in general excessively reduced compared to observation-based estimates. While potential model biases prevent a definitive attribution of this vertical mixing underestimation to the brine rejection parameterization, it is unlikely that the latter can be applied in all conditions. In that case, salt rejections do not play any role in mixed layer deepening, which is unrealistic. Applying the parameterization only for low ice-ocean relative velocities improves model results, but introduces additional parameters that are not well constrained by observations.

Modelling the interplay between sea ice formation and the oceanic mixed layer: limitations of simple brine rejection parameterizations

NASA Astrophysics Data System (ADS)

Barthélemy, Antoine; Fichefet, Thierry; Goosse, Hugues; Madec, Gurvan

2015-04-01

The subtle interplay between sea ice formation and ocean vertical mixing is hardly represented in current large-scale models designed for climate studies. Convective mixing caused by the brine release when ice forms is likely to prevail in leads and thin ice areas, while it occurs in models at the much larger horizontal grid cell scale. Subgrid-scale parameterizations have hence been developed to mimic the effects of small-scale convection using a vertical distribution of the salt rejected by sea ice within the mixed layer, instead of releasing it in the top ocean layer. Such a brine rejection parameterization is included in the global ocean--sea ice model NEMO-LIM3. Impacts on the simulated mixed layers and ocean temperature and salinity profiles, along with feedbacks on the sea ice cover, are then investigated in both hemispheres. The changes are overall relatively weak, except for mixed layer depths, which are in general excessively reduced compared to observation-based estimates. While potential model biases prevent a definitive attribution of this vertical mixing underestimation to the brine rejection parameterization, it is unlikely that the latter can be applied in all conditions. In that case, salt rejections do not play any role in mixed layer deepening, which is unrealistic. Applying the parameterization only for low ice--ocean relative velocities improves model results, but introduces additional parameters that are not well constrained by observations.

Corneal graft rejection in African Americans at Howard University Hospital

PubMed Central

Ferdinand, Larry; Ngakeng, Vanessa; Copeland, Robert A.

2011-01-01

Purpose There is scarcity of data in the literature on cornel graft rejection rate in patients exclusively of African ancestry. The purpose of this study was to evaluate the rejection rate of corneal transplant surgery performed at Howard University Hospital on such patients over a 15 year period. Design A retrospective evaluation was performed of the cornea graft rejection and corneal graft failure rate in 125 penetrating keratoplasties (PKPs) done by one corneal specialist at Howard University Hospital from January 1, 1990 to August 31, 2005. Methods Of the 125 patients, 62 were eliminated from the study because of re-grafted eyes, non-African descent, primary graft failures, follow-up less than 1 month and lack of availability of charts. This study, therefore, studied and recorded data from 63 penetrating keratoplasties of 63 eyes from 60 patients. Results Episodes of graft rejection were documented in 23 eyes (36.5% of cases). Nine out of the 23 graft rejections manifested to secondary graft failure (39%). Overall, there were nine out of the 63 PKPs (14.3%) that resulted in secondary graft failure over the past 15 years. The major diagnostic categories were bullous keratopathy 24 (38%), keratoconus 10 (15.8%), Fuch’s dystrophy 4 (6.3%), other 20 (31.7%). Of the cases with episodes of rejection and failure, 4.3% and none were attributable to keratoconus, 30.4% and 22.2% for bullous keratopathy, and 8.7% and 22.2% for Fuch’s dystrophy, respectively. Also, best visual acuity was looked at in patients with rejection episodes. None of the patients had a pre-op visual acuity 20/40 or better; however, post-op PKP 2 (8.7%) of patients achieved 20/40 or better. Also, 4 (17.4%) of patients had a pre-op visual acuity between 20/50 and 20/150, but post-op PKP best visual acuity between 20/50 and 20/150 was increased to 9 (39.1%). Conclusion At 36% the prevalence of corneal graft rejection was one of the highest in the reported literature. But only 14% of those

Corneal graft rejection in African Americans at Howard University Hospital.

PubMed

Ferdinand, Larry; Ngakeng, Vanessa; Copeland, Robert A

2011-07-01

There is scarcity of data in the literature on cornel graft rejection rate in patients exclusively of African ancestry. The purpose of this study was to evaluate the rejection rate of corneal transplant surgery performed at Howard University Hospital on such patients over a 15 year period. A retrospective evaluation was performed of the cornea graft rejection and corneal graft failure rate in 125 penetrating keratoplasties (PKPs) done by one corneal specialist at Howard University Hospital from January 1, 1990 to August 31, 2005. Of the 125 patients, 62 were eliminated from the study because of re-grafted eyes, non-African descent, primary graft failures, follow-up less than 1 month and lack of availability of charts. This study, therefore, studied and recorded data from 63 penetrating keratoplasties of 63 eyes from 60 patients. Episodes of graft rejection were documented in 23 eyes (36.5% of cases). Nine out of the 23 graft rejections manifested to secondary graft failure (39%). Overall, there were nine out of the 63 PKPs (14.3%) that resulted in secondary graft failure over the past 15 years. The major diagnostic categories were bullous keratopathy 24 (38%), keratoconus 10 (15.8%), Fuch's dystrophy 4 (6.3%), other 20 (31.7%). Of the cases with episodes of rejection and failure, 4.3% and none were attributable to keratoconus, 30.4% and 22.2% for bullous keratopathy, and 8.7% and 22.2% for Fuch's dystrophy, respectively. Also, best visual acuity was looked at in patients with rejection episodes. None of the patients had a pre-op visual acuity 20/40 or better; however, post-op PKP 2 (8.7%) of patients achieved 20/40 or better. Also, 4 (17.4%) of patients had a pre-op visual acuity between 20/50 and 20/150, but post-op PKP best visual acuity between 20/50 and 20/150 was increased to 9 (39.1%). At 36% the prevalence of corneal graft rejection was one of the highest in the reported literature. But only 14% of those episodes resulted in graft failure which is one of

Active disturbance rejection controller for chemical reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Both, Roxana; Dulf, Eva H.; Muresan, Cristina I., E-mail: roxana.both@aut.utcluj.ro

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 themore » 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.« less

On Rejecting Emotional Lures Created by Phonological Neighborhood Activation

ERIC Educational Resources Information Center

Starns, Jeffrey J.; Cook, Gabriel I.; Hicks, Jason L.; Marsh, Richard L.

2006-01-01

The authors conducted 2 experiments to assess how phonologically related lures are rejected in a false memory paradigm. Some phonological lures were emotional (i.e., taboo) words, and others were not. The authors manipulated the presence of taboo items on the study list and reduced the ability to use controlled rejection strategies by dividing…

Compensatory deficits following rejection: the role of social anxiety in disrupting affiliative behavior.

PubMed

Mallott, Michael A; Maner, Jon K; DeWall, Nathan; Schmidt, Norman B

2009-01-01

Managing perceived or actual social rejection is an important facet of meeting basic needs for affiliation. Social anxiety disorder (SAD) is characterized by significant distress and debilitation relating to affiliation and recent work suggests higher levels of social anxiety symptoms may adversely affect responses to social rejection. This study examined emotional and behavioral responding to a social rejection stressor to explore whether social anxiety moderates the effects of social rejection on prosocial compensatory behaviors. Individuals (N=37) evaluated on social anxiety symptoms were assigned to either a social rejection condition or control condition. Consistent with expectation, rejection promoted renewed interest in connecting with sources of positive social interaction among participants low in social anxiety. Participants with higher levels of social anxiety, however, failed to react to rejection in a positive or prosocial manner and exhibited some evidence of negative social responses. Such differential compensatory responding could have important implications for the genesis, maintenance, and treatment of SAD.

Children's Use of Memory Editing Strategies to Reject Source Misinformation

ERIC Educational Resources Information Center

Moore, Kara N.; Lampinen, James M.; Gallo, David A.; Adams, Eryn J.; Bridges, Ana J.

2018-01-01

This is the first reported study of children's use of two metacognitive strategies, recollection rejection and diagnostic monitoring, to reject misinformation. Recollection rejection involves the retrieval of details that disqualify an event, whereas diagnostic monitoring involves the failure to retrieve expected details. First (n = 56, age…

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

Comprehensive morphometric analysis of mononuclear cell infiltration during experimental renal allograft rejection.

PubMed

Hoffmann, Ute; Bergler, Tobias; Jung, Bettina; Steege, Andreas; Pace, Claudia; Rümmele, Petra; Reinhold, Stephan; Krüger, Bernd; Krämer, Bernhard K; Banas, Bernhard

2013-01-01

The role of specific subtypes of infiltrating cells in acute kidney allograft rejection is still not clear and was so far not examined by different analyzing methods under standardized conditions of an experimental kidney transplantation model. Immunohistochemical staining of CD3, CD20 and CD68 was performed in rat allografts, in syngeneically transplanted rats and in control rats with a test duration of 6 and 28 days. The detailed expression and localization of infiltrating cells were analyzed manually in different kidney compartments under light microscope and by the two different morphometric software programs. Data were correlated with the corresponding kidney function as well as with histopathological classification. The information provided by the morphometric software programs on the infiltration of the specific cell types after renal transplantation was in accordance with the manual analysis. Morphometric methods were solid to analyze reliably the induction of cellular infiltrates after renal transplantation. By manual analysis we could clearly demonstrate the detailed localization of the specific cell infiltrates in the different kidney compartments. Besides infiltration of CD3 and CD68 infiltrating cells, a robust infiltration of CD20 B-cells in allogeneically transplanted rats, even at early time points after transplantation was detected. Additionally an MHC class I expression could reliable be seen in allogeneically transplanted rats. The infiltration of B-cells and the reliable antigen presentation might act as a silent subclinical trigger for subsequent chronic rejection and premature graft loss. Copyright © 2012 Elsevier B.V. All rights reserved.

REJECTION OF CHRONIC SCHIZOPHRENIC PATIENTS : SOME PRELIMINARY OBSERVATIONS FROM KERALA

PubMed Central

Manickam, L. Sam S.; Chandran, Satheesh R.

1998-01-01

A study was conducted on 57 relatives (34 male and 23 female) of 57 (32 male and 25 female) schizophrenic patients in Kerala. The rejection response was found to be related to gender of patients and relatives, being significantly higher in males. The test reliability alpha of the Patient Rejection Scale was found to be 0.93 and it is higher than English and German version of the scale. Compared to the German and New York sample, the present sample tend to have high rejection feeling. PMID:21494484

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lowry, R.P.; Forbes, R.D.; Blackburn, J.H.

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 themore » 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.« less

Associative recognition: a case of recall-to-reject processing.

PubMed

Rotello, C M; Heit, E

2000-09-01

Two-process accounts of recognition memory assume that memory judgments are based on both a rapidly available familiarity-based process and a slower, more accurate, recall-based mechanism. Past experiments on the time course of item recognition have not supported the recall-to-reject account of the second process, in which the retrieval of an old item is used to reject a similar foil (Rotello & Heit, 1999). In three new experiments, using analyses similar to those of Rotello and Heit, we found robust evidence for recall-to-reject processing in associative recognition, for word pairs, and for list-discrimination judgments. Put together, these results have implications for two-process accounts of recognition.

Study of Background Rejection Systems for the IXO Mission.

NASA Astrophysics Data System (ADS)

Laurent, Philippe; Limousin, O.; Tatischeff, V.

2009-01-01

The scientific performances of the IXO mission will necessitate a very low detector background level. This will imply thorough background simulations, and efficient background rejection systems. It necessitates also a very good knowledge of the detectors to be shielded. In APC, Paris, and CEA, Saclay, we got experience on these activities by conceiving and optimising in parallel the high energy detector and the active and passive background rejection system of the Simbol-X mission. Considering that this work may be naturally extended to other X-ray missions, we have initiated with CNES a R&D project on the study of background rejection systems mainly in view the IXO project. We will detail this activity in the poster.

47 CFR 61.69 - Rejection.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) TARIFFS Specific... publication may not be referred to as either cancelled or revised. Within five business days of the release... must bear the notation: In lieu of __, rejected by the Federal Communications Commission. [64 FR 46592...

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.

The Daily Relation between Parental Rejection and Emotional Eating in Youngsters: A Diary Study

PubMed Central

Vandewalle, Julie; Mabbe, Elien; Debeuf, Taaike; Braet, Caroline; Moens, Ellen

2017-01-01

KEY POINTS  Cross-sectional survey studies have demonstrated significant associations between parental rejection and peer rejection on the one hand and disturbed eating in youngsters, like emotional eating, on the other hand. In this study, we wanted to expand our knowledge on these relationships by investigating the daily fluctuations in these variables. Youngsters completed a 7-day diary to assess daily parental rejection, peer rejection and emotional eating. Using multilevel analyses, our results showed that daily variations in parental rejection were related to daily variations in emotional eating of the youngsters. This highlights the importance of addressing the parent-child relationship in interventions for emotional eating in youngsters. Background: This study investigated the daily relation between parental rejection and peer rejection on the one hand and emotional eating in youngsters on the other hand. Methods: Participants (N = 55) between the ages of 11 and 15 years completed a 7-day diary. A multilevel design was used to examine day-to-day within-person relationships between parental and peer rejection (measured by CHS) and emotional eating (measured by DEBQ-C) of youngsters. Results: The results showed that daily variations in parental rejection were related to daily variations in emotional eating of the youngsters. Daily peer rejection was only marginally significantly related to the emotional eating of the youngsters. Conclusions: These results indicate that especially parental rejection, and to a lesser extent peer rejection, are associated with the emotional eating of youngsters. The findings highlight the importance of addressing the parent-child relationship in interventions for emotional eating in youngsters. PMID:28553239

Kidney transplantation: evaluation and clinical outcome of 237 recipients at low, medium, high, or strong immunological risk of rejection.

PubMed

Nascimento, E; Fabreti de Oliveira, R A; Maciel, M D; Pereira, A B; das Mercêz de Lucas, F; Salomão-Filho, A; Pereira, W A; Moreira, J B; Vilaça, S S; de Castro Gontijo, R; Lasmar, M F; Vianna, H R; Magalhâes, A; Calazans, C A C; Simão-Filho, C; Vilela, B

2014-01-01

Donor-specific antibodies (DSAs) play a fundamental role in kidney transplantation. The identification of DSAs is an essential rejection parameter. We evaluated a protocol in 237 patients receiving kidneys from living (LDs) and deceased donors (DDs). Recipients were classified as being at low (LR), medium (MR), high (HR), or strong (SR) risk of rejection based on Luminex panel reactive antibody (PRA)-single antigen beads (SABs). Grafts that survived for 1 year were evaluated. Of the 237 transplanted patients, 129 (54.43%) received a kidney from an LD and 108 (45.57%) from a DD. Of 95 LR recipients receiving kidneys from LDs, 2 patients lost the graft due to non-immunological causes. Of 34 MR recipients, 13 had rejection episodes, and 2 lost the graft by AMR and one by cellular rejection (CR). Of 108 recipients receiving a kidney from a DD, 59 (54.63%) were LR, 31 (28.70%) MR, 11 (10.19%) HR, and 7 (6.48%) SR. Twenty of all transplanted recipients lost their grafts; 4 were due to clinical causes, 4 by cellular rejection, and 12 by antibody-mediated rejection (AMR) with PRA-SAB mean fluorescent intensity of 530 to 12,591. One-year graft survival for LD transplanted LR and MR patients was 97.6% and 94.1%, respectively (P = .004). In DD recipients, the LR vs MR SD was P = .011, and for LR vs HR + SR it was P = .001. For MR vs HR+SR no SD was found (P = .323). Rejections were detected in 51 patients (21.52%). Graft failure occurred in 16 patients (6.75%). A total of 218 (91.98%) recipients maintained good kidney function after 1 year. This protocol based on fluxogram risk assessment of AMR provided fast and precise immunological evaluation of recipients and donors and stratification by immunological risk of AMR. Copyright © 2014 Elsevier Inc. All rights reserved.

Borderline Personality Features, Anger, and Intimate Partner Violence: An Experimental Manipulation of Rejection.

PubMed

Armenti, Nicholas A; Babcock, Julia C

2018-04-01

Individuals with borderline personality features may be susceptible to react to situational stressors with negative and interpersonally maladaptive emotionality (e.g., anger) and aggression. The current study attempted to test two moderated mediation models to investigate dispositional risk factors associated with borderline personality features and intimate partner violence (IPV). Results from an experimental rejection induction paradigm were examined using moderated regression to observe contextual reactions to imagined romantic rejection from a current romantic partner among individuals with borderline personality features. An ethnically diverse sample of 218 undergraduates at a large public university in the southwestern United States was recruited. Participants responded to demographic questions and self-report measures, and engaged in an experimental rejection induction paradigm. Borderline personality features was positively associated with rejection sensitivity, physical assault, and psychological aggression. Contrary to initial hypotheses, rejection sensitivity did not serve as a mediator of the relations between borderline personality features and physical assault and psychological aggression. However, trait anger mediated the relation between borderline personality features and psychological aggression. As such, trait anger may be an important explanatory variable in the relation between borderline personality features and psychological aggression specifically. Results of the rejection induction paradigm indicated that, for individuals who were asked to imagine an ambiguous rejection, the relation between borderline personality features and state anger post-rejection was strengthened. For individuals who imagined a critical rejection, there was no significant relation between borderline personality features and state anger post-rejection. Findings suggest that trait anger may be an important dispositional factor in the link between borderline personality

Rejection thresholds in solid chocolate-flavored compound coating.

PubMed

Harwood, Meriel L; Ziegler, Gregory R; Hayes, John E

2012-10-01

Classical detection thresholds do not predict liking, as they focus on the presence or absence of a sensation. Recently however, Prescott and colleagues described a new method, the rejection threshold, where a series of forced choice preference tasks are used to generate a dose-response function to determine hedonically acceptable concentrations. That is, how much is too much? To date, this approach has been used exclusively in liquid foods. Here, we determined group rejection thresholds in solid chocolate-flavored compound coating for bitterness. The influences of self-identified preferences for milk or dark chocolate, as well as eating style (chewers compared to melters) on rejection thresholds were investigated. Stimuli included milk chocolate-flavored compound coating spiked with increasing amounts of sucrose octaacetate, a bitter and generally recognized as safe additive. Paired preference tests (blank compared to spike) were used to determine the proportion of the group that preferred the blank. Across pairs, spiked samples were presented in ascending concentration. We were able to quantify and compare differences between 2 self-identified market segments. The rejection threshold for the dark chocolate preferring group was significantly higher than the milk chocolate preferring group (P= 0.01). Conversely, eating style did not affect group rejection thresholds (P= 0.14), although this may reflect the amount of chocolate given to participants. Additionally, there was no association between chocolate preference and eating style (P= 0.36). Present work supports the contention that this method can be used to examine preferences within specific market segments and potentially individual differences as they relate to ingestive behavior. This work makes use of the rejection threshold method to study market segmentation, extending its use to solid foods. We believe this method has broad applicability to the sensory specialist and product developer by providing a

T-cell acute lymphoblastic leukaemia after liver transplantation: post-transplant lymphoproliferative disorder or coincidental de novo leukaemia?

PubMed

Fang, Yanan; Pinkney, Kerice A; Lee, John C; Gindin, Tatyana; Weiner, Michael A; Alobeid, Bachir; Bhagat, Govind

2013-03-01

Post-transplant lymphoproliferative disorders of T-cell origin are quite uncommon, and the vast majority represent neoplasms of mature, post-thymic T- or natural killer cells. Here, we report a rare case of T-cell acute lymphoblastic leukaemia (T-ALL), which occurred in an 18-year-old man who had undergone three liver transplants, initially for biliary atresia and subsequently for graft failure due to chronic rejection. He had received immunosuppression with cyclosporine and tacrolimus, as well as short-term treatment with OKT3. The T-ALL occurred 16 years after the first liver transplant. This case highlights the challenge for classifying rare neoplasms occurring in recipients of solid organ transplants that are currently not recognized to lie within the spectrum of post-transplant lymphoproliferative disorders. Given the long interval between the liver transplants and the development of T-ALL, a coincidental occurrence of the leukaemia cannot be ruled out. However, the potential roles of immunosuppressive therapy and other co-morbid conditions of the individual as possible risk factors for the pathogenesis of T-ALL are discussed. Copyright © 2012 John Wiley & Sons, Ltd.

Selected Factors Related to Selective Service Rejection and Rejection Rate in Delaware (1967): A Study of the Characteristics of Young Men Failing to Meet Mental Qualifications for Military Service.

ERIC Educational Resources Information Center

Price, Jay R.

This study sought information about selective service rejection in Delaware, specifically rejectee characteristics, reasons for rejection, and the high rejection rate in Delaware. The basic design was a modified case study method in which a sample of individual records were examined. Differences between this sample and national samples were tested…

A Critical Role for the TLR4/TRIF Pathway in Allogeneic Hematopoietic Cell Rejection by Innate Immune Cells

PubMed Central

Xu, Hong; Yan, Jun; Zhu, Ziqiang; Hussain, Lala-Rukh; Huang, Yiming; Ding, Chuanlin; Bozulic, Larry D.; Wen, Yujie; Ildstad, Suzanne T.

2013-01-01

We show for the first time that signaling through the TLR4/TRIF pathway plays a critical role in allogeneic bone marrow cell (BMC) rejection. This appears to be unique to BMC as organ allografts are rejected mainly via MyD88 signaling. Using T or T/B cell-deficient mice, we found that BMC allorejection occurred early before T cell activation and was T and B cell-independent, suggesting an effector role for innate immune cells in BMC rejection. We further demonstrated the innate immune signaling in BMC allorejection by showing superior engraftment in mice deficient in TRIF or TLR4 but not MyD88 or TLR3. The restored cytotoxicity in TRIF deficient recipients transferred with wildtype F4/80+ or NK1.1+ cells suggests TRIF signaling dependence on macrophages or NK cells in early BMC rejection. Production of the proinflammatory cytokine IL-6 and TRIF relevant chemokine MCP-1 was significantly increased early after bone marrow transplantation. In vivo specific depletion of macrophages or NK innate immune cells in combination with anti-CD154/rapamycin resulted in additive-enhanced allogeneic engraftment. The requirement for irradiation was completely eliminated when both macrophages and NK cells were depleted in combination with anti-CD154/rapamycin to target T and B cells, supporting the hypothesis that two barriers involving innate and adaptive immunity exist in mediating rejection of allogeneic BMC. In summary, our results clearly demonstrate a previously unappreciated role for innate immunity in BMC allorejection via signaling through a unique MyD88-independent TLR4/TRIF mechanism. These findings may have direct clinical impact on strategies for conditioning recipients for stem cell transplantation. PMID:23146386

The influence of structural stigma and rejection sensitivity on young sexual minority men's daily tobacco and alcohol use

PubMed Central

Pachankis, John E.; Hatzenbuehler, Mark L.; Starks, Tyrel J.

2018-01-01

Stigma occurs at both individual and structural levels, but existing research tends to examine the effect of individual and structural forms of stigma in isolation, rather than considering potential synergistic effects. To address this gap, our study examined whether stigma at the individual level, namely gay-related rejection sensitivity, interacts with structural stigma to predict substance use among young sexual minority men. Sexual minority (n = 119) participants completed online measures of our constructs (e.g., rejection sensitivity). Participants currently resided across a broad array of geographic areas (i.e., 24 U.S. states), and had attended high school in 28 states, allowing us to capture sufficient variance in current and past forms of structural stigma, defined as (1) a lack of state-level policies providing equal opportunities for heterosexual and sexual minority individuals and (2) negative state-aggregated attitudes toward sexual minorities. To measure daily substance use, we utilized a daily diary approach, whereby all participants were asked to indicate whether they used tobacco or alcohol on nine consecutive days. Results indicated that structural stigma interacted with rejection sensitivity to predict tobacco and alcohol use, and that this relationship depended on the developmental timing of exposure to structural stigma. In contrast, rejection sensitivity did not mediate the relationship between structural stigma and substance use. These results suggest that psychological predispositions, such as rejection sensitivity, interact with features of the social environment, such as structural stigma, to predict important health behaviors among young sexual minority men. These results add to a growing body of research documenting the multiple levels through which stigma interacts to produce negative health outcomes among sexual minority individuals. PMID:24507912

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.

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.

Prediction of heart transplant rejection with a breath test for markers of oxidative stress.

PubMed

Phillips, Michael; Boehmer, John P; Cataneo, Renee N; Cheema, Taseer; Eisen, Howard J; Fallon, John T; Fisher, Peter E; Gass, Alan; Greenberg, Joel; Kobashigawa, Jon; Mancini, Donna; Rayburn, Barry; Zucker, Mark J

2004-12-15

The Heart Allograft Rejection: Detection with Breath Alkanes in Low Levels study evaluated a breath test for oxidative stress in heart transplant recipients, and we report here a mathematical model predicting the probability of grade 3 rejection. The breath test divided the heart transplant recipients into 3 groups: positive for grade 3 rejection, negative for grade 3 rejection, and intermediate. The test was 100% sensitive for grade 3 heart transplant rejection when the p value was >/=0.98, and 100% specific when the p value was rejection and the predictive value of the result.

Investigation of Periodic-Disturbance Identification and Rejection in Spacecraft

DTIC Science & Technology

2006-08-01

linear theory. Therefore, it is of interest to examine its efficacy on the current nonlinear spacecraft model. In addition, the robustness of the...School, Monterey, California 93943 Spacecraft periodic-disturbance rejection using a realistic spacecraft hardware simulator and its associated models...is investigated. The effectiveness of the dipole-type disturbance rejection filter on the current realistic nonlinear rigid-body spacecraft model is

Applied adaptive disturbance rejection using output redefinition on magnetic bearings

NASA Astrophysics Data System (ADS)

Matras, Alex Logan

Recent work has shown Adaptive Disturbance Rejection to be an effective technique for rejecting forces due to imbalance, runout and base motion disturbances on flywheels supported by magnetic bearings over a large span of frequencies. Often the applicability of some of the adaptive methods is limited because they require certain properties (such as almost-strict positive realness) that magnetic bearings do not possess. In this thesis, one method for adaptive disturbance rejection, called Adaptive Feedforward Cancellation (AFC), is modified to allow for a much wider range of frequencies to be rejected. This is accomplished by redefining the output of the original system to be the output from a reduced order state estimator instead. This can give a new system with an infinite gain margin. Additionally, the adaptation laws for the two disturbance rejection gains are slightly modified so that each adapts to a different signal in order to provide the best performance. A detailed model of a magnetic bearing is developed and computer simulations based on that model are performed to give an initial test of the new control law. A state-of-the-art magnetic bearing setup is then developed and used to implement the new control laws and determine their effectiveness. The results are successful and validate the new ideas that are presented.

The Identification of Novel Potential Injury Mechanisms and Candidate Biomarkers in Renal Allograft Rejection by Quantitative Proteomics*

PubMed Central

Sigdel, Tara K.; Salomonis, Nathan; Nicora, Carrie D.; Ryu, Soyoung; He, Jintang; Dinh, Van; Orton, Daniel J.; Moore, Ronald J.; Hsieh, Szu-Chuan; Dai, Hong; Thien-Vu, Minh; Xiao, Wenzhong; Smith, Richard D.; Qian, Wei-Jun; Camp, David G.; Sarwal, Minnie M.

2014-01-01

Early transplant dysfunction and failure because of immunological and nonimmunological factors still presents a significant clinical problem for transplant recipients. A critical unmet need is the noninvasive detection and prediction of immune injury such that acute injury can be reversed by proactive immunosuppression titration. In this study, we used iTRAQ -based proteomic discovery and targeted ELISA validation to discover and validate candidate urine protein biomarkers from 262 renal allograft recipients with biopsy-confirmed allograft injury. Urine samples were randomly split into a training set of 108 patients and an independent validation set of 154 patients, which comprised the clinical biopsy-confirmed phenotypes of acute rejection (AR) (n = 74), stable graft (STA) (n = 74), chronic allograft injury (CAI) (n = 58), BK virus nephritis (BKVN) (n = 38), nephrotic syndrome (NS) (n = 8), and healthy, normal control (HC) (n = 10). A total of 389 proteins were measured that displayed differential abundances across urine specimens of the injury types (p < 0.05) with a significant finding that SUMO2 (small ubiquitin-related modifier 2) was identified as a “hub” protein for graft injury irrespective of causation. Sixty-nine urine proteins had differences in abundance (p < 0.01) in AR compared with stable graft, of which 12 proteins were up-regulated in AR with a mean fold increase of 2.8. Nine urine proteins were highly specific for AR because of their significant differences (p < 0.01; fold increase >1.5) from all other transplant categories (HLA class II protein HLA-DRB1, KRT14, HIST1H4B, FGG, ACTB, FGB, FGA, KRT7, DPP4). Increased levels of three of these proteins, fibrinogen beta (FGB; p = 0.04), fibrinogen gamma (FGG; p = 0.03), and HLA DRB1 (p = 0.003) were validated by ELISA in AR using an independent sample set. The fibrinogen proteins further segregated AR from BK virus nephritis (FGB p = 0.03, FGG p = 0.02), a finding that supports the utility of

Multivariate prediction of upper limb prosthesis acceptance or rejection.

PubMed

Biddiss, Elaine A; Chau, Tom T

2008-07-01

To develop a model for prediction of upper limb prosthesis use or rejection. A questionnaire exploring factors in prosthesis acceptance was distributed internationally to individuals with upper limb absence through community-based support groups and rehabilitation hospitals. A total of 191 participants (59 prosthesis rejecters and 132 prosthesis wearers) were included in this study. A logistic regression model, a C5.0 decision tree, and a radial basis function neural network were developed and compared in terms of sensitivity (prediction of prosthesis rejecters), specificity (prediction of prosthesis wearers), and overall cross-validation accuracy. The logistic regression and neural network provided comparable overall accuracies of approximately 84 +/- 3%, specificity of 93%, and sensitivity of 61%. Fitting time-frame emerged as the predominant predictor. Individuals fitted within two years of birth (congenital) or six months of amputation (acquired) were 16 times more likely to continue prosthesis use. To increase rates of prosthesis acceptance, clinical directives should focus on timely, client-centred fitting strategies and the development of improved prostheses and healthcare for individuals with high-level or bilateral limb absence. Multivariate analyses are useful in determining the relative importance of the many factors involved in prosthesis acceptance and rejection.

MARS-MD: rejection based image domain material decomposition

NASA Astrophysics Data System (ADS)

Bateman, C. J.; Knight, D.; Brandwacht, B.; McMahon, J.; Healy, J.; Panta, R.; Aamir, R.; Rajendran, K.; Moghiseh, M.; Ramyar, M.; Rundle, D.; Bennett, J.; de Ruiter, N.; Smithies, D.; Bell, S. T.; Doesburg, R.; Chernoglazov, A.; Mandalika, V. B. H.; Walsh, M.; Shamshad, M.; Anjomrouz, M.; Atharifard, A.; Vanden Broeke, L.; Bheesette, S.; Kirkbride, T.; Anderson, N. G.; Gieseg, S. P.; Woodfield, T.; Renaud, P. F.; Butler, A. P. H.; Butler, P. H.

2018-05-01

This paper outlines image domain material decomposition algorithms that have been routinely used in MARS spectral CT systems. These algorithms (known collectively as MARS-MD) are based on a pragmatic heuristic for solving the under-determined problem where there are more materials than energy bins. This heuristic contains three parts: (1) splitting the problem into a number of possible sub-problems, each containing fewer materials; (2) solving each sub-problem; and (3) applying rejection criteria to eliminate all but one sub-problem's solution. An advantage of this process is that different constraints can be applied to each sub-problem if necessary. In addition, the result of this process is that solutions will be sparse in the material domain, which reduces crossover of signal between material images. Two algorithms based on this process are presented: the Segmentation variant, which uses segmented material classes to define each sub-problem; and the Angular Rejection variant, which defines the rejection criteria using the angle between reconstructed attenuation vectors.

Heat pipe cooled heat rejection subsystem modelling for nuclear electric propulsion

NASA Astrophysics Data System (ADS)

Moriarty, Michael P.

1993-11-01

NASA LeRC is currently developing a FORTRAN based computer model of a complete nuclear electric propulsion (NEP) vehicle that can be used for piloted and cargo missions to the Moon or Mars. Proposed designs feature either a Brayton or a K-Rankine power conversion cycle to drive a turbine coupled with rotary alternators. Both ion and magnetoplasmodynamic (MPD) thrusters will be considered in the model. In support of the NEP model, Rocketdyne is developing power conversion, heat rejection, and power management and distribution (PMAD) subroutines. The subroutines will be incorporated into the NEP vehicle model which will be written by NASA LeRC. The purpose is to document the heat pipe cooled heat rejection subsystem model and its supporting subroutines. The heat pipe cooled heat rejection subsystem model is designed to provide estimate of the mass and performance of the equipment used to reject heat from Brayton and Rankine cycle power conversion systems. The subroutine models the ductwork and heat pipe cooled manifold for a gas cooled Brayton; the heat sink heat exchanger, liquid loop piping, expansion compensator, pump and manifold for a liquid loop cooled Brayton; and a shear flow condenser for a K-Rankine system. In each case, the final heat rejection is made by way of a heat pipe radiator. The radiator is sized to reject the amount of heat necessary.

Heat pipe cooled heat rejection subsystem modelling for nuclear electric propulsion

NASA Technical Reports Server (NTRS)

Moriarty, Michael P.

1993-01-01

NASA LeRC is currently developing a FORTRAN based computer model of a complete nuclear electric propulsion (NEP) vehicle that can be used for piloted and cargo missions to the Moon or Mars. Proposed designs feature either a Brayton or a K-Rankine power conversion cycle to drive a turbine coupled with rotary alternators. Both ion and magnetoplasmodynamic (MPD) thrusters will be considered in the model. In support of the NEP model, Rocketdyne is developing power conversion, heat rejection, and power management and distribution (PMAD) subroutines. The subroutines will be incorporated into the NEP vehicle model which will be written by NASA LeRC. The purpose is to document the heat pipe cooled heat rejection subsystem model and its supporting subroutines. The heat pipe cooled heat rejection subsystem model is designed to provide estimate of the mass and performance of the equipment used to reject heat from Brayton and Rankine cycle power conversion systems. The subroutine models the ductwork and heat pipe cooled manifold for a gas cooled Brayton; the heat sink heat exchanger, liquid loop piping, expansion compensator, pump and manifold for a liquid loop cooled Brayton; and a shear flow condenser for a K-Rankine system. In each case, the final heat rejection is made by way of a heat pipe radiator. The radiator is sized to reject the amount of heat necessary.

Interactions Between Rejection Sensitivity and Supportive Relationships in the Prediction of Adolescents’ Internalizing Difficulties

PubMed Central

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

2013-01-01

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 depression and social anxiety during middle adolescence in an ethnically diverse sample of 277 youth (M age = 14.30 years; 46.93% male). Analyses revealed that angry rejection sensitivity was related to depressive symptoms, but only for adolescents reporting low support from parents and friends. Friend support moderated the association between (1) angry rejection sensitivity and social anxiety, and (2) anxious rejection sensitivity and depressive symptoms. For adolescents reporting low support from friends, support from parents was positively related to social anxiety. Findings highlight the importance of considering relationships in studies of rejection sensitivity and adjustment during adolescence. PMID:20213482

Pollen Acceptance or Rejection: A Tale of Two Pathways.

PubMed

Doucet, Jennifer; Lee, Hyun Kyung; Goring, Daphne R

2016-12-01

While the molecular and cellular basis of self-incompatibility leading to self-pollen rejection in the Brassicaceae has been extensively studied, relatively little attention has been paid to compatible pollen recognition and the corresponding cellular responses in the stigmatic papillae. This is now changing because research has started to uncover steps in the Brassicaceae 'basal compatible pollen response pathway' in the stigma leading to pollen hydration and germination. Furthermore, recent studies suggest that self-incompatible pollen activates both the basal compatible pathway and the self-incompatibility pathway in the stigma, with the self-incompatibility response ultimately prevailing to reject self-pollen. We review here recent discoveries in both pathways and discuss how compatible pollen is accepted by the stigma versus the rejection of self-incompatible pollen. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Kin Rejection: Social Signals, Neural Response and Perceived Distress During Social Exclusion

PubMed Central

Sreekrishnan, Anirudh; Herrera, Tania A.; Wu, Jia; Borelli, Jessica L.; White, Lars O.; Rutherford, Helena J. V.; Mayes, Linda C.; Crowley, Michael J.

2014-01-01

Across species, kin bond together to promote survival. We sought to understand the dyadic effect of exclusion by kin (as opposed to non-kin strangers) on brain activity of the mother and her child and their subjective distress. To this end, we probed mother-child relationships with a computerized ball-toss game Cyberball. When excluded by one another, rather than by a stranger, both mothers and children exhibited a significantly pronounced frontal P2. Moreover, upon kin-rejection versus stranger-rejection, both mothers and children showed incremented left frontal positive slow waves for rejection events. Children reported more distress upon exclusion than their own mothers. Similar to past work, relatively augmented negative frontal slow wave activity predicted greater self-reported ostracism distress. This effect, generalized to the P2, was limited to mother or child- rejection by kin, with comparable magnitude of effect across kin identity (mothers vs. children). For both mothers and children, the frontal P2 peak was significantly pronounced for kin-rejection versus stranger rejection. Taken together, our results document the rapid categorization of social signals as kin-relevant and the specificity of early and late neural markers for predicting felt ostracism. PMID:24909389

GalT-KO pig lungs are highly susceptible to acute vascular rejection in baboons, which may be mitigated by transgenic expression of hCD47 on porcine blood vessels.

PubMed

Watanabe, Hironosuke; Sahara, Hisashi; Nomura, Shunichiro; Tanabe, Tatsu; Ekanayake-Alper, Dilrukshi K; Boyd, Lennan K; Louras, Nathan J; Asfour, Arsenoi; Danton, Makenzie A; Ho, Siu-Hong; Arn, Scott J; Hawley, Robert J; Shimizu, Akira; Nagayasu, Takeshi; Ayares, David; Lorber, Marc I; Sykes, Megan; Sachs, David H; Yamada, Kazuhiko

2018-03-12

Despite recent progress in survival times of xenografts in non-human primates, there are no reports of survival beyond 5 days of histologically well-aerated porcine lung grafts in baboons. Here, we report our initial results of pig-to-baboon xeno-lung transplantation (XLTx). Eleven baboons received genetically modified porcine left lungs from either GalT-KO alone (n = 3), GalT-KO/humanCD47(hCD47)/hCD55 (n = 3), GalT-KO/hD47/hCD46 (n = 4), or GalT-KO/hCD39/hCD46/hCD55/TBM/EPCR (n = 1) swine. The first 2 XLTx procedures were performed under a non-survival protocol that allowed a 72-hour follow-up of the recipients with general anesthesia, while the remaining 9 underwent a survival protocol with the intention of weaning from ventilation. Lung graft survivals in the 2 non-survival animals were 48 and >72 hours, while survivals in the other 9 were 25 and 28 hours, at 5, 5, 6, 7, >7, 9, and 10 days. One baboon with graft survival >7 days, whose entire lung graft remained well aerated, was euthanized on POD 7 due to malfunction of femoral catheters. hCD47 expression of donor lungs was detected in both alveoli and vessels only in the 3 grafts surviving >7, 9, and 10 days. All other grafts lacked hCD47 expression in endothelial cells and were completely rejected with diffuse hemorrhagic changes and antibody/complement deposition detected in association with early graft loss. To our knowledge, this is the first evidence of histologically viable porcine lung grafts beyond 7 days in baboons. Our results indicate that GalT-KO pig lungs are highly susceptible to acute humoral rejection and that this may be mitigated by transgenic expression of hCD47. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sociocultural Influence and Appearance-Based Rejection Sensitivity among College Students

ERIC Educational Resources Information Center

Park, Lora E.; DiRaddo, Ann Marie; Calogero, Rachel M.

2009-01-01

The present research examined the influence of parents, peers, and the media in predicting college students' Appearance-based Rejection Sensitivity (Appearance-RS)--the degree to which individuals anxiously expect to be rejected based on their physical appearance. Given that women are socialized to be more appearance-focused than men, women were…

Psychological Sources of Systematic Rejection Among White and Black Adolescents.

ERIC Educational Resources Information Center

Long, Samuel

In this study, individual-oriented and system-oriented models of systemic rejection among white and black adolescents are investigated. Systemic rejection is defined as attitudes of political alienation and political violence justification. Twelve hypotheses were generated and tested using survey data collected in May 1976 from a random sample of…

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

PubMed

Schaan, Violetta K; Vögele, Claus

2016-11-01

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

Rejection Thresholds in Chocolate Milk: Evidence for Segmentation

PubMed Central

Harwood, Meriel L.; Ziegler, Gregory R.; Hayes, John E.

2012-01-01

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. PMID:22754143

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.

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.

Gene-Based Multiclass Cancer Diagnosis with Class-Selective Rejections

PubMed Central

Jrad, Nisrine; Grall-Maës, Edith; Beauseroy, Pierre

2009-01-01

Supervised learning of microarray data is receiving much attention in recent years. Multiclass cancer diagnosis, based on selected gene profiles, are used as adjunct of clinical diagnosis. However, supervised diagnosis may hinder patient care, add expense or confound a result. To avoid this misleading, a multiclass cancer diagnosis with class-selective rejection is proposed. It rejects some patients from one, some, or all classes in order to ensure a higher reliability while reducing time and expense costs. Moreover, this classifier takes into account asymmetric penalties dependant on each class and on each wrong or partially correct decision. It is based on ν-1-SVM coupled with its regularization path and minimizes a general loss function defined in the class-selective rejection scheme. The state of art multiclass algorithms can be considered as a particular case of the proposed algorithm where the number of decisions is given by the classes and the loss function is defined by the Bayesian risk. Two experiments are carried out in the Bayesian and the class selective rejection frameworks. Five genes selected datasets are used to assess the performance of the proposed method. Results are discussed and accuracies are compared with those computed by the Naive Bayes, Nearest Neighbor, Linear Perceptron, Multilayer Perceptron, and Support Vector Machines classifiers. PMID:19584932

Effectiveness of a social relations intervention program for aggressive and nonaggressive, rejected children.

PubMed

Lochman, J E; Coie, J D; Underwood, M K; Terry, R

1993-12-01

A sample of 52 Black aggressive, rejected and nonaggressive, rejected children were randomly assigned to receive a social relations intervention or to be in a nonintervention control group. The school-based intervention for fourth-grade children focused on positive social skill training and cognitive-behavioral strategies to promote deliberate, nonimpulsive problem solving. At both the post-treatment and the 1-year follow-up assessments, the social relations intervention was found to be effective only with the aggressive, rejected children. Implications for the importance of assessing subtypes of rejected children are discussed.

18 CFR 35.5 - Rejection of material submitted for filing.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Rejection of material submitted for filing. 35.5 Section 35.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... that fails to comply with this Part may be rejected by the Director of the Office of Energy Market...

Acute Toxoplasma infection among family members of patients with acute lymphadenopathic toxoplasmosis.

PubMed

Luft, B J; Remington, J S

1984-01-01

Studies were performed to determine how frequently acute infections with Toxoplasma gondii occur among family members of patients with acute acquired lymphadenopathic toxoplasmosis. In five of the nine families studied, more than one family member had serologic evidence of recent acute infection with T gondii. In three of the families, the immunoglobulin M and immunoglobulin G antibody titers to T gondii among infected family members were similar irrespective of whether lymphadenopathy was present. Lymphadenopathy developed in one family member in each of two families (families VIII and IX) three and eight months after lymphadenopathy had developed in the index case (proband). These results suggest that common-source outbreaks occur with surprising frequency among family members of patients with lymphadenopathic toxoplasmosis and that the humoral response is similar with different manifestations of the infection.

Self-esteem moderates neuroendocrine and psychological responses to interpersonal rejection.