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Sample records for acute cellular rejection

  1. Simkania negevensis and acute cellular rejection in lung transplant recipients.

    Jamal, Alainna J; Resende, Mariangela R; Prochnow, Taisa; McGilvray, Ian; Pilewski, Joseph M; Crespo, Maria M; Singer, Lianne G; McCurry, Kenneth R; Kolls, Jay K; Keshavjee, Shaf; Liles, W Conrad; Husain, Shahid

    2015-08-01

    Simkania negevensis infection has been hypothesized to play a role in lung transplant rejection. The incidence of S. negevensis infection and its association with acute cellular rejection (ACR) were determined in a prospective cohort study of 78 lung transplant recipients (LTRs) in Toronto, Canada, and Pittsburgh, USA, from July 2007 to January 2010. Simkania negevensis testing was detected by quantitative polymerase chain reaction (PCR) on bronchoalveolar lavage fluid. The relationship between S. negevensis and ACR was examined using Cox proportional hazards models and generalized linear and latent mixed models. Cumulative incidence estimates for time-to-ACR in S. negevensis PCR-positive vs. PCR-negative LTRs were 52.7% vs. 31.1% at six months and 68.9% vs. 44.6% at one yr, respectively. Although not statistically significant, there was a trend toward a higher risk of ACR among S. negevensis PCR-positive vs. PCR-negative LTRs in all statistical models. PMID:26009941

  2. Renal Contrast-Enhanced Sonography Findings in a Model of Acute Cellular Allograft Rejection.

    Grabner, A; Kentrup, D; Pawelski, H; Mühlmeister, M; Biermann, C; Edemir, B; Heitplatz, B; Van Marck, V; Bettinger, T; Pavenstädt, H; Schlatter, E; Stypmann, J; Tiemann, K; Reuter, S

    2016-05-01

    Noninvasive methods to diagnose and differentiate acute cellular rejection from acute tubular necrosis or acute calcineurin inhibitor toxicity are still missing. Because T lymphocytes play a decisive role in early states of rejection, we investigated the suitability and feasibility of antibody-mediated contrast-enhanced ultrasound by using microbubbles targeted to CD3(+) , CD4(+) , or CD8(+) T cells in different models of renal disease. In an established rat renal transplantation model, CD3-mediated ultrasound allows the detection of acute rejection as early as on postoperative day 2. Ultrasound signal intensities increased with the severity of inflammation. Further, an early response to therapy could be monitored by using contrast-enhanced sonography. Notably, acute tubular necrosis occurring after ischemia-reperfusion injury as well as acute calcineurin inhibitor toxicity could easily be differentiated. Finally, the quantified ultrasound signal correlated significantly with the number of infiltrating T cells obtained by histology and with CD3 mRNA levels, as well as with chemokine CXCL9, CXCL11, and CCL19 mRNA but not with KIM-1 mRNA expression, thereby representing the severity of graft inflammation but not the degree of kidney injury. In summary, we demonstrate that antibody-mediated contrast-enhanced ultrasound targeting T lymphocytes could be a promising tool for an easy and reproducible assessment of acute rejection after renal transplantation. PMID:26613381

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

    Jun Wang; Al-Lamki, Rafia S.

    2013-01-01

    Tumor necrosis factor receptor 2 (TNFR2) is a type I transmembrane glycoprotein and one of the two receptors that orchestrate the complex biological functions of tumor necrosis factor (TNF, also designed TNF- α ). Accumulating experimental evidence suggests that TNFR2 plays an important role in renal disorders associated with acute cellular rejection and clear cell renal carcinoma but its exact role in these settings is still not completely understood. This papers reviews the factors that may...

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

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

    2016-03-01

    Liver stiffness measurement (LSM) is a useful method to estimate liver fibrosis and portal hypertension. The inflammatory process that takes place in post-liver transplant acute cellular rejection (ACR) may also increase liver stiffness. We aimed to explore the association between liver stiffness and the severity of ACR, as well as to assess the relationship between liver stiffness and response to rejection treatment in a prospective study that included 27 liver recipients with biopsy-proven ACR, 30 stable recipients with normal liver tests, and 30 hepatitis C virus (HCV)-infected LT recipients with histologically diagnosed HCV recurrence. Patients with rejection were stratified into 2 groups (mild and moderate/severe) according to the severity of rejection evaluated with the Banff score. Routine biomarkers and LSM with FibroScan were performed at the time of liver biopsy (baseline) and at 7, 30, and 90 days in patients with rejection and at baseline in control patients. Median baseline liver stiffness was 5.9 kPa in the mild rejection group, 11 kPa in the moderate/severe group (P = 0.001), 4.2 kPa in stable recipients (P = 0.02 versus mild rejection), and 13.6 kPa in patients with recurrent HCV (P = 0.17 versus moderate/severe rejection). The area under the receiver operator characteristic curve of LSM to discriminate mild versus moderate/severe ACR was 0.924, and a LSM value of 8.5 kPa yielded a positive predictive value of 100% to diagnose moderate/severe rejection. Liver stiffness improved in 7%, 21%, and 64% of patients with moderate/severe rejection at 7, 30, and 90 days. In conclusion, according to the results of this exploratory study, LSM is associated with the severity of ACR in liver transplantation and thus may be of help in its assessment. Liver Transpl 22:298-304, 2016. © 2015 AASLD. PMID:26609794

  5. Serial changes in longitudinal graft function and implications of acute cellular graft rejections during the first year after heart transplantation

    Clemmensen, Tor Skibsted; Løgstrup, Brian Bridal; Eiskjær, Hans;

    2015-01-01

    AIMS: The aim of this prospective study was to use left ventricular global longitudinal strain (LV-GLS) as a non-invasive tool for the monitoring of graft function in relation to acute cellular rejection (ACR) during the first year after heart transplantation (HTX). METHODS AND RESULTS: The study...

  6. Is biliary bile acid a good predictor for acute cellular rejection in living donor liver transplantation?

    Mohammed Saied Hedaya; Walid M. El Moghazy; YamamotoYasutomo; Tomioka Kiyoshi; Toshimi Kaido; Hiroto Egawa; Shinji Uemoto; Yasutsugu Takada

    2009-01-01

    BACKGROUND: In liver transplantation, acute cellular rejection (ACR) is still a major complication that can lead to mortality. Bile secretion has been considered as a marker of early graft function. METHODS: The study included 41 adults who received living donor liver transplantation (LDLT) at Kyoto University Hospital between April 2007 and February 2008. The patients were stratified according to the presence or absence of ACR. Bile samples were collected from donors once and from recipients every other day for the first 2 weeks after transplantation. Total bile acid (BA) and taurine-conjugated bile acid (TCBA) in bile were measured by magnetic resonance spectroscopy. The recipient/donor (R/D) BA ratio and R/D TCBA ratio were calculated. RESULTS: The ACR group (n=12) showed a greater decrease in BA post-transplantation than the non-ACR group, but this difference was not statistically significant. On both day 7 and day 9 post-transplantation the R/D TCBA was significantly different between the two groups (P=0.038 on day 7 and P=0.036 on day 9). The R/D TCBA ratio ≥0.5 on days 7 and 9, and ≥0.38 on day 11 post-transplantation were associated with better ACR-free survival. CONCLUSION: The recipient/donor TCBA ratio can be a predictor for ACR after LDLT as early as post-transplantation day 7.

  7. Human herpesvirus-6 and cytomegalovirus DNA in liver donor biopsies and their correlation with HLA matches and acute cellular rejection

    Ana Carolina Guardia

    2014-04-01

    Full Text Available Herpesvirus reactivation is common after liver transplantation. OBJECTIVE: Analyze the presence of cytomegalovirus (HCMV and human herpesvirus-6 (HHV-6 DNA in liver donor biopsies, seeking to better understand issues involving human donor leukocyte antigens (HLA-A, B and DR, as well as correlations with acute cellular rejection. METHODS: Fifty-nine liver transplantation patients were investigated for the presence of HCMV and HHV-6 DNA in liver donor biopsies, using the Nested-PCR technique. The clinical donor information and HLA matches were obtained from the São Paulo State Transplant System. The recipients' records regarding acute cellular rejection were studied. RESULTS: Seven (11.8% biopsies were positive for HCMV DNA and 29 (49% were positive for HHV-6 DNA. In 14 donors with HLA-DR 15 nine had HHV-6 DNA positive liver biopsy with a tendency for significant association (p=0.09, 22 recipients developed acute cellular rejection and 9/22 were positive for HLA-DR 15 (p=0.03; χ 2=4.51, which was statistically significant in univariate analysis and showed a tendency after multivariate analysis (p=0.08. CONCLUSION: HHV-6 DNA was prevalent in liver donors studied as well as HLA-DR 15. These findings suggest that patients with HLA-DR 15 in liver donor biopsies develop more rejection after liver transplantation.

  8. Assessment of sub-clinical acute cellular rejection after heart transplantation: comparison of cardiac magnetic resonance imaging and endomyocardial biopsy

    Comparing the diagnostic value of multi-sequential cardiac magnetic resonance imaging (CMR) with endomyocardial biopsy (EMB) for sub-clinical cardiac allograft rejection. One hundred and forty-six examinations in 73 patients (mean age 53 ± 12 years, 58 men) were performed using a 1.5 Tesla system and compared to EMB. Examinations included a STIR (short tau inversion recovery) sequence for calculation of edema ratio (ER), a T1-weighted spin-echo sequence for assessment of global relative enhancement (gRE), and inversion-recovery sequences to visualize late gadolinium enhancement (LGE). Histological grade ≥1B was considered relevant rejection. One hundred and twenty-seven (127/146 = 87 %) EMBs demonstrated no or mild signs of rejection (grades ≤1A) and 19/146 (13 %) a relevant rejection (grade ≥1B). Sensitivity, specificity, positive predictive, and negative predictive values were as follows: ER: 63 %, 78 %, 30 %, and 93 %; gRE: 63 %, 70 %, 24 %, and 93 %; LGE: 68 %, 36 %, 13 %, and 87 %; with the combination of ER and gRE with at least one out of two positive: 84 %, 57 %, 23 %, and 96 %. ROC analysis revealed an area under the curve of 0.724 for ER and 0.659 for gRE. CMR parameters for myocarditis are useful to detect sub-clinical acute cellular rejection after heart transplantation. Comparable results to myocarditis can be achieved with a combination of parameters. (orig.)

  9. Assessment of sub-clinical acute cellular rejection after heart transplantation: comparison of cardiac magnetic resonance imaging and endomyocardial biopsy

    Krieghoff, Christian; Hildebrand, Lysann; Grothoff, Matthias; Lehmkuhl, Lukas; Luecke, Christian; Andres, Claudia; Nitzsche, Stefan; Riese, Franziska; Gutberlet, Matthias [University Leipzig - Heart Centre, Department of Diagnostic and Interventional Radiology, Leipzig (Germany); Barten, Markus J.; Strueber, Martin; Mohr, Friedrich Wilhelm [University Leipzig - Heart Centre, Department of Cardiac Surgery, Leipzig (Germany)

    2014-10-15

    Comparing the diagnostic value of multi-sequential cardiac magnetic resonance imaging (CMR) with endomyocardial biopsy (EMB) for sub-clinical cardiac allograft rejection. One hundred and forty-six examinations in 73 patients (mean age 53 ± 12 years, 58 men) were performed using a 1.5 Tesla system and compared to EMB. Examinations included a STIR (short tau inversion recovery) sequence for calculation of edema ratio (ER), a T1-weighted spin-echo sequence for assessment of global relative enhancement (gRE), and inversion-recovery sequences to visualize late gadolinium enhancement (LGE). Histological grade ≥1B was considered relevant rejection. One hundred and twenty-seven (127/146 = 87 %) EMBs demonstrated no or mild signs of rejection (grades ≤1A) and 19/146 (13 %) a relevant rejection (grade ≥1B). Sensitivity, specificity, positive predictive, and negative predictive values were as follows: ER: 63 %, 78 %, 30 %, and 93 %; gRE: 63 %, 70 %, 24 %, and 93 %; LGE: 68 %, 36 %, 13 %, and 87 %; with the combination of ER and gRE with at least one out of two positive: 84 %, 57 %, 23 %, and 96 %. ROC analysis revealed an area under the curve of 0.724 for ER and 0.659 for gRE. CMR parameters for myocarditis are useful to detect sub-clinical acute cellular rejection after heart transplantation. Comparable results to myocarditis can be achieved with a combination of parameters. (orig.)

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

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

    2009-01-01

    BACKGROUND: Post-transplant baseline forced expiratory volume in 1 second (FEV(1)) constitutes a systematic bias in analyses of bronchiolitis obliterans syndrome (BOS). This retrospective study evaluates risk factors for BOS adjusting for the confounding of post-transplant baseline FEV(1). METHODS......: A multivariate survival and competing risk analysis of a large consecutive series of patients (n = 389) from a national center 1992 to 2004. Exclusion criteria were patients not surviving at least 3 months after transplantation (n = 39) and no available lung function measurements (n = 4). RESULTS......: The first maximum FEV(1) occurred at a median 183 days post-transplant. Freedom from BOS was 81%, 53%, 38% and 15%, and cumulative incidence of BOS was 18%, 43%, 57% and 77% at 1, 3, 5 and 10 years post-transplantation, respectively. Acute cellular rejection was independently associated with an...

  11. MicroRNA signature of intestinal acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies.

    Asaoka, T; Sotolongo, B; Island, E R; Tryphonopoulos, P; Selvaggi, G; Moon, J; Tekin, A; Amador, A; Levi, D M; Garcia, J; Smith, L; Nishida, S; Weppler, D; Tzakis, A G; Ruiz, P

    2012-02-01

    Despite continuous improvement of immunosuppression, small bowel transplantation (SBT) is plagued by a high incidence of acute cellular rejection (ACR) that is frequently intractable. Therefore, there is a need to uncover novel insights that will lead to strategies to achieve better control of ACR. We hypothesized that particular miRNAs provide critical regulation of the intragraft immune response. The aim of our study was to identify miRNAs involved in intestinal ACR. We examined 26 small intestinal mucosal biopsies (AR/NR group; 15/11) obtained from recipients after SBT or multivisceral transplantation. We investigated the expression of 384 mature human miRNAs and 280 mRNAs associated with immune, inflammation and apoptosis processes. We identified differentially expressed 28 miRNAs and 58 mRNAs that characterized intestinal ACR. We found a strong positive correlation between the intragraft expression levels of three miRNAs (miR-142-3p, miR-886-3p and miR-132) and 17 mRNAs including CTLA4 and GZMB. We visualized these miRNAs within cells expressing CD3 and CD14 proteins in explanted intestinal allografts with severe ACR. Our data suggested that miRNAs have a critical role in the activation of infiltrating cells during intestinal ACR. These differences in miRNA expression patterns can be used to identify novel biomarkers and therapeutic targets for immunosuppressive agents. PMID:22026534

  12. Non-invasive Diagnosis of Acute Cellular Rejection in Liver Transplant Recipients: A Proteomic Signature Validated by ELISA

    Massoud, Omar; Heimbach, Julie; Viker, Kimberly; Krishnan, Anuradha; Poterucha, John; Sanchez, William; Watt, Kymberly; Wiesner, Russell; Charlton, Michael

    2011-01-01

    Diagnosis of acute cellular rejection (ACR) requires a liver biopsy with attendant expense, and risk. The first aim was to prospectively determine, in an exploratory analysis, whether there is a serum proteome signature associated with histologically confirmed ACR. The second aim was to use simpler and faster ELISA-based assays for proteins identified as differentially abundant in the proteomic analysis to identify patients with ACR in a separate validation cohort. We used sequential high abundance protein depletion and iTRAQ LC/MS/MS mass spectrometry to characterize the serum proteome in serum samples of patients with ACR and without ACR. Of the 41 proteins identified as differentially abundant, 7 (serum amyloid A (SAA), complement 4 (C4), fibrinogen, complement 1q (C1q), complement 3 (C3), Heat Shock Protein 60 (HSP60), and Heat Shock Protein 70 (HSP70)) could be measured using ELISA-based assays in a validation cohort of patients with ACR (n=25) and without ACR (n=21). Mean ALT levels in patients with and without ACR were (mean +/− SD) 198+/−27 and 153+/−34 U/L respectively. Among the seven proteins for which ELISA assays were available, C4 and C1q were both independent predictors for ACR. C4 had the greatest predictivity in differentiating patients with/without ACR. C4 of ≤0.31gm/L had a 97% sensitivity, 62% specificity, 74% positive predictive value and 94% negative predictive value. The combination C4 ≤0.31 gm/L and ALT ≥70 IU/ml had 96% sensitivity, 81% specificity, 86% positive predictive value and 94% negative predictive value. In summary, in this exploratory analysis, serum complement C4 and ALT levels are highly predictive of ACR in liver transplant recipients. Confirmation in a prospective, larger, diverse population is needed. PMID:21618694

  13. A new molecular approach to the diagnosis of acute rejection

    Chandraker, Anil; Strom, Terry B.

    2013-01-01

    Renal biopsy is the gold standard for detection of rejection in kidney transplant recipients but is not considered until evidence of renal dysfunction is apparent. Now, Suthanthiran and colleagues suggest that mRNA levels in urinary cells from these patients might be diagnostic and prognostic of acute cellular rejection.

  14. Pre-Transplant Donor-Specific T-Cell Alloreactivity Is Strongly Associated with Early Acute Cellular Rejection in Kidney Transplant Recipients Not Receiving T-Cell Depleting Induction Therapy

    Crespo, Elena; Lucia, Marc; Cruzado, Josep M.; Luque, Sergio; Melilli, Edoardo; Manonelles, Anna; Lloberas, Nuria; Torras, Joan; Grinyó, Josep M.; Bestard, Oriol

    2015-01-01

    Preformed T-cell immune-sensitization should most likely impact allograft outcome during the initial period after kidney transplantation, since donor-specific memory T-cells may rapidly recognize alloantigens and activate the effector immune response, which leads to allograft rejection. However, the precise time-frame in which acute rejection is fundamentally triggered by preformed donor-specific memory T cells rather than by de novo activated naïve T cells is still to be established. Here, preformed donor-specific alloreactive T-cell responses were evaluated using the IFN-γ ELISPOT assay in a large consecutive cohort of kidney transplant patients (n = 90), to assess the main clinical variables associated with cellular sensitization and its predominant time-frame impact on allograft outcome, and was further validated in an independent new set of kidney transplant recipients (n = 67). We found that most highly T-cell sensitized patients were elderly patients with particularly poor HLA class-I matching, without any clinically recognizable sensitizing events. While one-year incidence of all types of biopsy-proven acute rejection did not differ between T-cell alloreactive and non-alloreactive patients, Receiver Operating Characteristic curve analysis indicated the first two months after transplantation as the highest risk time period for acute cellular rejection associated with baseline T-cell sensitization. This effect was particularly evident in young and highly alloreactive individuals that did not receive T-cell depletion immunosuppression. Multivariate analysis confirmed preformed T-cell sensitization as an independent predictor of early acute cellular rejection. In summary, monitoring anti-donor T-cell sensitization before transplantation may help to identify patients at increased risk of acute cellular rejection, particularly in the early phases after kidney transplantation, and thus guide decision-making regarding the use of induction therapy. PMID:25689405

  15. Complement and hyper acute rejection

    Al-Rabia Mohammed

    2009-01-01

    Full Text Available Organ transplantation has been a major development in clinical medicine but its success has been marred by the immune system′s capacity to respond to "non-self" cells and tissues. A full molecular understanding of this mechanism and the myriad triggers for immune rejection is yet to be elucidated. Consequently, immunosuppressive drugs remain the mainstay of post-transplant ma-nagement; however, these interventions have side effects such as increased incidence of cancer, post-transplant lymphoproliferative disorders, susceptibility to infection if not managed appro-priately and the inconvenience to the patient of lifelong treatment. Novel therapeutic approaches based on molecular understanding of immunological processes are thus needed in this field. The notion that factors influencing successful transplants might be of use as therapeutic approaches is both scientifically and medically appealing. Recent developments in the understanding of successful transplants are expected to provide new opportunities for safer transplantation. This article reviews the present understanding of the molecular basis of rejection and the role of complement in this process as well as the possibility of generating "intelligent" therapy that better target crucial components of hyper-acute rejections.

  16. Successful use of the TandemHeart percutaneous ventricular assist device as a bridge to recovery for acute cellular rejection in a cardiac transplant patient.

    Velez-Martinez, M; Rao, K; Warner, J; Dimaio, J; Ewing, G; Mishkin, J D; Mammen, P P A; Drazner, M H; Markham, D W; Patel, P C

    2011-12-01

    In this report, we presented a patient who benefited from hemodynamic support with the TandemHeart percutaneous ventricular assist device (pVAD; Cardiac Assist, Inc) implantation in the setting of early acute graft rejection 2 months after orthotopic heart transplant. The TandemHeart initially had been used for temporary hemodynamic assistance during postcardiotomy heart failure and high-risk coronary interventions. More recently, its use in patients with cardiogenic shock from acute myocardial infarction, fulminant myocarditis, and critical aortic stenosis has been reported. To our knowledge, this is one of the first reported cases in which the TandemHeart pVAD served as a successful device for support during acute cardiac transplant rejection. PMID:22172864

  17. Monitoring of Acute Rejection after Orthotopic Heart Tranplantation

    Meng chun ying; Huang ke li; Luo bin; Wen ding guo

    2006-01-01

    Objectives To study the monitoring of rejection after orthotopic heart thansplantation.Methods From 1998 to 2005, 10 othotopic heart thansplans were performed, and acute rejection was monitored by endomyocardial biopsy as well as by clinical features, ECG, ultrasonocardiography and blood serum determination of Tropin I, and by the combination of these methods, we analysed the monitoring of acute rejection after the heart transplantation. Results With the combination of clinical features, ECG, ultrasonocardiography and blood serum test, 5 occurences of acute rejection were judged in the postoperative course, which were comfirmed by endomyocardial biopsy to be 2 acute rejections in Ⅰ b degree, 3 acute rejections in Ⅲ a degree. Endomyocardial biopsy were routinely performed 21 times postoperatively in which there were 1 acute rejection in Ⅰ a degree and 5 acute rejections in Ⅰ b degree. Conclusions Acute rejection is an important factor influencing the postoperative course of heart transplantation, so it is imperative to have an intime, effective and planned monitoring procedure for acute rejection. Endomyocardial biopsy is a sensitive and reliable method in diagnosis of acute rejection, but it is invasive and probable for some complications. The noninvasive method such as clinical features, ECG,ultrasonocardiography and blood serum test can be used as additive means in the diagnosis of acute rejection.Endomyocardial biopsy should be combined with some noninvasive methods in monitoring acute rejection after the heart transplantation.

  18. Cellular and Functional Imaging of Cardiac Transplant Rejection

    Wu, Yijen L.; Ye, Qing

    2011-01-01

    Heart transplantation is now an established treatment for patients suffering from end-stage heart diseases. With the advances in immunosuppressive treatment, the survival rate for transplant patients has improved greatly. However, allograft rejection, both acute and chronic, after heart transplantation is still a limitation leading to morbidity and mortality. The current clinical gold standard for screening rejection is endomyocardial biopsy (EMB), which is not only invasive, but also error-prone, due to the limited sample size and the site location of sampling. It would be highly desirable to have reliable and noninvasive alternatives for EMB in monitoring cardiac allograft rejection. The objective of this review is to highlight how cardiovascular imaging can contribute to noninvasively detecting and to evaluating both acute and chronic allograft rejection after heart transplantation, in particular, cardiovascular MRI (CMRI); and how CMRI can assess both immune cell infiltration at the rejecting organ, and the cardiac dysfunctions resulting from allograft rejection. PMID:21359095

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

    Talwalkar N; Javali D; Venkatesh K; Iyer S; Venkatesh M; Joshi U

    1994-01-01

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

  20. Acute Rejection and Humoral Sensitization in Lung Transplant Recipients

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

    2009-01-01

    Despite the recent introduction of many improved immunosuppressive agents for use in transplantation, acute rejection affects up to 55% of lung transplant recipients within the first year after transplant. Acute lung allograft rejection is defined as perivascular or peribronchiolar mononuclear inflammation. Although histopathologic signs of rejection often resolve with treatment, the frequency and severity of acute rejections represent the most important risk factor for the subsequent develop...

  1. Non-invasive diagnosis of acute heart- or lung-transplant rejection using radiolabeled annexin V

    Blankenberg, F.G. [Stanford Univ., CA (United States). Dept. of Radiology; Strauss, H.W. [Stanford Univ., CA (United States). Nuclear Medicine Div.

    1999-05-01

    Background. Apoptosis is a ubiquitous set of cellular processes by which superfluous or unwanted cells are eliminated in the body without harming adjacent healthy tissues. When apoptosis is inappropriate (too little or too much), a variety of human diseases can occur, including acute heart or lung transplant rejection. Objective. Our group has developed a new radiopharmaceutical, radiolabeled annexin V, which can image apoptosis. Results and conclusion. Here we briefly review the biomolecular basis of apoptosis and its role in acute rejection. We also describe the possible use of radiolabeled annexin V to screen children noninvasively for acute rejection following organ transplantation. (orig.) With 6 figs., 53 refs.

  2. Non-invasive diagnosis of acute heart- or lung-transplant rejection using radiolabeled annexin V

    Background. Apoptosis is a ubiquitous set of cellular processes by which superfluous or unwanted cells are eliminated in the body without harming adjacent healthy tissues. When apoptosis is inappropriate (too little or too much), a variety of human diseases can occur, including acute heart or lung transplant rejection. Objective. Our group has developed a new radiopharmaceutical, radiolabeled annexin V, which can image apoptosis. Results and conclusion. Here we briefly review the biomolecular basis of apoptosis and its role in acute rejection. We also describe the possible use of radiolabeled annexin V to screen children noninvasively for acute rejection following organ transplantation. (orig.)

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

    Talwalkar N

    1994-01-01

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

  4. Cellular and Functional Imaging of Cardiac Transplant Rejection

    Wu, Yijen L.; Ye, Qing; Ho, Chien

    2011-01-01

    Heart transplantation is now an established treatment for patients suffering from end-stage heart diseases. With the advances in immunosuppressive treatment, the survival rate for transplant patients has improved greatly. However, allograft rejection, both acute and chronic, after heart transplantation is still a limitation leading to morbidity and mortality. The current clinical gold standard for screening rejection is endomyocardial biopsy (EMB), which is not only invasive, but also error-p...

  5. LATE ACUTE REJECTION IN LIVER TRANSPLANT: A SYSTEMATIC REVIEW

    Nacif, Lucas Souto; Pinheiro, Rafael Soares; PÉCORA, Rafael Antônio de Arruda; Ducatti, Liliana; ROCHA-SANTOS, Vinicius; Andraus, Wellington; D'ALBUQUERQUE, Luiz Carneiro

    2015-01-01

    Introduction: Late acute rejection leads to worse patient and graft survival after liver transplantation. Aim: To analyze the reported results published in recent years by leading transplant centers in evaluating late acute rejection and update the clinical manifestations, diagnosis and treatment of liver transplantation. Method: Systematic literature review through Medline-PubMed database with headings related to late acute rejection in articles published until November 2013 was done. Were a...

  6. Acute pulmonary rejection in heart and lung transplant recipients

    Acute pulmonary rejection occurs in up to 50% of patients undergoing heart and lung transplant procedures. These patients are also susceptible to volume overload and pneumonia. To evaluate the radiographic and high-resolution CT appearances of acute pulmonary rejection, we compared chest radiographs and high-resolution CT scans with the clinical findings and with histologic and lavage data from 91 serial transbronchial biopsies in 13 patients. The radiographic appearance of acute pulmonary rejection is characterized by prominent septal lines and pleural effusions. The authors conclude that in the appropriate clinical setting, the appearance of new pleural effusions and prominent septal lines is highly suggestive of acute pulmonary rejections

  7. Pre-Transplant Donor-Specific T-Cell Alloreactivity Is Strongly Associated with Early Acute Cellular Rejection in Kidney Transplant Recipients Not Receiving T-Cell Depleting Induction Therapy

    Crespo, Elena; Lucia, Marc; Cruzado, Josep M.; Luque, Sergio; Melilli, Edoardo; Manonelles, Anna; Lloberas, Nuria; Torras, Joan; Grinyó, Josep M.; Bestard, Oriol

    2015-01-01

    Preformed T-cell immune-sensitization should most likely impact allograft outcome during the initial period after kidney transplantation, since donor-specific memory T-cells may rapidly recognize alloantigens and activate the effector immune response, which leads to allograft rejection. However, the precise time-frame in which acute rejection is fundamentally triggered by preformed donor-specific memory T cells rather than by de novo activated naïve T cells is still to be established. Here, p...

  8. Can deconvolution of renal transplant curves discriminate acute necrosis for acute rejection?

    Full text: The management of allogeneic renal transplants in the acute post-operative period is diagnostically challenging when there is poor or no function of the graft, which occurs in about 10-15% of cases. Although acute tubular necrosis (ATN) is most common, acute transplant rejection remains a possibility in 25% of cases. Radionuclide renography (RRG) allows a non invasive assessment of graft perfusion and function. However, the ability to differentiate ATN from acute rejection, in particular mild cellular type, is quite limited. Thus we sought to improve the diagnostic value of RRG. From a pool of 137 renal transplant recipients from 1997 to 1998, we studied 21 subjects who had had a renal transplant biopsy with a tissue diagnosis of ATN (13) or rejection (8). They were chosen because they had also had serial RRG done at day + 1 and another close to the day of biopsy (day X). For each study, using deconvolution analysis of the input iliac artery bolus as reference, and comparing it with the dispersion of radioactivity over time in the whole graft, which corresponds to the initial iliac artery bolus, we derived a graft delay index (GDI). We then compared the GDIs of day + 1 vs day X, as a simple subtraction and as a linear ratio. In 1 of 13 subjects with ATN, we found that the GDI decreased at day X compared with day + 1. In 7 of 8 with rejection, the GDI increased at day X. Thus by comparing the graft delay index of a study done at some point in the acute post-operative period with day + 1, we can discriminate between ATN and rejection. It is our intention to apply our method in a prospective study

  9. Imaging-based diagnosis of acute renal allograft rejection

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

    2016-01-01

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

  10. Bronchoalveolar Immunologic Profile of Acute Human Lung Transplant Allograft Rejection

    Gregson, Aric L.; Hoji, Aki; Saggar, Rajan; Ross, David J; Kubak, Bernard M; Jamieson, Beth D.; Weigt, S. Samuel; Lynch, Joseph P.; Ardehali, Abbas; Belperio, John A.; Yang, Otto O

    2008-01-01

    Bronchoalveolar lavage fluid (BALF) offers a potential means to diagnose acute rejection and could provide insight into the immune mechanisms responsible for lung allograft rejection. Transbronchial biopsies from 29 bronchoscopic procedures were assessed for rejection. Concurrent BALF lymphocyte subsets were examined by flow cytometry, including CD4+ and CD8+ T cells and their activation status via CD38 expression, NK, NK-like T (NT), B, T regulatory (Treg) and invariant receptor NK-T cells (...

  11. Acute rejection episodes after kidney transplantation

    Hamida Fethi

    2009-01-01

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

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

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

    2010-01-04

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

  13. Prediction of acute cardiac rejection using radionuclide techniques

    Radionuclide scanning of the donor left ventricle using technetium-99m-labelled red cells was used to monitor acute rejection after heterotopic heart transplantation and compared with histopathological evidence of rejection obtained at examination of an endomyocardial biopsy specimen. The ejection fraction and end-diastolic, end-systolic and stroke volumes were calculated at each examination; an equation was derived from these data to predict the degree of acute rejection, using histopathological examination of endomyocardial biopsy specimens as criteria of the presence and severity of rejection. A highly significant multiple correlation between radionuclide scanning parameters and endomyocardial biopsy was found. The advantages of non-invasive radionuclide scanning over the invasive procedure of endomyocardial biopsy are discussed

  14. Prediction of acute cardiac rejection using radionuclide techniques

    Novitzky, D.; Bonioszczuk, J.; Cooper, D.K.C.; Isaacs, S.; Rose, A.G.; Smith, J.A.; Uys, C.J.; Barnard, C.N.; Fraser, R. (Cape Town Univ. (South Africa))

    1984-01-07

    Radionuclide scanning of the donor left ventricle using technetium-99m-labelled red cells was used to monitor acute rejection after heterotopic heart transplantation and compared with histopathological evidence of rejection obtained at examination of an endomyocardial biopsy specimen. The ejection fraction and end-diastolic, end-systolic and stroke volumes were calculated at each examination; an equation was derived from these data to predict the degree of acute rejection, using histopathological examination of endomyocardial biopsy specimens as criteria of the presence and severity of rejection. A highly significant multiple correlation between radionuclide scanning parameters and endomyocardial biopsy was found. The advantages of non-invasive radionuclide scanning over the invasive procedure of endomyocardial biopsy are discussed.

  15. Early diagnosis of acute postoperative renal transplant rejection

    A prospective evaluation of In-111 labeled autologous platelet scintigraphy for the early diagnosis of acute postoperative renal transplant rejection was undertaken. To date, 28 consecutive patients between 7 and 14 days post-op have been injected with 500μCi of In-111 platelets followed by imaging at 24 and 48 hours. Activity within the renal transplant exceeding activity in the adjacent iliac vessels was considered to be evidence of rejection, and both chemical evidence and clinical impression of rejection at 5 days after completion of imaging was accepted as proof of ongoing or incipient rejection at the time of scintigraphy. In addition, to visual inspection, independent quantitative analysis compared the area-normalized activity over the transplant with the adjacent iliac vessels (normal <1.0). For 5 patients, positive In-111 scintigraphy was present before convincing clinical evidence of rejection. In-111 platelet scintigraphy is useful not only to confirm the clinical diagnosis of rejection but also to establish the early, pre-clinical diagnosis of incipient acute postoperative renal transplant rejection

  16. Early diagnosis of acute postoperative renal transplant rejection

    Tisdale, P.L.; Collier, B.D.; Kauffman, H.M.; Adams, M.B.; Isitman, A.T.; Hellman, R.S.; Rao, S.A.; Joestgen, T.; Krohn, L.

    1985-05-01

    A prospective evaluation of In-111 labeled autologous platelet scintigraphy for the early diagnosis of acute postoperative renal transplant rejection was undertaken. To date, 28 consecutive patients between 7 and 14 days post-op have been injected with 500..mu..Ci of In-111 platelets followed by imaging at 24 and 48 hours. Activity within the renal transplant exceeding activity in the adjacent iliac vessels was considered to be evidence of rejection, and both chemical evidence and clinical impression of rejection at 5 days after completion of imaging was accepted as proof of ongoing or incipient rejection at the time of scintigraphy. In addition, to visual inspection, independent quantitative analysis compared the area-normalized activity over the transplant with the adjacent iliac vessels (normal <1.0). For 5 patients, positive In-111 scintigraphy was present before convincing clinical evidence of rejection. In-111 platelet scintigraphy is useful not only to confirm the clinical diagnosis of rejection but also to establish the early, pre-clinical diagnosis of incipient acute postoperative renal transplant rejection.

  17. Acute renal transplant rejections: A single center experience

    Jabur Wael

    2008-01-01

    Full Text Available We undertook this observational study to assess the incidence of acute rejections (AR in the first six months after transplantation at Al-Karama Hospital, Iraq. Sixty eight patients (49 males and 19 females underwent renal transplantation in 2006 and were followed up weekly. Forty six received kidneys from related donors and 22 from unrelated donors. During the first six months after transplantation AR occurred in 16 patients (23%; 11 (23% related and 5 (23% unrelated donor transplantation. We conclude that the incidence of acute rejection was similar in related and unrelated donor transplantation and the general incidence was comparable to that reported from most centers.

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

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

    1993-01-01

    Transplantation has become an accepted treatment of many cardiac end-stage diseases. Acute cellular rejection accounts for 15% to 20% of all graft failures. The first grading system of acute cellular rejection, the Stanford Classification, was introduced in 1979, and since then many other grading...... systems have evolved. Most recently, the International Grading System was introduced in The Journal of Heart and Lung Transplantation. In this study the interobserver reproducibility of both the Stanford Classification and the International Grading System is evaluated using Kappa statistics. Three...

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

    Norsworthy Kelly J

    2009-06-01

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

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

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

    2010-01-01

    Acute rejection (AR) remains the primary risk factor for renal transplant outcome; development of non-invasive diagnostic biomarkers for AR is an unmet need. We used shotgun proteomics applying LC-MS/MS and ELISA to analyze a set of 92urine samples, from patients with AR, stable grafts (STA), proteinuria (NS), and healthy controls (HC). A total of 1446 urinary proteins were identified along with a number of NS specific, renal transplantation specific and AR specific proteins. Relative abundan...

  1. Radiation therapy treatment of acute refractory renal allograft rejection

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

  2. Late-onset acute rejection after living donor liver transplantation

    Nobuhisa Akamatsu; Yasuhiko Sugawara; Sumihito Tamura; Junichi Keneko; Yuichi Matsui; Kiyoshi Hasegawa; Masatoshi Makuuchi

    2006-01-01

    AIM: To investigate the incidence and risk factors of late-onset acute rejection (LAR) and to clarify the effectiveness of our immunosuppressive regime consisting of life-long administration of tacrolimus and steroids.METHODS: Adult living donor liver transplantation recipients (n = 204) who survived more than 6 mo after living donor liver transplantation were enrolled.Immunosuppression was achieved using tacrolimus and methylprednisolone. When adverse effects of tacrolimus were detected, the patient was switched to cyclosporine. Six months after transplantation,tacrolimus or cyclosporine was carefully maintained at a therapeutic level. The methylprednisolone dosage was maintained at 0.05 mg/kg per day by oral administration.Acute rejections that occurred more than 6 mo after the operation were defined as late-onset. The median followup period was 34 mo.RESULTS: LAR was observed in 15 cases (7%) and no chronic rejection was observed. The incidence of hyperlipidemia, chronic renal failure, new-onset posttransplantation diabetes, and deep fungal infection were 13%, 2%, 24%, and 17%, respectively. Conversion from tacrolimus to cyclosporine was required in 38 patients (19%). Multivariate analysis revealed that a cyclosporinebased regimen was significantly associated with LAR.CONCLUSION: Both LAR and drug-induced adverse events happen at a low incidence, supporting the safety and efficacy of the present immunosuppression regimen for living donor liver transplantation.

  3. Pathological and clinical correlates of FOXP3+ cells in renal allografts during acute rejection.

    Veronese, F; Rotman, S; Smith, R N; Pelle, T D; Farrell, M L; Kawai, T; Benedict Cosimi, A; Colvin, R B

    2007-04-01

    The localization and significance of regulatory T cells (Treg) in allograft rejection is of considerable clinical and immunological interest. We analyzed 80 human renal transplant biopsies (including seven donor biopsies) with a double immunohistochemical marker for the Treg transcription factor FOXP3, combined with a second marker for CD4 or CD8. Quantitative FOXP3 cell counts were performed and analyzed for clinical and pathologic correlates. FOXP3(+) cells were present in the interstitium in acute cellular rejection (ACR) type I and II, at a greater density than in acute humoral rejection or CNI toxicity (p attraction or generation at that site. Considering only patients with ACR, a higher density of FOXP3(+) correlated with HLA class II match (p = 0.03), but paradoxically with worse graft survival. We conclude that infiltration of FOXP3(+) cells occurs in ACR to a greater degree than in humoral rejection, however, within the ACR group, no beneficial effect on outcome was evident. Tregs concentrate in tubules, probably contributing to FOXP3 mRNA in urine; the significance and pathogenesis of 'Treg tubulitis' remains to be determined. PMID:17286616

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

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

  5. Clinical and pathological analysis of acute rejection following orthotopic liver transplantation

    MA Yi; WANG Guo-dong; HE Xiao-shun; LI Jun-liang; ZHU Xiao-feng; HU Rui-de

    2009-01-01

    Background Acute rejection is one of the most important factors for prognosis following liver transplantation. With the use of potent immunosuppressants, acute rejection does not always present typical manifestations. Moreover, other complications often occur concomitantly after liver transplantation, which makes early diagnosis of acute rejection more difficult. Acute rejection is best diagnosed by liver biopsy. Differentiation of clinical manifestations and pathological features plays an important role in achieving individualized immunosuppressive treatment and prolonging long term survival of patients given orthotopic liver transplants.Methods From January 2004 to December 2006, 516 orthotopic liver transplantations were performed at the First Affiliated Hospital, Sun Yat-sen University. For patients who suffered acute rejection, clinical manifestations, histopathological features, diagnosis and anti-rejection treatment were summarized and analyzed. Results In 86 cases (16.7%), of the 516 recipients, 106 episodes of acute rejection occurred, which included 9 with histopathological borderline changes, 36 Banff Ⅰ rejections, 48 Banff Ⅱ and 13 Banff Ⅲ. Among these, 36 were cured by adjusting the dose of immunosuppressant and 65 were reversed by methylprednisolone pulse treatment. Five were methylprednisolone resistant, 3 of whom were given OKT3 treatment and 2 underwent liver retransplantation. Conclusions Due to potent immunosuppressive agents, acute rejection following an orthotopic liver transplantation lacks typical clinical manifestations and pathological features. Acute rejection is best diagnosed by liver biopsy. Designing rational individualized immunosuppressive regimen based on clinical and pathological features of acute rejection plays an important role in prolonging long term survival of patients.

  6. Outcome of Acute Graft Rejection Associated with Hemodynamic Compromise in Pediatric Heart Transplant Recipients

    Phelps, Christina M.; Tissot, Cecile; Buckvold, Shannon; Gralla, Jane; Ivy, D. Dunbar; Pietra, Biagio A.; Miyamoto, Shelley D.

    2010-01-01

    We sought to analyze the outcome of hemodynamically significant acute graft rejection in pediatric heart transplant recipients from a single-center experience. Acute graft rejection remains a major cause of morbidity and mortality for patients who undergo orthotopic heart transplantation and has been associated with the severity of the rejection episode. A retrospective review of all children experiencing a hemodynamically significant rejection episode after orthotopic heart transplantation w...

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

    2012-01-01

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

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

    Schiffer Lena

    2012-10-01

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

  9. 111-Indium-labelled platelets for diagnosis of acute kidney transplant rejection and monitoring of prostacyclin anti-rejection treatment

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

  10. 111-Indium-labelled platelets for diagnosis of acute kidney transplant rejection and monitoring of prostacyclin anti-rejection treatment

    Leithner, C.; Pohanka, E.; Schwarz, M. (Vienna Univ. (Austria). 2. Medizinische Klinik); Sinzinger, H. (Vienna Univ. (Austria). Abt. fuer Nuklearmedizin); Syre, G. (Vienna Univ. (Austria). Pathologisch-Anatomisches Inst.)

    1984-01-01

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

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

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

    2014-01-01

    Antibody mediated rejection (AMR) can significantly influence the results of orthotopic heart transplantation (OHT). However, AMR and cellular rejection (CR) coexistence is poorly described. Therefore we performed a prospective pilot study to assess AMR/CR concomitance in endomyocardial biopsies (EMBs) obtained electively in 27 OHT recipients (21 M/6 F, 45.4 ± 14.4 y/o). Biopsy samples were paraffin embedded and processed typically with hematoxylin/eosin staining to assess CR, and, if a suffi...

  12. HLA-G Polymorphism (rs16375) and Acute Rejection in Liver Transplant Recipients

    2014-01-01

    Background. HLA-G molecules exhibit immunomodulatory properties that can delay graft rejection. The 14 bp insertion/deletion polymorphism (INDEL) (rs16375) influences the stability of final HLA-G mRNA and its soluble isoforms. Objective. The present study aimed to investigate the possible association between this polymorphism and the incidence of acute rejection in Iranian liver transplant recipients. Methods. Different genotypes were evaluated by PCR. The patients who had acute rejection wit...

  13. Acute Rejection Associated with Donor-Specific Anti-MICA Antibody in a Highly Sensitized Pediatric Renal Transplant Recipient

    Narayan, Shoba; Tsai, Eileen W.; Zhang, Qiuheng; Wallace, William D.; Reed, Elaine F.; Ettenger, Robert B.

    2013-01-01

    Allograft rejection in HLA identical transplant recipients and in patients without detectable donor specific anti-HLA antibodies has lead to the identification of non-HLA antigens as targets of the alloimmune response. Major Histocompatibility Complex class I-related chain A (MICA) antigen has been recognized as an important non-HLA target in renal transplantation. Recent studies have shown that anti-MICA antibodies are associated with acute renal allograft rejection and failure. Current cross match procedures using donor lymphocytes fail to detect MICA antibodies. Transplant candidates are not routinely tested for pre-sensitization to MICA antigens nor are transplant donors typed for MICA alleles. Optimal classification and treatment of acute rejection associated with MICA antibody remains unknown. In this case report, we are the first to describe the clinical course and treatment of donor specific MICA antibody associated with both Banff type II A acute cellular rejection (ACR) and antibody mediated rejection (AMR) in a highly sensitized pediatric renal re-transplant recipient. This case also emphasizes the importance of pre-transplant screening for donor specific MICA antibody especially in highly sensitized renal transplant patients.. PMID:21199204

  14. A bedside technique for the diagnosis of acute rejection in renal transplants using 111-In platelets

    A total of 33 patients was studied with the aim of developing a bedside method for providing early diagnosis of acute rejection using 111-In labelled platelets. Platelet deposition was detected in all patients suffering acute rejection. A significant increase in kidney/aortic arch ratio, as measured by the portable bedside system, preceded the clinical diagnosis in 70% of patients. Using this system, it appeared possible not only to diagnose acute rejection at an earlier stage but also to predict irrecoverable transplant loss even in the presence of tubular necrosis. By labelling the platelets repeatedly for at least two weeks after transplantation, the period of highest risk for acute rejection and other complications. The gamma camera should still be employed in the event of markedly increased platelet deposition to differentiate between rejection and vascular complications

  15. SPECT- and PET-Based Approaches for Noninvasive Diagnosis of Acute Renal Allograft Rejection

    Helga Pawelski

    2014-01-01

    photon emission computed tomography (SPECT or positron emission tomography are promising tools for noninvasive diagnosis of acute allograft rejection (AR. Given the importance of renal transplantation and the limitation of available donors, detailed analysis of factors that affect transplant survival is important. Episodes of acute allograft rejection are a negative prognostic factor for long-term graft survival. Invasive core needle biopsies are still the “goldstandard” in rejection diagnostics. Nevertheless, they are cumbersome to the patient and carry the risk of significant graft injury. Notably, they cannot be performed on patients taking anticoagulant drugs. Therefore, a noninvasive tool assessing the whole organ for specific and fast detection of acute allograft rejection is desirable. We herein review SPECT- and PET-based approaches for noninvasive molecular imaging-based diagnostics of acute transplant rejection.

  16. Sonographic findings in borderline changes and subclinical acute renal allograft rejection

    Krejci, Karel [3rd Department of Internal Medicine and Nephrology, Faculty Hospital Olomouc, I.P. Pavlova 6, 775 20 Olomouc (Czech Republic)], E-mail: karel.krejci@fnol.cz; Zadrazil, Josef [3rd Department of Internal Medicine and Nephrology, Faculty Hospital Olomouc, I.P. Pavlova 6, 775 20 Olomouc (Czech Republic)], E-mail: josef.zadrazil@fnol.cz; Tichy, Tomas [Institute of Pathology, Faculty Hospital Olomouc, I.P. Pavlova 6, 775 20 Olomouc (Czech Republic)], E-mail: tomas.tichy@fnol.cz; Al-Jabry, Sadek [3rd Department of Internal Medicine and Nephrology, Faculty Hospital Olomouc, I.P. Pavlova 6, 775 20 Olomouc (Czech Republic)], E-mail: sadekj@seznam.cz; Horcicka, Vladko [3rd Department of Internal Medicine and Nephrology, Faculty Hospital Olomouc, I.P. Pavlova 6, 775 20 Olomouc (Czech Republic)], E-mail: vl.horcicka@fnol.cz; Strebl, Pavel [3rd Department of Internal Medicine and Nephrology, Faculty Hospital Olomouc, I.P. Pavlova 6, 775 20 Olomouc (Czech Republic)], E-mail: apolik@centrum.cz; Bachleda, Petr [2nd Surgical Department and Transplant Centrum, Faculty Hospital Olomouc, I.P. Pavlova 6, 775 20 Olomouc (Czech Republic)], E-mail: petr.bachleda@fnol.cz

    2009-08-15

    Purpose: A clinically manifested acute rejection is associated with graft dysfunction and with some ultrasound findings. The aim of our study was to determine the potential of ultrasound evaluation in the detection of subclinical acute rejective changes diagnosed in stable grafts by protocol biopsy. Methods: Gray-scale evaluation, color Doppler imaging (CDI) and power Doppler imaging (PDI) was performed before each of 184 protocol graft biopsies in 77 patients in the third week, third month and first year after transplantation. The group was divided into four subgroups-normal histological finding, borderline changes, subclinical acute rejection of IA grade, and a clinically manifested acute rejection of IA grade. The sonographic findings were compared with individual groups. Results: Detection of parenchymal edema using gray-scale imaging significantly differentiated borderline changes and subclinical acute rejection of IA grade from normal histological findings in the third week and in the third month (P = 0.013, P = 0.002 and P = 0.024, P < 0.001), respectively. A similar finding could be recorded in the latter group in the first year after transplantation (P = 0.024). The presence of edema and reduced peripheral parenchymal perfusion in PDI significantly more often indicated a clinically manifested acute IA rejection (P = 0.019, P = 0.004, P = 0.044). Parenchymal CDI hyperperfusion had a high specificity (89.5%) but a low sensitivity (60%) in the detection of the subclinical form of acute IA rejection. Conclusion: A composite gray-scale, PDI and CDI evaluation provide a significant differentiation of groups with borderline changes and subclinical acute rejection and groups with normal histological finding and clinically manifested acute rejection.

  17. The Value of Laboratory Diagnostics of Acute Renal Graft Rejection Compared to the Goldstandard Transplant Biopsy

    Fornara, P; Fischer, K; O. Rettkowski; Loertzer, H.; Wicht, A.; L. Kielwagen; Hamza, A.

    2006-01-01

    The main problem of organ transplantation is acute rejection and its therapy. Clinical symptoms (oliguria, hypertension, pain in the transplant, fever, weight gain) and laboratory chemical/histological findings are possible signs of a rejection after kidney transplantation. A suspicion for a rejection is firstly expressed by finding clinical signs. The laboratory chemistry and the histology prove this suspicion true or not. Deviate findings in laboratory chemistry and histology are possible. ...

  18. Impact of Acute Rejection on Kidney Allograft Outcomes in Recipients on Rapid Steroid Withdrawal

    Hamawi, K.; Mazur, M.J.; Mulligan, D. C.; Moss, A. A.; Y. Devarapalli; Chakkera, H.A.; Nijim, S.; R. L. Heilman; Williams, J. W.; Reddy, K.S.

    2011-01-01

    Background. Our aim was to study the impact of clinical acute rejection (CR) and subclinical rejection (SR) on outcomes in kidney transplant recipients treated with rapid steroid withdrawal (RSW). Methods. All patients who received a living or deceased donor kidney transplant and were treated with RSW were included. The primary outcome was death-censored graft survival. Biopsies with Banff borderline changes were included with the rejection groups. Results. 457 kidney transplant recipients tr...

  19. Renography and biopsy-verified acute rejection in renal allotransplanted patients receiving cyclosporin A

    Thomsen, H.S.; Nielsen, S.L.; Larsen, S.; Lokkegaard, H.

    1987-01-01

    Acute impairment of renal function caused by cyclosporin A can be hard to differentiate from acute rejection. Therefore, kidney function after cadaveric allograft transplantation was repeatedly determined by renography in 42 patients receiving either high dose cyclosporin A (32 patients) or azathioprine and prednisone (10 patients) until a graft biopsy showed either acute rejection or no rejection within the first 5 postoperative weeks. The graft function as judged from the renograms was significantly poorer when cyclosporin A was used than when azathioprine and prednisone were the immunosuppressants. In the azathioprine and prednisone group a biopsy showing acute rejection was always preceded by a deterioration in the renogram. In cyclosporin A treated patients a graft biopsy following an early deterioration in the renogram showed acute rejection in only 56% of the biopsies. It was not possible to identify a time course or a function level of the renogram that could predict rejection in these patients. It is concluded that graft biopsies should be used liberally to diagnose rejection during cyclosporin A treatment if surgical complications after transplantations have been ruled out. Radionuclide studies may offer an invaluable aid in determining a nonnephrotoxic initial dose of the drug.

  20. Renography and biopsy-verified acute rejection in renal allotransplanted patients receiving cyclosporin A

    Acute impairment of renal function caused by cyclosporin A can be hard to differentiate from acute rejection. Therefore, kidney function after cadaveric allograft transplantation was repeatedly determined by renography in 42 patients receiving either high dose cyclosporin A (32 patients) or azathioprine and prednisone (10 patients) until a graft biopsy showed either acute rejection or no rejection within the first 5 postoperative weeks. The graft function as judged from the renograms was significantly poorer when cyclosporin A was used than when azathioprine and prednisone were the immunosuppressants. In the azathioprine and prednisone group a biopsy showing acute rejection was always preceded by a deterioration in the renogram. In cyclosporin A treated patients a graft biopsy following an early deterioration in the renogram showed acute rejection in only 56% of the biopsies. It was not possible to identify a time course or a function level of the renogram that could predict rejection in these patients. It is concluded that graft biopsies should be used liberally to diagnose rejection during cyclosporin A treatment if surgical complications after transplantations have been ruled out. Radionuclide studies may offer an invaluable aid in determining a nonnephrotoxic initial dose of the drug. (orig.)

  1. Pretransplant thymic function predicts acute rejection in antithymocyte globulin-treated renal transplant recipients.

    Bamoulid, Jamal; Courivaud, Cécile; Crepin, Thomas; Carron, Clémence; Gaiffe, Emilie; Roubiou, Caroline; Laheurte, Caroline; Moulin, Bruno; Frimat, Luc; Rieu, Philippe; Mousson, Christiane; Durrbach, Antoine; Heng, Anne-Elisabeth; Rebibou, Jean-Michel; Saas, Philippe; Ducloux, Didier

    2016-05-01

    Lack of clear identification of patients at high risk of acute rejection hampers the ability to individualize immunosuppressive therapy. Here we studied whether thymic function may predict acute rejection in antithymocyte globulin (ATG)-treated renal transplant recipients in 482 patients prospectively studied during the first year post-transplant of which 86 patients experienced acute rejection. Only CD45RA(+)CD31(+)CD4(+) T cell (recent thymic emigrant [RTE]) frequency (RTE%) was marginally associated with acute rejection in the whole population. This T-cell subset accounts for 26% of CD4(+) T cells. Pretransplant RTE% was significantly associated with acute rejection in ATG-treated patients (hazard ratio, 1.04; 95% confidence interval, 1.01-1.08) for each increased percent in RTE/CD4(+) T cells), but not in anti-CD25 monoclonal (αCD25 mAb)-treated patients. Acute rejection was significantly more frequent in ATG-treated patients with high pretransplant RTE% (31.2% vs. 16.4%) or absolute number of RTE/mm(3) (31.7 vs. 16.1). This difference was not found in αCD25 monclonal antibody-treated patients. Highest values of both RTE% (>31%, hazard ratio, 2.50; 95% confidence interval, 1.09-5.74) and RTE/mm(3) (>200/mm(3), hazard ratio, 3.71; 95% confidence interval, 1.59-8.70) were predictive of acute rejection in ATG-treated patients but not in patients having received αCD25 monoclonal antibody). Results were confirmed in a retrospective cohort using T-cell receptor excision circle levels as a marker of thymic function. Thus, pretransplant thymic function predicts acute rejection in ATG-treated patients. PMID:27083287

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

    Kurian, S M; Williams, A N; Gelbart, T.; Campbell, D.; Mondala, T. S.; Head, S. R.; Horvath, S; Gaber, L; R. Thompson; Whisenant, T; Lin, W; Langfelder, P; Robison, E. H.; Schaffer, R. L.; Fisher, J S

    2014-01-01

    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 exce...

  3. Increased T cell glucose uptake reflects acute rejection in lung grafts

    Chen, Delphine L.; Wang, Xingan; Yamamoto, Sumiharu; Carpenter, Danielle; Engle, Jacquelyn T.; Li, Wenjun; Lin, Xue; Kreisel, Daniel; Krupnick, Alexander S.; Huang, Howard J.; Gelman, Andrew E.

    2013-01-01

    Although T cells are required for acute lung rejection, other graft-infiltrating cells such as neutrophils accumulate in allografts and are also high glucose utilizers. Positron emission tomography (PET) with the glucose probe [18F]fluorodeoxyglucose ([18F]FDG) has been employed to image solid organ acute rejection, but the sources of glucose utilization remain undefined. Using a mouse model of orthotopic lung transplantation, we analyzed glucose probe uptake in the graft...

  4. 19F MRI Detection of Acute Allograft Rejection with In Vivo Perfluorocarbon Labeling of Immune Cells

    Hitchens, T. Kevin; Ye, Qing; Eytan, Danielle F.; Janjic, Jelena M.; Ahrens, Eric T.; Ho, Chien

    2011-01-01

    Current diagnosis of organ rejection following transplantation relies on tissue biopsy, which is not ideal due to sampling limitations and risks associated with the invasive procedure. We have previously shown that cellular MRI of iron-oxide labeled immune-cell infiltration can provide a non-invasive measure of rejection status by detecting areas of hypointensity on T2*-weighted images. In the current study, we tested the feasibility of using a fluorine-based cellular tracer agent to detect m...

  5. Efficacy of rabbit anti-thymocyte globulin for steroid-resistant acute rejection after liver transplantation.

    Lee, Jae Geun; Lee, Juhan; Lee, Jung Jun; Song, Seung Hwan; Ju, Man Ki; Choi, Gi Hong; Kim, Myoung Soo; Choi, Jin Sub; Kim, Soon Il; Joo, Dong Jin

    2016-06-01

    Acute cellular rejection after liver transplantation (LT) can be treated with steroid pulse therapy, but there is no ideal treatment for steroid-resistant acute rejection (SRAR). We aimed to determine the feasibility and potential complications of rabbit anti-thymocyte globulin (rATG) application to treat SRAR in liver transplant recipients. We retrospectively reviewed medical records of 429 recipients who underwent LT at Severance Hospital between January 2010 and March 2015. We compared clinical features and graft survival between patients with steroid-sensitive acute rejection (SSAR; n = 23) and SRAR (n = 11). We also analyzed complications and changes in laboratory findings after 2.5 mg/kg rATG treatment in patients with SRAR for 6 to 10 days. There were no significant differences in gender, age, model for end-stage liver disease score, Child-Turcotte-Pugh score, or original liver diseases between patients with SSAR and SRAR, although deceased donors were more frequently associated with the SRAR group (P = 0.004). All SRAR patients responded positively to rATG treatment; after treatment, the patients' median AST levels decreased from 138 to 63 IU/L, and their median ALT levels dropped from 327 to 70 IU/L 1 day after rATG treatment (P = 0.022 and 0.017, respectively). Median aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels significantly decreased 1 month post-treatment (P = 0.038, 0.004, and 0.041, respectively). Median survival after LT was 23 months, and median survival after rATG was 22 months in patients with SRAR. Adverse effects included hepatitis C virus (HCV) reactivation, fungemia, and cytomegalovirus (CMV) infection. Nine SRAR patients survived with healthy liver function, 1 died from a traffic accident during follow-up, and 1 died from graft-versus-host disease and fungemia. Administration of rATG is an effective therapeutic option for SRAR with acceptable complications in liver transplant recipients

  6. P-31 MR spectroscopy of acute rejection in transplanted rat hearts

    To investigate the potential utility of P-31 NMR spectroscopy in the diagnosis of acute cardiac allograft rejection, the authors obtained high resolution in vitro spectra of perchloric acid extracts of freeze clamped transplanted rat hearts. These preliminary results suggest P-32 NMR spectroscopy may have utility in monitoring rejection in heart transplantation. In the acutely rejecting allografts they observed a marked increase in several resonances in the region downfield (to the left) from phosphocreatine (PCr) compared with the isografts. Specifically, the resonance of inorganic phosphate (Pi) which accounts for 55% - 65% of the total signal in the downfield region increased 1.85-fold. A fourfold increase was observed in the largest of three resonances present in the monophosphate region. Located at a chemical shift of 4.3 ppm, this resonance constituted 33% of the total signal in the downfield region. The PCr/B-ATP ratio decreased only slightly in the acutely rejecting allograft

  7. Doppler sonography in renal transplants; differential diagnosis of normal from acute rejection

    We undertook a combined retrospective and prospective analysis of duplex Doppler examinations performed over a perion of 10 months in order to assess the value of Doppler study(DS)in evaluating renal allograft dysfunction. A total of 110 DS on 82 transplant patients were performed including 79 normal transplants, 29 acute rejections and 2 acute tubular necrosis(ATN). Resistive Index(RI) in 79 normal transplants ranged from 0.44 to 0.7 (Mean;0.59+0.07) in the arcuate artery, and from 0.45 to 0.75(mean;0.61+0.08) in the interlobar artery. RI in 29 cases of acute rejection ranged from 0.61 to 1.0(mean ;0.77+0.10)in the interlobar artery. In ATNRI ranged from 0.59 to 0.63(mean 0.62) in the arcuate artery, and from 0.59 to 0.62(mean 0.61) in the interlobar artery. The RI in acute rejection is significantly higher than that of the normal transplants (p<0.001). With a resistive index greater than 0.8, 100% positive predictive value was obtained for the diagnosis of acute rejection. The value less than 0.7 was unlikely to suggest acute rejection(negative predictive value 92%)

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

    Krustrup, Dorrit; Iversen, Martin; Martinussen, Torben;

    2014-01-01

    Background: Regulatory T lymphocytes (Tregs) play an important role in acute rejection after lung transplantation. However, the importance of the time elapsed after transplantation on the Treg response requires further investigation.We aim to evaluate the change over time in the frequency of Tregs...... in lung allograft biopsies and to assess how Tregs relate to simultaneous and subsequent acute cellular rejection. Materials and methods: A total of 258 biopsy samples obtained 0.5, 1, 3, 12 and 24. months after transplantation from 58 consecutive lung transplant patients were included. The biopsies...... were scored for acute rejection according to the ISHLT criteria (A0-A4) and immunohistochemically stained with antibodies against FoxP3. Results: There was a tendency for a decrease in the number of Tregs/mm2 with time. However, the previous levels of Tregs/mm2 did not have any significant effect on...

  9. Antibody-Mediated Lung Transplant Rejection

    Hachem, Ramsey

    2012-01-01

    Antibody-mediated rejection after lung transplantation remains enigmatic. However, emerging evidence over the past several years suggests that humoral immunity plays an important role in allograft rejection. Indeed, the development of donor-specific antibodies after transplantation has been identified as an independent risk factor for acute cellular rejection and bronchiolitis obliterans syndrome. Furthermore, cases of acute antibody-mediated rejection resulting in severe allograft dysfunctio...

  10. Graft irradiation in the treatment of acute rejection of renal transplants: a randomized study

    A randomized study of graft irradiation in the treatment of acute rejection of renal transplants was conducted from 1978 to 1981. Patients developing clinical signs of an acute graft rejection received customary antirejection treatment in the form of intravenous administration of high-dose (1 gm per day) of methylprednisolone. They were at the same time randomized to either receive therapeutic irradiation (175 rad every other day to a total of 525 rad) or sham irradiation. Neither the patient nor the Transplant Service surgeons knew at any time whether the radiation treatment had been given. Eighty-three rejection episodes occurring in 64 grafts were entered into the study. Acute rejection was reversed in 84.5% of grafts in the control and 75% in the treated group. The incidence of recurrent rejection was higher in the treated group (66 vs. 46%) and graft survival was lower (22% vs. 54%). The study failed to demonstrate a beneficial effect of graft irradiation in the treatment of acute renal allograft rejection, when used in conjunction with high dose steriods

  11. Graft irradiation in the treatment of acute rejection of renal transplants: a randomized study

    Pilepich, M.V.; Anderson, C.B.; Etheredge, E.E.; Sicard, G.A.; Melzer, J.S.; Blum, J.

    1982-05-01

    A randomized study of graft irradiation in the treatment of acute rejection of renal transplants was conducted from 1978 to 1981. Patients developing clinical signs of an acute graft rejection received customary antirejection treatment in the form of intravenous administration of high-dose (1 gm per day) of methylprednisolone. They were at the same time randomized to either receive therapeutic irradiation (175 rad every other day to a total of 525 rad) or sham irradiation. Neither the patient nor the Transplant Service surgeons knew at any time whether the radiation treatment had been given. Eighty-three rejection episodes occurring in 64 grafts were entered into the study. Acute rejection was reversed in 84.5% of grafts in the control and 75% in the treated group. The incidence of recurrent rejection was higher in the treated group (66 vs. 46%) and graft survival was lower (22% vs. 54%). The study failed to demonstrate a beneficial effect of graft irradiation in the treatment of acute renal allograft rejection, when used in conjunction with high dose steriods.

  12. Diagnosis and Treatment of Pancreas Rejection

    Redfield, R. R.; Kaufman, D. B.; Odorico, J. S.

    2015-01-01

    Despite significant improvement in pancreas allograft survival, rejection of the pancreas remains a major clinical problem. In addition to cellular rejection of the pancreas, antibody-mediated rejection of the pancreas is now a well-described entity. The 2011 Banff update established comprehensive guidelines for the diagnosis of acute and chronic AMR. The pancreas biopsy is critical in order to accurately diagnose and treat pancreas rejection. Other modes of monitoring pancreas rejection we f...

  13. Maximum entropy, fractal dimension and lacunarity in quantification of cellular rejection in myocardial biopsy of patients submitted to heart transplantation

    This paper presents a method for the quantification of cellular rejection in endomyocardial biopsies of patients submitted to heart transplant. The model is based on automatic multilevel thresholding, which employs histogram quantification techniques, histogram slope percentage analysis and the calculation of maximum entropy. The structures were quantified with the aid of the multi-scale fractal dimension and lacunarity for the identification of behavior patterns in myocardial cellular rejection in order to determine the most adequate treatment for each case.

  14. Maximum entropy, fractal dimension and lacunarity in quantification of cellular rejection in myocardial biopsy of patients submitted to heart transplantation

    Neves, L. A.; Oliveira, F. R.; Peres, F. A.; Moreira, R. D.; Moriel, A. R.; de Godoy, M. F.; Murta Junior, L. O.

    2011-03-01

    This paper presents a method for the quantification of cellular rejection in endomyocardial biopsies of patients submitted to heart transplant. The model is based on automatic multilevel thresholding, which employs histogram quantification techniques, histogram slope percentage analysis and the calculation of maximum entropy. The structures were quantified with the aid of the multi-scale fractal dimension and lacunarity for the identification of behavior patterns in myocardial cellular rejection in order to determine the most adequate treatment for each case.

  15. Use of surface-enhanced Raman scattering as a prognostic indicator of acute kidney transplant rejection

    Chi, Jingmao; Zaw, Thet; Cardona, Iliana; Hosnain, Mujtaba; Garg, Neha; Lefkowitz, Heather R.; Tolias, Peter; Du, Henry

    2015-01-01

    We report an early, noninvasive and rapid prognostic method of predicting potential acute kidney dysfunction using surface-enhanced Raman scattering (SERS). Our analysis was performed on urine samples collected prospectively from 58 kidney transplant patients using a He-Ne laser (632.8 nm) as the excitation source. All abnormal kidney function episodes (three acute rejections and two acute kidney failures that were eventually diagnosed independently by clinical biopsy) consistently exhibited ...

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

    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. PMID:26924055

  17. Insights from Computational Modeling in Inflammation and Acute Rejection in Limb Transplantation

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

    2014-01-01

    Acute skin rejection in vascularized composite allotransplantation (VCA) is the major obstacle for wider adoption in clinical practice. This study utilized computational modeling to identify biomarkers for diagnosis and targets for treatment of skin rejection. Protein levels of 14 inflammatory mediators in skin and muscle biopsies from syngeneic grafts [n = 10], allogeneic transplants without immunosuppression [n = 10] and allografts treated with tacrolimus [n = 10] were assessed by multiplex...

  18. Successful therapy with rituximab of refractory acute humoral renal transplant rejection: a case report.

    Celik, A; Saglam, F; Cavdar, C; Sifil, A; Atila, K; Sarioglu, S; Bora, S; Gulay, H; Camsari, T

    2008-01-01

    Acute humoral rejection (AHR) is generally less responsive to conventional anti-rejection treatment with consequent allograft losses. Therapeutic options include antilymphocyte antibody (ATG), intravenous immunglobulin (IVIG), plasmapheresis, or immunoadsorption with protein A together with intensification of immunsuppression with a tacrolimus/mycophenolate mofetil combination. This report describes a transplant recipient who responded to rituximab therapy as treatment for steroid-, ATG-, IVIG-, and plasmapheresis-resistant AHR. PMID:18261611

  19. Antimyosin imaging in acute myocardial infarction and cardiac transplant rejection

    Antimyosin imaging both diagnosed and quantitated heterotopic cardiac transplant rejection in a small number of dogs with either recent or remote transplantation. The authors describe study in humans which showed 80% diagnostic accuracy of planar antimyosin imaging in patients with a wide range of times posttransplantation. A larger multicenter study including SPECT imaging will either confirm or extend these preliminary findings. Multiple injections of antimyosin will probably be safe if HAMA levels are followed

  20. Acute renal allograft rejection after immune checkpoint inhibitor therapy for metastatic melanoma.

    Spain, L; Higgins, R; Gopalakrishnan, K; Turajlic, S; Gore, M; Larkin, J

    2016-06-01

    Immune checkpoint inhibitors such as ipilimumab and nivolumab improve survival in patients with advanced melanoma and are increasingly available to clinicians for use in the clinic. Their safety in organ transplant recipients is not well defined but published case reports describing treatment with ipilimumab have not been complicated by graft rejection. No cases of anti-programmed cell death protein 1 administration are reported in this group. We describe a case of acute graft rejection in a kidney transplant recipient after treatment with nivolumab, after progression on ipilimumab. Potential factors increasing the risk of graft rejection in this case are discussed, in particular the contribution of nivolumab. PMID:26951628

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

    Priscila Cilene León Bueno de Camargo

    2014-08-01

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

  2. Outcome of Acute Graft Rejection Associated with Hemodynamic Compromise in Pediatric Heart Transplant Recipients

    Tissot, Cecile; Buckvold, Shannon; Gralla, Jane; Ivy, D. Dunbar; Pietra, Biagio A.; Miyamoto, Shelley D.

    2011-01-01

    We sought to analyze the outcome of hemodynamically significant acute graft rejection in pediatric heart transplant recipients from a single-center experience. Acute graft rejection remains a major cause of morbidity and mortality for patients who undergo orthotopic heart transplantation and has been associated with the severity of the rejection episode. A retrospective review of all children experiencing a hemodynamically significant rejection episode after orthotopic heart transplantation was performed. Fifty-three patients with 54 grafts had 70 rejection episodes requiring intravenous inotropic support. Forty-one percent of these patients required high-dose inotropic support, with the remaining 59% of patients requiring less inotropic support. Overall graft survival to hospital discharge was 41% for patients in the high-dose group compared to 94% in the low-dose group. Six-month graft survival in patients who required high-dose inotropes remained at 41% compared to 44% in the low-dose group. Hemodynamically significant acute graft rejection in pediatric heart transplant recipients is a devastating problem with poor short- and long-term outcomes. Survival to hospital discharge is dismal in patients who require high-dose inotropic support. In contrast, survival to discharge is quite good in patients who require only low-dose inotropic support; however, six-month graft survival in this group is low secondary to a high incidence of graft failure related to worsening or aggressive transplant coronary artery disease. PMID:20963408

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

    Li Li

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

  4. Doppler Ultrasound in Chronic Renal Allograft Dysfunction : Can Acute Rejection be Predicted

    To investigate Doppler sonographic findings valuable for detecting acute rejection in transplanted kidney with chronic allograft dysfunction. Forty-three renal allografts who underwent renal Doppler sonography and renal biopsy due to chronic allograft dysfunction were included. According to histopathologic findings, patients were classified into 2 groups: chronic component only(group 1, n=30) and acute rejection with or without chronic component 2 groups were performed. No definite difference in radio of renal size, cortical echogenecity, corticomedullary differentiation was noted between group 1 and group 2.Resistive index was 0.61±0.18 in group 1 and 0.64±0.22 in group 2, which showed no statistically significant difference. Characteristic Doppler sonographic findings suggesting acute rejection in cases of chronic allograft dysfunction were not found inauther's study. Therefore, minimal invasive renal biopsy to determine histopathologic status of transplanted kidney is essential in evaluation of the chronic allograft dysfunction

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

    2013-01-01

    Objective Lung transplant volume has been increasing. However, inaccurate and uncertain diagnosis for lung transplant rejection hurdles long-term outcome due to, in part, interobserver variability in rejection grading. Therefore, a more reliable method to facilitate diagnosing and grading rejection is warranted. Method Rat lung grafts were harvested on day 3, 7, 14 and 28 post transplant for histological and immunohistochemical assessment. No immunosuppressive treatment was administered. We explored the value of interstitial T lymphocytes quantification by immunohistochemistry and compared the role of T cell immunohistochemistry with H&E staining in diagnosing and grading lung transplant rejection. Results Typical acute rejection from grade A1 to A4 was found. Rejection severity was heterogeneously distributed in one-third transplanted lungs (14/40): lesions in apex and center were more augmented than in the base and periphery of the grafts, respectively. Immunohistochemistry showed profound difference in T lymphocyte infiltration among grade A1 to A4 rejections. The coincidence rate of H&E and immunohistochemistry was 77.5%. The amount of interstitial T lymphocyte infiltration increased gradually with the upgrading of rejection. The statistical analysis demonstrated that the difference in the amount of interstitial T lymphocytes between grade A2 and A3 was not obvious. However, T lymphocytes in lung tissue of grade A4 were significantly more abundant than in other grades. Conclusions Rejection severity was heterogeneously distributed within lung grafts. Immunohistochemistry improves the sensitivity and specificity of rejection diagnosis, and interstitial T lymphocyte quantitation has potential value in diagnosing and monitoring lung allograft rejection. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1536075282108217. PMID:24330571

  6. HLA-G Polymorphism (rs16375) and Acute Rejection in Liver Transplant Recipients

    Azarpira, Negar; Aghdaie, Mahdokht H.; Kazemi, Kurosh; Darai, Masumeh

    2014-01-01

    Background. HLA-G molecules exhibit immunomodulatory properties that can delay graft rejection. The 14 bp insertion/deletion polymorphism (INDEL) (rs16375) influences the stability of final HLA-G mRNA and its soluble isoforms. Objective. The present study aimed to investigate the possible association between this polymorphism and the incidence of acute rejection in Iranian liver transplant recipients. Methods. Different genotypes were evaluated by PCR. The patients who had acute rejection within 6 months after transplantation were classified as acute rejection (AR) group, while others were considered as nonacute rejection (NAR) group. Results. Among the recipients, 21 patients (21%) had at least one episode of AR, while the other 79 patients (79%) had normal liver function. No significant differences were found between the two groups regarding sex, MELD score, and primary liver disease. Also, no difference was observed concerning rs16375 genotype and allele frequency (P = 0.44, OR: 0.69; CI: 0.21–2.10). Conclusion. The study results revealed no significant difference between the AR and the NAR groups regarding the 14 bp INDEL genotypes and alleles. Further studies are recommended to be conducted on other polymorphic sites as well as monitoring of serum HLA-G concentration in order to ascertain the potential implications of this marker in our population. PMID:24591768

  7. Efficacy of mycofenolate mofetil for steroid-resistant acute rejection after living donor liver transplantation

    Nobuhisa Akamatsu; Yasuhiko Sugawara; Sumihito Tamura; Yuichi Matsui; Junichi Kaneko; Masatoshi Makuuchi

    2006-01-01

    AIM: To discuss the use of mycophenolate mofetil (MMF) as an immunosuppressant in steroid resistant rejection after liver transplantation. METHODS: The clinical records of 260 adult patients who underwent living donor liver transplantation (LDLT) were reviewed. Tacrolimus and methylprednisolone were used for primary immunosuppression. Acute rejection was first treated with steroids. When steroid resistance occurred, the patient was treated with a combination of steroids and MMF. Anti-T-cell monoclonal antibody was administered to patients who were not responsive to steroids in combination with MMF.RESULTS: A total of 90 (35%) patients developed acute rejection. The median interval time from transplantation to the first episode was 15 d. Fifty-four patients were steroid resistant. Forty-four patients were treated with MMF and the remaining 10 required anti-T-cell monoclonal antibody treatment. Progression to chronic rejection was observed in one patient. Bone marrow suppression and gastrointestinal symptoms were the most common side effects associated with MMF use. There was no significant increase in opportunistic infections. CONCLUSION: Our results demonstrate that MMF is a potent and safe immunosuppressive agent for rescue therapy in patients with acute rejection after LDLT.

  8. Perfusatory recovery of the grafted lung during convalescence from acute rejection.

    Yamamoto, H; Okada, M; Tobe, S; Tsuji, F; Ohbo, H; Yamashita, C

    2000-01-01

    The aim of this study was to evaluate whether or not perfusatory recovery of the grafted lung occurs is the early stage of convalesce from acute rejection following a single lung transplantation. Eight adult mongrel dogs underwent an allotransplantation of the left lung with treatment of 10 mg/kg cyclosporine and 4 mg/kg azathioprine. Doppler flow probes were placed to the ascending aorta and the left pulmonary artery. Immunosuppressant therapy was discontinued to induce rejection after postoperative day 14. When the left pulmonary artery flow rate (l-PAFR) decreased to less than 20%, methylprednisolone (20 mg/kg) was administered for 3 days along with a resumption of cyclosporine and azathioprine. Pulmonary circulation and chest roentgenograms were evaluated every day through the rejection episode. An open lung biopsy was also performed in each dog to obtain specimens of the grafts and native lungs for histologic examination. When l-PAFR decreased to less than 20%, mild acute rejection was found in all dogs. l-PAFR increased significantly on the third day after methylprednisolone treatment. Thereafter, a histologic examination revealed minimal acute rejection in one dog and no abnormality in seven dogs. The perfusatory recovery of the grafted lung was thought to reflect the histological change in the course of convalescence. PMID:10664339

  9. GATED SPECT IN PATIENTS WITH BIOPSY-NEGATIVE CARDIAC TRANSPLANT REJECTION

    E. N. Ostroumov; V. M. Zakharevich; E. D. Kotina; N. N. Mojeiko; A. G. Kupriyanova; E. I. Ryaboshtanova; B. N. Morozov; N.Z. Meboniya; Mironov, S. V.; A. Y. Kormer; I. M. Ilynsky; L. V. Beletskaya; E. N. Kazakov

    2009-01-01

    Humoral rejection of the cardiac allograft is still a challenging problem associated with high incidence of graft loss and patient mortality. These episodes of rejection are often more severe, and more difficult to treat, than classical acute cellular rejection. Hemodynamic compromise, in the absence of acute cellular rejection, called biopsy-negative rejection occurs in 10 to 20% of cardiac allograft recipients. The assessment of hemodynamic compromise can provide functional data in transpla...

  10. Blockade of 4-1BB/4-1BB ligand interactions prevents acute rejection in rat liver transplantation

    QIN Lei; GUAN Hong-geng; ZHOU Xiao-jun; YIN Jun; LAN Jing; QIAN Hai-xin

    2010-01-01

    Background Blocking the 4-1BB/4-1BB ligand (4-1BBL) signal may modulate the secretion of Th1/Th2 cytokines and prolong the survival of the grafts, which play a key role in organ transplantation tolerance. The aim of this study was to investigate the role of blockade of the 4-1BB/4-1BBL co-stimulatory pathway with 4-1 BBL monoclonal antibody (mAB) in acute rejection of rat orthotopic liver transplantation. Methods The orthotopic liver transplantation model was set up, while male Lewis rats were used as liver donors and Brown-Norway rats as recipients. The recipient rats were intravenously injected with anti 4-1BBL mAB or isotype control antibody. Groups were monitored for graft survival after transplantation. Plasma chemistry, including aspartate transaminase (AST), alanine aminotransferase (ALT), and bilirubin (BIL), was assayed. The concentrations of interleukin (IL)-2, IL-10 and interferon (IFN)- γ in plasma were also measured by enzyme-linked immunosorbent assay. Allograft histology images were collected under light microscope and electron microscope. Results Isotype antibody treated recipients exhibited elevated plasma levels of liver injury markers including AST, ALT and BIL, progressive portal and venous inflammation and cellular infiltration of the liver allografts, and a mean graft survival time (MST) of 10.9 days. Administration of anti 4-1 BBL mAB resulted in a decrease in plasma levels of liver injury markers and the concentrations of IL-2, IL-10 and IFN-γ. The histological grade of rejection on day 7 decreased and MST (17.3 days) increased substantially.Conclusions These results demonstrate that attenuation of acute rejection follows the blockade of the 4-1BB/4-1BBL co-stimulatory pathway with 4-1BBL monoclonal antibody and strongly suggest it is a promising strategy to prevent progression of graft rejection by suppressing T cell-mediated immunity.

  11. Harmful Effect of Anti-Class II Antibodies in Kidney Transplant Patients who Experienced an Acute Rejection Episode

    Berthou, F.; Absi, L.; Mariat, C; Alamartine, E.; M. Phayphet

    2006-01-01

    The presence of anti-lymphocytes antibodies is associated with the occurrence of acute rejection after kidney transplantation but few is known on their role after the rejection episode. We conducted a retrospective study in kidney transplant recipients who experienced a biopsy proven acute rejection episode to analyse the influence of anti-lymphocytes antibodies on clinical outcome. Anti-lymphocytes antibodies were detected before and after transplantation and characterized for isotype, class...

  12. Variation of T cell subset during acute rejection after liver transplantation in rhesus monkeys

    Ran Jiang-hua; Liu Jing; Zhang Xi-bing; Zhang Sheng-ning; Wu Shu-yuan; Li Lai-bang; Li Wang; Li Li

    2014-01-01

    Abstract BACKGROUND: Looking for the early diagnosis of acute rejection indicators after liver transplantation can assess the risk after liver transplantation quickly and effectively, and T lymphocytes play the significant role in acute rejection. OBJECTIVE:To observe the relationship between acute rejection and variation of expression of T cel subset in blood after liver transplantation in rhesus monkey. METHODS: The sixteen liver transplant models in rhesus monkey which were constructed successfuly by the method of “double-cuff and one support tube” were divided into two groups randomly: experiment group (no treated by immunosuppressant in perioperative period) and control group (treated by immunosuppressant in perioperative period). Then the blood specimen and liver tissue respectively were colected at 6, 12, 24 and 72 hours after operation. The levels of alanine transferase, aspartate aminotransferase, and total bilirubin were detected with the fuly automatic biochemical analyser. The levels of CD4+/CD8+were tested by flow cytometry. The liver tissue in rhesus monkey after liver transplantation was detected by hematoxylin-eosin staining. The degree of acute rejection was evaluated by Banff Score System. RESULTS AND CONCLUSION: Acute rejection appeared in the experiment group at 12, 24, and 72 hours after liver transplantation. Levels of alanine transferase, aspartate aminotransferase, and total bilirubin were significantly higher in the experimental group than in the control group at 24 and 72 hours after transplantation (P < 0.05). The expression of CD4+/CD8+of the experiment group and control group began to rise at 6 hours after surgery, but the experiment group increased the most obvious. CD4+/CD8+ expression was significantly greater in the experimental group than in the control group at 24 and 72 hours after transplantation (P < 0.05). Morphological pathology was severer, and Banff score was higher in the experiment group than in the control group at

  13. Use of surface-enhanced Raman scattering as a prognostic indicator of acute kidney transplant rejection

    Chi, Jingmao; Zaw, Thet; Cardona, Iliana; Hosnain, Mujtaba; Garg, Neha; Lefkowitz, Heather R.; Tolias, Peter; Du, Henry

    2015-01-01

    We report an early, noninvasive and rapid prognostic method of predicting potential acute kidney dysfunction using surface-enhanced Raman scattering (SERS). Our analysis was performed on urine samples collected prospectively from 58 kidney transplant patients using a He-Ne laser (632.8 nm) as the excitation source. All abnormal kidney function episodes (three acute rejections and two acute kidney failures that were eventually diagnosed independently by clinical biopsy) consistently exhibited unique SERS spectral features in just one day following the transplant surgery. These results suggested that SERS analysis provides an early and more specific indication to kidney function than the clinically used biomarker, serum creatinine (sCr). PMID:25798301

  14. Lymphotactin: a key regulator of lymphocyte trafficking during acute graft rejection.

    Wang, J D; Nonomura, N; Takahara, S; Li, B S; Azuma, H; Ichimaru, N; Kokado, Y; Matsumiya, K; Miki, T; Suzuki, S; Okuyama, A

    1998-09-01

    The attraction of leucocytes to allografts is essential for rejection. The process is controlled by chemokines. In order to clarify the role of lymphotactin (a cytokine that represents a novel branch of the chemokine superfamily) in regulating leucocyte trafficking during graft rejection, we used rat renal transplantation models to examine its gene expression and the distribution of lymphotactin-expressing cells in renal grafts. Lymphotactin mRNA was upregulated strongly in acutely rejecting renal allografts. The mRNA was undetectable in isografts, chronically rejecting renal allografts or normal kidney. Once lymphotactin was expressed, large numbers of infiltrating lymphocytes were seen. Moreover extended studies demonstrated that in cultured rat spleen cells the expression of lymphotactin mRNA was markedly induced by phytohaemagglutinin (PHA) or phorbol myristate acetate (PMA), and such induction was inhibited by the immunosuppressive drugs FK506 and cyclosporin. Collectively, these observations provide new evidence demonstrating that lymphotactin is a key regulator of lymphocyte motility and adhesiveness during acute allograft rejection. FK506 and cyclosporin inhibition of lymphotactin expression is likely to represent an important molecular mechanism of the action of the drugs. PMID:9767457

  15. Pulmonary circulatory parameters as indices for the early detection of acute rejection after single lung transplantation.

    Yamamoto, H; Okada, M; Tobe, S; Tsuji, F; Ohbo, H; Nakamura, H; Yamashita, C

    1998-01-01

    We investigated the relationship between the changes in the pulmonary blood flow and histology during acute rejection following single lung transplantation. In single lung transplantation using adult mongrel dogs, immunosuppression with cyclosporine and azathioprine was discontinued after postoperative day 14 to induce rejection. Doppler flow probes were placed adjacent to the ascending aorta and the left pulmonary artery to measure the blood flow on a daily basis. In addition, chest roentgenograms were also examined daily. The pulmonary pressure was measured using a Swan-Ganz catheter prior to and following the induction of rejection. Open lung biopsies were performed when the left pulmonary artery flow decreased to half of the prerejection value. The pulmonary artery flow decreased to 14.3% of the aortic flow 5 days after the discontinuation of immunosuppression. The graft pulmonary vascular resistance increased significantly compared to the prerejection values (P < 0.001). This was not accompanied by any abnormalities on chest roentgenography. The histology was consistent, with marked perivascular lymphocytic infiltration with little alveolar or interstitial changes. During rejection, the increased pulmonary vascular resistance in the graft was probably the result of perivascular inflammatory cell infiltration, which was seen prior to changes on chest roentgenography. Changes in the left pulmonary artery flow and histology thus appear to be closely correlated in the early stages of acute rejection. PMID:9744398

  16. Acute or chronic transplant rejection - high resolution CT of the chest in lung transplant recipients

    Purpose: Aim of the study was to evaluate the postoperative changes in patients with single (SLTX) or double lung transplantation (DLTX) with HRCT and to correlate those findings with the clinical diagnosis. Material and methods: 29 patients with SLTX (n = 14) or DLTX (n = 15) were observed for more than 6 years after transplantation by HRCT (n = 82). CT examinations were performed in inspiration and expiration (n = 70) with a slice thickness of 1 mm and a feed of 10 mm. The image material was evaluated by 2 experienced radiologists in consensus. Criteria for acute rejection at HRCT were: ground glass opacities and focal air trapping in expiration. Criteria for chronic transplant rejection were: bronchial dilatation, bronchial wall thickening and thickening of interlobar septae. The clinical evaluation consisted of laboratory tests, lung function tests, and bronchoscopy including bronchial lavage in special cases. Results: 20/29 patients are still alive (mean 21 months). 5/9 patients died because of chronic transplantant rejection, 1 patient suffered from a non-Hodgkin's lymphoma localised at the right hilus. Severe threatening pneumonia occurred in 13 cases. 10/29 patients showed symptoms of acute rejection. Expiratory HRCT found a focal air trapping in all cases and extended ground glass opacities in 11/14 cases. Also a bronchial dilatation was observed in more than 50% (9/14). 12/29 patients suffered from chronic transplant rejection. HRCT showed bronchial dilatation in 26/27 investigations and severe ground glass opacities in 21/27 investigations. Thickening of the interlobal septa as well as centrilobular opacities were found in more than 50% of the examinations. Conclusion: High resolution CT of the chest in patients after lung transplantation is able to show numerous pathological alterations. Without clinical information a confident differentiation in acute or chronic transplant rejection or pneumonia can be difficult or impossible. (orig.)

  17. Haptoglobin activates innate immunity to enhance acute transplant rejection in mice

    Shen, Hua; Song, Yang; Colangelo, Christopher M.; Wu, Terence; Bruce, Can; Scabia, Gaia; Galan, Anjela; Maffei, Margherita; Goldstein, Daniel R.

    2011-01-01

    Immune tolerance to transplanted organs is impaired when the innate immune system is activated in response to the tissue necrosis that occurs during harvesting and implantation procedures. A key molecule in this immune pathway is the intracellular TLR signal adaptor known as myeloid differentiation primary response gene 88 (MyD88). After transplantation, MyD88 induces DC maturation as well as the production of inflammatory mediators, such as IL-6 and TNF-α. However, upstream activators of MyD88 function in response to transplantation have not been identified. Here, we show that haptoglobin, an acute phase protein, is an initiator of this MyD88-dependent inflammatory process in a mouse model of skin transplantation. Necrotic lysates from transplanted skin elicited higher inflammatory responses in DCs than did nontransplanted lysates, suggesting DC-mediated responses are triggered by factors released during transplantation. Analysis of transplanted lysates identified haptoglobin as one of the proteins upregulated during transplantation. Expression of donor haptoglobin enhanced the onset of acute skin transplant rejection, whereas haptoglobin-deficient skin grafts showed delayed acute rejection and antidonor T cell priming in a MyD88-dependent graft rejection model. Thus, our results show that haptoglobin release following skin necrosis contributes to accelerated transplant rejection, with potential implications for the development of localized immunosuppressive therapies. PMID:22156194

  18. Incidence and Severity of Acute Allograft Rejection in Liver Transplant Recipients Treated With Alfa lnterferon

    Jain, Ashokkumar; Demetris, Anthony J.; Manez, Rafael; Tsamanadas, Athanassisos C.; Thiel, David; Rakela, Jorge; Starzl, Thomas E.; Fung, John J.

    1998-01-01

    Interferon alfa-2b (IFN-α) therapy has been shown to be effective in the treatment of viral hepatitis B (HBV) or viral hepatitis C (HCV) in patients who did not undergo transplantation. However, in allograft recipients, treatment with IFN-α often leads to allograft rejection. The aim of the present study was to determine if IFN-α therapy increases the incidence or severity of acute rejection in human liver allograft recipients. One hundred five orthotopic liver transplant (OLT) recipients wit...

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

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

  20. Renal and urinary levels of endothelial protein C receptor correlate with acute renal allograft rejection.

    Lionel Lattenist

    Full Text Available The Endothelial Protein C Receptor (EPCR is expressed on leukocytes, on endothelium of large blood vessels and to a lesser extent on capillaries. Membrane bound EPCR plays an important role in the activation of protein C which has anticoagulant, anti-inflammatory and cytoprotective effects. After cleavage by a protease EPCR is also found as a soluble protein. Acute rejection of kidney allografts can be divided in T-cell-mediated rejection (TCMR and antibody-mediated (ABMR rejection. The latter is characterized by strong activation of coagulation. Currently no reliable non-invasive biomarkers are available to monitor rejection. Renal biopsies were available from 81 renal transplant patients (33 without rejection, 26 TCMR and 22 ABMR, we had access to mRNA material, matched plasma and urine samples for a portion of this cohort. Renal EPCR expression was assessed by RT-PCR and immunostaining. Plasma and urine sEPCR levels were measured by ELISA. ABMR patients showed higher levels of EPCR mRNA than TCMR patients. EPCR expression on glomeruli was significantly elevated in ABMR patients than in TCMR or control patients. In the peritubular capillaries EPCR expression was higher in ABMR patients than in control patients. EPCR expression was higher in tubules and arteries of rejection patients than in control patients. Plasma sEPCR levels did not differ. Urine sEPCR levels were more elevated in the ABMR group than in patients with TCMR or without rejection. ROC analysis demonstrated that urinary sEPCR is appropriate to discriminate between ABMR patients and TCMR or control patients. We conclude that urinary sEPCR could be a novel non-invasive biomarker of antibody mediated rejection in renal transplantation.

  1. Renal blood flow after transplantation: Effects of acute tubular necrosis, rejection, and cyclosporine toxicity

    The authors incorporated their recently developed radionuclide first pass-technique for the quantitative measurement of renal transplant perfusion into routine DTPA imaging. Using this technique they investigated the effects of acute tubular necrosis (ATN), rejection, and cyclosporing toxicity on renal blood flow in a series of 80 studies in 35 patients, with independent evaluation of renal function. Transplant flow values were as follows: normal functioning, 439 mL/min +-83; ATN 248 mL/min +-63; rejection, 128 mL/min +-58; cyclosporing toxicity, 284 mL/min +-97; (normal flow in nontransplanted kidneys, approximately 550 mL/min). Differences between normal functioning, ATN, and rejection were significant (P < .05). Interestingly, immediate postsurgical hyperemia frequently occurred, with flow values sometimes exceeding 700 mL/min

  2. Infusion of nonmyeloablative bone marrow alleviates acute rejection reaction in liver allotransplantation

    XIE Hai-yang; HUANG Dong-sheng; JIA Chang-ku; ZHENG Shu-sen

    2005-01-01

    Objective: To study the effect and implication of nonmyeloablative donor specific bone marrow (DSBM) infusion on the immunoreaction of liver allotransplantation. Methods: Orthotopic liver transplantation model was used in this study. Groups were set as follows: Group Ⅰ, syngeneic control (Wistar-to-Wistar); Group Ⅱ, acute rejection (SD-to-Wistar); Group Ⅲ, acute rejection treated with cyclosporine A (CsA) by intramuscular injection (SD-to-Wistar+CsA); Group Ⅳ, bone marrow infusion at 7 d pretransplantation followed by short-term CsA treatment (SD-to-Wistar+DSBM); Another group of short-term CsA treatment preoperatively without bone marrow infusion was also set as control. General characteristics and survival time were observed.Histological grades of rejection were determined by pathological examination. IL-2 and IFN-γ level in peripheral blood and donor liver were detected respectively by Enzyme-Linked Immuno-Sorbent Assay (ELISA) and Western blot. Chimerism of donor cells was measured by PCR for a male-specific marker (Y-chromosome-specific sequence, Sry). Results: No signs of rejection were found in Group Ⅰ. Acute rejection occurred in both Group Ⅱ and the short-term CsA treated group. All the recipients died at (9~15)d posttransplantation with a median survival time of (10.7±0.5) d and (11.2±2.4) d, respectively. Only mild rejection could be seen in Group Ⅲ. In Group Ⅳ, 4 out of 6 recipients had long-term survival (>100 d), the histological grade of rejection was significantly lower than that of Group Ⅱ, so did the expression level of IL-2 and IFN-γ in both peripheral blood and grafted liver.Y-chromosome-specific sequence (Sry) of male SD rats could be detected in the bone marrow, spleen and thymus of female recipients at 15 d after bone marrow infusion. Conclusion: Mild preconditioning nonmyeloablative donor specific bone marrow infusion can enhance chimerism formation in recipients, alleviate the rejection of liver allotransplantation

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

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

    2016-01-01

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

  4. Quantitative study of Indium-111-oxine platelet kinetics in acute and chronic renal transplant rejection

    Heyns, A.duP.; Pieters, H.; Badenhorst, P.N.; Wessels, P.; Loetter, M.G.; Minnaar, P.C.; Pauw, F.H.

    1982-01-01

    Thirteen patients were investigated on 22 occasions at times varying from 1 day to 10 years after living family donor or cadaver renal transplantation. Platelet survival in the circulation, and in vivo platelet distribution and sites of deposition and sequestration was quantitatively determined with Indium-111-oxine (In-111-oxine) labelled platelets and a scintillation camera interfaced with a computer assisted imaging system. In all patients platelet survival was shortened and the platelet survival curve exponential. In patients with no evidence of transplant rejection and those with chronic rejection, there was no measurable or visible accumulation of labelled platelets in the kidney. The sequestration pattern of In-111 labelled platelets at the end of platelet life span was within normal limits and located in the reticuloendothelial system. In those patients with acute transplant rejection, platelet survival was shortened. Labelled platelets accumulated in the kidney: this was clearly visualized on scintigraphy and reflected by a significant increase in the radioactivity count density of the kidney. Platelets not deposited in the transplant were sequestrated in the reticuloendothelial system. This study demonstrates the diagnostic value of In-111 labelled platelet kinetics in the investigation of acute renal failure after renal transplantation. This investigation appears of limited clinical value in chronic rejection.

  5. A quantitative study of Indium-111-oxine platelet kinetics in acute and chronic renal transplant rejection

    Thirteen patients were investigated on 22 occasions at times varying from 1 day to 10 years after living family donor or cadaver renal transplantation. Platelet survival in the circulation, and in vivo platelet distribution and sites of deposition and sequestration was quantitatively determined with Indium-111-oxine (In-111-oxine) labelled platelets and a scintillation camera interfaced with a computer assisted imaging system. In all patients platelet survival was shortened and the platelet survival curve exponential. In patients with no evidence of transplant rejection and those with chronic rejection, there was no measurable or visible accumulation of labelled platelets in the kidney. The sequestration pattern of In-111 labelled platelets at the end of platelet life span was within normal limits and located in the reticuloendothelial system. In those patients with acute transplant rejection, platelet survival was shortened. Labelled platelets accumulated in the kidney: this was clearly visualized on scintigraphy and reflected by a significant increase in the radioactivity count density of the kidney. Platelets not deposited in the transplant were sequestrated in the reticuloendothelial system. This study demonstrates the diagnostic value of In-111 labelled platelet kinetics in the investigation of acute renal failure after renal transplantation. This investigation appears of limited clinical value in chronic rejection. (orig.)

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

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

  7. Vascularized composite allotransplantation: current standards and novel approaches to prevent acute rejection and chronic allograft deterioration.

    Kueckelhaus, Maximilian; Fischer, Sebastian; Seyda, Midas; Bueno, Ericka M; Aycart, Mario A; Alhefzi, Muayyad; ElKhal, Abdallah; Pomahac, Bohdan; Tullius, Stefan G

    2016-06-01

    The advent of more potent immunosuppressants led to the first successful human upper extremity transplantation in 1998. At this time, >100 upper extremity transplants, 30 face transplants, and a variety of other vascularized composite allotransplantation (VCA) procedures have been performed around the world. VCA recipients present unique challenges for transplantation. The incidence of acute rejection exceeds 80% in hand and face transplantation and is well documented, whereas reports about antibody-mediated rejection and chronic rejection remain scarce. Immunosuppression protocols commonly used at US centers are derived from solid organ transplantation protocols. Novel approaches to minimize rejections in VCA may include improved HLA matching and considerations toward cytomegalovirus infection status. New graft preservation techniques may decrease immunogenicity prior to transplant. Novel monitoring methods such as valid biomarkers, ultrasound biomicroscopy, and sentinel flaps may enable earlier diagnosis of rejection. Cell-based therapies are being explored to achieve immunosuppressive regimen minimization or even tolerance induction. The efficacy of local immunosuppression in clinical VCA remains controversial. In conclusion, although immunosuppressive strategies adapted from SOT have demonstrated good midterm results, focusing on the unique features of VCA grafts may enable additional, more specific treatment strategies in the future and improved long-term graft outcomes. PMID:26265179

  8. Sodium nuclear magnetic resonance imaging of acute cardiac rejection in heterotopic heart transplantation

    Nuclear magnetic resonance (NMR) imagings have been applied to the observation of tissue sodium-23 in myocardium undergoing cardiac rejection. Six canine donor hearts were heterotopically transplanted in the recipient's chest cavity. The dogs were then killed and sodium-23 image of the excised donor hearts were obtained using a high field NMR imaging system (1.5 Tesla, Magnetom). Proton NMR imaging was also performed and T1, T2 relaxation times were calculated. Subsequently, these data were correlated with pathologic findings such as mild, moderate and severe rejection. The correlation coefficients between rejection score, and T1, T2 times and sodium NMR signal intensity were 0.79, 0.70 and 0.80, respectively. The moderate or severe rejected myocardium were clearly visible as areas of increased sodium NMR signal. These data suggested that increase of sodium may be mainly caused by the myocardial cellular necrosis. Sodium NMR will allow us to evaluate the location and extent of rejected myocardium undergoing heart transplantation. (author)

  9. Disseminated Intravascular Coagulation (DIC) Accompanied by Acute Rejection in a Post Renal Transplant Recipient

    Dohi, Kiyohiko; Eto, Takaaki; Ono, Eiji; Fukuda, Yasuhiko; Takenaka, Masaharu; Yahata, Hiroshi; Asahara, Toshimasa; Tabe, Yasuji; Marubayashi, Seiji; Ezaki, Haruo

    1984-01-01

    A kidney transplant recipient with disseminated intravascular coagulation (DIC) accompanied by acute rejection was described. The principal symptome of the patient was massive gross hematuria. She showed thrombocytopenia, marked decrease of fibrinogen and elevation of fibrinogen degradation products (FDP) level. The patient was treated by continuous intravenous heparin infusion (total dose was 85, 800 units), and it was very effective. The symtoms due to DIC were improved on the 9th day after...

  10. Myocardial scintigraphy with gallium-67 in the detection of cardiac acute rejection

    In order to evaluate the myocardial scintigraphy with Gallium-67 potentiality in the detection of acute rejection phenomenon, 105 studies were performed in 20 patients after they had a heart transplantation. The scintigraphic images were obtained by a conventional camera-computer system. These images were acquired 48 hours after all the patients were given an intravenous injection of 111 MBq of Gallium-67 Citrate. The biopsies were done according to the Mason technique and the histological analysis followed the Billingham standards. (author)

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

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

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

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

  13. Differentiation of acute untreated rejection from cyclosporine nephrotoxicity and acute tubular necrosis by indium-111 labeled platelet scintigraphy

    The authors have previously reported that unlike normal and nephrotic native kidneys, acutely rejecting kidney transplants show significant platelet uptake by Indium-111 labeled platelet scintigraphy (lPLS). To determine if lLPS can differentiate acute rejection (AR) from cyclosporine (CY) nephrotoxicity and acute tubular necrosis (ATN). The authors studied 5 groups of kidney transplant recipients. Group 1, n=6 (3 on Imuran, 3 on CY, CR=1.4 +- 0.6, mean +- SD) had no evidence for rejection (kidney biopsy in 2). Group 11, n=4(1 on Imuran, 3 on CY, Cr=2.8 +- 1.1) had ATN (biopsy in 2). Group 111, n=3(all on CY, Cr=2.3 +- 1.9) had suspected CY nephrotoxicity:all patients (pts) improved upon withdrawal of CY and biopsies were negative for rejection in 2. Group IV, n=11 (10 on Imuran 1 on CY, CR=5.6 +- 4.1) had acute rejection on biopsy. In group V, n=7 (3 on imuran 4 on CY, Cr=6.1 +- 3.4) pts were treated for rejection for 12 +- 4 days. All pts received Prednisone. The first image was obtained 6 +- 4 hrs after injection of 215 +- 30μ Ci of lN-111 and thereafter 1 to 3 times a day for a maximum of 6 days. Platelet Uptake Index (PUl) was calculated as the ratio of uptake over the transplant against a contralateral reference area. One way analysis of variance was carried out. PUIs from groups I, II, III and V were significantly different from groups IV: 1.1 +- .07 (p<0.004), 1.22 +- .09 (p<0.05), 1.14 +- .05 (p<0.04) and 1.21 +- .07 (p<0.004) versus 1.52 +- .17. The authors conclude that 1) ILP can be used for the diagnosis of untreated AR. 2) Untreated AR can be differentiated from CY nephrotoxicity and ATN

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

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

    2016-01-01

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

  15. GATED SPECT IN PATIENTS WITH BIOPSY-NEGATIVE CARDIAC TRANSPLANT REJECTION

    E. N. Ostroumov

    2009-05-01

    Full Text Available Humoral rejection of the cardiac allograft is still a challenging problem associated with high incidence of graft loss and patient mortality. These episodes of rejection are often more severe, and more difficult to treat, than classical acute cellular rejection. Hemodynamic compromise, in the absence of acute cellular rejection, called biopsy-negative rejection occurs in 10 to 20% of cardiac allograft recipients. The assessment of hemodynamic compromise can provide functional data in transplant patients that is complementary to myocardial biopsies if the biopsy can miss significant rejection. We present three cases of the biopsy-negative rejection. All patients have studied with gated SPECT phase analysis. 

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

    Stefan Reuter

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

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

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

    2014-01-01

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

  18. Urinary proteomic shotgun approach for identification of potential acute rejection biomarkers in renal transplant recipients

    2012-01-01

    Background Acute rejection (AR) episodes in renal transplant recipients are suspected when plasma creatinine is elevated and other potential causes out ruled. Graft biopsies are however needed for definite diagnosis. Non-invasive AR-biomarkers is an unmet clinical need. The urinary proteome is an interesting source in the search for such a biomarker in this population. Methods In this proof of principle study, serial urine samples in the early post transplant phase from 6 patients with biopsy verified acute rejections and 6 age-matched controls without clinical signs of rejection were analyzed by shotgun proteomics. Results Eleven proteins fulfilled predefined criteria for regulation in association with AR. They presented detectable regulation already several days before clinical suspicion of AR (increased plasma creatinine). The regulated proteins could be grouped by their biological function; proteins related to growth and proteins related to immune response. Growth-related proteins (IGFBP7, Vasorin, EGF and Galectin-3-binding protein) were significantly up-regulated in association with AR (P = 0.03) while proteins related to immune response (MASP2, C3, CD59, Ceruloplasmin, PiGR and CD74) tended to be up-regulated ( P = 0.13). Conclusion The use of shotgun proteomics provides a robust and sensitive method for identification of potentially predictive urinary biomarkers of AR. Further validation of the current findings is needed to establish their potential clinical role with regards to clinical AR diagnosis. Trial registration ClinicalTrials.gov number NCT00139009 PMID:23369437

  19. Cellular Mechanisms of L-arginine Induced Experimental Acute Pancreatitis

    Masood, Omar

    2013-01-01

    AbstractThe University Of ManchesterOmar MasoodMD Thesis 2013Cellular Mechanisms of L-arginine Induced Experimental Acute Pancreatitis. IntroductionImpairment of cytosolic calcium ([Ca2+]i) signaling and in particular calcium overload has emerged as a possible unifying mechanism for precipitating acute pancreatitis (AP.)In the L-arginine (L-arg) experimental model of AP, nitric oxide (NO) has been implicated however the disease progression is largely unaffected by nitric oxide synthase (NOS) ...

  20. Utility of Double Filtration Plasmapheresis in Acute Antibody Mediated Renal Allograft Rejection: Report of Three Cases

    Yalçın SOLAK

    2011-09-01

    Full Text Available Plasmapheresis is an extracorporeal procedure, which is often employed to rapidly lower circulating titers of autoantibodies, immune complexes or toxins. There are two types of plasmapheresis namely, regular plasmapheresis (RPP by centrifugation and membrane filtration, and double filtration plasmapheresis (DFPP which is a special form of membrane filtration in which two membranes called as plasma separator and plasma fractionator are employed to filter macromolecules more selectively. DFPP have several advantages over RP. Despite widespread utilization of DFPP in the setting of ABO blood group incompatible kidney transplantation, there is no report regarding DFPP in patients with antibody mediated acute renal allograft rejection who are good candidates for beneficial effects of DFPP. Here we report three renal transplant recipients in whom DFPP was applied as a component of anti-rejection treatment regimen.

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

    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

  2. Cortical perfusion index: A predictor of acute rejection in transplanted kidneys

    The presently available non-invasive methods for the diagnosis of acute rejection crisis (ARC) of renal transplants are not satisfactory. However, the need for such a test is of paramount clinical importance. A prospective study of 74 post-transplantation events in renal allograft recipients was performed. Clinical, surgical exploration and biopsy data were correlated with TC-99m DTPA scintigraphy using the following indices: Global perfusion index (GPI), cortical perfusion index (CPI), medullary perfusion index (MPI), the peak-to-plateau ratio (P/P), iliac artery peak to renal peak time (delta-P) and washout half-time (T1/2). Of the 74 events, 24 were proven to be due to acute rejection crisis (ARC), 13 were of ureteral obstruction, 18 various nephropathies and 19 in stable renal transplant function. The P/P, delta-P and T1/2 were not good predictors of ARC; the sensitivity was 79%, 79% and 80% respectively. The sensitivity of the GPI was 58% and the specificity was 87%. The cortical perfusion index rated better: specificity=84% and sensitivity=87%. However, the best indicator of ARC seemed to be the percent increase in cortical perfusion index over previous values obtained during stable graft function. Thus the sensitivity was found to be 91% and specificity was 96%. The difference between global and cortical perfusion indices reflects shunting of blood for cortex to medulla. This study suggest that the cortical perfusion index (CPI) and the percent increase in CPI can be used to non-invasively diagnose acute renal allograft rejection

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

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

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

    Tisdale, P.L.; Collier, B.D.; Kauffman, H.M.; Adams, M.B.; Isitman, A.T.; Hellman, R.S.; Hoffmann, R.G.; Rao, S.A.; Joestgen, T.; Krohn, L.

    1986-08-01

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

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

    A. I. Sushkov

    2016-01-01

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

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

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

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

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

    2015-04-10

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

  8. Inflammatory cells and activation markers in BAL during acute rejection and infection in lung transplant recipients: a prospective, longitudinal study.

    Riise, G C; Kjellström, C; Ryd, W; Scherstén, H; Nilsson, F; Mårtensson, G; Andersson, B A

    1997-08-01

    Acute rejection of the transplanted lung is a clinical problem, since it decreases graft survival and predisposes the patient to chronic rejection and obliterative bronchiolitis (OB). In an earlier study, we had indications that eosinophil cationic protein (ECP) from activated eosinophils and hyaluronan (HYA) from fibroblasts were associated with acute pulmonary rejection. This prospective longitudinal study was designed to investigate whether molecules from activated inflammatory cells in bronchoalveolar lavage (BAL) fluid could serve as clinically useful diagnostic markers for acute rejection. BAL fluid from 138 bronchoscopies performed in 10 single lung, four bilateral lung and five heart-lung transplant recipients were analysed. Nine patients were studied for a period of more than 1 yr (mean 13.4 months) after surgery. Differential cell counts were made from the BAL fluid. ECP, myeloperoxidase (MPO), HYA and interleukin-8 (IL-8) were used as indirect markers for activation and attraction of eosinophils, neutrophils and fibroblasts, respectively. Fifty four episodes of acute rejection were diagnosed. Two patients developed OB. Nine episodes of bacterial infection, 13 episodes of cytomegalovirus (CMV) pneumonitis, three of Pneumocystis carinii infection and one of respiratory syncytial virus (RSV) infection were diagnosed. The mean levels of ECP, MPO, HYA and IL-8 were all higher during rejection episodes, but differences were not statistically significant compared to no rejection, when the confounding factors of time, concomitant infection, and repeated measures in the same individual had been accounted for. We could not confirm that measurements of eosinophil cationic protein, myeloperoxidase, hyaluronan and interleukin-8 in bronchoalveolar lavage fluid can be used as diagnostic markers for acute rejection in the postoperative follow-up of lung transplant recipients. PMID:9272913

  9. Studies of CTLA4Ig in acute rejection of pancreas transplantation in rats

    Junbo Yu; Zekuan Xu; Shuguang Han; Yi Miao

    2006-01-01

    Objective: To investigate the protective effect of CTLA4Ig in rejection of pancreaticoduodenal transplantation model of rat. Methods: Pancreaticoduodenal transplantion models were established from the donor F344 rats to the Lewis recipients. The models were divided into 2 groups: Group A and B with 12 rats in each group.2 days after transplantation, reciepients in group A were treated with i.p. injection of sailine, and those in group B CTLA4I were injected(200 μg). On day 1,4,7,10after transplantation, the grafts were harvested for histopathological examination. On day 4 after transplantation, the CD4+CD25+Tcells in the grafts were detected by Flow Cytometry. Results: Compared with group A: the degree of the rejection of grafts in group B was lower. The number of CD4+CD25+ T cells of graft was (7.91±1.26)% in group A and (13.81±1.71)% in group B, which had significant difference(P<0.01). Conclusion: CTLA4Ig could inhibit T cell costimulatory pathway, prevent acute rejection, which might be mediated by increasing the number of CD4+CD25+ regulatory T cells.

  10. Comparison of multiplex meta analysis techniques for understanding the acute rejection of solid organ transplants

    Khatri Purvesh

    2010-10-01

    Full Text Available Abstract Background Combining the results of studies using highly parallelized measurements of gene expression such as microarrays and RNAseq offer unique challenges in meta analysis. Motivated by a need for a deeper understanding of organ transplant rejection, we combine the data from five separate studies to compare acute rejection versus stability after solid organ transplantation, and use this data to examine approaches to multiplex meta analysis. Results We demonstrate that a commonly used parametric effect size estimate approach and a commonly used non-parametric method give very different results in prioritizing genes. The parametric method providing a meta effect estimate was superior at ranking genes based on our gold-standard of identifying immune response genes in the transplant rejection datasets. Conclusion Different methods of multiplex analysis can give substantially different results. The method which is best for any given application will likely depend on the particular domain, and it remains for future work to see if any one method is consistently better at identifying important biological signal across gene expression experiments.

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

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

    2016-05-01

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

  12. Donor liver natural killer cells alleviate liver allograft acute rejection in rats

    Jian-Dong Yu; Tian-Zhu Long; Guo-Lin Li; Li-Hong Lv; Hao-Ming Lin; Yong-Heng Huang; Ya-Jin Chen; Yun-Le Wan

    2011-01-01

    BACKGROUND: Liver enriched natural killer (NK) cells are of high immune activity. However, the function of donor liver NK cells in allogeneic liver transplantation (LTx) remains unclear. METHODS: Ten Gy of whole body gamma-irradiation (WBI) from a 60Co source at 0.6 Gy/min was used for depleting donor-derived leukocytes, and transfusion of purified liver NK cells isolated from the same type rat as donor (donor type liver NK cells, dtlNKs) through portal vein was performed immediately after grafting the irradiated liver. Post-transplant survival observation on recipients and histopathological detection of liver grafts were adoptive to evaluate the biological impact of donor liver NK cells on recipients' survival in rat LTx. RESULTS: Transfusion of dtlNKs did not shorten the survival time among the recipients of spontaneous tolerance model (BN to LEW rat) after rat LTx, but prolonged the liver graft survival among the recipients depleted of donor-derived leukocytes in the acute rejection model (LEW to BN rat). Compared to the recipients in the groups which received the graft depleted of donor-derived leukocytes, better survival and less damage in the allografts were also found among the recipients in the two different strain combinations of liver allograft due to transfusion of dtlNKs. CONCLUSIONS: Donor liver NK cells alone do not exacerbate liver allograft acute rejection. Conversely, they can alleviate it, and improve the recipients' survival.

  13. Mycophenolate mofetil: safety and efficacy in the prophylaxis of acute kidney transplantation rejection

    Pranav Dalal

    2009-01-01

    Full Text Available Pranav Dalal1, Monica Grafals2, Darshika Chhabra2, Lorenzo Gallon21Department of Medicine, Mount Sinai Hospital, Chicago, USA; 2Northwestern University–Feinberg School of Medicine, Chicago, USAAbstract: Mycophenolate mofetil (MMF, a prodrug of mycophenolic acid (MPA, is an inhibitor of inosine monophosphate dehydrogenase (IMPDH. It preferentially inhibits denovo pathway of guanosine nucleotide synthesis in T and B-lymphocytes and prevents their proliferation, thereby suppresses both cell mediated and humoral immune responses. Clinical trials in kidney transplant recipients have shown the efficacy of MMF in reducing the incidence and severity of acute rejection episodes. It also improves long term graft function as well as graft and patient survival in kidney transplant recipients. MMF is useful as a component of toxicity sparing regimens to reduce or avoid exposure of steroids or calcineurin inhibitor (CNI. Enteric-coated mycophenolate sodium (EC-MPS can be used as an alternative immunosuppressive agent in kidney transplant recipients with efficacy and safety profile similar to MMF.Keywords: mycophenolate mofetil, kidney transplantation, acute rejection, toxicity sparing

  14. Urinary proteomic shotgun approach for identification of potential acute rejection biomarkers in renal transplant recipients

    Loftheim Håvard

    2012-08-01

    Full Text Available Abstract Background Acute rejection (AR episodes in renal transplant recipients are suspected when plasma creatinine is elevated and other potential causes out ruled. Graft biopsies are however needed for definite diagnosis. Non-invasive AR-biomarkers is an unmet clinical need. The urinary proteome is an interesting source in the search for such a biomarker in this population. Methods In this proof of principle study, serial urine samples in the early post transplant phase from 6 patients with biopsy verified acute rejections and 6 age-matched controls without clinical signs of rejection were analyzed by shotgun proteomics. Results Eleven proteins fulfilled predefined criteria for regulation in association with AR. They presented detectable regulation already several days before clinical suspicion of AR (increased plasma creatinine. The regulated proteins could be grouped by their biological function; proteins related to growth and proteins related to immune response. Growth-related proteins (IGFBP7, Vasorin, EGF and Galectin-3-binding protein were significantly up-regulated in association with AR (P = 0.03 while proteins related to immune response (MASP2, C3, CD59, Ceruloplasmin, PiGR and CD74 tended to be up-regulated ( P = 0.13. Conclusion The use of shotgun proteomics provides a robust and sensitive method for identification of potentially predictive urinary biomarkers of AR. Further validation of the current findings is needed to establish their potential clinical role with regards to clinical AR diagnosis. Trial registration ClinicalTrials.gov number NCT00139009

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

    Salomon Daniel R

    2008-02-01

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

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

    Wojciechowski D; Vincenti F

    2012-01-01

    David Wojciechowski, Flavio VincentiKidney Transplant Service, University of California, San Francisco, CA, USAAbstract: In June 2011, the US Food and Drug Administration approved belatacept for the prophylaxis of organ rejection in adult kidney transplant recipients. This review discusses the use of belatacept for the prevention of acute rejection as part of a maintenance immunosuppression regimen. Belatacept is a selective costimulation blocker designed to provide effective immunosuppressio...

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

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

    2013-01-01

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

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

    Just, Søren Andreas; Marcussen, Niels; Sprogøe, Ulrik; Koefoed-Nielsen, Pernille; Bistrup, Claus

    2010-01-01

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

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

    Just, Søren Andreas; Marcussen, Niels; Sprogøe, Ulrik; Kofoed-Nielsen, Pernille Bundgaard; Bistrup, Claus

    2009-01-01

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

  20. 99mTc-tin colloid scintigraphy in the diagnosis of acute rejection. Reactions of renal transplants

    Quantitative measurements of 99mTc-tin colloid uptake in renal transplants permits differentiation of acute rejection from other causes of deteriorating renal function, such as acute tubular necrosis, cyclosporin A nephrotoxicity or chronic rejection. 144 99mTc-tin colloid scintigrams were performed on 71 renal transplants; the results were compared with clinical, biochemical and histological findings. Sensitivity of colloid scintigraphy is 97.4% and specificity is 80%. Compared with other isotope methods, this has the advantage that it does not depend on comparison with repeated examinations. (orig.)

  1. Low incidence of acute rejection in hepatitis B virus positive liver transplant recipients and the impact of hepatitis B immunoglobulin.

    Veerappan, Annapoorani; VanWagner, Lisa B; Mathew, James M; Huang, Xuemei; Miller, Joshua; Lapin, Brittany; Levitsky, Josh

    2016-04-01

    Historically, hepatitis B virus (HBV) liver transplantation (LT) recipients have less acute cellular rejection (ACR) than those without HBV. We questioned whether this has persisted in an era of decreased Hepatitis B immunoglobulin use (HBIG) given its in vitro immunoregulatory effects. We compared the incidence, risk factors and outcomes of ACR among 40,593 primary LT recipients with HBV, hepatitis C, steatohepatitis, and immune liver disease (OPTN 2000-2011). We also assessed the in vitro effect of HBIG on alloimmune lymphoproliferation and regulatory T cell generation using mixed lymphocyte reactions. In multivariate analysis, HBV status remained a strong independent predictor of freedom from ACR (OR 0.58, 95% CI: 1.5-2.1). Patient (67.7% vs 72.3%) and graft (60.8% vs 69.1%) survival were significantly lower in patients with ACR versus no ACR for all causes except HBV. HBIG use had no statistical association with ACR. In vitro, HBIG at concentrations equivalent to clinical dosing did not inhibit lymphoproliferation or promote regulatory T cell development. In summary, the incidence and impact of ACR is lower now for HBV LT and does not appear to be secondary to HBIG by our in vitro and in vivo analyses. Rather, it may be due to the innate immunosuppressive properties of chronic HBV infection. PMID:26924082

  2. Functional changes of dendritic cells derived from allogeneic partial liver graft undergoing acute rejection in rats

    Ming-Qing Xu; Zhen-Xiang Yao

    2003-01-01

    4 days after transplantation (P<0.001) was observed.CONCLUSION: DCs derived from allogeneic partial liver graftundergoing acute rejection display features of mature DC.

  3. Derivation and Validation of a Cytokine-Based Assay to Screen for Acute Rejection in Renal Transplant Recipients

    De Serres, Sacha A.; Mfarrej, Bechara G.; Grafals, Monica; Riella, Leonardo V.; Magee, Ciara N.; Yeung, Melissa Y.; Dyer, Christine; Ahmad, Usaila; Chandraker, Anil

    2012-01-01

    Summary Background and objectives Acute rejection remains a problem in renal transplantation. This study sought to determine the utility of a noninvasive cytokine assay in screening of acute rejection. Design, setting, participants, & measurements In this observational cross-sectional study, 64 patients from two centers were recruited upon admission for allograft biopsy to investigate acute graft dysfunction. Blood was collected before biopsy and assayed for a panel of 21 cytokines secreted by PBMCs. Patients were classified as acute rejectors or nonrejectors according to a classification rule derived from an initial set of 32 patients (training cohort) and subsequently validated in the remaining patients (validation cohort). Results Although six cytokines (IL-1β, IL-6, TNF-α, IL-4, GM-CSF, and monocyte chemoattractant protein-1) distinguished acute rejectors in the training cohort, logistic regression modeling identified a single cytokine, IL-6, as the best predictor. In the validation cohort, IL-6 was consistently the most accurate cytokine (area under the receiver-operating characteristic curve, 0.85; P=0.006), whereas the application of a prespecified cutoff level, as determined from the training cohort, resulted in a sensitivity and specificity of 92% and 63%, respectively. Secondary analyses revealed a strong association between IL-6 levels and acute rejection after multivariate adjustment for clinical characteristics (P<0.001). Conclusions In this pilot study, the measurement of a single cytokine can exclude acute rejection with a sensitivity of 92% in renal transplant recipients presenting with acute graft dysfunction. Prospective studies are needed to determine the utility of this simple assay, particularly for low-risk or remote patients. PMID:22498498

  4. Temporal profile of calcineurin phosphatase activity during acute allograft rejection in the heterotopic rat heart transplantation model

    Karamperis, N; Koefoed-Nielsen, P B; Marcussen, N;

    2008-01-01

    it can be utilized as a pharmacodynamic marker to identify and monitor the rejection process. METHODS: The heterotopic cervical rat heart transplantation model was used (dark Agouti to Lewis). We performed 25 control isogeneic and 46 allogeneic transplantations. Rats were sacrificed at various...... as a pharmacodynamic biomarker of acute allograft rejection in the heterotopic rat heart transplantation model. Further research is required in order to reveal the precise role of CaN during acute allograft rejection....... postoperative time points. CaN activity was measured in isolated peripheral blood and spleen mononuclear cells and in graft heart homogenates. CaN activity was measured as the release of radiolabeled phosphate from a previously phosphorylated 19 amino acid peptide. RESULTS: We have shown that CaN's activity...

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

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

    2010-01-01

    Regulatory T cells (Tregs) have been related to acute rejection as have the cytotoxic T cells, their immunological counterpart. High expression of cytotoxic markers has been related to acute rejection incidents following both kidney and intestine transplantation, while the correlation between FoxP3...

  6. On the interference rejection capabilities of triangular antenna array for cellular base stations

    Atat, Rachad

    2012-03-01

    In this paper, we present the performance analysis of the triangular antenna arrays in terms of the interference rejection capability. In this context, we derive an expression to calculate the spatial interference suppression coefficient for the triangular antenna array with variable number of antenna elements. The performance of the triangular antenna array has been compared with the circular antenna array with respect to interference suppression performance, steering beam pattern, beamwidth and directivity. Simulation results show that the triangular array with large number of elements produces a sharper beamwidth and better interference suppression performance than the circular antenna array. © 2012 IEEE.

  7. Lack of association of recipient MCP-1 gene promoter polymorphism with acute graft rejection after orthotopic liver transplantation.

    Franco-López, E; González-Escribano, M F; Aguilera, I; Pascasio, J M; Pareja, F; Bernardos, A; Núñez-Roldán, A

    2005-04-01

    Acute graft rejection after orthotopic liver transplantation (OLT) is associated with leukocyte infiltration of the graft. Monocyte chemoattractant protein-1 (MCP-1) is a beta-chemokine involved in the attraction and accumulation of mononuclear granulocytes toward sites of inflammation. A biallelic polymorphism (G/A) at position -2518 of the MCP-1 gene has been described. Cells obtained from individuals with the GG or AG genotypes have been found to produce more MCP-1 than those obtained from individuals with the AA genotype. The goal of this study was to assess the possible association between this polymorphism and susceptibility to acute graft rejection after OLT. One hundred fifty Caucasian liver transplant recipients from the South of Spain underwent genotyping using a polymerase chain reaction (PCR) amplification followed by restriction fragment length polymorphism (RFLP). No significant differences were observed when patients with versus without acute rejection episodes were compared for the distribution of -2518 MCP-1 genotypes. The present study supports the lack of involvement of polymorphism at position -2518 (A/G) of the MCP-1 gene on the susceptibility to acute allograft rejection among OLT recipients. PMID:15866653

  8. Performance of polymerase chain reaction techniques detecting perforin in the diagnosis of acute renal rejection: a meta-analysis.

    Yushu Shang

    Full Text Available BACKGROUND: Studies in the past have shown that perforin expression is up-regulated during acute renal rejection, which provided hopes for a non-invasive and reliable diagnostic method to identify acute rejection. However, a systematic assessment of the value of perforin as a diagnostic marker of acute renal rejection has not been performed. We conducted this meta-analysis to document the diagnostic performance of perforin mRNA detection and to identify potential variables that may affect the performance. METHODOLOGY/PRINCIPAL FINDINGS: Relevant materials that reported the diagnostic performance of perforin mRNA detection in acute renal rejection patients were extracted from electronic databases. After careful evaluation of the studies included in this analysis, the numbers of true positive, true negative, false positive and false negative cases of acute renal rejection identified by perforin mRNA detection were gathered from each data set. The publication year, sample origin, mRNA quantification method and housekeeping gene were also extracted as potential confounding variables. Fourteen studies with a total of 501 renal transplant subjects were included in this meta-analysis. The overall performance of perforin mRNA detection was: pooled sensitivity, 0.83 (95% confidence interval: 0.78 to 0.88; pooled specificity, 0.86 (95% confidence interval: 0.82 to 0.90; diagnostic odds ratio, 28.79 (95% confidence interval: 16.26 to 50.97; and area under the summary receiver operating characteristic curves value, 0.9107±0.0174. The univariate analysis of potential variables showed some changes in the diagnostic performance, but none of the differences reached statistical significance. CONCLUSIONS/SIGNIFICANCE: Despite inter-study variability, the test performance of perforin mRNA detected by polymerase chain reaction was consistent under circumstances of methodological changes and demonstrated both sensitivity and specificity in detecting acute renal

  9. Increased coronary lipid accumulation in heart transplant recipients with prior high-grade cellular rejection: novel insights from near-infrared spectroscopy.

    Zheng, Bo; Maehara, Akiko; Mintz, Gary S; Nazif, Tamim M; Waksman, Yarden; Qiu, Fuyu; Jaquez, Luz; Rabbani, LeRoy E; Apfelbaum, Mark A; Ali, Ziad A; Dalton, Kate; Song, Lei; Xu, Ke; Marboe, Charles C; Mancini, Donna M; Weisz, Giora

    2016-02-01

    Cardiac allograft vasculopathy is a major cause of morbidity and mortality among patients after heart transplantation. We sought to assess the amount of lipid accumulation in the coronary arteries of transplant patients according to rejection grade. Overall, 39 consecutive heart transplant recipients undergoing annual routine surveillance coronary angiography underwent near-infrared spectroscopy and intravascular ultrasound imaging of 1 coronary artery. Rejection history was graded according to the International Society of Heart and Lung Transplantation (ISHLT) classification as none/mild/moderate-grade rejection (ISHLT 0, 1A/1B, or 2) compared to high-grade rejection (≥3A). Patients with prior history of high-grade rejection had larger plaque burden in the distal coronary segments [45.7 % (25.5-63.7) vs 25.1 % (19.9-37.8), p = 0.02] and a higher maximum lipid core burden index in any 4-mm long segment (maxLCBI(4mm)) [243 (91-400) vs 41 (1-170), p = 0.016] as compared with patients with prior history of none/mild/moderate-grade rejection. By multivariable linear regression analysis, prior history of high-grade rejection was an independent predictor for maxLCBI(4mm). A maxLCBI(4mm) >200 distinguished prior history of high-grade from none/mild/moderate rejection with a sensitivity of 61.5 % and specificity of 84.6 %. The current study demonstrates that the coronary arteries of post heart-transplant patients with a prior history of high-grade cellular rejection have increasing amounts of lipid-rich plaque. MaxLCBI(4mm) >200 might differentiate patients with previous high-grade cellular rejection from heart transplant recipients with none/mild/moderate-grade rejection. PMID:26408106

  10. Gastroesophageal Reflux Disease Is Associated With an Increased Rate of Acute Rejection in Lung Transplant Allografts

    Shah, N.S.; Force, S.D.; Mitchell, P.O.; Lin, E.; Lawrence, E.C.; Easley, K.; Qian, J.; Ramirez, A.; Neujahr, D.C.; Gal, A.; Leeper, K.; Pelaez, A.

    2012-01-01

    Purpose Gastric fundoplication (GF) for gastroesophageal reflux disease (GERD) may protect against the progression of chronic rejection in lung transplant (LT) recipients. However, the association of GERD with acute rejection episodes (ARE) is uncertain. This study sought to identify if ARE were linked to GERD in LT patients. Methods This single-center retrospective observational study, of patients transplanted from January 1, 2000, to January 31, 2009, correlated results of pH probe testing for GERD with ARE (≥International Society for Heart and Lung Transplantation A1 or B1). We compared the rates of ARE among patients with GERD (DeMeester Score > 14.7) versus without GERD as number of ARE per 1,000 patient-days after LT. Patients undergoing GF prior to LT were excluded. Results The analysis included 60 LT subjects and 9,249 patient-days: 33 with GERD versus 27 without GERD. We observed 51 ARE among 60 LT recipients. The rate of ARE was highest among patients with GERD: 8.49 versus 2.58, an incidence density ratio (IDR) of 3.29 (P = .00016). Upon multivariate negative binomial regression modeling, only GERD was associated with ARE (IDR 2.15; P = .009). Furthermore, GERD was associated with multiple ARE (36.4% vs 0%; P < .0001) and earlier onset compared with patients without GERD: ARE proportion at 2 months was 0.55 versus 0.26 P = .004). Conclusion In LT recipients, GERD was associated with a higher rate, multiple events, and earlier onset of ARE. The efficacy of GF to reduce ARE among patients with GERD needs further evaluation. PMID:20832573

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

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

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

    Wojciechowski, David; Vincenti, Flavio

    2012-01-01

    In June 2011, the US Food and Drug Administration approved belatacept for the prophylaxis of organ rejection in adult kidney transplant recipients. This review discusses the use of belatacept for the prevention of acute rejection as part of a maintenance immunosuppression regimen. Belatacept is a selective costimulation blocker designed to provide effective immunosuppression while avoiding the toxicities associated with calcineurin inhibitors. Phase III trial data have demonstrated that belatacept is noninferior to cyclosporine in 1-year patient and allograft survival. Three-year data demonstrate an ongoing improvement in mean measured glomerular filtration rate in belatacept-treated versus cyclosporine-treated patients. However, the rate of acute rejection was higher in belatacept-treated patients compared with cyclosporine. Specifically, there was a higher incidence of Banff type II rejections in patients treated with belatacept. Despite the higher Banff grade, rejections on belatacept were not associated with other factors associated with poor outcomes, such as the development of donor-specific antibodies or reduced estimated glomerular filtration rate. One safety issue that must be considered when using belatacept is the potential for increased risk of post-transplant lymphoproliferative disease. There were more cases of post-transplant lymphoproliferative disease in belatacept-treated patients, especially in recipients seronegative for Epstein–Barr virus or patients treated with lymphocyte-depleting agents. Therefore, belatacept can be recommended for use in Epstein–Barr virus antibody-positive recipients. PMID:23152668

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

    Penno, E.; Johnsson, C.; Johansson, L.; Ahlstroem, H. [Uppsala Univ. Hospital (Sweden). Depts. of Diagnostic Radiology and of Transplantation Surgery

    2006-04-15

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

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

    Wojciechowski D

    2012-11-01

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

  15. Changes in dendritic cells and dendritic cell subpopulations in peripheral blood of recipients during acute rejection after kidney transplantation

    Ma Linlin; Liu Yong; Wu Junjie; Xu Xiuhong; Liu Fen; Feng Lang; Xie Zelin

    2014-01-01

    Background Advances in transplantation immunology show that the balance between dendritic cells (DCs) and their subsets can maintain stable immune status in the induction of tolerance after transplantation.The aim of this study was to investigate if DCs and DC subpopulations in recipient peripheral blood are effective diagnostic indicators of acute rejection following kidney transplantation.Methods Immunofluorescent flow cytometry was used to classify white blood cells (WBCs),the levels of mononuclear cells and DCs (including the dominant subpopulations,plasmacytoid DC (pDC) and myeloid DC (mDC)) in peripheral blood at 0,1,7,and 28 days and 1 year after kidney transplantation in 33 patients.In addition,the blood levels of interleukin-10 (IL-10) and IL-12 were monitored before and after surgery.Fifteen healthy volunteers served as normal controls.Patients were undertaking hemodialysis owing to uremia before surgery.Results The total number of DCs,pDC,and mDC in peripheral blood and the pDC/mDC ratio were significantly lower in patients than controls (P <0.05).Peripheral DCs suddenly decreased at the end of day 1,then gradually increased through day 28 but remained below normal levels.After 1 year,levels were higher than before surgery but lower than normal.The mDC levels were higher in patients with acute rejection before and 1 day after surgery (P <0.005).There was no significant difference in IL-10 and IL-12 levels between patients with and without acute rejection.Conclusion The changes in DCs and DC subpopulations during the acute rejection period may serve as effective markers and referral indices for monitoring the immune state,and predicting rejection and reasonably adjusting immunosuppressants.

  16. Recipient Cytotoxic T Lymphocyte Antigen 4 +49 Single-Nucleotide Polymorphism Is Not Associated with Acute Rejection after Liver Transplantation in Chinese Population

    Zhijun Jiang, Ying Chen, Xiaonin Feng, Haiyang Xie, Lin Zhou, Shusen Zheng

    2013-01-01

    Full Text Available Objective: Single-nucleotide polymorphisms (SNPs in Cytotoxic T lymphocyte antigen 4 (CTLA-4 gene have been detected and proved to associate with the incidence of rejection after transplantation. However, previous studies gained inconsistent results about the association between CTLA-4 +49 single-nucleotide polymorphism and susceptibility of allograft rejection. Therefore we sought to clarify whether CTLA-4 +49 SNP influences the incidence of acute rejection after liver transplantation in Chinese population. Methods: Genomic DNA from 335 liver transplant recipients was genotyped for CTLA-4 +49 SNP by DNA sequencing. Acute rejection was confirmed by pathologic evidences. The association between CTLA-4 +49 SNP and incidence of acute rejection was then analyzed by dominant, recessive, codominant and overdominant models. Results: The incidence of acute rejection within the first 3 months was 11.9%. In acute rejectors, the frequency was 45% for G/G, 10% for A/A and 45% for A/G respectively, compared with 47.5% for G/G, 10.8% for A/A and 41.7% for A/G in non-acute rejectors. And no significant difference of allele distribution between these 2 groups was detected. Conclusions: This study suggests that CTLA-4 +49 SNP is not associated with acute rejection after liver transplantation in Chinese population.

  17. Cortex perfusion index: a sensitive detector of acute rejection crisis in transplanted kidneys

    Damage to the renal cortical microcirculation, an early event in the course of acute rejection crisis (ARC), usually precedes measurable functional derangements in the transplanted kidney. Direct assessment of cortical blood flow by radionuclide renography may provide a sensitive and reliable index to the diagnosis of ARC, with particular regard to the differential diagnosis of ARC and ATN. Computer generated time-activity curves of global, cortical, and medullary renal blood flow were analyzed in 67 instances (35 patients) of renal allograft dysfunction and correlated with needle biopsy of these kidneys. No increase in cortex perfusion index (CPI), i.e., decrease in cortical perfusion, was found when the patients were suffering from ureteral obstruction or drug and viral nephropathy (mean perfusion index (PI) increase (8%). In contrast, a marked increase in CPI of 193% was noted in ARC. Global and medullary PI increased only 116%. As a result, global and medullary PI were capable of diagnosing ARC in only 73% and 55% of the cases, respectively, whereby cortex PI correctly diagnosed ARC in 94% of the cases. Selective analysis of cortical perfusion may thus enhance the accuracy of [99mTc]DTPA scans (radionuclide renograph) for the early detection of ARC and in differentiating ARC from nonimmunological causes of kidney allograft dysfunction

  18. Early plasmapheresis and rituximab for acute humoral rejection after ABO-compatible liver transplantation

    Nassim Kamar; Laurence Lavayssière; Fabrice Muscari; Janick Selves; Céline Guilbeau-Frugier; Isabelle Cardeau; Laure Esposito; Olivier Cointault; Marie Béatrice Nogier; Jean Marie Peron; Philippe Otal; Marylise Fort; Lionel Rostaing

    2009-01-01

    Acute humoral rejection (AHR) is uncommon after ABOcompatible liver transplantation. Herein, we report two cases of AHR treated with plasmapheresis and rituximab in two ABO-compatible liver-transplant patients with preformed anti-human leukocyte antigen donor-specific antibodies. Patient 1 experienced a biopsy-proven AHR at day 10 post-transplant. She was treated by steroid pulses, and OKT3. Because of persisting signs of biopsy-proven AHR at day 26, she was treated by plasmapheresis and rituximab. Liver enzyme levels did not improve, and she died on day 41. Patient 2 experienced a biopsy-proven AHR on day 10 post-transplant. She was treated by steroid pulses, plasmapheresis, and rituximab.Liver enzymes returned to within normal range 18 dafter diagnosis. Liver biopsies, at 3 and 9 mo post-transplant,showed complete resolution of AHR. We conclude that plasmapheresis should be started as soon as AHR is diagnosed, and be associated with a B-cell depleting agent. Rituximab may be considered as a first-line therapy.

  19. Expression of VE-Cadherin in Peritubular Endothelial Cells during Acute Rejection after Human Renal Transplantation

    Brigitte McGregor

    2007-07-01

    Full Text Available Genes involved in acute rejection (AR after organ transplantation remain to be further elucidated. In a previous work we have demonstrated the under-expression of VE-Cadherin by endothelial cells (EC in AR following murine and human heart transplantation. Serial sections from 15 human kidney Banff-graded transplant biopsies were examined for the presence of VE-Cadherin and CD34 staining by immunohistochemistry (no AR (n=5, AR grade IA (n=5, or AR grade IIA (n=5. Quantification of peritubular EC staining were evaluated and results were expressed by the percentage of stained cells per surface analysed. There was no difference in CD34 staining between the 3 groups. VE-Cadherin expression was significantly reduced in AR Grade IIA when compared to no AR (P=.01 and to AR grade IA (P=.02. This study demonstrates a reduced VE-Cadherin expression by EC in AR after renal transplantation. The down-regulation of VE-Cadherin may strongly participate in human AR.

  20. Experimental diabetes exacerbates skin transplant rejection in rats

    Flávio Pola dos Reis

    2013-05-01

    Full Text Available PURPOSE: To investigate the effect of chronic experimental diabetes on skin allografts in rats as a simple model that could clarify some basic aspects and mechanisms involved in transplant rejection in diabetes compared to normal animals. METHODS: Skin grafting was performed with fragments of tail skin from sex matched non diabetic Wistar rats engrafted onto the thoracic area of diabetic and non diabetic recipients. Grafts were scored for rejection every other day and were removed on day 14. Skin grafts were graded according to the following itens: no rejection; or rejection including: acute, chronic and humoral and/or cellular rejection. Statistical analysis was performed using JMP 5.1 software with ANOVA test. Diabetes was induced with IV injection of alloxan 40 mg/kg. RESULTS: Inflammatory vascular infiltrate compromising the endothelium with areas of fibrinoid necrosis and thrombosis characteristics of acute humoral rejection and subendothelial lymphocyte infiltrate typical of acute cellular rejection were significantly (p<0.003 higher in diabetic than in non diabetic recipients as the inflammatory infiltrate in the epidermis (p<0.002. CONCLUSION: Skin transplant acute rejection from chronic alloxan diabetic rats to normal tissue was significantly more intense than the acute rejection between normal rats.

  1. Antibody-Mediated Lung Transplant Rejection

    Hachem, Ramsey

    2012-01-01

    Antibody-mediated rejection after lung transplantation remains enigmatic. However, emerging evidence over the past several years suggests that humoral immunity plays an important role in allograft rejection. Indeed, the development of donor-specific antibodies after transplantation has been identified as an independent risk factor for acute cellular rejection and bronchiolitis obliterans syndrome. Furthermore, cases of acute antibody-mediated rejection resulting in severe allograft dysfunction have been reported, and these demonstrate that antibodies can directly injure the allograft. However, the incidence and toll of antibody-mediated rejection are unknown because there is no widely accepted definition and some cases may be unrecognized. Clearly, humoral immunity has become an important area for research and clinical investigation. PMID:23002428

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

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

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

    Dai Yong

    2008-01-01

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

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

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

    2013-01-01

    Objective Lung transplant volume has been increasing. However, inaccurate and uncertain diagnosis for lung transplant rejection hurdles long-term outcome due to, in part, interobserver variability in rejection grading. Therefore, a more reliable method to facilitate diagnosing and grading rejection is warranted. Method Rat lung grafts were harvested on day 3, 7, 14 and 28 post transplant for histological and immunohistochemical assessment. No immunosuppressive treatment was administered. We e...

  5. Methylprednisolone-hemisuccinate and its metabolites in serum, urine and bile from two patients with acute graft rejection.

    Lawson, G. J.; Chakraborty, J; Tredger, J M; Baylis, E M

    1995-01-01

    Methylprednisolone-hemisuccinate (MPHS), methylprednisolone (MP), 20-alpha-hydroxy- (20 alpha HMP) and 20-beta-hydroxymethyl-prednisolone (20 beta HMP) concentrations were measured in serum, urine and bile from two liver transplant recipients who had received 1 g MPHS by a 1 h intravenous infusion for treatment of an acute rejection episode. These patients excreted similar total amounts of the dose in urine as patients with rheumatoid arthritis (historical controls) who had normal liver funct...

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

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

  7. Thallium kinetics in rat cardiac transplant rejection

    Cardiac transplant rejection is a very complex process involving both cellular and vascular injury. Recently, thallium imaging has been used to assess acute transplant rejection. It has been suggested that changes in thallium kinetics might be a sensitive indicator of transplant rejection. Accordingly, thallium kinetics were assessed in vivo in acute untreated rat heterotopic (cervical) transplant rejection. Male Lewis rats weighing 225-250 g received heterotopic heart transplants from syngeneic Lewis rats (group A; n = 13), or allogeneic Brown Norway rats (group B; n = 11). Rats were imaged serially on the 2nd and the 7th postoperative days. Serial cardiac thallium content was determined utilizing data collected every 150 sec for 2 hr. The data were fit to a monoexponential curve and the decay rate constant (/sec) derived. By day 7 all group B hearts had histological evidence of severe acute rejection, and demonstrated decreased global contraction. Group A hearts showed normal histology and contractility. However, thallium uptakes and washout of the two groups were the same. Peak thallium uptake of group B was +/- 3758 1166 counts compared with 3553 +/- 950 counts in the control group A (P = 0.6395); The 2-hr percentage of washout was 12.1 +/- 1.04 compared with 12.1 +/- 9.3 (P = 1.0000); and the decay constant was -0.00002065 +/- 0.00001799 compared with -0.00002202 +/- 0.00001508 (P = 0.8409). These data indicate that in vivo global thallium kinetics are preserved during mild-to-severe acute transplant rejection. These findings suggest that the complex cellular and extracellular processes of acute rejection limit the usefulness of thallium kinetics in the detection of acute transplant rejection

  8. Thallium kinetics in rat cardiac transplant rejection

    Barak, J.H.; LaRaia, P.J.; Boucher, C.A.; Fallon, J.T.; Buckley, M.J.

    1988-04-01

    Cardiac transplant rejection is a very complex process involving both cellular and vascular injury. Recently, thallium imaging has been used to assess acute transplant rejection. It has been suggested that changes in thallium kinetics might be a sensitive indicator of transplant rejection. Accordingly, thallium kinetics were assessed in vivo in acute untreated rat heterotopic (cervical) transplant rejection. Male Lewis rats weighing 225-250 g received heterotopic heart transplants from syngeneic Lewis rats (group A; n = 13), or allogeneic Brown Norway rats (group B; n = 11). Rats were imaged serially on the 2nd and the 7th postoperative days. Serial cardiac thallium content was determined utilizing data collected every 150 sec for 2 hr. The data were fit to a monoexponential curve and the decay rate constant (/sec) derived. By day 7 all group B hearts had histological evidence of severe acute rejection, and demonstrated decreased global contraction. Group A hearts showed normal histology and contractility. However, thallium uptakes and washout of the two groups were the same. Peak thallium uptake of group B was +/- 3758 1166 counts compared with 3553 +/- 950 counts in the control group A (P = 0.6395); The 2-hr percentage of washout was 12.1 +/- 1.04 compared with 12.1 +/- 9.3 (P = 1.0000); and the decay constant was -0.00002065 +/- 0.00001799 compared with -0.00002202 +/- 0.00001508 (P = 0.8409). These data indicate that in vivo global thallium kinetics are preserved during mild-to-severe acute transplant rejection. These findings suggest that the complex cellular and extracellular processes of acute rejection limit the usefulness of thallium kinetics in the detection of acute transplant rejection.

  9. Cardiovascular magnetic resonance in the diagnosis of acute heart transplant rejection: a review

    Toma Mustafa

    2009-03-01

    Full Text Available Abstract Background Screening for organ rejection is a critical component of care for patients who have undergone heart transplantation. Endomyocardial biopsy is the gold standard screening tool, but non-invasive alternatives are needed. Cardiovascular magnetic resonance (CMR is well suited to provide an alternative to biopsy because of its ability to quantify ventricular function, morphology, and characterize myocardial tissue. CMR is not widely used to screen for heart transplant rejection, despite many trials supporting its use for this indication. This review summarizes the different CMR sequences that can detect heart transplant rejection as well as the strengths and weaknesses of their application. Results T2 quantification by spin echo techniques has been criticized for poor reproducibility, but multiple studies show its utility in screening for rejection. Human and animal data estimate that T2 quantification can diagnose rejection with sensitivities and specificities near 90%. There is also a suggestion that T2 quantification can predict rejection episodes in patients with normal endomyocardial biopsies. T1 quantification has also shown association with biopsy proven rejection in a small number of trials. T1 weighted gadolinium early enhancement appeared promising in animal data, but has had conflicting results in human trials. Late gadolinium enhancement in the diagnosis of rejection has not been evaluated. CMR derived measures of ventricular morphology and systolic function have insufficient sensitivity to diagnose mild to moderate rejection. CMR derived diastolic function can demonstrate abnormalities in allografts compared to native human hearts, but its ability to diagnose rejection has not yet been tested. There is promising animal data on the ability of iron oxide contrast agents to illustrate the changes in vascular permeability and macrophage accumulation seen in rejection. Despite good safety data, these contrast agents have

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

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

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

    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. PMID:25820657

  12. Increased Numbers of Circulating CD8 Effector Memory T Cells before Transplantation Enhance the Risk of Acute Rejection in Lung Transplant Recipients

    San Segundo, David; Ballesteros, María Ángeles; Naranjo, Sara; Zurbano, Felipe; Miñambres, Eduardo; López-Hoyos, Marcos

    2013-01-01

    The effector and regulatory T cell subpopulations involved in the development of acute rejection episodes in lung transplantation remain to be elucidated. Twenty-seven lung transplant candidates were prospectively monitored before transplantation and within the first year post-transplantation. Regulatory, Th17, memory and naïve T cells were measured in peripheral blood of lung transplant recipients by flow cytometry. No association of acute rejection with number of peripheral regulatory T cells and Th17 cells was found. However, effector memory subsets in acute rejection patients were increased during the first two months post-transplant. Interestingly, patients waiting for lung transplant with levels of CD8+ effector memory T cells over 185 cells/mm3 had a significant increased risk of rejection [OR: 5.62 (95% CI: 1.08-29.37), p=0.04]. In multivariate analysis adjusted for age and gender the odds ratio for rejection was: OR: 5.89 (95% CI: 1.08-32.24), p=0.04. These data suggest a correlation between acute rejection and effector memory T cells in lung transplant recipients. The measurement of peripheral blood CD8+ effector memory T cells prior to lung transplant may define patients at high risk of acute lung rejection. PMID:24236187

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

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

    2012-01-01

    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 posttransplantation 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.

  14. Cardiovascular magnetic resonance in the diagnosis of acute heart transplant rejection: a review

    Toma Mustafa; Haykowsky Mark; Thompson Richard; Butler Craig R; Paterson Ian

    2009-01-01

    Abstract Background Screening for organ rejection is a critical component of care for patients who have undergone heart transplantation. Endomyocardial biopsy is the gold standard screening tool, but non-invasive alternatives are needed. Cardiovascular magnetic resonance (CMR) is well suited to provide an alternative to biopsy because of its ability to quantify ventricular function, morphology, and characterize myocardial tissue. CMR is not widely used to screen for heart transplant rejection...

  15. Combined use of myeloid-related protein 8/14 and procalcitonin as diagnostic markers for acute allograft rejection in kidney transplantation recipients.

    Jung, Da-Yeon; Park, Jae Berm; Lee, Eun-Na; Lee, Hyun-Ah; Joh, Jae-Won; Kwon, Choon Hyuck; Ki, Chang-Seok; Lee, Soo-Youn; Kim, Sung-Joo

    2008-02-01

    The myeloid-related proteins 8 and 14 exist as a dimeric complex (MRP 8/14) and serve as early and highly specific markers for inflammatory processes, such as allograft rejection and non-viral (bacterial or fungal) infections. An elevated procalcitonin (PCT) concentration in serum also serves as a diagnostic indicator of non-viral infection. Therefore, by measuring both MRP 8/14 and PCT serum concentrations, one may be able to distinguish between acute allograft rejection and non-viral infections in non-rejection transplant recipients. Here, we investigated whether MRP 8/14 and PCT can function as prognostic (Study I) or diagnostic (Study II) markers for allograft rejection in renal transplant recipients. In Study I, the serum concentrations of MRP 8/14 and PCT during the first 2 weeks after transplantation did not differ between patients who did and did not suffer organ rejection within 1 year post-transplantation; these findings suggest that the MRP 8/14 and PCT parameters are not valid prognostic markers. However, in Study II, patients with acute rejection or non-rejection/non-viral infection groups displayed a significant increase in serum MRP 8/14 concentration, and non-rejection patients with non-viral infections only had elevation in the PCT serum concentrations. These results indicate that the combined use of MRP 8/14 and PCT serum concentrations can allow one to distinguish between allograft rejection and other inflammatory processes, such as infection. PMID:18158120

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

    Thomas H Waid

    2009-06-01

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

  17. CXCL9 and CXCL10 accelerate acute transplant rejection mediated by alloreactive memory T cells in a mouse retransplantation model

    ZHUANG, JIAWEI; SHAN, ZHONGGUI; MA, TENG; LI, CHUN; QIU, SHUIWEI; ZHOU, XIAOBIAO; LIN, LIANFENG; QI, ZHONGQUAN

    2014-01-01

    C-X-C motif chemokine ligand (CXCL) 9 and CXCL10 play key roles in the initiation and development of acute transplant rejection. Previously, higher levels of RANTES expression and secretion were demonstrated in retransplantation or T-cell memory-transfer models. In the present study, the effect of the chemokines, CXCL9 and CXCL10, were investigated in a mouse retransplantation model. BALB/c mice were used as donors, while C57BL/6 mice were used as recipients. In the experimental groups, a heterotopic heart transplantation was performed six weeks following skin grafting. In the control groups, a heterotopic heart transplantation was performed without skin grafting. Untreated mice served as blank controls. The mean graft survival time of the heterotopic heart transplantations was 7.7 days in the experimental group (n=6), as compared with 3.25 days in the control group (n=6; P<0.001). On day three following cardiac transplantation, histological evaluation of the grafts revealed a higher International Society for Heart & Lung Transplantation grade in the experimental group as compared with the control group. In addition, gene expression and serum concentrations of CXCL9, CXCL10, interferon-γ, and interleukin-2 were markedly higher in the experimental group when compared with the control group. Differences between the levels of CXCL9 and CXCL10 in the pre- and post-transplant mice indicated that the chemokines may serve as possible biomarkers to predict acute rejection. The results of the present study demonstrated that CXCL9 and CXCL10 play a critical role in transplantation and retransplantation. High levels of these cytokines during the pre-transplant period may lead to extensive acute rejection. Thus, the observations enhance the understanding of the mechanism underlying the increased expression and secretion of CXCL9 and CXCL10 by alloreactive memory T cells. PMID:24944628

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

    Junichiro Sageshima

    2009-06-01

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

  19. Uninfected and cytomegalic endothelial cells in blood during cytomegalovirus infection : Effect of acute rejection

    Kas-Deelen, AM; de Maar, EF; Harmsen, MC; van Son, WJ; The, TH; Driessen, C.

    2000-01-01

    After transplantation, human cytomegalovirus (HCMV) infections can cause vascular damage to both the graft and the host. To study a possible relationship between the degree of vascular injury, clinical symptoms of HCMV infection, and transplant rejection, the appearance and numbers of endothelial ce

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

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

    2002-01-01

    We investigated whether determination in fine-needle aspiration biopsy (FNAB) specimens of cells expressing granzymes (Grs) and Fas ligand would provide a reliable, easy, and quantitative measure of rejection activity in the transplanted liver. Retrospectively, 13 FNAB specimens obtained during clin

  1. A suspected case of plasma cell-rich acute renal transplant rejection associated with de novo donor-specific antibody.

    Yoshikawa, Mikiko; Kitamura, Ken; Ishimura, Takeshi; Hara, Shigeo; Fujisawa, Masato; Nishi, Shinichi

    2015-07-01

    A kidney transplant case with de novo donor-specific antibody showed monoclonal plasma cell infiltration into the graft with ABO incompatibility. Three years after transplantation, the patient's graft function suddenly deteriorated. Interstitial edema and the predominant infiltration of inflammatory plasma cells with kappa chain monoclonality were observed in biopsy specimens. The in situ hybridization of Epstein-Barr virus was negative and post-transplant lymphoproliferative disorder was not evident from radiological examinations. On laboratory examination, the patient had de novo donor-specific antibody for HLA-DQ. We suspected plasma cell-rich acute rejection for which methylprednisolone pulse therapy, plasma exchange, rituximab, and 15-deoxyspergualin were given. In the ensuing biopsy, the degree of plasma cell infiltration was similar to the first biopsy; however, kappa chain monoclonality relatively weakened. Owing to resistance to these treatments, intravenous immunoglobulin (IVIG) (0.5 g/kg/day) was added. The serum creatinine level gradually declined to 3.1 mg/dL; however, it increased up to 3.6 mg/dL again. In the final biopsy, the infiltrated plasma cells disappeared but severe interstitial fibrosis developed. This case showed difficulty in the diagnosis and treatment of plasma cell-rich acute rejection. A detailed consideration of this case may be helpful in understanding the clinical features and pathogenesis of this condition. PMID:26031590

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

    Fabricio Ferreira Coelho

    2003-01-01

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

  3. Serum sickness following rabbit anti-thymocyte globulin for acute vascular renal allograft rejection

    Teng, Jessie; Hoo, Xing Ning; Tan, Sven-Jean; Dwyer, Karen

    2012-01-01

    A simultaneous pancreas–kidney transplant recipient developed serum sickness manifesting with severe upper limb allodynia, arthralgia and myalgia 17 days following rabbit anti-thymocyte globulin (rATG) infusion for biopsy-proven vascular rejection. Rapid resolution of symptoms followed treatment with high-dose glucocorticoids. rATG is increasingly favoured over equine ATG in solid-organ transplantation, and although rATG has a superior safety profile, it is important to maintain a high index ...

  4. Comparison of the Th1, IFN-γ secreting cells and FoxP3 expression between patients with stable graft function and acute rejection post kidney transplantation.

    Banafsheh Nazari

    2013-09-01

    Full Text Available There are limited clinical investigations identifying the percentage of T helper 1 (Th1 and T regulatory (Treg cells in stable as well as rejected kidney allografts, a concept which needs to be more studied. The aim of our study was to compare the percentage of CD4+ IFN-γ+ cells, the number of IFN-γ secreting cells and the amount of FoxP3 expression in patients with or without stable graft function, to determine the roles of these immunological factors in stable and rejected renal allografts. In this prospective study, 3 months after transplantation 30 patients who received renal transplants from unrelated living donors were enrolled and divided into two groups, 20 patients with stable graft function and 10 patients with biopsy proven acute rejection. The percentage of Th1 CD4+ IFN-γ+ cells was determined on PBMC by flow cytometry and the number of IFN-γ secreting cells by ELISPOT method. Furthermore, FoxP3 expression of PBMCs was measured by Real Time PCR method. The results of these assessments in both groups were statistically analyzed by SPSS 14.0. Our results showed that the percentage of Th1 CD4+ IFN-γ+ cells and the number of IFN-γ secreting cells were significantly higher in the patients with acute rejection in comparison to the stable graft function group (p<0.001. In addition, the level of FoxP3 gene expression was higher in the group with stable graft compared to the acute rejection group. The higher percentage of CD4+ IFN-γ+Th1 subset and number of IFN-γ secreting cells and also the lower expression of Foxp3 could prone the patients to acute rejection episode post transplantation. By these preliminary data, it is suggested that monitoring of Th1 cells post transplantation, as an immunologic marker could predict the possibility of rejection episodes.

  5. Effect of operation-synchronizing transfusion of apoptotic spleen cells from donor rats on acute rejection of recipient rats after liver transplantation

    Jing Liu; Yi Gao; Shuan Wang; Er-Wei Sun; Yu Wang; Zhi Zhang; Yi-Qiang Shan; Shi-Zheng Zhong

    2005-01-01

    AIM: To study effect of operation-synchronizing transfusion of apoptotic spleen cells from donor rats on acute rejection of recipient rats after liver transplantation.METHODS: Two of Wistar rats were chosen randomly for normal liver pathology control and ten of SD rats chosen randomly for liver function control as blank group (no operation). The rest of Wistar and SD rats were divided into four groups: control group (only liver transplantation),Dex group (donors receiving intraperitoneal injection of dexamethasone), SpC group (recipients receiving infusion of spleen cells of donors), Dex-SpC group (recipients receiving infusion of apoptotic spleen cells of donors),with each group except blank group, containing 10 SD rats and 10 Wistar rats, respectively. Wistar rats received liver transplantation from SD rats, in the meantime they received infusion of spleen cells of donors, which were induced by an intraperitoneal injection of dexamethasone The serum alanine transaminase (ALT), total bilirubin (T bili), liver pathological changes and survival time were analysed. Statistical analysis was carried out using SPSS 10.0 for Windows. Differences of the parametric data of ALT in means were examined by one-way ANOVA.Differences of ALT between two groups were examined by LSD. Differences of the nonparametric data of T bili in means and scores of pathology classification for acute rejection were examined by Kruskal-Willis H test. The correlations between ALT and T bili were analysed by Bivariate. Kaplan-Meier curves were used to demonstrate survival distribution. The log-rank test was used to compare the survival data.RESULTS: There were significant differences in ALT of the five groups (F= 23.164 P= 0.000), and ALT in DexSpC group was significantly higher than that in blank control, control, Dex, and SpC groups (P = 0.000), and ALT in SpC group was significantly higher than that in blank control (P = 0.000), control (P = 0.004), and Dex groups (P = 0.02). Results of

  6. Methylprednisolone-hemisuccinate and its metabolites in serum, urine and bile from two patients with acute graft rejection.

    Lawson, G J; Chakraborty, J; Tredger, J M; Baylis, E M

    1995-01-01

    Methylprednisolone-hemisuccinate (MPHS), methylprednisolone (MP), 20-alpha-hydroxy- (20 alpha HMP) and 20-beta-hydroxymethyl-prednisolone (20 beta HMP) concentrations were measured in serum, urine and bile from two liver transplant recipients who had received 1 g MPHS by a 1 h intravenous infusion for treatment of an acute rejection episode. These patients excreted similar total amounts of the dose in urine as patients with rheumatoid arthritis (historical controls) who had normal liver function. The transplant patients showed a ratio in urine of 'total metabolites'/MPHS that was one third that of patients with rheumatoid arthritis. Less than 0.2% of the administered MPHS appeared in bile as MPHS, MP, 20 alpha HMP and 20 beta HMP during the 24 h following infusion. Liver transplantation did not affect the overall elimination of drug in urine. However, the impaired liver function following transplantation resulted in reduced conversion of MPHS to its active form (MP). PMID:7742157

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

    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.

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

    O'Seaghdha, C M

    2011-04-06

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

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

    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. PMID:26693703

  10. The Natural History of Biopsy-Negative Rejection after Heart Transplantation

    Zhaoyi Tang; Jon Kobashigawa; Matthew Rafiei; Lily Kagan Stern; Michele Hamilton

    2013-01-01

    Purpose. The most recent International Society for Heart and Lung Transplantation (ISHLT) biopsy scale classifies cellular and antibody-mediated rejections. However, there are cases with acute decline in left ventricular ejection fraction (LVEF ≤ 45%) but no evidence of rejection on biopsy. Characteristics and treatment response of this biopsy negative rejection (BNR) have yet to be elucidated. Methods. Between 2002 and 2012, we found 12 cases of BNR in 11 heart transplant patients as previou...

  11. Role of 1, 25-dihydroxyvitamin D3 in preventing acute rejection of allograft following rat orthotopic liver transplantation

    章爱斌; 郑树森; 贾长库; 王雁

    2004-01-01

    Background We investigated the role of 1, 25-dihydroxyvitamin D3 (1, 25-(OH)2D3) in preventing allograft from acute rejection following orthotopic liver transplantation. Methods A rat orthotopic liver transplantation model was used in this study. SD-Wistar rats served as a high responder strain combination. Recipients were subjected to administration of 1, 25-(OH)2 D3 at dosages ranging from 0.25 μg·kg-1*d-1 to 2.5 μg·kg-1*d-1. Survival after transplantation as well as pathological rejection grades and IFN-γ mRNA, IL-10 mRNA transcription intragraft on day 7, and day 30 post-transplantation were observed. Results After recipients were treated with 1, 25(OH)2 D3 at dosages of 0.5 μg*kg-1*d-1 or 1.0 μ g*kg-1*d-1, survivals of recipients were prolonged. Ninety-five percent confidence intervals of survival were 46-87 days and 69-102 days (both P=0.0005 vs control group), respectively. On day seven post-transplantation, relative levels of IFN-γ mRNA transcription were 0.59±0.12 and 0.49±0.16, which was higher than the control group (P=0.005, P=0.003, respectively). Relative levels of IL-10 mRNA transcription were 0.83±0.09 and 0.76±0.09, which was lower than the control group (P=0.002, P=0.003, respectively). At a dosage of 0.5 μg·kg-1*d-1, the median of pathological rejection grade on day seven and on day thirty post-transplantation were 1.5 and 2.0 in comparison with the CsA-treated group (P=0.178, P=0.171, respectively). At a dosage of 0.5 μg·kg-1*d-1, the median of pathological rejection grade on day seven and day thirty post-transplantation were 1.5 and 1.5 in comparison with CsA-treated group (P=0.350, P=0.693, respectively).Conclusion After each recipient was treated with 1,25-(OH)2 D3 at a dosage of (0.5-1.0) μg·kg-1*d-1, transcription of cytokine intragraft was accommodated effectively and deviated to Th2 type, resulting in alleviation of acute rejection. 1, 25-(OH)2 D3 can prolong survival of recipient after orthotopic liver transplantation.

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

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

    1999-01-01

    Background: A widely held view is that any increase in the potency of an immunosuppressive agent will lead to an increase in infection and malignancy, such as life-threatening Epstein-Barr virus (EBV) induced posttransplant lymphoproliferative disorders (PTLD), We tested this paradigm by studying......: (1) primary or reactivated EBV infection (PREBV) was correlated to acute rejection (treated with OKT3; P<0.00005) and to the incidence of PTLD (P=0.03; P=0.01, if Hodgkin's disease is included); (2) aciclovir protected against PREBV (P<0.00005) and (3) adding mofetil to the immunosuppressive protocol...... immunosuppression with mofetil protects against acute rejection. In combination with aciclovir, there is also a reduction in the number of PREBVs, apparently as a result of both direct viral prophylaxis and better rejection control, and in the incidence of EBV-induced PTLD Udgivelsesdato: 1999...

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

    Saueressig M.G.

    2005-01-01

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

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

    Silke Roedder

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

  15. Cyclosporine Does Not Prevent Microvascular Loss in Transplantation but Can Synergize With a Neutrophil Elastase Inhibitor, Elafin, to Maintain Graft Perfusion During Acute Rejection.

    Jiang, X; Nguyen, T T; Tian, W; Sung, Y K; Yuan, K; Qian, J; Rajadas, J; Sallenave, J-M; Nickel, N P; de Jesus Perez, V; Rabinovitch, M; Nicolls, M R

    2015-07-01

    The loss of a functional microvascular bed in rejecting solid organ transplants is correlated with fibrotic remodeling and chronic rejection; in lung allografts, this pathology is predicted by bronchoalveolar fluid neutrophilia which suggests a role for polymorphonuclear cells in microcirculatory injury. In a mouse orthotopic tracheal transplant model, cyclosporine, which primarily inhibits T cells, failed as a monotherapy for preventing microvessel rejection and graft ischemia. To target neutrophil action that may be contributing to vascular injury, we examined the effect of a neutrophil elastase inhibitor, elafin, on the microvascular health of transplant tissue. We showed that elafin monotherapy prolonged microvascular perfusion and enhanced tissue oxygenation while diminishing the infiltration of neutrophils and macrophages and decreasing tissue deposition of complement C3 and the membrane attack complex, C5b-9. Elafin was also found to promote angiogenesis through activation of the extracellular signal-regulated kinase (ERK) signaling pathway but was insufficient as a single agent to completely prevent tissue ischemia during acute rejection episodes. However, when combined with cyclosporine, elafin effectively preserved airway microvascular perfusion and oxygenation. The therapeutic strategy of targeting neutrophil elastase activity alongside standard immunosuppression during acute rejection episodes may be an effective approach for preventing the development of irreversible fibrotic remodeling. PMID:25727073

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

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

    2015-01-01

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

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

    Zhou J; Ju W; Yuan X; Zhu X; Wang D; He X

    2014-01-01

    Jian Zhou,* Weiqiang Ju,* Xiaopeng Yuan, Xiaofeng Zhu, Dongping Wang, Xiaoshun HeOrgan Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China *These authors contributed equally to this work Abstract: Hyperosmolar nonketotic hyperglycemic coma (HNKHC) is a serious, rare complication induced by methylprednisolone (MP) pulse therapy for acute rejection after orthotopic liver transplantation (OLT). Herein, we report an unusual case of a 58...

  18. Changes in left ventricular function and wall thickness in heart transplant recipients and their relation to acute rejection: an assessment by digitised M mode echocardiography

    Mannaerts, H F J; Balk, Aggie; Simoons, Maarten; Tijssen, Jan,; Borden, S.G.; Sutherland, G. R.; Roelandt, Jos; Zondervan, Pieter

    1992-01-01

    textabstractOBJECTIVE--Assessment of changes in left ventricular diastolic function and wall thickness after heart transplantation to verify whether these changes predicted acute rejection assessed by endomyocardial biopsy. DESIGN--Follow up according to a predefined protocol of consecutive patients from the first week after transplantation. SETTING--Heart transplantation unit of the Thoraxcentre, University Hospital Rotterdam Dijkzigt, The Netherlands. PATIENTS--All 32 patients undergoing or...

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

    Zhou J

    2014-12-01

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

  20. Cellular and molecular mechanisms of repair in acute and chronic wound healing

    Martin, P.; Nunan, R

    2015-01-01

    Summary A considerable understanding of the fundamental cellular and molecular mechanisms underpinning healthy acute wound healing has been gleaned from studying various animal models, and we are now unravelling the mechanisms that lead to chronic wounds and pathological healing including fibrosis. A small cut will normally heal in days through tight orchestration of cell migration and appropriate levels of inflammation, innervation and angiogenesis. Major surgeries may take several weeks to ...

  1. NF-κB activation and zinc finger protein A20 expression in mature dendritic cells derived from liver allografts undergoing acute rejection

    Ming-Qing Xu; Wei Wang; Lan Xue; Lv-Nan Yan

    2003-01-01

    AIM: To investigate the role of NF-κB activation and zinc finger protein A20 expression in the regulation of maturation of dendritic cells (DCs) derived from liver allografts undergoing acute rejection. METHODS: Sixty donor male SD rats and sixty recipient male LEW rats weighing 220-300 g were randomly divided into whole liver transplantation group and partial liver transplantation group. Allogeneic (SD rat to LEW rat) whole and 50 % partial liver transplantation were performed. DCs from liver grafts 0 hour and 4 days after transplantation were isolated and propagated in the presence of GM-CSF in vitro. Morphological characteristics and phenotypical features of DCs propagated for 10 days were analyzed by electron microscopy and flow cytometry, respectively. NF-κB binding activity, IL-12p70 protein and zinc finger protein A20expression in these DCs were measured by EMSA and Western blotting, respectively. Histological grading of rejection was determined. RESULTS: Allogeneic whole liver grafts showed no signs of rejection on day 4 after the transplantation. In contrast,allogeneic partial liver grafts demonstrated moderate to severe rejection on day 4 after the transplantation. After propagation for 10 days in the presence of GM-CSF in vitro,DCs from allogeneic whole liver grafts exhibited features of immature DC with absence of CD40 surface expression,these DCs were found to exhibit detectable but very low level of NF-κB activity, IL-12 p70 protein and zinc finger protein A20 expression. Whereas, DCs from allogeneic partial liver graft 4 days after transplantation displayed features of mature DC, with high level of CD40 surface expression, and as a consequence, higher expression of IL-12p70 protein, higher activities of NF-κB and higher expression of zinc finger protein A20 compared with those of DCs from whole liver grafts (P<0.001). CONCLUSION: These results suggest that A20expression is up-regulated in response to NF-κB activation in mature DCs derived from

  2. Chronic alloantibody mediated rejection

    Smith, R. Neal; Colvin, Robert B.

    2011-01-01

    Alloantibodies clearly cause acute antibody mediated rejection, and all available evidence supports their pathogenic etiology in the development of chronic alloantibody mediated rejection (CAMR). But the slow evolution of this disease, the on-going immunosuppression, the variations in titer of alloantibodies, and variation in antigenic targets all complicate identifying which dynamic factors are most important clinically and pathologically. This review highlights the pathological factors rela...

  3. Disturbance Rejection

    2005-01-01

    This interactive tutorial reviews the disturbance rejection capabilities of different feedback control schemes. The interactions in this tutorial involve students analyzing 4 cases of step-like disturbance rejection. ME2801 Introduction to Engineering System Dynamics

  4. Chronic allograft rejection: A significant hurdle to transplant success

    Malgorzata Kloc

    2014-01-01

    Full Text Available The state-of-the-art immunosuppression drugs do not ensure indefinite transplant survival, and most transplants are continuously lost to chronic rejection even years posttransplantation. This form of rejection is responsible for long-term failure of transplanted organs. The mechanisms involved in development of chronic rejection are not well-understood. One of the main features of chronic rejection is progressive luminal narrowing of graft vessels, which results in compromised blood flow, ischemia, cell death, and finally graft failure. All the existing immunosuppressive regimens are targeting acute rejection, and at present there is no available therapy for prevention of chronic rejection. Chronic rejection involves two major, but interrelated responses: The first is the host immune response against the transplant mediated primarily by alloreactive T and B cells, and the second is injury and repair of the graft (vasculopathy of graft vessels. Here we focus on recent advances in understanding the cellular and molecular aspects of chronic transplant vasculopathy and function of macrophages, topics pivotal for development of novel antichronic rejection therapies.

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

    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 evi...

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

    MING, YINGZI; Hu, Juan; Luo, Qizhi; Ding, Xiang; Luo, Weiguang; Zhuang, Quan; Zou, Yizhou

    2015-01-01

    The presence of donor-specific alloantibodies (DSAs) against the MICA antigen results in high risk for antibody-mediated rejection (AMR) of a transplanted kidney, especially in patients receiving a re-transplant. We describe the incidence of acute C4d+ AMR in a patient who had received a first kidney transplant with a zero HLA antigen mismatch. Retrospective analysis of post-transplant T and B cell crossmatches were negative, but a high level of MICA alloantibody was detected in sera collecte...

  7. The Cellular Differences between Acute and Chronic Neutron and Gamma-Ray Irradiation in Mice

    Data on the shortening of the life span in mice by radiation show that an acute dose of gamma-rays may be as much as four times as effective as an equal dose of the same radiation administered chronically. However, for neutrons, chronic and acute administrations are equally effective. An analysis of these effects shows that for gamma-rays a certain fraction of the radiation injury is reparable, and that the value of this fraction depends on the dose and the dose rate. With neutrons, none of the damage appears reparable. For acute irradiation, the RBE is about 2 for shortening of the life span, but for chronic, may be as high as 8. Chromosome aberrations have been scored in liver cells of mice when treated with both chronic and acute doses of both gamma-rays and thermal neutrons. In all cases the percentage of aberrent cells is proportional to the shortening of the life span produced by the treatment. Further, with neutrons, acute and chronic irradiation is equally effective in producing chromosome abberations. For gamma-rays, acute irradiation may produce as much as four times the chromosomal damage as does chronic irradiation. This shows that some chromosomes can heal themselves following small doses of gamma-rays, but there is no chromosome healing following any dose of neutrons. The RBE using chromosome aberrations as a criterion is the same as for life shortening. These results give a firm cellular basis for the known biological differences between gamma rays and neutrons, and in addition give strong support to the concept that natural and radiation-induced aging are caused by spontaneous and radiation-induced mutations, respectively, in the somatic cells of animals. (author)

  8. Indium-111 myosin-specific antibodies and technetium-99m pyrophosphate in the detection of acute cardiac rejection of transplanted hearts

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

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

    Christopher Vollmers

    2015-10-01

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

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

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

    2008-04-01

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

  11. Transplant rejection in terrestrial molluscs

    E Furuta; Yamaguchi, K

    2011-01-01

    To know whether or not molluscs are capable of recognizing tissue allo-antigens, dorsal skin-allografts were exchanged between adult terrestrial slug, Incilaria fruhstorferi. We succeeded for the first time in orthotopic transplantation of allografts and observed chronic rejection of allografts. Cellular changes in the rejection process continued over for 40 days. Two functional types of “effector” cells were recognized at the rejection site, but they were observed to be macrophages possessin...

  12. Acute or chronic transplant rejection - high resolution CT of the chest in lung transplant recipients; Akute oder chronische Transplantat-Abstossung? - HRCT des Thorax bei Patienten nach Lungentransplantation

    Herber, S.; Heussel, C.P.; Thelen, M.; Kauczor, H.U. [Mainz Univ. (Germany). Klinik und Poliklinik fuer Radiologie; Lill, J. [3. Medizinische Klinik, Schwerpunkt Pneumologie, Johannes-Gutenberg-Univ. Mainz (Germany); Mayer, E. [Klinik und Poliklinik fuer Herz-Thorax-Gefaess-Chirurgie, Johannes-Gutenberg-Univ. Mainz (Germany)

    2001-09-01

    Purpose: Aim of the study was to evaluate the postoperative changes in patients with single (SLTX) or double lung transplantation (DLTX) with HRCT and to correlate those findings with the clinical diagnosis. Material and methods: 29 patients with SLTX (n = 14) or DLTX (n = 15) were observed for more than 6 years after transplantation by HRCT (n = 82). CT examinations were performed in inspiration and expiration (n = 70) with a slice thickness of 1 mm and a feed of 10 mm. The image material was evaluated by 2 experienced radiologists in consensus. Criteria for acute rejection at HRCT were: ground glass opacities and focal air trapping in expiration. Criteria for chronic transplant rejection were: bronchial dilatation, bronchial wall thickening and thickening of interlobar septae. The clinical evaluation consisted of laboratory tests, lung function tests, and bronchoscopy including bronchial lavage in special cases. Results: 20/29 patients are still alive (mean 21 months). 5/9 patients died because of chronic transplantant rejection, 1 patient suffered from a non-Hodgkin's lymphoma localised at the right hilus. Severe threatening pneumonia occurred in 13 cases. 10/29 patients showed symptoms of acute rejection. Expiratory HRCT found a focal air trapping in all cases and extended ground glass opacities in 11/14 cases. Also a bronchial dilatation was observed in more than 50% (9/14). 12/29 patients suffered from chronic transplant rejection. HRCT showed bronchial dilatation in 26/27 investigations and severe ground glass opacities in 21/27 investigations. Thickening of the interlobal septa as well as centrilobular opacities were found in more than 50% of the examinations. Conclusion: High resolution CT of the chest in patients after lung transplantation is able to show numerous pathological alterations. Without clinical information a confident differentiation in acute or chronic transplant rejection or pneumonia can be difficult or impossible. (orig.) [German

  13. Rejecting Change

    KERRY; BROWN

    2011-01-01

    British voters overwhelmingly reject an alternative voting system The British electorate,in only the second ever national referendum held in their history (the first was on joining the EU,over 35 years ago) rejected alterations to their voting system from the current first-past-the-post system to a form of alternative voting similar to that used

  14. Autophagy in allografts rejection: A new direction?

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

    2016-03-18

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

  15. The Use of Amnion-Derived Cellular Cytokine Solution to Improve Healing in Acute and Chronic Wound Models

    Franz, Michael G.; Payne, Wyatt G.; Xing, Liyu; Naidu, D. K; Salas, R. E; Marshall, Vivienne S.; Trumpower, C. J; Smith, Charlotte A; Steed, David L.; Robson, M. C.

    2008-01-01

    Objective: Growth factors demonstrate mixed results improving wound healing. Amnion-derived multipotent cells release physiologic levels of growth factors and tissue inhibitors of metalloproteinases. This solution was tested in models of acute and chronic wound healing. Methods: Acute model: Sprague-Dawley rats underwent laparotomy incisions. The midline fascia was primed with phosphate-buffered saline, unconditioned media, or amnion-derived cellular cytokine suspension prior to incision. Bre...

  16. Gene Expression in Biopsies of Acute Rejection and Interstitial Fibrosis/Tubular Atrophy Reveals Highly Shared Mechanisms That Correlate With Worse Long-Term Outcomes.

    Modena, B D; Kurian, S M; Gaber, L W; Waalen, J; Su, A I; Gelbart, T; Mondala, T S; Head, S R; Papp, S; Heilman, R; Friedewald, J J; Flechner, S M; Marsh, C L; Sung, R S; Shidban, H; Chan, L; Abecassis, M M; Salomon, D R

    2016-07-01

    Interstitial fibrosis and tubular atrophy (IFTA) is found in approximately 25% of 1-year biopsies posttransplant. It is known that IFTA correlates with decreased graft survival when histological evidence of inflammation is present. Identifying the mechanistic etiology of IFTA is important to understanding why long-term graft survival has not changed as expected despite improved immunosuppression and dramatically reduced rates of clinical acute rejection (AR) (Services UDoHaH. http://www.ustransplant.org/annual_reports/current/509a_ki.htm). Gene expression profiles of 234 graft biopsy samples were obtained with matching clinical and outcome data. Eighty-one IFTA biopsies were divided into subphenotypes by degree of histological inflammation: IFTA with AR, IFTA with inflammation, and IFTA without inflammation. Samples with AR (n = 54) and normally functioning transplants (TX; n = 99) were used in comparisons. A novel analysis using gene coexpression networks revealed that all IFTA phenotypes were strongly enriched for dysregulated gene pathways and these were shared with the biopsy profiles of AR, including IFTA samples without histological evidence of inflammation. Thus, by molecular profiling we demonstrate that most IFTA samples have ongoing immune-mediated injury or chronic rejection that is more sensitively detected by gene expression profiling. These molecular biopsy profiles correlated with future graft loss in IFTA samples without inflammation. PMID:26990570

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

    Sonia Badwal

    2015-01-01

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

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

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

    2015-11-01

    This single-center study was carried out on living related and unrelated renal transplant recipients (RTRs) to evaluate the usefulness of surveillance biopsies in monitoring stable renal allografts using immuno-histological markers for immune-activation. This is a prospective, longitudinal study. Protocol biopsies of 60 RTRs with stable graft function were evaluated at three, six and 12 months post-transplant. Immuno-histological evaluation was carried out using immune-activation markers (perforins, granzyme and interleukin-2R), phenotypic markers (CD-3 and CD-20), viral markers and C4d. The demographic and clinical profile was recorded for each patient. All cases of acute sub-clinical rejection (SCR) were treated and borderline SCR cases were followed-up without treatment. SCR at three and six months post-transplant was evident in 16.7% and 3.7% of RTRs, respectively. Positive statistical association of SCR was seen with HLA-DR mismatches, whereas patients receiving induction therapy and tacrolimus-based immunosuppression exhibited a lower incidence of SCR. T cell phenotype with persistent expression of immune-activation markers exhibited positive statistical association with interstitial fibrosis and tubular atrophy at 12-month follow-up biopsy. The mean creatinine levels were significantly lower in the protocol biopsy group than the non-protocol biopsy group. No significant difference was found between the mean creatinine levels of the SCR group after treatment and the non-SCR cases within the protocol biopsy group. Early treatment of sub-clinical acute rejection leads to better functional outcomes. However, persistent immune-activation is associated with chronicity and may have implications on long-term graft survival. PMID:26586064

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

    Kazuaki Yamanaka

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

  20. Transplant rejection

    ... is usually not perfect. No two people, except identical twins, have identical tissue antigens. Doctors use medicines to ... has no blood supply. Also, transplants from one identical twin to another are almost never rejected. There are ...

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

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

    2014-01-01

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

  2. Universal noninvasive detection of solid organ transplant rejection

    Snyder, Thomas M.; Khush, Kiran K.; Valantine, Hannah A.; Quake, Stephen R.

    2011-01-01

    It is challenging to monitor the health of transplanted organs, particularly with respect to rejection by the host immune system. Because transplanted organs have genomes that are distinct from the recipient's genome, we used high throughput shotgun sequencing to develop a universal noninvasive approach to monitoring organ health. We analyzed cell-free DNA circulating in the blood of heart transplant recipients and observed significantly increased levels of cell-free DNA from the donor genome at times when an endomyocardial biopsy independently established the presence of acute cellular rejection in these heart transplant recipients. Our results demonstrate that cell-free DNA can be used to detect an organ-specific signature that correlates with rejection, and this measurement can be made on any combination of donor and recipient. This noninvasive test holds promise for replacing the endomyocardial biopsy in heart transplant recipients and may be applicable to other solid organ transplants. PMID:21444804

  3. Early Acute Antibody-Mediated Rejection of a Negative Flow Crossmatch 3rd Kidney Transplant with Exclusive Disparity at HLA-DP

    Mierzejewska, Beata; Schroder, Paul M.; Baum, Caitlin E.; Blair, Annette; Smith, Connie; Duquesnoy, Rene J.; Marrari, Marilyn; Gohara, Amira; Malhotra, Deepak; Kaw, Dinkar; Liwski, Robert; Rees, Michael A.; Stepkowski, Stanislaw

    2014-01-01

    Donor-specific alloantibodies (DSA) to HLA-DP may cause antibody-mediated rejection (AMR), especially in re-transplants. We describe the immunization history of a patient who received 3 kidney transplants; the 3rd kidney was completely matched except at DPA1 and DPB1. Prior to the 3rd transplant, single antigen bead analysis (SAB) showed DSA reactivity against DPA1 shared by the 1st and 3rd donors, but B and T flow crossmatch (FXM) results were negative. Within 11 days the 3rd transplant underwent acute C4d+ AMR which coincided with the presence of complement (C1q)-binding IgG1 DSA against donor DPA1 and DPB1. Using HLAMatchmaker and SAB, we provide evidence that eplet (epitope) spreading on DPA1 and eplet sharing on differing DPB1 alleles of the 1st and 3rd transplants was associated with AMR. Since weak DSA to DPA1/DPB1 may induce acute AMR with negative FXM, donor DPA1/DPB1 high resolution typing should be considered in sensitized patients with DP-directed DSA. PMID:24755353

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

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

    2016-04-01

    The Pleximmune(TM) test (Plexision Inc., Pittsburgh, PA, USA) is the first cell-based test approved by the US FDA, which predicts acute cellular rejection in children with liver- or intestine transplantation. The test addresses an unmet need to improve management of immunosuppression, which incurs greater risks of opportunistic infections and Epstein-Barr virus-induced malignancy during childhood. High-dose immunosuppression and recurrent rejection after intestine transplantation also result in a 5-year graft loss rate of up to 50%. Such outcomes seem increasingly unacceptable because children can experience rejection-free survival with reduced immunosuppression. Pleximmune test sensitivity and specificity for predicting acute cellular rejection is 84% and 80% respectively in training set-validation set testing of 214 children. Among existing gold standards, the biopsy detects but cannot predict rejection. Anti-donor antibodies, which presage antibody-mediated injury, reflect late-stage allosensitization as a downstream effect of engagement between recipient and donor cells. Therefore, durable graft and patient outcomes also require accurate management of cellular immune responses in clinical practice. PMID:26760313

  5. Beneficial Immune Effects of Myeloid-Related Proteins in Kidney Transplant Rejection.

    Rekers, N V; Bajema, I M; Mallat, M J K; Petersen, B; Anholts, J D H; Swings, G M J S; van Miert, P P M C; Kerkhoff, C; Roth, J; Popp, D; van Groningen, M C; Baeten, D; Goemaere, N; Kraaij, M D; Zandbergen, M; Heidt, S; van Kooten, C; de Fijter, J W; Claas, F H J; Eikmans, M

    2016-05-01

    Acute rejection is a risk factor for inferior long-term kidney transplant survival. Although T cell immunity is considered the main effector in clinical acute rejection, the role of myeloid cells is less clear. Expression of S100 calcium-binding protein A8 (S100A8) and S100A9 was evaluated in 303 biopsies before and after transplantation from 190 patients. In two independent cohorts of patients with acute rejection (n = 98 and n = 11; mostly cellular rejections), high expression of S100 calcium-binding protein A8 (S100A8) and A9 (S100A9) was related to improved graft outcome. Mechanisms of action of the S100 molecules were investigated. In the graft and peripheral blood cells, S100A8 and S100A9 expression correlated with myeloid-derived suppressor markers. In line with this finding, recombinant S100A8 and S100A9 proteins inhibited maturation and the allogeneic T cell stimulatory capacity of dendritic cells. S100A9 enhanced the production of reactive oxygen species by macrophages, which suppressed T cell activity at low concentrations in the form of hydrogen peroxide. Intragraft S100A8 and S100A9 expression linked to reduced expression of T cell immunity and tissue injury markers and higher expression of immune regulatory molecules. This study sheds new light on the importance of myeloid cell subsets in directing the outcome of T cell-mediated acute rejection. PMID:26607974

  6. A pilot study of reduced dose cyclosporine and corticosteroids to reduce new onset diabetes mellitus and acute rejection in kidney transplant recipients

    2013-01-01

    Background New onset diabetes mellitus (NODM) and acute rejection (AR) are important causes of morbidity and risk factors for allograft failure after kidney transplantation. Methods In this multi-center, open label, single-arm pilot study, 49 adult (≥18 years of age), low immunologic risk, non-diabetic recipients of a first deceased or living donor kidney transplant received early steroid reduction to 5 mg/day combined with Thymoglobulin® (Genzyme Transplant, Cambridge, MA, USA) induction, low dose cyclosporine (2-hour post-dose (C2) target of 600 to 800 ng/ml) and mycophenolic acid (MPA) therapy. Results Six months after transplantation, two patients (4%) developed NODM and one patient (2%) developed AR. Four patients had impaired fasting glucose tolerance based on 75-g oral glucose tolerance testing (OGTT). There was one patient death. There were no episodes of cytomegalovirus (CMV) infection or BK virus nephritis. In contrast, in a historical cohort of n = 27 patients treated with Thymoglobulin induction, and conventional doses of cyclosporine and corticosteroids, the incidence of NODM and AR was 18% and 15%. Conclusions The pilot study results suggest that Thymoglobulin induction combined with early steroid reduction, reduced cyclosporine exposure and MPA, may reduce the incidence of both NODM and AR in low immunological risk patients. A future controlled study enriched for patients at high risk for NODM is under consideration. Trial registration ClinicalTrials.gov: http://NCT00706680 PMID:23369458

  7. Validation of Single Nucleotide Polymorphisms (SNPs) Associated with Acute Rejection in Kidney Transplant Recipients Using a Large Multi-Center Cohort

    Oetting, William S.; Schladt, David P.; Leduc, Robert E.; Jacobson, Pamala A.; Guan, Weihua; Matas, Arthur J.; Israni, Ajay

    2011-01-01

    There have been numerous reports proposing a statistically significant association between a genetic variant, usually in the form of a single nucleotide polymorphism (SNP), and acute rejection (AR). Unfortunately, there are additional publications reporting a lack of association with AR when a different cohort of recipients was analyzed for the same SNP. The objective of this report was to attempt replication of these published finding in our own kidney allograft recipient cohort. We analyzed 23 genetic variants, previously reported to have a significant association with AR, using a cohort of 969 clinically well defined kidney transplant recipients. Only one SNP, rs6025 (Leiden mutation), within the coagulation factor V gene, showed a significant association with a p-value of 0.011 in a race adjusted analysis and 0.0003 in multiple variable analysis. An additional SNP, rs11706052 in IMPDH2, gave a modest p-value of 0.044 using multiple variable analysis which is not significant when multiple testing is taken into consideration. Our results suggest that careful validation of previously reported associations with AR is necessary and different strategies other than candidate gene studies can help to identify causative genetic variants associated with AR. PMID:21955043

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

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

    2015-01-01

    The presence of donor-specific alloantibodies (DSAs) against the MICA antigen results in high risk for antibody-mediated rejection (AMR) of a transplanted kidney, especially in patients receiving a re-transplant. We describe the incidence of acute C4d+ AMR in a patient who had received a first kidney transplant with a zero HLA antigen mismatch. Retrospective analysis of post-transplant T and B cell crossmatches were negative, but a high level of MICA alloantibody was detected in sera collected both before and after transplant. The DSA against the first allograft mismatched MICA*018 was in the recipient. Flow cytometry and cytotoxicity tests with five samples of freshly isolated human umbilical vein endothelial cells demonstrated the alloantibody nature of patient’s MICA-DSA. Prior to the second transplant, a MICA virtual crossmatch and T and B cell crossmatches were used to identify a suitable donor. The patient received a second kidney transplant, and allograft was functioning well at one-year follow-up. Our study indicates that MICA virtual crossmatch is important in selection of a kidney donor if the recipient has been sensitized with MICA antigens. PMID:26024219

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

    Yingzi Ming

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

  10. CXCR3 and Its Ligand CXCL10 Are Expressed by Inflammatory Cells Infiltrating Lung Allografts and Mediate Chemotaxis of T Cells at Sites of Rejection

    Agostini, Carlo; Calabrese, Fiorella; Rea, Federico; Facco, Monica; Tosoni, Alicia; Loy, Monica; Binotto, Gianni; VALENTE, MARIALUISA; Trentin, Livio; Semenzato, Gianpietro

    2001-01-01

    The attraction of T lymphocytes into the pulmonary parenchyma represents an essential step in mechanisms ultimately leading to lung allograft rejection. In this study we evaluated whether IP-10 (CXCL10), a chemokine that is induced by interferon-γ and stimulates the directional migration of activated T cells, plays a role in regulating the trafficking of effector T cells during lung allograft rejection episodes. Immunohistochemical examination showed that areas characterized by acute cellular...

  11. Cell-Based Therapies in the Prevention of Solid Organ Transplant Rejection

    Adrian E. Morelli

    2012-01-01

    Full Text Available Problem statement: Organ transplantation is a life-saving and increasingly common procedure, as it often serves as the only treatment available for end-stage organ disease. Although the constant development of new and more effective immunosuppressive drugs has revolutionized the prevention and treatment of acute graft rejection, these drugs have significant toxicity, greatly increase patient susceptibility to neoplasms and infection and exert little impact on chronic rejection. Approach: The literature was reviewed to illuminate the mechanisms by which the anti-donor immune response is initiated and how cellular therapies impact this response. Results: Data show that Donor Specific Transfusion, Apoptotic Cell therapies and Dendritic Cell therapies all function as a source of alloantigen to suppress the anti-donor T cell response. Conclusion: Cellular therapies hold promise in the prevention of solid organ allograft rejection, but require optimization and study in large animal models before clinical implementation."

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

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

    2016-08-15

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

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

    Witt CA

    2014-10-01

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

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

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

    2013-01-01

    In order to define the intensity of immunosuppression, we examined risk factors for acute rejection in desensitization protocols that use baseline donor specific antibody levels measured as mean fluorescence intensity (MFImax). The study included 146 patients transplanted with a negative flow crossmatch and a mean follow-up of 18 months with the majority (83%) followed for at least 1 year. At the time of transplant, mean calculated panel reactive antibody and MFImax ranged from 10.3% to 57.2%...

  15. LATE RENAL GRAFT REJECTION: PATHOLOGY AND PROGNOSIS

    E.S. Stolyarevich

    2014-01-01

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

  16. Effect of diabetes and acute rejection on liver transplant outcomes: An analysis of the organ procurement and transplantation network/united network for organ sharing database.

    Kuo, Hung-Tien; Lum, Erik; Martin, Paul; Bunnapradist, Suphamai

    2016-06-01

    The effects of diabetic status and acute rejection (AR) on liver transplant outcomes are largely unknown. We studied 13,736 liver recipients from the United Network for Organ Sharing/Organ Procurement Transplant Network database who underwent transplantation between 2004 and 2007 with a functioning graft for greater than 1 year. The association of pretransplant diabetes mellitus (PDM), new-onset diabetes after transplant (NODAT), and AR rates on allograft failure, all-cause mortality, and cardiovascular mortality were determined. To determine the differential and joint effects of diabetic status and AR on transplant outcomes, recipients were further stratified into 6 groups: neither (reference, n = 6600); NODAT alone (n = 2054); PDM alone (n = 2414); AR alone (n = 1448); NODAT and AR (n = 707); and PDM and AR (n = 513). An analysis with hepatitis C virus (HCV) serostatus was also performed (HCV recipients, n = 6384; and non-HCV recipient, n = 5934). The median follow-up was 2537 days. The prevalence of PDM was 21.3%. At 1 year after transplant, the rates of NODAT and AR were 25.5% and 19.4%, respectively. Overall, PDM, NODAT, and AR were associated with increased risks for graft failure (PDM, hazard ratio [HR] = 1.31, P < 0.01; NODAT, HR = 1.11, P = 0.02; AR, HR = 1.28, P < 0.01). A multivariate Cox regression analysis of the 6 recipient groups demonstrated that NODAT alone was not significantly associated with any study outcomes. The presence of PDM, AR, NODAT and AR, and PDM and AR were associated with higher overall graft failure risk and mortality risk. The presence of PDM was associated with higher cardiovascular mortality risk. The analyses in both HCV-positive and HCV-negative cohorts showed a similar trend as in the overall cohort. In conclusion, PDM and AR, but not NODAT, is associated with increased mortality and liver allograft failure. Liver Transplantation 22 796-804 2016 AASLD. PMID:26850091

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

    Bjarte Fosby; Tom H Karlsen; Espen Melum

    2012-01-01

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

  18. TLR Signals Promote IL-6/IL-17-Dependent Transplant Rejection1

    Chen, Luqiu; Ahmed, Emily; Wang, Tongmin; Wang, Ying; Ochando, Jordi; Chong, Anita S.; Alegre, Maria-Luisa

    2009-01-01

    Acute allograft rejection has often been correlated with Th1 differentiation, whereas transplantation tolerance is frequently associated with induction of regulation. The discovery of the Th17 phenotype has prompted its scrutiny in transplant rejection. Although IL-17 has recently been observed in settings of acute allograft rejection and drives rejection in T-bet-deficient mice that have impaired type 1 T cell responses, there is little evidence of its requirement during acute rejection in w...

  19. Case of Acute Graft Failure during Suspected Humoral Rejection with Preserved Ejection Fraction, but Severely Reduced Longitudinal Deformation Detected by 2D-Speckle Tracking

    Clemmensen, Tor Skibsted; Eiskjær, Hans; Kofoed-Nielsen, Pernille B;

    2014-01-01

    remained unchanged, indicating need of more reliable noninvasive methods for graft function surveillance. Global longitudinal strain relates to clinical heart failure, filling pressure, and cardiac index during suspected humoral rejection and microvascular dysfunction in this HTX patient. We suggest...

  20. Acute dosing and p53-deficiency promote cellular sensitivity to DNA methylating agents.

    Chapman, Katherine E; Doak, Shareen H; Jenkins, Gareth J S

    2015-04-01

    Risk assessment of human exposure to chemicals is crucial for understanding whether such agents can cause cancer. The current emphasis on avoidance of animal testing has placed greater importance on in vitro tests for the identification of genotoxicants. Selection of an appropriate in vitro dosing regime is imperative in determining the genotoxic effects of test chemicals. Here, the issue of dosing approaches was addressed by comparing acute and chronic dosing, uniquely using low-dose experiments. Acute 24 h exposures were compared with equivalent dosing every 24 h over 5-day, fractionated treatment periods. The in vitro micronucleus assay was used to measure clastogenicity induced by methyl methanesulfonate (MMS) and N-methyl-N-nitrosourea (MNU) in human lymphoblastoid cell line, TK6. Quantitative real-time (qRT) PCR was used to measure mRNA level induction of DNA repair enzymes. Lowest observed genotoxic effect levels (LOGELs) for MMS were obtained at 0.7 µg/ml for the acute study and 1.0 µg/ml for the chronic study. For acute MNU dosing, a LOGEL was observed at 0.46 µg/ml, yet genotoxicity was completely removed following the chronic study. Interestingly, acute MNU dosing demonstrated a statistically significant decrease at 0.009 µg/ml. Levels of selected DNA repair enzymes did not change significantly following doses tested. However, p53 deficiency (using the TK6-isogenic cell line, NH32) increased sensitivity to MMS during chronic dosing, causing this LOGEL to equate to the acute treatment LOGEL. In the context of the present data for 2 alkylating agents, chronic dosing could be a valuable in vitro supplement to acute dosing and could contribute to reduction of unnecessary in vivo follow-up tests. PMID:25595616

  1. Loss of cellular immune reactivity during acute Plasmodium falciparum malaria

    Hviid, L; Theander, T G; Abu-Zeid, Y A; Abdulhadi, N H; Jakobsen, P H; Saeed, B O; Jepsen, S; Bayoumi, R A; Jensen, J B

    1991-01-01

    Sixteen patients suffering from acute Plasmodium falciparum malaria were studied. All were residents of an area of unstable malaria-transmission in Eastern Sudan. Blood-samples were drawn at diagnosis, and 7 and 30 days later. Blood-samples from thirteen donors, drawn outside the malaria...... transmission season 5 months prior to the attack, were included in the study. Lymphoproliferative responsiveness to purified soluble malarial antigens and to the unrelated antigen PPD was lost during the acute phase of the disease in most donors, but was regained during convalescence, except in four donors...... convalescence. Five donors examined by fluorescence-activated cell sorting (FACS) showed no increase in surface expression of IL-2 receptor on peripheral lymphocytes. The data indicate that acute P. falciparum malaria causes a depletion of antigen-reactive T-cells from the peripheral circulation, probably due...

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

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

  3. Acute dyskerin depletion triggers cellular senescence and renders osteosarcoma cells resistant to genotoxic stress-induced apoptosis

    Lin, Ping; Mobasher, Maral E.; Alawi, Faizan, E-mail: falawi@upenn.edu

    2014-04-18

    Highlights: • Dyskerin depletion triggers cellular senescence in U2OS osteosarcoma cells. • Dyskerin-depleted cells are resistant to apoptosis induced by genotoxic stress. • Chromatin relaxation sensitizes dyskerin-depleted cells to apoptosis. - Abstract: Dyskerin is a conserved, nucleolar RNA-binding protein implicated in an increasing array of fundamental cellular processes. Germline mutation in the dyskerin gene (DKC1) is the cause of X-linked dyskeratosis congenita (DC). Conversely, wild-type dyskerin is overexpressed in sporadic cancers, and high-levels may be associated with poor prognosis. It was previously reported that acute loss of dyskerin function via siRNA-mediated depletion slowed the proliferation of transformed cell lines. However, the mechanisms remained unclear. Using human U2OS osteosarcoma cells, we show that siRNA-mediated dyskerin depletion induced cellular senescence as evidenced by proliferative arrest, senescence-associated heterochromatinization and a senescence-associated molecular profile. Senescence can render cells resistant to apoptosis. Conversely, chromatin relaxation can reverse the repressive effects of senescence-associated heterochromatinization on apoptosis. To this end, genotoxic stress-induced apoptosis was suppressed in dyskerin-depleted cells. In contrast, agents that induce chromatin relaxation, including histone deacetylase inhibitors and the DNA intercalator chloroquine, sensitized dyskerin-depleted cells to apoptosis. Dyskerin is a core component of the telomerase complex and plays an important role in telomere homeostasis. Defective telomere maintenance resulting in premature senescence is thought to primarily underlie the pathogenesis of X-linked DC. Since U2OS cells are telomerase-negative, this leads us to conclude that loss of dyskerin function can also induce cellular senescence via mechanisms independent of telomere shortening.

  4. Remote noninvasive allograft rejection monitoring for heart transplant recipients: study protocol for the novel evaluation with home electrocardiogram and remote transmission (NEW HEART) study

    2012-01-01

    Background Acute allograft rejection is a major cause of early mortality in the first year after heart transplantation in adults. Although endomyocardial biopsy (EMB) is not a perfect "gold standard" for a correct diagnosis of acute allograft rejection, it is considered the best available test and thus, is the current standard practice. Unfortunately, EMB is an invasive and costly procedure that is not without risk. Recent evidence suggests that acute allograft rejection causes delays in ventricular repolarization and thereby increases the cellular action potential duration resulting in a longer QT interval on the electrocardiogram (ECG). No prospective study to date has investigated whether such increases in the QT interval could provide early detection of acute allograft rejection. Therefore, in the Novel Evaluation With Home Electrocardiogram And Remote Transmission (NEW HEART) study, we plan to investigate the potential benefit of daily home QT interval monitoring to predict acute allograft rejection. Methods/design The NEW HEART study is a prospective, double-blind, multi-center descriptive research study. A sample of 325 adult heart transplant recipients will be recruited within six weeks of transplant from three sites in the United States. Subjects will receive the HeartView™ ECG recorder and its companion Internet Transmitter, which will transmit the subject's ECG to a Core Laboratory. Subjects will be instructed to record and transmit an ECG recording daily for 6 months. An increase in the QTC interval from the previous day of at least 25 ms that persists for 3 consecutive days will be considered abnormal. The number and grade of acute allograft rejection episodes, as well as all-cause mortality, will be collected for one year following transplant surgery. Discussion This study will provide "real world" prospective data to determine the sensitivity and specificity of QTC as an early non invasive marker of cellular rejection in transplant recipients

  5. Remote noninvasive allograft rejection monitoring for heart transplant recipients: study protocol for the novel evaluation with home electrocardiogram and remote transmission (NEW HEART study

    Doering Lynn V

    2012-03-01

    Full Text Available Abstract Background Acute allograft rejection is a major cause of early mortality in the first year after heart transplantation in adults. Although endomyocardial biopsy (EMB is not a perfect "gold standard" for a correct diagnosis of acute allograft rejection, it is considered the best available test and thus, is the current standard practice. Unfortunately, EMB is an invasive and costly procedure that is not without risk. Recent evidence suggests that acute allograft rejection causes delays in ventricular repolarization and thereby increases the cellular action potential duration resulting in a longer QT interval on the electrocardiogram (ECG. No prospective study to date has investigated whether such increases in the QT interval could provide early detection of acute allograft rejection. Therefore, in the Novel Evaluation With Home Electrocardiogram And Remote Transmission (NEW HEART study, we plan to investigate the potential benefit of daily home QT interval monitoring to predict acute allograft rejection. Methods/design The NEW HEART study is a prospective, double-blind, multi-center descriptive research study. A sample of 325 adult heart transplant recipients will be recruited within six weeks of transplant from three sites in the United States. Subjects will receive the HeartView™ ECG recorder and its companion Internet Transmitter, which will transmit the subject's ECG to a Core Laboratory. Subjects will be instructed to record and transmit an ECG recording daily for 6 months. An increase in the QTC interval from the previous day of at least 25 ms that persists for 3 consecutive days will be considered abnormal. The number and grade of acute allograft rejection episodes, as well as all-cause mortality, will be collected for one year following transplant surgery. Discussion This study will provide "real world" prospective data to determine the sensitivity and specificity of QTC as an early non invasive marker of cellular rejection in

  6. 肝移植术后迟发型急性排斥反应的发生和治疗%Late acute rejection following orthoptic liver transplantation

    易述红; 陈规划; 蔡常洁; 陆敏强; 杨扬; 邵春奎; 许赤; 李华; 易慧敏; 汪根树

    2007-01-01

    目的 探讨肝移植术后迟发型急性排斥反应(late acute rejection,LAR)的发生率、处理和预后.方法 回顾性分析我科2004年8月至2006年8月收治的15例迟发型急性排斥反应(肝移植术6个月后发生的急性排斥反应)患者的临床资料.结果 15例LAR发生在术后6.6~27个月,平均(14.7±7.5)个月.其中男14例,女1例.年龄32~66岁,平均年龄(49.5±12.7)岁.原发疾病为重症肝炎或肝功能衰竭者8例,占53.3%(8/15);发生于血型不合移植者2例,免疫抑制治疗方案为单一普乐可复(FK506)治疗8例,单一环孢素A(CsA)治疗3例,已经停用激素13例,占86.7%.属于免疫抑制剂量不足者共10例,占66.7%.免疫抑制剂浓度正常范围者5例.按Banff分级标准排斥反应的程度为轻度者9例,中度6例,无重度排斥反应发生.治疗方法均首先加强或调整免疫抑制治疗,包括提高药物浓度、FK506/CsA转换、联合其他免疫抑制剂和激素冲击治疗,3例患者需长期口服激素.总的治愈率为80%,3例患者逐渐出现缺血型胆道病变,其中1例行再移植后死亡.结论 迟发型急性排斥反应是肝移植术后常见但预后较好的并发症之一,免疫抑制不足是其发生的主要原因,及时地加强免疫抑制治疗可逆转排斥反应.

  7. Transplant rejection in terrestrial molluscs

    E Furuta

    2011-01-01

    Full Text Available To know whether or not molluscs are capable of recognizing tissue allo-antigens, dorsal skin-allografts were exchanged between adult terrestrial slug, Incilaria fruhstorferi. We succeeded for the first time in orthotopic transplantation of allografts and observed chronic rejection of allografts. Cellular changes in the rejection process continued over for 40 days. Two functional types of “effector” cells were recognized at the rejection site, but they were observed to be macrophages possessing perforin granules and phagocytosing damaged cells of the allograft. Three days after transplantation, the perforin-positive cells were recognized only in the recipient tissue surrounding the allograft. Five days after transplantation, these cells started to appear in the graft, while they disappeared from the host tissue. However, TUNEL-positive cells (apoptotic cells were not observed throughout the graft-rejection process. Electron microscopic examination of the graft tissue revealed autophagic degeneration of epithelial cells, mucous cells, pigment cells, fibroblasts, and muscle cells. These observations suggest that the slugs have the capability to recognize differences in cell-surface molecules between the allogeneic and recipient tissue, and that an allograft is chronically rejected due to a type of immunocyte (macrophage that can induce perforin-dependent cell death

  8. High expression of CD38, CD69, CD95 and CD154 biomarkers in cultured peripheral T lymphocytes correlates with an increased risk of acute rejection in liver allograft recipients.

    Boix, Francisco; Millan, Olga; Segundo, David San; Mancebo, Esther; Rimola, Antoni; Fabrega, Emilio; Fortuna, Virginia; Mrowiec, Anna; Castro-Panete, Maria J; Peña, Jesus de la; Llorente, Santiago; Minguela, Alfredo; Bolarin, Jose M; Paz-Artal, Estela; Lopez-Hoyos, Marcos; Brunet, Mercé; Muro, Manuel

    2016-05-01

    The mayor goal still outstanding into the solid organ transplantation field involves the search of surrogate biomarkers able to predict several clinical events, such as acute rejection (AR) or opportunistic infection. In the present multicenter study, a series of interesting surface antigens with important activator or inhibitory immune functions on cultured peripheral T cells were monitored in liver transplant recipients drawn at baseline and up to one year after transplantation. Sixty-four patients were included in the multicenter study during 3 years. Pre- and post-transplantation surface antigens levels displayed significant differences between AR and non acute rejection (NAR) groups, and also this differential expression was used to construct a risk predictive model based on a composite panel of outcome biomarkers (CD38, CD69, CD95 and CD154). The model was able to stratify these patients at high risk of AR. These preliminary results could provide basic information to improve the immunosuppressive treatment and it might better help to predict AR episodes. PMID:26850323

  9. Characteristics of cadaveric renal allograft recipients developing chronic rejection.

    Foster, M. C.; Rowe, P. A.; Dennis, M J; Morgan, A G; Burden, R. P.; Blamey, R. W.

    1990-01-01

    As the early results of renal transplantation improve, chronic rejection is increasing in relative importance as a cause of graft loss. The aetiology of the condition is unknown. In order to identify possible predisposing factors, the characteristics of 22 patients with chronic rejection were compared with those of 50 patients with stable graft function 2 years or more after transplantation. Patients with chronic rejection had significantly more acute rejection episodes in the first 6 months ...

  10. Expression of Silencer of Death Domains and Death-Receptor-3 in Normal Human Kidney and in Rejecting Renal Transplants

    Al-Lamki, Rafia S.; Wang, Jun; Thiru, Sathia; Pritchard, Nicholas R.; Bradley, J Andrew; Pober, Jordan S.; Bradley, John R

    2003-01-01

    We have previously reported the pattern of cellular expression of tumor necrosis factor receptors (TNFR) in human kidney and their altered expression in transplant rejection. We have extended our studies to examine the expression of Silencer of Death Domains (SODD), a protein that binds to the cytoplasmic portion of TNFR1 to inhibit signaling in the absence of ligand. In normal human kidney SODD is expressed in glomerular endothelial cells where it colocalizes with TNFR1. During acute rejecti...

  11. Low-Dose Rituximab Therapy for Antibody-Mediated Rejection in a Highly Sensitized Heart-Transplant Recipient

    Aggarwal, Ashim; Pyle, Joseph; Hamilton, John; Bhat, Geetha

    2012-01-01

    Antibody-mediated rejection is the B-cell–mediated production of immunoglobulin G antibody against the transplanted heart. The currently available therapies for antibody-mediated rejection have had marginal success, and chronic manifestations of rejection can result in an increased risk of graft vasculopathy and perhaps require repeat transplantation. Rituximab, a monoclonal antibody directed against the CD20 receptor of B-lymphocytes and approved as therapy for lymphoma, can be used in heart-transplant patients for the management of antibody-mediated rejection. We present the case of a 52-year-old woman with high allosensitization (pre-transplantation panel reactive antibody level, 72%) who underwent successful orthotopic heart transplantation. Postoperatively, her acute antibody-mediated rejection with concomitant cellular rejection was successfully treated with low-dose rituximab. The patient died 5 months later because of multiple other medical problems. The present case suggests a role for low-dose rituximab as therapy for antibody-mediated rejection in heart-transplant patients. PMID:23304051

  12. Diagnosis of Rejection by Analyzing Ventricular Late Potentials in Heart Transplant Patients

    Vítor Nogueira Mendes; Telmo Santos Pereira; Vítor Azevedo Matos

    2016-01-01

    Background: Heart transplant rejection originates slow and fragmented conduction. Signal-averaged ECG (SAECG) is a stratification method in the risk of rejection. Objective: To develop a risk score for rejection, using SAECG variables. Methods: We studied 28 transplant patients. First, we divided the sample into two groups based on the occurrence of acute rejection (5 with rejection and 23 without). In a second phase, we divided the sample considering the existence or not of rejection in at...

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

    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. PMID:26663361

  14. Mechanism of acute cadmium toxicity in the testis of the rat: a cellular and molecular inquiry

    The more sensitive Sertoli cells were chosen as a model to investigate a molecular mechanism of toxicity. Primary rat Sertoli cells were exposed to sublethal concentrations of cadmium and the changes in [32P]-orthophosphate-labelled phosphoproteins using two-dimensional polyacrylamide gel electrophoresis were examined. Resultant autoradiograms showed a delayed dose- and time-dependent increase in intensity of two acidic proteins having identical molecular weights. These changes were most probably a result of increased synthesis of the proteins. Pretreatment of the cells with zinc, a cadmium antagonist, partially reduced the effect of cadmium. This research concludes that Sertoli cells are relatively more sensitive to the effects of cadmium than interstitial cells. A time- and dose dependent increase in [32P]-associated activity to two small Sertoli cell phosphoproteins was consistently seen after cadmium exposure, whereas no effect could be seen using essential, non-toxic metals. This response may be an early indicator in the disruption of cellular homeostasis by cadmium, and will hopefully contribute positive evidence in the search for a molecular mechanism of cadmium toxicity

  15. Risk of renal allograft rejection following angiography

    In a retrospective study of 173 immediately functioning primary kidney transplants, correlation between angiography and renal allograft rejection was studied during the first 14 days. It was found that rejection was more frequent in kidneys undergoing angiography than in those not undergoing angiography. It was also found that in kidneys undergoing angiography an overwhelming number of the rejections started the day after angiography. These differences in rejection frequency could not be explained by differences in HLA matching or the origin of the kidneys. These findings suggest a possible connection indicating that the angiography might elicit an acute rejection episode. A possible mechanism for starting this reaction might be activation of the complement system which was found in 50 percent of the patients undergoing angiography in peripheral blood and in 100 percent when studied in vitro

  16. The Natural History of Biopsy-Negative Rejection after Heart Transplantation

    Zhaoyi Tang

    2013-01-01

    Full Text Available Purpose. The most recent International Society for Heart and Lung Transplantation (ISHLT biopsy scale classifies cellular and antibody-mediated rejections. However, there are cases with acute decline in left ventricular ejection fraction (LVEF ≤ 45% but no evidence of rejection on biopsy. Characteristics and treatment response of this biopsy negative rejection (BNR have yet to be elucidated. Methods. Between 2002 and 2012, we found 12 cases of BNR in 11 heart transplant patients as previously defined. One of the 11 patients was treated a second time for BNR. Characteristics and response to treatment were noted. Results. 12 cases (of 11 patients were reviewed and 11 occurred during the first year after transplant. 8 cases without heart failure symptoms were treated with an oral corticosteroids bolus and taper or intravenous immunoglobulin. Four cases with heart failure symptoms were treated with thymoglobulin, intravenous immunoglobulin, and intravenous methylprednisolone followed by an oral corticosteroids bolus and taper. Overall, 7 cases resulted in return to normal left ventricular function within a mean of 14 ± 10 days from the initial biopsy. Conclusion. BNR includes cardiac dysfunction and can be a severe form of rejection. Characteristics of these cases of rejection are described with most cases responding to appropriate therapy.

  17. From molecular interaction to acute promyelocytic leukemia: Calculating leukemogenesis and remission from endogenous molecular-cellular network.

    Yuan, Ruoshi; Zhu, Xiaomei; Radich, Jerald P; Ao, Ping

    2016-01-01

    Acute promyelocytic leukemia (APL) remains the best example of a malignancy that can be cured clinically by differentiation therapy. We demonstrate that APL may emerge from a dynamical endogenous molecular-cellular network obtained from normal, non-cancerous molecular interactions such as signal transduction and translational regulation under physiological conditions. This unifying framework, which reproduces APL, normal progenitor, and differentiated granulocytic phenotypes as different robust states from the network dynamics, has the advantage to study transition between these states, i.e. critical drivers for leukemogenesis and targets for differentiation. The simulation results quantitatively reproduce microarray profiles of NB4 and HL60 cell lines in response to treatment and normal neutrophil differentiation, and lead to new findings such as biomarkers for APL and additional molecular targets for arsenic trioxide therapy. The modeling shows APL and normal states mutually suppress each other, both in "wiring" and in dynamical cooperation. Leukemogenesis and recovery under treatment may be a consequence of spontaneous or induced transitions between robust states, through "passes" or "dragging" by drug effects. Our approach rationalizes leukemic complexity and constructs a platform towards extending differentiation therapy by performing "dry" molecular biology experiments. PMID:27098097

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

    Roedder, Silke; Sigdel, Tara; Salomonis, Nathan; Hsieh, Sue; Dai, Hong; Bestard, Oriol; Metes, Diana; Zeevi, Andrea; Gritsch, Albin; Cheeseman, Jennifer; Macedo, Camila; Peddy, Ram; Medeiros, Mara; Vincenti, Flavio; Asher, Nancy

    2014-01-01

    Editors' Summary Background Throughout life, the kidneys filter waste products (from the normal breakdown of tissues and food) and excess water from the blood to make urine. If the kidneys stop working for any reason, the rate at which the blood is filtered decreases, and dangerous amounts of creatinine and other waste products build up in the blood. The kidneys can fail suddenly (acute kidney failure) because of injury or poisoning, but usually failing kidneys stop working gradually over man...

  19. Is Serum Transforming Growth Factor beta-1 Superior to Serum Creatinine for assessing Renal Failure and Renal Transplant Rejection

    Gyanendra Kumar Sonkar, Usha

    2009-04-01

    Full Text Available A sustained overexpression of Transforming Growth Factor beta1 (TGF beta1, a cytokine has beenimplicated in the pathogenesis of fibrosis of kidney leading to end stage . The main aim of present studywas to find the utility of TGF beta1 and serum creatinine in differentiating chronic renal failure (CRFfrom acute renal failure (ARF, renal transplant rejection (Tx Rej and stable renal transplant (Tx Stband to study has attempted histopathological correlation of rejection cases with TGF beta1 and serumcreatinine. TGF beta1 was determined by using ELISA and serum creatinine was done by autoanalyser.In normal healthy controls (NHC, in majority of cases (80.0% TGF beta1 was below 25 ng/ml while in6.0% cases it was upto 34 ng/ml. Rise of TGF beta1 was significant in CRF patients as compared to ARFand NHC (p<0.05 .In rejection cases, TGF beta1 level was significantly raised as compared to NHCand stable graft cases (p<0.05. In rejection cases, it was raised above 40 ng/ml in only 50% cases. In twocases inspite of more than 70% glomerular fibrosis, the patient had TGF beta1 level of only 5 ng/ml and inother three cases of acute cellular rejection the level was 70, 35 and 28 ng/ml respectively.Contrary to itserum creatinine was raised above 2 mg/dl in all cases of transplant rejection but in stable transplant casesin majority (70.6% it was below 1.5 mg/dl and in 5 cases it was between 1.5 – 1.9 mg/dl.Thus the studysuggests that TGF beta1 may not be a good marker for chronic transplant rejection, as it does notcorrelate well with glomerular fibrosis, probably it is more associated with interstitial inflammation but itcan differentiate CRF from ARF if cut off of 40 ng/ml is taken.

  20. MDMA DECREASES THE EFFECTS OF SIMULATED SOCIAL REJECTION

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

    2013-01-01

    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...

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

    Fernando Giron

    2010-01-01

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

  2. Soluble CD30 in renal transplant recipients: Is it a good biomarker to predict rejection?

    Azarpira Negar; Aghdaie Mahdokht; 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 ...

  3. Local Graft Irradiation for Kidney Allograft Rejection: A Case Series and Review of the Literature

    Fallahzadeh, Mohammad Kazem; Khan, Sarah; Zibari, Gazi B.; Patil, Sandeep; Singh, Neeraj

    2014-01-01

    Introduction: Due to its immunosuppressive properties, local graft irradiation (LGI) has been proposed as a second line therapy for treatment of acute kidney rejection. Case Presentation: In this case-series we report 6 patients with biopsy proven acute kidney allograft rejection refractory to conventional antirejection therapy who underwent LGI for treatment of acute rejection at our center. Three of these patients had living donor transplants, 2 had deceased donor transplants, and one had r...

  4. Continuous reject analysis

    The results of continuous film reject analysis conducted within the Medical Imaging Department of the Prince Charles Hospital over a thirty month period are reported. A computer program to record reject films was installed as part of normal computerized operations of the Department. This required discarded films to be recorded according to site, reason and operator. Repeat/reject rates in chest examinations that differ significantly from reported acceptable reject rates are described. It is suggested that previously reported overall repeat rates of 10% to 14%, which are heavily influenced by the frequency of chest examinations, should not be regarded as normal. The findings from the survey provide data that is both consistent and inconsistent with previous studies. The implications of the results with respect to costs, radiation exposure, student training and the need to monitor continuously reject rates to maintain suitable standards are commented on. 8 figs

  5. Antibody-mediated rejection: Importance of lactate dehydrogenase and neutrophilia in early diagnosis

    Taqi Toufeeq Khan

    2011-01-01

    Full Text Available We report the importance of elevated serum lactate dehydrogenase (LDH and neutrophilia (NT in two renal transplant recipients who developed renal impairment in the early post-operative period. One of our recipients developed oliguria and increased serum creatinine with unexplained elevation of LDH and NT. The biopsy was C4d positive with platelet and fibrin thrombi in the glomerular capillaries and arterioles and interpreted as acute vasculitis or thrombotic form of antibody-mediated rejection (VAMR with positive donor-specific antibodies (DSA. Despite intensive treatment, this graft was lost. When another patient developed a similar picture, prompt immunoadsorption was started without waiting for a confirmatory biopsy or DSA, and both were later reported as positive. Improvement in renal function was associated with decreasing levels of LDH and NT. Neither of these was elevated in cases of acute cellular rejection (ACR or antibody mediated rejection (AMR with isolated tubular injury (TAMR. It may therefore be reasonable to assume that LDH and NT are potential diagnostic and prognostic markers of VAMR.

  6. Countering Rejection Anxiety.

    Hanselman, Peggy Riley

    1989-01-01

    Outlines a step-by-step approach for guidance counselors in holding a preliminary college planning conference with high school juniors and their families in order to help students subsequently deal with possible rejection from a college. (TE)

  7. Quantum rejection sampling

    Ozols, Maris; Roland, Jérémie

    2011-01-01

    Rejection sampling is a well-known technique to sample from a target distribution, given the ability to sample from another distribution. The method has been first formalized by von Neumann (1951) and has many applications in classical computing. We define a quantum analogue of rejection sampling: given a black box producing a coherent superposition of quantum states with some amplitudes, the problem is to prepare a coherent superposition of the same states with different target amplitudes. The main result of this paper is a tight characterization of the query complexity of this quantum state generation problem. We exhibit an algorithm, which we call quantum rejection sampling, and analyze its cost using semidefinite programming. We prove a matching lower bound based on symmetrizing over the automorphism group of the problem and using a hybrid argument. Perhaps interestingly, the automorphism group turns out to be continuous in this case. Furthermore, we illustrate how quantum rejection sampling may be used a...

  8. Clinical evaluation of radionuclide dynamic renography in renal transplant rejections

    The radionuclide dynamic renography was performed in 125 cases of renal transplant. That was a correlation between radionuclide dynamic renography types and serum creatinine concentration. There are characteristic changes in phase imaging of radionuclide dynamic renography at acute, ultra-acute and chronic rejection. This dynamic imaging can show kidney function. The dynamic renography is more informative than renogram

  9. Dimensão fractal na quantificação do grau de rejeição celular miocárdica pós-transplante cardíaco Fractal dimension in quantifying the degree of myocardial cellular rejection after cardiac transplantation

    Roberto Douglas Moreira

    2011-06-01

    Full Text Available INTRODUÇÃO: O termo "fractal" é derivado do latim fractus, que significa "irregular" ou "quebrado", considerando a estrutura observada como tendo uma dimensão não-inteira. Há muitos estudos que empregaram a Dimensão Fractal (DF como uma ferramenta de diagnóstico. Um dos métodos mais comuns para o seu estudo é a "Box-plot counting" (Método de contagem de caixas. OBJETIVO: O objetivo do estudo foi tentar estabelecer a contribuição da DF na quantificação da rejeição celular miocárdica após o transplante cardíaco. MÉTODOS: Imagens microscópicas digitalizadas foram capturadas na resolução 800x600 (aumento de 100x. A DF foi calculada com auxílio do "software ImageJ", com adaptações. A classificação dos graus de rejeição foi de acordo com a "Sociedade Internacional de Transplante Cardíaco e Pulmonar" (ISHLT 2004. O relatório final do grau de rejeição foi confirmado e redefinido após exaustiva revisão das lâminas por um patologista experiente externo. No total, 658 lâminas foram avaliadas, com a seguinte distribuição entre os graus de rejeição (R: 335 (0R, 214 (1R, 70 (2R, 39 (3R. Os dados foram analisados estatisticamente com os testes Kruskal-Wallis e curvas ROC sendo considerados significantes valores de P INTRODUCTION: The term "Fractal" is derived from the Latin fractus meaning "irregular" or "broken" considering the observed structure with a non-integer dimension. There are many studies which employed the Fractal Dimension (FD as a diagnostic tool. One of the most common methods for its study is the "Box Counting Method". OBJECTIVE: The aim of the present study was to try to establish the contribution of FD in the quantification of myocardial cellular rejection after cardiac transplantation. METHODS: Microscopic digital images were captured at 800x600 resolution (magnification 100x. FD was calculated with the aid of "ImageJ software" with adaptations. The classification of the degrees of rejection was in

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

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

    2016-01-01

    Rejection is one of the key factors that determine the long-term allograft function and survival in renal transplant patients. Reliable and timely diagnosis is important to treat rejection as early as possible. Allograft biopsies are not suitable for continuous monitoring of rejection. Thus, there is an unmet need for non-invasive methods to diagnose acute and chronic rejection. Proteomics in urine and blood samples has been explored for this purpose in 29 studies conducted since 2003. This r...

  11. Staged Approach to Mechanical Circulatory Support and Recovered Allograft Function after Transplantation Rejection with Cardiogenic Shock

    Caceres, Manuel; Czer, Lawrence S. C.; Esmailian, Fardad; Luthringer, Daniel; Ramzy, Danny; Moriguchi, Jaime

    2013-01-01

    Cardiogenic shock resulting from acute rejection after heart transplantation is an infrequent but life-threatening condition. Intensified immunosuppressive therapy and the timely initiation of properly selected mechanical circulatory support can be life-saving and enable recovery of graft function. The few published reports on mechanical circulatory support for acute transplantation rejection have focused on short-term devices.

  12. Posttransplantation antibody mediated rejection: new insights into mechanism, treatment and protective strategies

    MAO You-ying; CHEN Jiang-hua

    2011-01-01

    @@ Acute antibody mediated rejection (AMR) is receiving more and more attention, which is mediated by different mechanisms from T cell mediated rejection, thereby requiring other approaches to prevention and treatment. Preexisting alloantibodies and pre-transplant sensitization are important risk factors for development of acute AMR early after renal transplantation.

  13. Acute rejection episodes after kidney transplantation

    Obesity in nontransplant patients has been associated with hypertension, hyperlipidemia, diabetes, and proteinuria. To determine whether renal transplant recipients with an elevated BMI have worse long term graft survival, we prospectively studied 92 patients transplanted between April 1999 and July 2000. Weight (Wt) and height of the patients were recorded prior to transplantation and two weeks, one, two and three years post transplantation. Blood urea nitrogen (BUN), creatinine (Cr) and blood pressure were checked monthly, while triglyceride, cholesterol, high density lipoprotein (HDL), and low density lipoprotein (LDL) were obtained 3 monthly for 3 years post transplantation. Graft dysfunction was defined as serum Cr> 1.8 mg/dL. While BMI and Wt of the patients before transplantation did not show any significant correlation with chronic renal allograft dysfunction (CRAD), patients with higher Wt and BMI two weeks after transplantation showed an increased risk of developing CRAD during the three year post transplant independent of other risk factors (P< 0.05). Patients with greater Wt loss in the first two weeks post transplantation showed a decreased risk of developing CRAD in the following 3 years (P< 0.001). Our study suggests that high Wt and BMI are significantly associated with worse graft survival 3 years post renal transplantation. (author)

  14. SOC REJECTION BY NANOFILTRATION

    A study was conducted to evaluate the rejection of six synthetic organic compounds (SOCs) from a potable water source by a nanofiltration membrane process. The S0Cs were ethylene dibromide (EDB), dibromochloropropane (DBCP), chlordane, heptachlor, methoxychlor and alachlor. To in...

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

    Fernando Giron; Yenny Baez

    2010-01-01

    Fernando Giron, Yenny BaezKidney Transplant Service, Colombiana de Trasplantes, Bogota, ColombiaAbstract: Everolimus is a proliferation inhibitor designed to target chronic allograft nephropathy including prevention of acute rejection. Acute renal allograft rejection incidence varies with the therapy used for immunosuppression. Registry data show that 15% to 35% of kidney recipients will undergo treatment for at least one episode of acute rejection within the first post-transplant year. Evero...

  16. Cxcr3 and its ligand CXCL10 are expressed by inflammatory cells infiltrating lung allografts and mediate chemotaxis of T cells at sites of rejection.

    Agostini, C; Calabrese, F; Rea, F; Facco, M; Tosoni, A; Loy, M; Binotto, G; Valente, M; Trentin, L; Semenzato, G

    2001-05-01

    The attraction of T lymphocytes into the pulmonary parenchyma represents an essential step in mechanisms ultimately leading to lung allograft rejection. In this study we evaluated whether IP-10 (CXCL10), a chemokine that is induced by interferon-gamma and stimulates the directional migration of activated T cells, plays a role in regulating the trafficking of effector T cells during lung allograft rejection episodes. Immunohistochemical examination showed that areas characterized by acute cellular rejection (grades 1 to 4) and active obliterative bronchiolitis (chronic rejection, Ca) were infiltrated by T cells expressing CXCR3, i.e., the specific receptor for CXCL10. In parallel, T cells accumulating in the bronchoalveolar lavage of lung transplant recipients with rejection episodes were CXCR3+ and exhibited a strong in vitro migratory capability in response to CXCL10. In lung biopsies, CXCL10 was abundantly expressed by graft-infiltrating macrophages and occasionally by epithelial cells. Alveolar macrophages expressed and secreted definite levels of CXCL10 capable of inducing chemotaxis of the CXCR3+ T-cell line 300-19; the secretory capability of alveolar macrophages was up-regulated by preincubation with interferon-gamma. Interestingly, striking levels of CXCR3 ligands could be demonstrated in the fluid component of the bronchoalveolar lavage in individuals with rejection episodes. These data indicate the role of the CXCR3/CXCL10 interactions in the recruitment of lymphocytes at sites of lung rejection and provide a rationale for the use of agents that block the CXCR3/CXCL10 axis in the treatment of lung allograft rejection. PMID:11337368

  17. Macrophage mediated endothelial injury and proliferation in renal transplant rejection.

    Adair, Anya

    2008-01-01

    Macrophages (Mφ) have previously been implicated in both acute and chronic renal allograft rejection however the mechanisms remain unclear. In this thesis I set out to explore the effect of the Mφ on the endothelium in the context of renal graft rejection. Initial studies focussed upon human renal allograft tissue from transplant nephrectomies performed because of chronic allograft nephropathy (CAN). Immunostaining was carried out on these tissues (n=29) and control kidne...

  18. Cellular correlates of enhanced anxiety caused by acute treatment with the selective serotonin reuptake inhibitor fluoxetine in rats

    Shilpa Ravinder

    2011-12-01

    Full Text Available Selective serotonin reuptake inhibitors (SSRIs are used extensively in the treatment of depression and anxiety disorders. The therapeutic benefits of SSRIs typically require several weeks of continuous treatment. Intriguingly, according to clinical reports, symptoms of anxiety may actually increase during the early stages of treatment although more prolonged treatment alleviates affective symptoms. Consistent with earlier studies that have used animal models to capture this paradoxical effect of SSRIs, we find that rats exhibit enhanced anxiety-like behavior on the elevated plus-maze one hour after a single injection of the SSRI fluoxetine. Next we investigated the potential neural substrates underlying the acute anxiogenic effects by analyzing the morphological and physiological impact of acute fluoxetine treatment on principal neurons of the basolateral amygdala (BLA, a brain area that plays a pivotal role in fear and anxiety. Although earlier studies have shown that behavioral or genetic perturbations that are anxiogenic for rodents also increase dendritic spine-density in the BLA, we find that a single injection of fluoxetine does not cause spinogenesis on proximal apical dendritic segments on BLA principal neurons an hour later. However, at the same time point when a single dose of fluoxetine caused enhanced anxiety, it also enhanced action potential firing in BLA neurons in ex vivo slices. Consistent with this finding, in vitro bath application of fluoxetine caused higher spiking frequency and this increase in excitability was correlated with an increase in the input resistance of these neurons. Our results suggest that enhanced excitability of amygdala neurons may contribute to the increase in anxiety-like behavior observed following acute fluoxetine treatment.

  19. Combined Effects of TGFB1 +869 T/C and +915 G/C Polymorphisms on Acute Rejection Risk in Solid Organ Transplant Recipients: A Systematic Review and Meta-Analysis

    Jia, Rui-Peng; Li, Ming-Hao; Gao, Xiao-Fei; Jiang, Xiao-Min; Zhu, Xian-Bo; Li, Liang-Peng; Tan, Si-Jia; Song, Qun; Li, Wen-Cheng; Zhu, Jia-Geng

    2014-01-01

    Background Transforming growth factor-beta 1(TGF-β1) is involved in the development of acute rejection (AR) episodes in solid organ transplant recipients; and a number of studies have been conducted to investigate the combined effects of human TGF-β1 gene (TGFB1) +869 T/C and +915 G/C polymorphisms on AR risk. However, the results obtained are inconclusive. Methods Eligible studies that investigated the haplotypic association between TGFB1 +869 T/C and +915 G/C polymorphisms and AR risk were comprehensively searched in the PUBMED, EMBASE, China National Knowledge Infrastructure, and Wanfang Database. Statistical analyses were performed by using STATA 12.0 and Review Manager 5.0. Results Fourteen eligible studies with 565 AR cases and 1219 non-AR cases were included. Overall, a significantly decreased risk was detected in patients carried with intermediate producer (IP) haplotypes (T/C G/C, T/T G/C, and C/C G/G) and/or low producer (LP) haplotypes (C/C G/C, C/C C/C, T/T C/C, and T/C C/C) compared with high producer (HP) haplotypes (T/T G/G and T/C G/G; IP vs. HP: OR = 0.75, 95% CI, 0.58–0.96, P heterogeneity  = 0.238; IP/LP vs. HP: OR  = 0.77, 95% CI, 0.61–0.98, P heterogeneity  = 0.144). In addition, subgroup analysis by transplant types demonstrated a similar association in patients receiving heart transplant (IP vs. HP: OR  = 0.32, 95% CI, 0.14–0.73, P heterogeneity  = 0.790; IP/LP vs. HP: OR  = 0.41, 95% CI, 0.20–0.85, P heterogeneity  = 0.320). Conclusions The current meta-analysis and systematic review indicated that recipient TGFB1 HP haplotypes were significantly associated with an increased risk for AR in solid organ transplant recipients, particularly patients receiving cardiac allograft. PMID:24705444

  20. Action against Kruemmel rejected

    In its verdict dated September 2nd, 1976 - 10 A 211/74 -, the administrative court of Schleswig-Holstein at Schleswig has rejected with costs the action of a plaintiff resident in Hessen concerning the contestation of the 2nd partial licence for the erection of a nuclear power station at Kruemmel near Hamburg. The verdict is not subject to appeal. Furthermore, the administrative court of Schleswig-Holstein at Schleswig, in its verdict dated September 2nd, 1976 - 10 A 214/74 - has rejected with costs the actions of eight plaintiffs living in Hamburg and surroundings, concerning the contestation of the 1st, 2nd and 3rd partial licence for the erection of a nuclear power station at Kruemmel near Hamburg. An appeal against this verdict has been lodged at the higher administrative court at Lueneburg. The main gounds for the two judgments are given in full text. (orig./HP)

  1. Interstitial Pneumonitis and the Risk of Chronic Allograft Rejection in Lung Transplant Recipients

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

    2013-01-01

    Background: 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). Methods: 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. Results: 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. Conclusions: 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. PMID:23715594

  2. Allograft renal rejection and chemokine polymorphism

    Y Gorgi

    2011-01-01

    Full Text Available Chemokines play a major role in the process by which leukocytes are recruited from the bloodstream into the sites of inflammation. Genes for the chemokine receptors CCR5, CCR2 and MCP-1 are characterized by functional polymorphisms implicated in transplant rejection. To investigate this association, we analyzed polymorphisms of CCR5-∆32, CCR5-59029-A/G, CCR2-V64I and MCP-1 G/A (-2518 in 173 renal transplant recipients and 169 healthy blood donors. The patients were classified in two groups: Group-1 (G-1 included 33 HLA-identical recipients and Group-2 (G-2 included 140 (one or more mismatched graft recipients. Forty-two patients had developed acute rejection episodes (ARs: seven in G-1 and 35 in G-2. Thirteen G-2 patients developed chronic allograft dysfunction (CAD. The genotypic and allelic frequencies of all polymorphisms studied did not reveal significant differences between patients and controls and among G-1 and G-2 recipients. However, a significant risk of acute renal transplant rejection was found in G-1 patients who possessed the CCR2-64I allele (odds ratio 0.24, 95% confidence inter-val [CI], 0.05-1.06; P = 0.035. There was no significant association of this polymorphism and CAD. In conclusion, the observed association of CCR2-64I with AR should be added to the spectrum of immunogenetic factors known to be involved in allograft renal loss.

  3. Inmunofenotipaje celular en el diagnóstico de las leucemias agudas híbridas Cellular immunophenotyping in the diagnosis of acute hybrid leukemias

    Vianed Marsán Suárez

    1999-12-01

    Full Text Available Se estudiaron 118 leucemias agudas en un período de 4 años. El fenotipaje celular se realizó a través del ultramicrométodo inmunocitoquímico (UMICIQ, mediante la utilización de un panel de anticuerpos monoclonales con el que se evaluó la expresión de antígenos linfoides y mieloides. La expresión de antígenos mieloides en pacientes con leucemia linfoide aguda se encontró en el 28,4 % y de antígenos linfoides en pacientes con leucemia mieloide aguda en el 56,7 %. Las leucemias agudas híbridas representaron el 16,1 % del total de pacientes estudiados: 73,7 % al inicio de la enfermedad y el 26,3 % restante en el estudio posterior al tratamiento de inducción de la remisión, lo que sugiere en estos últimos la posibilidad de cambio de linaje por la selección de variantes resistentes a drogas procedentes del clon original, o la aparición de neoplasias secundarias por el uso de drogas genotóxicas118 acute leukemias were studied during 4 years. The cellular phenotyping was carried out through the immunocytochemical ultramicromethod by using a panel of monoclonal antibodies with which the expression of lymphoid and myeloid antigens was evaluated. The expression of myeloid antigens in patients with acute lymphoid leukemia was found in 28.4 %, whereas the expression of lymphoid antigens in patients suffering from acute myeloid leukemia was observed in 56.7 %. The acute hybrid leukemias accounted for 16.1 % of the total of patients studied: 73.7 % at the onset of the disease and the other 26.3 % in the study following the induction treatment of the referred patients, which suggests in the latter the possibility of changing lineage by selecting variantes resistant to drugs from the original clon, or the appearance of secondary neoplasias due to the use of genotoxic drugs

  4. Short-term acute hypercapnia affects cellular responses to trace metals in the hard clams Mercenaria mercenaria

    Highlights: •PCO2 alters accumulation of Cd and Cu in clam cells. •Accumulation of Cd induces release of free Zn2+. •Accumulation of Cu induces an increase in free Cu2+ and Fe2+. •Metal-induced oxidative stress is alleviated at high PCO2. •Toxicity of Cu in likely enhanced while that of Cd alleviated by high PCO2. -- Abstract: Estuarine and coastal habitats experience large fluctuations of environmental factors such as temperature, salinity, partial pressure of CO2 (PCO2) and pH; they also serve as the natural sinks for trace metals. Benthic filter-feeding organisms such as bivalves are exposed to the elevated concentrations of metals in estuarine water and sediments that can strongly affect their physiology. The effects of metals on estuarine organisms may be exacerbated by other environmental factors. Thus, a decrease in pH caused by high PCO2 (hypercapnia) can modulate the effects of trace metals by affecting metal bioavailability, accumulation or binding. To better understand the cellular mechanisms of interactions between PCO2 and trace metals in marine bivalves, we exposed isolated mantle cells of the hard clams (Mercenaria mercenaria) to different levels of PCO2 (0.05, 1.52 and 3.01 kPa) and two major trace metal pollutants – cadmium (Cd) and copper (Cu). Elevated PCO2 resulted in a decrease in intracellular pH (pHi) of the isolated mantle cells from 7.8 to 7.4. Elevated PCO2 significantly but differently affected the trace metal accumulation by the cells. Cd uptake was suppressed at elevated PCO2 levels while Cu accumulation has greatly accelerated under hypercapnic conditions. Interestingly, at higher extracellular Cd levels, labile intracellular Cd2+ concentration remained the same, while intracellular levels of free Zn2+ increased suggesting that Cd2+ substitutes bound Zn2+ in these cells. In contrast, Cu exposure did not affect intracellular Zn2+ but led to a profound increase in the intracellular levels of labile Cu2+ and Fe2+. An increase

  5. Heat rejection system

    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.

  6. Cross acclimation between heat and hypoxia: Heat acclimation improves cellular tolerance and exercise performance in acute normobaric hypoxia

    Ben James Lee

    2016-03-01

    Full Text Available Background. The potential for cross acclimation between environmental stressors is not well understood. Thus the aim of this investigation was to determine the effect of fixed-workload heat or hypoxic acclimation on cellular, physiological and performance responses during post acclimation hypoxic exercise in humans. Method. Twenty-one males (age 22 ± 5 years; stature 1.76 ± 0.07m; mass 71.8 ± 7.9kg; V ̇O2 peak 51 ± 7mL.kg-1.min-1 completed a cycling hypoxic stress test (HST and self-paced 16.1km time trial (TT before (HST1, TT1, and after (HST2, TT2 a series of 10 daily 60 min training sessions (50% N V ̇O2peak in control (CON, n = 7; 18°C, 35%RH, hypoxic (HYP, n = 7; or hot (HOT, n = 7; 40°C, 25% RH conditions. Results. TT performance in hypoxia was improved following both acclimation treatments, HYP (-3:16 ± 3:10 mins:sec; p = 0.0006 and HOT (-2:02 ± 1:02 mins:sec; p = 0.005, but unchanged after CON (+0:31 ± 1:42 mins:sec. Resting monocyte heat shock protein 72 (mHSP72 increased prior to HST2 in HOT (62 ± 46% and HYP (58 ± 52%, but was unchanged after CON (9 ± 46%, leading to an attenuated mHSP72 response to hypoxic exercise in HOT and HYP HST2 compared to HST1 (p < 0.01. Changes in extracellular hypoxia-inducible factor 1-α followed a similar pattern to those of mHSP72. Physiological strain index (PSI was attenuated in HOT (HST1 = 4.12 ± 0.58, HST2 = 3.60 ± 0.42; p = 0.007 as a result of a reduced HR (HST1 = 140 ± 14 b.min-1; HST2 131 ± 9 b.min-1 p = 0.0006 and Trectal (HST1 = 37.55 ± 0.18°C; HST2 37.45 ± 0.14°C; p = 0.018 during exercise. Whereas PSI did not change in HYP (HST1 = 4.82 ± 0.64, HST2 4.83 ± 0.63. Conclusion. Heat acclimation improved cellular and systemic physiological tolerance to steady state exercise in moderate hypoxia. Additionally we show, for the first time, that heat acclimation improved cycling time trial performance to a magnitude similar to that achieved by hypoxic acclimation.

  7. Short-term acute hypercapnia affects cellular responses to trace metals in the hard clams Mercenaria mercenaria

    Ivanina, Anna V. [Department of Biology, University of North Carolina at Charlotte, 9201 University City Boulevard, Charlotte, NC 28223 (United States); Beniash, Elia [Department of Oral Biology, University of Pittsburgh, 589 Salk Hall, 3501 Terrace Street, Pittsburgh, PA 15261 (United States); Etzkorn, Markus; Meyers, Tiffany B. [Department of Chemistry, University of North Carolina at Charlotte, 9201 University City Boulevard, Charlotte, NC 28223 (United States); Ringwood, Amy H. [Department of Biology, University of North Carolina at Charlotte, 9201 University City Boulevard, Charlotte, NC 28223 (United States); Sokolova, Inna M., E-mail: isokolov@uncc.edu [Department of Biology, University of North Carolina at Charlotte, 9201 University City Boulevard, Charlotte, NC 28223 (United States)

    2013-09-15

    Highlights: •P{sub CO{sub 2}} alters accumulation of Cd and Cu in clam cells. •Accumulation of Cd induces release of free Zn{sup 2+}. •Accumulation of Cu induces an increase in free Cu{sup 2+} and Fe{sup 2+}. •Metal-induced oxidative stress is alleviated at high P{sub CO{sub 2}}. •Toxicity of Cu in likely enhanced while that of Cd alleviated by high P{sub CO{sub 2}}. -- Abstract: Estuarine and coastal habitats experience large fluctuations of environmental factors such as temperature, salinity, partial pressure of CO{sub 2} (P{sub CO{sub 2}}) and pH; they also serve as the natural sinks for trace metals. Benthic filter-feeding organisms such as bivalves are exposed to the elevated concentrations of metals in estuarine water and sediments that can strongly affect their physiology. The effects of metals on estuarine organisms may be exacerbated by other environmental factors. Thus, a decrease in pH caused by high P{sub CO{sub 2}} (hypercapnia) can modulate the effects of trace metals by affecting metal bioavailability, accumulation or binding. To better understand the cellular mechanisms of interactions between P{sub CO{sub 2}} and trace metals in marine bivalves, we exposed isolated mantle cells of the hard clams (Mercenaria mercenaria) to different levels of P{sub CO{sub 2}} (0.05, 1.52 and 3.01 kPa) and two major trace metal pollutants – cadmium (Cd) and copper (Cu). Elevated P{sub CO{sub 2}} resulted in a decrease in intracellular pH (pH{sub i}) of the isolated mantle cells from 7.8 to 7.4. Elevated P{sub CO{sub 2}} significantly but differently affected the trace metal accumulation by the cells. Cd uptake was suppressed at elevated P{sub CO{sub 2}} levels while Cu accumulation has greatly accelerated under hypercapnic conditions. Interestingly, at higher extracellular Cd levels, labile intracellular Cd{sup 2+} concentration remained the same, while intracellular levels of free Zn{sup 2+} increased suggesting that Cd{sup 2+} substitutes bound Zn{sup 2

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

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

    2016-07-01

    Subclinical rejection (SCR) is a common event in protocol biopsies after liver transplantation (LT). So far the interpretation of the underlying histological changes and clinical significance is limited. Previous studies were restricted to SCR manifestations within the first weeks after transplantation with limited follow-up. We analyzed clinical data from our prospective protocol biopsy program and found late SCR (at least 3 months after transplantation) to be a common event (41/94 patients). SCR manifested much later than acute cellular rejection (ACR). In the second year after transplantation, the SCR incidence in protocol biopsies reached a plateau of approximately 25% and remained at this level until the latest observed manifestations more than 5 years after transplantation. During a median follow-up of 32 months after SCR, no acute or chronic rejection, relevant graft fibrosis, graft loss, or liver-related death occurred even without specific therapy for SCR. Immunophenotyping of liver biopsies during SCR showed that similar to ACR, the composition of intrahepatic T cells depended on the severity of histological rejection. However, SCR showed a different pattern of infiltrating T cells with a stronger accumulation of CD4(+) cells, an increasing CD4(+) /CD8(+) ratio, and an increasing CD4(+) forkhead box P3 (FOXP3)(+) regulatory T cell (Treg)/CD8(+) ratio, which was not seen in ACR. These intrahepatic T cell patterns were not reflected in the peripheral blood. In conclusion, late SCR after LT has a good clinical prognosis, and it seems safe to leave it untreated. This benign clinical course compared to ACR is associated with intrahepatic T cell infiltration patterns showing less cytotoxic T cells and more CD4(+) FOXP3(+) Tregs. Liver Transplantation 22 943-955 2016 AASLD. PMID:26929119

  9. Prostanoids modulate inflammation and alloimmune responses during graft rejection

    P.N. Rocha

    2005-12-01

    Full Text Available Acute rejection of a transplanted organ is characterized by intense inflammation within the graft. Yet, for many years transplant researchers have overlooked the role of classic mediators of inflammation such as prostaglandins and thromboxane (prostanoids in alloimmune responses. It has been demonstrated that local production of prostanoids within the allograft is increased during an episode of acute rejection and that these molecules are able to interfere with graft function by modulating vascular tone, capillary permeability, and platelet aggregation. Experimental data also suggest that prostanoids may participate in alloimmune responses by directly modulating T lymphocyte and antigen-presenting cell function. In the present paper, we provide a brief overview of the alloimmune response, of prostanoid biology, and discuss the available evidence for the role of prostaglandin E2 and thromboxane A2 in graft rejection.

  10. Specific cellular signal-transduction responses to in vivo combination therapy with ATRA, valproic acid and theophylline in acute myeloid leukemia.

    Skavland, J; Jørgensen, K M; Hadziavdic, K; Hovland, R; Jonassen, I; Bruserud, O; Gjertsen, B T

    2011-02-01

    Acute myeloid leukemia (AML) frequently comprises mutations in genes that cause perturbation in intracellular signaling pathways, thereby altering normal responses to growth factors and cytokines. Such oncogenic cellular signal transduction may be therapeutic if targeted directly or through epigenetic regulation. We treated 24 selected elderly AML patients with all-trans retinoic acid for 2 days before adding theophylline and the histone deacetylase inhibitor valproic acid (ClinicalTrials.gov NCT00175812; EudraCT no. 2004-001663-22), and sampled 11 patients for peripheral blood at day 0, 2 and 7 for single-cell analysis of basal level and signal-transduction responses to relevant myeloid growth factors (granulocyte-colony-stimulating factor, granulocyte/macrophage-colony-stimulating factor, interleukin-3, Flt3L, stem cell factor, erythropoietin, CXCL-12) on 10 signaling molecules (CREB, STAT1/3/5, p38, Erk1/2, Akt, c-Cbl, ZAP70/Syk and rpS6). Pretreatment analysis by unsupervised clustering and principal component analysis divided the patients into three distinguishable signaling clusters (non-potentiated, potentiated basal and potentiated signaling). Signal-transduction pathways were modulated during therapy and patients moved between the clusters. Patients with multiple leukemic clones demonstrated distinct stimulation responses and therapy-induced modulation. Individual signaling profiles together with clinical and hematological information may be used to early identify AML patients in whom epigenetic and signal-transduction targeted therapy is beneficial. PMID:22829110

  11. Specific cellular signal-transduction responses to in vivo combination therapy with ATRA, valproic acid and theophylline in acute myeloid leukemia

    Acute myeloid leukemia (AML) frequently comprises mutations in genes that cause perturbation in intracellular signaling pathways, thereby altering normal responses to growth factors and cytokines. Such oncogenic cellular signal transduction may be therapeutic if targeted directly or through epigenetic regulation. We treated 24 selected elderly AML patients with all-trans retinoic acid for 2 days before adding theophylline and the histone deacetylase inhibitor valproic acid (ClinicalTrials.gov NCT00175812; EudraCT no. 2004-001663-22), and sampled 11 patients for peripheral blood at day 0, 2 and 7 for single-cell analysis of basal level and signal-transduction responses to relevant myeloid growth factors (granulocyte-colony-stimulating factor, granulocyte/macrophage-colony-stimulating factor, interleukin-3, Flt3L, stem cell factor, erythropoietin, CXCL-12) on 10 signaling molecules (CREB, STAT1/3/5, p38, Erk1/2, Akt, c-Cbl, ZAP70/Syk and rpS6). Pretreatment analysis by unsupervised clustering and principal component analysis divided the patients into three distinguishable signaling clusters (non-potentiated, potentiated basal and potentiated signaling). Signal-transduction pathways were modulated during therapy and patients moved between the clusters. Patients with multiple leukemic clones demonstrated distinct stimulation responses and therapy-induced modulation. Individual signaling profiles together with clinical and hematological information may be used to early identify AML patients in whom epigenetic and signal-transduction targeted therapy is beneficial

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

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

  13. Remote noninvasive allograft rejection monitoring for heart transplant recipients: study protocol for the novel evaluation with home electrocardiogram and remote transmission (NEW HEART) study

    Doering Lynn V; Hickey Kathleen; Pickham David; Chen Belinda; Drew Barbara J

    2012-01-01

    Abstract Background Acute allograft rejection is a major cause of early mortality in the first year after heart transplantation in adults. Although endomyocardial biopsy (EMB) is not a perfect "gold standard" for a correct diagnosis of acute allograft rejection, it is considered the best available test and thus, is the current standard practice. Unfortunately, EMB is an invasive and costly procedure that is not without risk. Recent evidence suggests that acute allograft rejection causes delay...

  14. Transplant rejection and paradigms lost

    Strom, Terry B.

    2013-01-01

    During transplant rejection, migrating T cells infiltrate the grafted organ, but the signals that direct this migration are incompletely understood. In this issue of the JCI, Walch et al. debunk two classical paradigms concerning transplant rejection, with important consequences for the design of antirejection therapeutics. PMID:23676457

  15. Transplant rejection and paradigms lost

    Strom, Terry B.

    2013-01-01

    During transplant rejection, migrating T cells infiltrate the grafted organ, but the signals that direct this migration are incompletely understood. In this issue of the JCI, Walch et al. debunk two classical paradigms concerning transplant rejection, with important consequences for the design of antirejection therapeutics.

  16. Rejection sampling in demand systems

    Ley, Eduardo; Mark F.J. Steel

    1992-01-01

    We illustrate the method of rejection sampling in a Bayesian application of a new approach toı estimating Demand Systems. This approach, suggested by Varian (1990), is based on a generalization of Afriat's (1967) efficiency index. Rejection sampling is applied to the prior-to-posterior mapping enabling us to obtain posterior results in a nonstandard model.

  17. Emotional responses to interpersonal rejection.

    Leary, Mark R

    2015-12-01

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

  18. Emotional responses to interpersonal rejection

    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

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

    Reschen ME; O'Callaghan CA

    2014-01-01

    Michael E Reschen, Christopher A O’Callaghan Henry Wellcome Building, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom Abstract: Tacrolimus is the key immunosuppressant used to prevent allograft rejection in kidney and liver transplant recipients. Despite the efficacy of tacrolimus and adjunctive immunosuppressants, a substantial number of patients experience episodes of acute rejection and late graft loss. Nonadherence is an etiological factor in both acute...

  20. INTRATHYMIC INOCULATION OF LIVER SPECIFIC ANTIGEN ALLEVIATES LIVER TRANSPLANT REJECTION

    贾长库; 郑树森; 朱有法

    2004-01-01

    Objective To study the effects of liver specific antigen (LSA) on liver allotransplantation rejection. Methods Orthotopic liver transplantation was performed in this study. Group Ⅰ: syngeneic control (Wistar-to-Wistar); Group Ⅱ: acute rejection (SD-to-Wistar). Group Ⅲ: thymic inoculation of SD rat LSA day 7 before transplantation. The observation of general condition and survival time, rejection grades and the NF-κB activity of splenocytes were used to analyze severity of acute rejection and immune state of animals in different groups. Results The general condition of group Ⅰ was fair post transplantation with no sign of rejection. All recipients of group Ⅱ died within days 9 to 13 post transplantation with median survival time of 10.7 ±1.37 days. As for group Ⅲ, 5 out of 6 recipients survived for a long period with remarkably better general condition than that of group Ⅱ. Its rejection grades were significantly lower than group Ⅱ (P< 0.05).NF-κB activity was only detected in group Ⅰ between days 5 and 7 after transplantation, whereas high activity of NF-κB was detected at all points in group Ⅱ and low NF-κB activity was detected in group Ⅲ which was significantly lower than that of group Ⅱ (P < 0.05). Conclusions LSA is an important transplantation antigen directly involved in the immunorejection of liver transplantation. Intrathymic inoculation of LSA can alleviate the rejection of liver allotransplantation,grafts survive for a period of time thereby, allowing a novel way to liver transplantation immunotolerance.

  1. Prevention trumps treatment of antibody-mediated transplant rejection

    Knechtle, Stuart J.; Kwun, Jean; Iwakoshi, Neal

    2010-01-01

    Belying the spectacular success of solid organ transplantation and improvements in immunosuppressive therapy is the reality that long-term graft survival rates remain relatively unchanged, in large part due to chronic and insidious alloantibody-mediated graft injury. Half of heart transplant recipients develop chronic rejection within 10 years — a daunting statistic, particularly for young patients expecting to achieve longevity by enduring the rigors of a transplant. The current immunosuppressive pharmacopeia is relatively ineffective in preventing late alloantibody-associated chronic rejection. In this issue of the JCI, Kelishadi et al. report that preemptive deletion of B cells prior to heart transplantation in cynomolgus monkeys, in addition to conventional posttransplant immunosuppressive therapy with cyclosporine, markedly attenuated not only acute graft rejection but also alloantibody elaboration and chronic graft rejection. The success of this preemptive strike implies a central role for B cells in graft rejection, and this approach may help to delay or prevent chronic rejection after solid organ transplantation. PMID:20335653

  2. Renal washout parameter as an indicator of transplant rejection

    Jackson, S.A.; Ehrlich, L.; Martin, R.H.

    1986-06-01

    The accumulation of intravascular fibrin thrombosis in both acute and chronic renal rejection leads to a delay in the transit of perfusion. This study examines the renal washout parameter as an indicator of transit time. By mathematical simulation of renal time-activity curves various factors which can influence this parameter are investigated, a simple analysis is proposed and clinical results are correlated with biopsy findings. A washout parameter greater than 28 s is found to be consistent with histologically diagnosed rejection over a range of bolus qualities.

  3. The renal washout parameter as an indicator of transplant rejection

    The accumulation of intravascular fibrin thrombosis in both acute and chronic renal rejection leads to a delay in the transit of perfusion. This study examines the renal washout parameter as an indicator of transit time. By mathematical simulation of renal time-activity curves various factors which can influence this parameter are investigated, a simple analysis is proposed and clinical results are correlated with biopsy findings. A washout parameter greater than 28 s is found to be consistent with histologically diagnosed rejection over a range of bolus qualities. (orig.)

  4. Variable Heat Rejection (VHR) Project

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

  5. LMS filters for cellular CDMA overlay

    Wang, J.

    1996-01-01

    This paper extends and complements previous research we have performed on the performance of nonadaptive narrowband suppression filters when used in cellular CDMA overlay situations. In this paper, an adaptive LMS filter is applied to cellular CDMA overlay situations in order to reject narrowband interference.

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

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

    2016-03-24

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

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

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

    2016-01-01

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

  8. Diagnosis of Rejection by Analyzing Ventricular Late Potentials in Heart Transplant Patients

    Vítor Nogueira Mendes

    2016-01-01

    Full Text Available Background: Heart transplant rejection originates slow and fragmented conduction. Signal-averaged ECG (SAECG is a stratification method in the risk of rejection. Objective: To develop a risk score for rejection, using SAECG variables. Methods: We studied 28 transplant patients. First, we divided the sample into two groups based on the occurrence of acute rejection (5 with rejection and 23 without. In a second phase, we divided the sample considering the existence or not of rejection in at least one biopsy performed on the follow-up period (rejection pm1: 18 with rejection and 10 without. Results: On conventional ECG, the presence of fibrosis was the only criterion associated with acute rejection (OR = 19; 95% CI = 1.65-218.47; p = 0.02. Considering the rejection pm1, an association was found with the SAECG variables, mainly with RMS40 (OR = 0.97; 95% CI = 0.87-0.99; p = 0.03 and LAS40 (OR = 1.06; 95% IC = 1.01-1.11; p = 0.03. We formulated a risk score including those variables, and evaluated its discriminative performance in our sample. The presence of fibrosis with increasing of LAS40 and decreasing of RMS40 showed a good ability to distinguish between patients with and without rejection (AUC = 0.82; p < 0.01, assuming a cutoff point of sensitivity = 83.3% and specificity = 60%. Conclusion: The SAECG distinguished between patients with and without rejection. The usefulness of the proposed risk score must be demonstrated in larger follow-up studies.

  9. Decreased chronic cellular and antibody-mediated injury in the kidney following simultaneous liver-kidney transplantation.

    Taner, Timucin; Heimbach, Julie K; Rosen, Charles B; Nyberg, Scott L; Park, Walter D; Stegall, Mark D

    2016-04-01

    In simultaneous liver-kidney transplantation (SLK), the liver can protect the kidney from hyperacute rejection and may also decrease acute cellular rejection rates. Whether the liver protects against chronic injury is unknown. To answer this we studied renal allograft surveillance biopsies in 68 consecutive SLK recipients (14 with donor-specific alloantibodies at transplantation [DSA+], 54 with low or no DSA, [DSA-]). These were compared with biopsies of a matched cohort of kidney transplant alone (KTA) recipients (28 DSA+, 108 DSA-). Overall 5-year patient and graft survival was not different: 93.8% and 91.2% in SLK, and 91.9% and 77.1% in KTA. In DSA+ recipients, KTA had a significantly higher incidence of acute antibody-mediated rejection (46.4% vs. 7.1%) and chronic transplant glomerulopathy (53.6% vs. 0%). In DSA- recipients at 5 years, KTA had a significantly higher cumulative incidence of T cell-mediated rejection (clinical plus subclinical, 30.6% vs. 7.4%). By 5 years, DSA+ KTA had a 44% decline in mean GFR while DSA+SLK had stable GFR. In DSA- KTA, the incidence of a combined endpoint of renal allograft loss or over a 50% decline in GFR was significantly higher (20.4% vs. 7.4%). Simultaneously transplanted liver allograft was the most predictive factor for a significantly lower incidence of cellular (odds ratio 0.13, 95% confidence interval 0.06-0.27) and antibody-mediated injury (odds ratio 0.11, confidence interval 0.03-0.32), as well as graft functional decline (odds ratio 0.22, confidence interval 0.06-0.59). Thus, SLK is associated with reduced chronic cellular and antibody-mediated alloimmune injury in the kidney allograft. PMID:26924059

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

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

    2013-01-01

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

  11. Nucleic Acid Drugs for Prevention of Cardiac Rejection

    Jun-ichi Suzuki

    2009-01-01

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

  12. Further evaluation of /sup 99m/Tc sulfur colloid accumulation in rejecting renal transplants in man and a canine model

    Renal transplant accumulation of /sup 99m/Tc sulfur colloid was evaluated in 41 patients. Ninety-five examinations were performed comparing transplant with bone marrow activity and clinical or pathological diagnosis. The /sup 99m/Tc sulfur colloid accumulated in acute or chronic rejection as long as the vascular supply of the grafted kidney was not severely impaired. Accumulation was marked in chronic rejection, slight in acute rejection and absent in normally functioning transplants or in those with acute tubular necrosis. In the 10 dog models, no accumulation was seen in autografted transplants and early accumulation was demonstrated within the hyperacutely rejecting kidneys of allografted dogs. (U.S.)

  13. Novel Insights into Lung Transplant Rejection by Microarray Analysis

    Lande, Jeffrey D.; Patil, Jagadish; Li, Na; Berryman, Todd R.; King, Richard A.; Hertz, Marshall I.

    2007-01-01

    Gene expression microarrays can estimate the prevalence of mRNA for thousands of genes in a small sample of cells or tissue. Organ transplant researchers are increasingly using microarrays to identify specific patterns of gene expression that predict and characterize acute and chronic rejection, and to improve our understanding of the mechanisms underlying organ allograft dysfunction. We used microarrays to assess gene expression in bronchoalveolar lavage cell samples from lung transplant rec...

  14. Perturbations in the Urinary Exosome in Transplant Rejection

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

    2015-01-05

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

  15. Leukocytic acetylcholine in chronic rejection of renal allografts

    Wilczynska, Joanna

    2011-01-01

    Leukocytes, which accumulate in graft blood vessels during fatal acute rejection of experimental renal allografts, synthesise and release acetylcholine (ACh). In this study, I tested the hypothesis that ACh produced by leukocytes accumulating in graft blood vessels contributes to the pathogenesis of chronic renal allograft vasculopathy (CAV). Kidneys were transplanted in the allogeneic Fischer 344 to Lewis rat strain combination. Isogeneic transplantations were performed in Lew...

  16. Soluble CD30 in renal transplant recipients: Is it a good biomarker to predict rejection?

    Azarpira Negar

    2010-01-01

    Full Text Available 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 trans-plant 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.

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

    André Dong Won Lee

    2004-06-01

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

  18. 细胞间黏附分子-1靶向微泡超声造影成像评价肾移植后急性排异反应%Ultrasound imaging of acute renal allograft rejection with microbubbles targeted to intercellular adhesion molecule-1

    纪丽景; 王宝平; 罗利红; 吴凤林

    2011-01-01

    目的 探讨靶向超声分子成像评价肾移植后急性排异反应的可行性.方法 采用“亲和素-生物素”桥接法构建携抗细胞间黏附分子-1(ICAM-1)靶向微泡(MBI)和携同型抗体对照微泡(MB).10只SD大鼠行左侧肾异种移植术,术后72 h移植肾随机先后注入MBI和MB(间隔30 min),分别于注入3 min后行移植肾超声造影检查,并测量移植肾声强度(VI),最后进行肾组织病理及免疫组化检测.结果 移植肾在注入靶向超声微泡后可见肾区域明显灌注显影,延迟3 min显像MBI组在移植肾可见显著的超声显影增强.而MB组移植肾仅见轻度的超声显影增强,其显影强度较前者明显减弱.MBI组和MB组移植肾VI值分别为(27.0±7.4)U、(10.2±2.4)U,两者之间差异有统计学意义(F=64.744,P<0.05).结论应用靶向ICAM-1超声微泡和超声造影结合能有效评价大鼠肾移植急性排异.%Objective To assess the feasibility of evaluation of renal allograft acute rejection in rat with contrast-enhanced ultrasound ( CEUS ) and targeted microbubbles.Methods Phospholipid microbubbles targeted to intercellular adhesion molecule -1 (ICAM-1)(MBI) and control microbubbles (MB) were created by conjugating monoclonal antibody against ICAM-1 or isotype control antibody to the lipid capsule via “avidin-biotin” bridging.Ten SD rats with acute renal allograft rejection were injected intravenous of MBI and MB in random order with a 30-min interval.After 3 min of intravenous injection of microbubbles,targeted CEUS imaging was performed in all rats.And then the video intensity (VI) was determined.Results In MBI group,a significant ultrasonic enhancement was observed,but it was not very obvious in MB group.Increment in VI value of transplant kidney in MBI group was great and it amounted to (27.0 ± 7.4)U,however,increment in VI value of in MB group was minor and it was merely (10.2 ± 2.4) U,Difference was evident in transplant kidney between of the two

  19. Cell-Based Therapies in the Prevention of Solid Organ Transplant Rejection

    Morelli, Adrian E.; Divito, Sherrie J

    2012-01-01

    Problem statement: Organ transplantation is a life-saving and increasingly common procedure, as it often serves as the only treatment available for end-stage organ disease. Although the constant development of new and more effective immunosuppressive drugs has revolutionized the prevention and treatment of acute graft rejection, these drugs have significant toxicity, greatly increase patient susceptibility to neoplasms and infection and exert little impact on chronic rejection. Approach: The...

  20. Integrin antagonists prevent costimulatory blockade-resistant transplant rejection by CD8+ memory T cells

    Kitchens, W. H.; Haridas, D.; Wagener, M. E.; Song, M.; Kirk, A D; Larsen, C P; Ford, M. L.

    2011-01-01

    The success of belatacept in late-stage clinical trials inaugurates the arrival of a new class of immunosuppressants based on costimulatory blockade, an immunosuppression strategy that disrupts essential signals required for alloreactive T cell activation. Despite having improved renal function, kidney transplant recipients treated with belatacept experienced increased rates of acute rejection. This finding has renewed focus on costimulatory blockade-resistant rejection and specifically the r...

  1. Monoclonal Antibody Therapy does not Abrogate Rejection Risk in Renal Transplant Recipients

    Sanjeev Goswami

    2013-01-01

    Monoclonal antibodies are being increasingly used as therapeutic agents in medicine. Rituximab (anti-CD20) and Daclizumab (anti-IL2Rα) are two such monoclonal antibodies used to prevent organ rejection, but are not fail-safe. We have analyzed the pre and post-transplant antibody profile in serum of renal transplant recipients receiving Rituximab and /or Daclizumab. Study Group: Kidney recipients with acute rejection and having PRA > 10% pre-transplant were selected for the study (n=11). Those...

  2. Non-organ-specific Autoantibodies and CMV Infection in Renal Transplant Recipients with or without Rejection

    R. Cavallo; F. Giacchino; G. P. Segoloni; C. Merlino; F. Sidoti; S. Margio; G. A. Touscoz; M. Bergallo; Costa, C.

    2007-01-01

    Aim/Background: A relation between cytomegalovirus (CMV) infection and development of non-organ-specific autoantibodies (NOSAs) has been reported in several studies and it has been hypothesized that CMV and NOSAs may be involved in the development of rejection in transplant recipients. Aim of this study was to investigate the presence of NOSAs, relation to CMV infection and development of acute or chronic rejection in a population of renal transplant recipients. Material/Methods: The presence...

  3. 7 CFR 58.136 - Rejected milk.

    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...

  4. Molecular analysis of transplant rejection: marching onward

    Lakkis, Fadi G.; Billiar, Timothy R.

    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.

  5. Molecular analysis of transplant rejection: marching onward

    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

  6. Cellular automata

    Codd, E F

    1968-01-01

    Cellular Automata presents the fundamental principles of homogeneous cellular systems. This book discusses the possibility of biochemical computers with self-reproducing capability.Organized into eight chapters, this book begins with an overview of some theorems dealing with conditions under which universal computation and construction can be exhibited in cellular spaces. This text then presents a design for a machine embedded in a cellular space or a machine that can compute all computable functions and construct a replica of itself in any accessible and sufficiently large region of t

  7. Sodium MRI in Multiple Sclerosis is Compatible with Intracellular Sodium Accumulation and Inflammation-Induced Hyper-Cellularity of Acute Brain Lesions

    Biller, Armin; Pflugmann, Isabella; Badde, Stephanie; Diem, Ricarda; Wildemann, Brigitte; Nagel, Armin M.; Jordan, J.; Benkhedah, Nadia; Kleesiek, Jens

    2016-01-01

    The cascade of inflammatory pathogenetic mechanisms in multiple sclerosis (MS) has no specific conventional MRI correlates. Clinicians therefore stipulate improved imaging specificity to define the pathological substrates of MS in vivo including mapping of intracellular sodium accumulation. Based upon preclinical findings and results of previous sodium MRI studies in MS patients we hypothesized that the fluid-attenuated sodium signal differs between acute and chronic lesions. We acquired brain sodium and proton MRI data of N = 29 MS patients; lesion type was defined by the presence or absence of contrast enhancement. N = 302 MS brain lesions were detected, and generalized linear mixed models were applied to predict lesion type based on sodium signals; thereby controlling for varying numbers of lesions among patients and confounding variables such as age and medication. Hierarchical model comparisons revealed that both sodium signals average tissue (χ2(1) = 27.89, p < 0.001) and fluid-attenuated (χ2(1) = 5.76, p = 0.016) improved lesion type classification. Sodium MRI signals were significantly elevated in acute compared to chronic lesions compatible with intracellular sodium accumulation in acute MS lesions. If confirmed in further studies, sodium MRI could serve as biomarker for diagnostic assessment of MS, and as readout parameter in clinical trials promoting attenuation of chronic inflammation. PMID:27507776

  8. Sodium MRI in Multiple Sclerosis is Compatible with Intracellular Sodium Accumulation and Inflammation-Induced Hyper-Cellularity of Acute Brain Lesions.

    Biller, Armin; Pflugmann, Isabella; Badde, Stephanie; Diem, Ricarda; Wildemann, Brigitte; Nagel, Armin M; Jordan, J; Benkhedah, Nadia; Kleesiek, Jens

    2016-01-01

    The cascade of inflammatory pathogenetic mechanisms in multiple sclerosis (MS) has no specific conventional MRI correlates. Clinicians therefore stipulate improved imaging specificity to define the pathological substrates of MS in vivo including mapping of intracellular sodium accumulation. Based upon preclinical findings and results of previous sodium MRI studies in MS patients we hypothesized that the fluid-attenuated sodium signal differs between acute and chronic lesions. We acquired brain sodium and proton MRI data of N = 29 MS patients; lesion type was defined by the presence or absence of contrast enhancement. N = 302 MS brain lesions were detected, and generalized linear mixed models were applied to predict lesion type based on sodium signals; thereby controlling for varying numbers of lesions among patients and confounding variables such as age and medication. Hierarchical model comparisons revealed that both sodium signals average tissue (χ(2)(1) = 27.89, p < 0.001) and fluid-attenuated (χ(2)(1) = 5.76, p = 0.016) improved lesion type classification. Sodium MRI signals were significantly elevated in acute compared to chronic lesions compatible with intracellular sodium accumulation in acute MS lesions. If confirmed in further studies, sodium MRI could serve as biomarker for diagnostic assessment of MS, and as readout parameter in clinical trials promoting attenuation of chronic inflammation. PMID:27507776

  9. Rejection index for pressure tubes

    The objective of the present study was to establish a set of criteria (or Rejection Index) which could be used to decide whether a zirconium-2 1/2 w/o niobium pressure tube in a CANDU reactor should be removed from service due to in-service degradation. A critique of key issues associated with establishing a realistic rejection index was prepared. Areas of uncertainty in available information were identified and recommendations for further analysis and laboratory testing made. A Rejection Index based on the following limits has been recommended: 1) Limits related to design intent and normal operation: any garter spring must remain within the tolerance band specified for its design location; the annulus gas system must normally be operated in a circulating mode with a procedure in place for purging to prevent accumulation of deuterium. It must remain sensitive to leaks into any part of the systems; and pressure tube dimensions and distortions must be limited to maintain the fuel channels within the original design intent; 2) Limits related to defect tolerance: adequate time margins between occurrence of a leaking crack and unstable failure must be demonstrated for all fuel channels; long lap-type flaws are unacceptable; crack-like defects of any size are unacceptable; and score marks, frat marks and other defects with contoured profiles must fall below certain depth, length and stress intensity limits; and 3) Limits related to property degradation: at operating temperature each pressure tube must be demonstrated to have a critical length in excess of a stipulated value; the maximum equivalent hydrogen level in any pressure tube should not exceed a limit which should be defined taking into account the known history of that tube; the maximum equivalent hydrogen level in any rolled joint should not exceed a limit which is presently recommended as 200 ppm equivalent hydrogen; and the maximum diametral creep strain should be limited to less than 5%

  10. Liver transplant rejection and cholestasis

    This paper reports on liver transplant biopsies with Tc-99m hepatobiliary scintigraphy in patients with and without rejection (RE) and or cholestasis (CS). The authors reviewed 76 Tc-99m disofenin hepatobiliary studies and corresponding liver biopsies. Uptake was assigned a value of 0 to 3 (0 = normal). Excretion was assigned a value of 0 to 2 (0 = normal). Biopsies were graded on scales of (1) 0 to 12 for findings of CS (0 = normal) and (2) 0 to 2 for RE (0 = normal)

  11. Perturbations in the Urinary Exosome in Transplant Rejection

    Tara eSigdel

    2015-01-01

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

  12. Rejection in the cardiac transplant

    Standard chest radiography remains the most frequent applied method for monitoring post surgical cardiac transplant patients. Evidence suggests that after the 1st month cardiac enlargement is indeed a useful indicator of rejection, sometimes being caused by pericardial effusion and/or changes in left ventricular mass. Opportunistic infections, either pulmonary lesions or mediastinal abscesses, as well as malignant tumours may all occur and require evaluation or exclusion. Conventional computed transmission tomography is an excellent technique for surveying the entire thorax relatively non-invasively and is recommended whenever pulmonary, cardiac or mediastinal changes are unexplained. Coronary arteriography with or without digital subtraction remains the definitive method for examining the coronary arteries. Left ventricular function can be evaluated with either angiography or other non-invasive methods including such techniques as echocardiography and nuclear medicine. More recently monoclonal antibody labels for antimyosin show promise for identifying rejection. Ultrafast CT scanning is now available in a number of centres. It allows millisecond cross-sectional cine-tomography of the heart as well as of the whole chest, and also provides 3-D quantitative analyses of end-diastolic and systolic function including regional wall thickening dynamics and estimations of myocardial mass. Right, as well as left-sided cardiac chambers, are demonstrated routinely during the same ultrafast CT procedure. MRI, like ultrafast CT, is a new technique still being explored. MRI as well as MR spectroscopy are regarded as diagnostic radiology procedures. (author). 32 refs.; 3 figs.; 3 tabs

  13. CD57(+) CD4 T Cells Underlie Belatacept-Resistant Allograft Rejection.

    Espinosa, J; Herr, F; Tharp, G; Bosinger, S; Song, M; Farris, A B; George, R; Cheeseman, J; Stempora, L; Townsend, R; Durrbach, A; Kirk, A D

    2016-04-01

    Belatacept is a B7-specific fusion protein used to prevent allograft rejection by blocking T cell costimulation. Generally efficacious, it fails to prevent acute rejection in a sizable minority of patients. In experimental models, memory T cells mediate costimulation blockade-resistant rejection (CoBRR), but this remains undefined in humans. To explore relationships between individual patients' immune cell phenotypes and CoBRR, we studied patients receiving belatacept or conventional calcineurin inhibitor-based immunosuppression. We identified a population of CD57(+) PD1(-) CD4 T cells present prior to transplantation that correlated with CoBRR. Contrary to data recognizing CD57 as a marker of senescence on CD8 T cells, we discovered a nonsenescent, cytolytic phenotype associated with CD57 on CD4 T cells. Moreover, CD57(+) CD4 T cells expressed high levels of adhesion molecules implicated in experimental CoBRR, were CD28(-) , expressed a transcriptional phenotype broadly defining allograft rejection and were shown to be present in rejecting human kidney allografts. These data implicate CD57(+) CD4 T cells in clinical CoBRR. If prospectively validated, this characteristic could identify patients at higher risk for acute rejection on belatacept-based therapy. PMID:26603381

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

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

    2013-12-01

    Perceiving that one is rejected is an important correlate of emotional maladjustment. Yet, self-perceptions can substantially differ from classmate-reports of who is rejected. In this study, discrepancies between self- and classmate-reports of rejection were identified in 359 Australian adolescents (age 10-12 years). As expected, adolescents who overestimated rejection reported more rejection sensitivity and felt more victimized by their peers, but were not seen by peers as more victimized. Adolescents who underestimated rejection identified themselves as high in overt aggression, and their peers identified them as high in overt and relational aggression and low in prosocial behavior. Yet, underestimators' feelings of friendship satisfaction did not seem to suffer and they reported low rejection sensitivity. Results suggest that interventions to promote adolescent health should explicitly recognize the different needs of those who do and do not seem to perceive their high rejection, as well as adolescents who overestimate their rejection. PMID:24215970

  15. Significance of 99mTc-tin Colloid Scan in Rejection of Transplanted Kidney

    Renal transplant uptake of 99mTc-tin colloid was evaluated in 26 patients. Seventy-seven examinations were performed comparing transplant with bone marrow activity, clinical and/or pathological diagnosis. There were 13 instances of acute rejection; 7 of these exhibited slight uptake of radiocolloid in the renal transplant, 1 had marked uptake, and 5 had no evidence of uptake. There were 7 instances of chronic rejection; 5 of which demonstrated marked transplant uptake of radiocolloid, 1 had slight uptake, and 1 had no evidence of uptake. There were 2 instances of acute tubular necrosis and 55 instances of normal transplant function, but none of these exhibited transplant uptake of radiocolloid. From the result, the uptake of 99mTc-tin colloid by renal transplant appears to signal rejection as long as the vascular supply is not severely compromised. Acute rejection may be represented by slight radiocolloid uptake, and chronic rejection by marked uptake when compared to bone marrow activity.

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

    Bhatti, Adnan Bashir; Usman, Muhammad

    2015-01-01

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

  17. An analysis of dynamic CT curves of renal transplants with rejection and cyclosporin A intoxication

    The early differential diagnosis between transplant rejection and cyclosporin intoxication is often difficult, although it is important for treatment. We carried out dynamic CT on 48 occasions in patients with normal function, with acute tubular necrosis, rejection and cyclosporin A intoxication. Analysis of the timedensity of the cortex showed significantly slower enhancement with cyclosporin A intoxication than during rejection. The peak and the arterial curve were also delayed in cyclosporin A intoxication. This evidence of reduced cortical perfusion during cyclosporin A intoxication can be explained by the results of modern pathophysiological studies. In principle, it is possible to distinguish between cyclosporin A intoxication and rejection by means of dynamic CT, but for its routine use the nephrotoxicity of the contrast medium must be taken into account. (orig.)

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

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

  19. Fractional active disturbance rejection control.

    Li, Dazi; Ding, Pan; Gao, Zhiqiang

    2016-05-01

    A fractional active disturbance rejection control (FADRC) scheme is proposed to improve the performance of commensurate linear fractional order systems (FOS) and the robust analysis shows that the controller is also applicable to incommensurate linear FOS control. In FADRC, the traditional extended states observer (ESO) is generalized to a fractional order extended states observer (FESO) by using the fractional calculus, and the tracking differentiator plus nonlinear state error feedback are replaced by a fractional proportional-derivative controller. To simplify controller tuning, the linear bandwidth-parameterization method has been adopted. The impacts of the observer bandwidth ωo and controller bandwidth ωc on system performance are then analyzed. Finally, the FADRC stability and frequency-domain characteristics for linear single-input single-output FOS are analyzed. Simulation results by FADRC and ADRC on typical FOS are compared to demonstrate the superiority and effectiveness of the proposed scheme. PMID:26928516

  20. A rendezvous before rejection: Where do T cells meet transplant antigens?

    Briscoe, David M.; Sayegh, Mohamed H.

    2002-01-01

    Interactions between recipient T cells and donor endothelial graft cells may be an important mechanism for both acute and chronic rejection of vascularized allografts. This finding provides a starting point for investigations to develop novel ways of inducing long-lasting immunologic tolerance to donor antigens.

  1. Are You Being Rejected or Excluded? Insights from Neuroimaging Studies Using Different Rejection Paradigms

    Premkumar, Preethi

    2012-01-01

    Rejection sensitivity is the heightened tendency to perceive or anxiously expect disengagement from others during social interaction. There has been a recent wave of neuroimaging studies of rejection. The aim of the current review was to determine key brain regions involved in social rejection by selectively reviewing neuroimaging studies that employed one of three paradigms of social rejection, namely social exclusion during a ball-tossing game, evaluating feedback about preference from peer...

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

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

    2000-12-01

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

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

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

  4. Cellular Automata

    Bagnoli, Franco

    1998-01-01

    An introduction to cellular automata (both deterministic and probabilistic) with examples. Definition of deterministic automata, dynamical properties, damage spreading and Lyapunov exponents; probabilistic automata and Markov processes, nonequilibrium phase transitions, directed percolation, diffusion; simulation techniques, mean field. Investigation themes: life, epidemics, forest fires, percolation, modeling of ecosystems and speciation. They represent my notes for the school "Dynamical Mod...

  5. 21 CFR 1230.47 - Rejected containers.

    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...

  6. Expression of MRP1 and GSTP1-1 modulate the acute cellular response to treatment with the chemopreventive isothiocyanate, sulforaphane.

    Sibhatu, Mebrahtu B; Smitherman, Pamela K; Townsend, Alan J; Morrow, Charles S

    2008-04-01

    A major component of the anticarcinogenic activity of the dietary chemopreventive agent sulforaphane (SFN) is attributed to its ability to induce expression of phase II detoxification genes containing the antioxidant response element (ARE) within their promoters. Because SFN is a reactive electrophile--readily forming conjugates with glutathione (GSH)--we asked whether expression of glutathione S-transferase (GST) P1-1 and the GSH conjugate efflux pump, multidrug resistance or resistance-associated protein (MRP) 1, would significantly modify the cellular response to SFN exposure. This was investigated using GST- and MRP1-poor parental MCF7 cells and transgenic derivatives expressing GSTP1-1 and/or MRP1. Compared with parental cells, expression of GSTP1-1 alone enhanced the rate of intracellular accumulation of SFN and its glutathione conjugate, SFN-SG--an effect that was associated with increased ARE-containing reporter gene induction. Expression of MRP1 greatly reduced SFN/SFN-SG accumulation and resulted in significant attenuation of SFN-mediated induction of ARE-containing reporter and endogenous gene expression. Coexpression of GSTP1-1 with MRP1 further reduced the level of induction. Depletion of GSH prior to SFN treatment or the substitution of tert-butylhydroquinone for SFN abolished the effects of MRP1/GSTP1-1 on ARE-containing gene induction-indicating that these effects are GSH dependent. Lastly, analysis of NF-E2-related factor 2 (Nrf2)--a transcription factor operating via binding to the ARE--showed that the increased levels of Nrf2 following SFN treatment were considerably less sustained in MRP1-expressing, especially those coexpressing GSTP1-1, than in MRP1-poor cells. These results suggest that the regulating effects of MRP1 and GSTP1-1 expression on SFN-dependent induction of phase II genes are ultimately mediated by altering nuclear Nrf2 levels. PMID:18204073

  7. MR imaging of renal transplant rejection

    Hanna, S.; Helenon, O.; Legendre, C.; Chichie, J.F.; Di Stefano, D.; Kreis, H.; Moreau, J.F. (Hopital Necker, 75 - Paris (France). Dept. of Uro-Radiology Hopital Necker, 75 - Paris (France). Dept. of Renal Transplantation)

    1991-01-01

    The results of 62 consecutive MR examinations were correlated with the subsequent clinical course and histologic results. Twenty-six cases of rejection showed a marked diminution of cortico-medullary differentiation (CMD). The renal parenchymal vascular pattern and visibility of renal sinus fat were not markedly altered in rejection and there was no difference between normal and rejected allograft shape. The ability of MR imaging to diagnose renal transplant rejection is only based on CMD, which, however, is non-specific. In 2 cases of severe rejection, T2 weighted images showed an abnormal signal intensity of the cortex due to renal infarction. Our preliminary results in 8 patients with Gd-DOTA injection showed 2 cases with necrosis seen as areas with absent contrast enhancement. This technique seems to be promising in the detection of perfusion defects. (orig.).

  8. MR imaging of renal transplant rejection

    The results of 62 consecutive MR examinations were correlated with the subsequent clinical course and histologic results. Twenty-six cases of rejection showed a marked diminution of cortico-medullary differentiation (CMD). The renal parenchymal vascular pattern and visibility of renal sinus fat were not markedly altered in rejection and there was no difference between normal and rejected allograft shape. The ability of MR imaging to diagnose renal transplant rejection is only based on CMD, which, however, is non-specific. In 2 cases of severe rejection, T2 weighted images showed an abnormal signal intensity of the cortex due to renal infarction. Our preliminary results in 8 patients with Gd-DOTA injection showed 2 cases with necrosis seen as areas with absent contrast enhancement. This technique seems to be promising in the detection of perfusion defects. (orig.)

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

    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 recu...

  10. The Effect of Adding Low dose Daclizumab to Renal Transplantation Standard Protocol on Reduction the Risk of Kidney Rejection in Renal Allograft Recipients

    Jalal Azmandian; Zahra Shafii; Seyed Mojtaba Sohrevardi; Faramarz Fazeli; Abbas Etminan; Sara AziziShoul

    2012-01-01

    Introduction: Transplantation of the kidney is the choice treatment of advanced chronic renal failure. One of the most important therapeutic problems in these patients is the prevention of acute graft rejection. The purpose of this study was to investigate the efficiency of low dose Daclizumab for prevention of acute kidney graft rejection in living donor recipients. Methods: This clinical trial study was performed on 120 living donor kidney recipients who were admitted to kidney transplant w...

  11. Graft vasculopathy in the skin of a human hand allograft: implications for diagnosis of rejection of vascularized composite allografts.

    Kanitakis, Jean; Karayannopoulou, Georgia; Lanzetta, Marco; Petruzzo, Palmina

    2014-11-01

    Whereas vascularized composite allografts often undergo acute rejections early in the postgraft period, rejection manifesting with severe vascular changes (graft vasculopathy) has only been observed on three occasions in humans. We report a hand-allografted patient who developed severe rejection following discontinuation of the immunosuppressive treatment. It manifested clinically with erythematous maculopapules on the skin and pathologically with graft vasculopathy that affected both large vessels and smaller cutaneous ones. The observation that graft vasculopathy can affect skin vessels shows that it is amenable to diagnosis with usual skin biopsy as recommended for the follow-up of these allografts. Graft vasculopathy developing in the setting of vascularized composite allografts likely represents chronic rejection due to under-immunosuppression and, if confirmed, should be included in a future update of the Banff classification of vascularized composite allograft rejection. PMID:25041139

  12. Image rejects/retakes-radiographic challenges

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

  13. Ultra-Localization of Foxp3+ T Cells within Renal Allografts Shows Infiltration of Tubules Mimicking Rejection

    Brown, Kathryn; Moxham, Victoria; Karegli, Julieta; Phillips, Richard; Sacks, Steven H.; Wong, Wilson

    2007-01-01

    Kidney transplant recipients are monitored for rejection by measurement of serum creatinine and graft biopsies. Biopsy samples are evaluated according to the Banff classification, which states that infiltration of tubules by mononuclear cells is an indicator of acute rejection. However, regulatory T cells play a crucial role in the overall immune response and are also present within transplanted tissue. We hypothesize that infiltration of mononuclear cells within kidney grafts is not always a...

  14. Pachymic acid, a novel compound for anti-rejection: effect in rats following cardiac allograft transplantation

    ZHANG Fan; WANG Fei; ZHANG Xue-feng; WANG Bai-chun; LIU Hong-yu; LI Chun-yu; LIU Zong-hong; ZHANG Guo-wei; L(U) Hang; CHI Chao

    2009-01-01

    Background Pachymic acid (PA), a natural triterpenoid, is known to significantly reduce cell proliferation and induce apoptosis in vitro through initiation of mitochondria dysfunction. However, its effect on immune cells and anti-rejection following organ transplantation remains unknown.Methods In this study, we investigated PA as a treatment to control acute rejection occurred in rats which had accepted cardiac transplantation. We measured apoptosis of peripheral blood lymphocyte (PBLs), and CD4~+ lymphocyte, as well as the number of CD4~+ and CD8~+ lymphocytes and the effect of PA on acute rejection in rats 7 days after cardiac transplantation.Results PA treatment might decrease allograft rejection, protect PBLs from apoptosis, and reduce the percentage of CD8~+ lymphocyte. PA neither regulated the number nor the apoptosis rate of CD4~+ lymphocyte.Conclusions Our findings indicated that PA has an anti-apoptotic effect acting on PBLs through a novel mechanism involving stabilization of the PBLs mitochondrial transmembrane potential, an anti-rejection effect in rats after cardiac transplantation and an inhibiting effect to CD8~+ lymphocyte.

  15. The Presence of HLA-E-Restricted, CMV-Specific CD8+ T Cells in the Blood of Lung Transplant Recipients Correlates with Chronic Allograft Rejection

    Sullivan, Lucy C.; Westall, Glen P.; Widjaja, Jacqueline M. L.; Mifsud, Nicole A.; Nguyen, Thi H. O.; Meehan, Aislin C.; Kotsimbos, Tom C.; Brooks, Andrew G.

    2015-01-01

    The human cytomegalovirus (CMV) immune evasion protein, UL40, shares an identical peptide sequence with that found in the leader sequence of many human leukocyte antigen (HLA)-C alleles and when complexed with HLA-E, can modulate NK cell functions via interactions with the CD94-NKG2 receptors. However the UL40-derived sequence can also be immunogenic, eliciting robust CD8+ T cell responses. In the setting of solid organ transplantation these T cells may not only be involved in antiviral immunity but also can potentially contribute to allograft rejection when the UL40 epitope is also present in allograft-encoded HLA. Here we assessed 15 bilateral lung transplant recipients for the presence of HLA-E-restricted UL40 specific T cells by tetramer staining of peripheral blood mononuclear cells (PBMC). UL40-specific T cells were observed in 7 patients post-transplant however the magnitude of the response varied significantly between patients. Moreover, unlike healthy CMV seropositive individuals, longitudinal analyses revealed that proportions of such T cells fluctuated markedly. Nine patients experienced low-grade acute cellular rejection, of which 6 also demonstrated UL40-specific T cells. Furthermore, the presence of UL40-specific CD8+ T cells in the blood was significantly associated with allograft dysfunction, which manifested as Bronchiolitis Obliterans Syndrome (BOS). Therefore, this study suggests that minor histocompatibility antigens presented by HLA-E can represent an additional risk factor following lung transplantation. PMID:26302084

  16. Anti-Leukocyte Function-Associated Antigen 1 Therapy in a Nonhuman Primate Renal Transplant Model of Costimulation Blockade-Resistant Rejection.

    Anderson, D J; Lo, D J; Leopardi, F; Song, M; Turgeon, N A; Strobert, E A; Jenkins, J B; Wang, R; Reimann, K A; Larsen, C P; Kirk, A D

    2016-05-01

    Costimulation blockade with the fusion protein belatacept provides a desirable side effect profile and improvement in renal function compared with calcineurin inhibition in renal transplantation. This comes at the cost of increased rates of early acute rejection. Blockade of the integrin molecule leukocyte function-associated antigen 1 (LFA-1) has been shown to be an effective adjuvant to costimulation blockade in a rigorous nonhuman primate (NHP) model of islet transplantation; therefore, we sought to test this combination in an NHP renal transplant model. Rhesus macaques received belatacept maintenance therapy with or without the addition of LFA-1 blockade, which was achieved using a murine-derived LFA-1-specific antibody TS1/22. Additional experiments were performed using chimeric rhesus IgG1 (TS1/22R1) or IgG4 (TS1/22R4) variants, each engineered to limit antibody clearance. Despite evidence of proper binding to the target molecule and impaired cellular egress from the intravascular space indicative of a therapeutic effect similar to prior islet studies, LFA-1 blockade failed to significantly prolong graft survival. Furthermore, evidence of impaired protective immunity against cytomegalovirus was observed. These data highlight the difficulties in translating treatment regimens between organ models and suggest that the primarily vascularized renal model is more robust with regard to belatacept-resistant rejection than the islet model. PMID:26602755

  17. Rejection of pharmaceuticals by forward osmosis membranes.

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

    2012-08-15

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

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

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

  19. Transfusion Induced Bone Marrow Transplant Rejection Due to Minor Histocompatibility Antigens

    Patel, Seema R; Zimring, James C

    2014-01-01

    Traditionally, alloimmunization to transfused blood products has focused exclusively upon recipient antibodies recognizing donor alloantigens present on the cell surface. Accordingly, the immunological sequelae of alloimmunization have been antibody mediated effects (i.e. hemolytic transfusion reactions, platelet refractoriness, anti-HLA and anti-HNA effects, etc.). However, in addition to the above sequelae, there is also a correlation between the number of antecedent transfusions in humans and the rate of bone marrow transplant (BMT) rejection - under reduced intensity conditioning with HLA matched or HLA identical marrow. BMT of this nature is the only existing cure for a series of non-malignant hematological diseases (e.g. sickle cell disease, thalassemias, etc.); however, rejection remains a clinical problem. It has been hypothesized that transfusion induces subsequent BMT rejection through immunization. Studies in animal models have observed the same effect and have demonstrated that transfusion induced BMT rejection can occur in response to alloimmunization. However, unlike traditional antibody responses, sensitization in this case results in cellular immune effects, involving populations such as T cell or NK cells. In this case, rejection occurs in the absence of alloantibodies, and would not be detected by existing immune-hematological methods. We review human and animal studies in light of the hypothesis that, for distinct clinical populations, enhanced rejection of BMT may be an unappreciated adverse consequence of transfusion which current blood bank methodologies are unable to detect. PMID:24090731

  20. Rejeição de transplante de córnea Corneal Transplant Rejection

    Dácio Carvalho Costa

    2008-10-01

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

  1. Anti-rejection effect of ethanol extract of Poria cocos wolf in rats after cardiac allograft implantation

    张国伟; 刘宏宇; 夏求明; 李君权; 吕航; 张庆华; 姚志发

    2004-01-01

    Background A living fetus within the maternal uterus provides an example of allogene tolerance in mammals. Poria cocos Wolf is the main component of many Chinese medicinal combination drugs that have therapeutic effects on recurrent spontaneous abortion and that can maintain pregnancy until delivery. It was hypothesized that this herbal medicine can also prolong allograft survival after organ transplantation. Here, in an in vivo study, we report the anti-rejection effect of the ethanol extract of Poria cocos Wolf (EEPCW) in rats after cardiac allograft implantation. Methods Ten normal rats were healthy controls. Eighty rats receiving homologous heart transplants were divided into 4 groups of 20 rats each based on type of treatment: olive oil 8 ml*kg-1*d-1, EEPCW 25 mg*kg-1*d-1, EEPCW 50 mg*kg-1*d-1 or cyclosporin A 5mg*kg-1*d-1. Allograft survival was observed in 10 rats from each group. On the seventh day post transplantation, pathological lesions and percentages of CD3+, CD4+, and CD8+ lymphocytes and the CD4+/CD8+ ratio in peripheral blood were assessed in another 10 rats from each group and in 10 normal rats. Results The survival time of donor hearts in the two EEPCW groups was significantly prolonged, to (15.9±2.4) days and (30.0±0.0) days, respectively, compared with (6.7±0.8) days in the control group. Pathological lesions in the two EEPCW groups were also less severe, and the percentages of CD3+, CD4+, and CD8+ lymphocytes and CD4+/CD8+ ratio were significantly lower in the EEPCW groups.Conclusions Acute rejection of heart transplants and cellular immune reaction can be effectively suppressed using the EEPCW. Taking advantage of novel immunosuppressants derived from Chinese medicinal herbs used to treat abnormal pregnancy provides a hopeful road for future research and treatment in organ transplantation.

  2. Cellular resilience.

    Smirnova, Lena; Harris, Georgina; Leist, Marcel; Hartung, Thomas

    2015-01-01

    Cellular resilience describes the ability of a cell to cope with environmental changes such as toxicant exposure. If cellular metabolism does not collapse directly after the hit or end in programmed cell death, the ensuing stress responses promote a new homeostasis under stress. The processes of reverting "back to normal" and reversal of apoptosis ("anastasis") have been studied little at the cellular level. Cell types show astonishingly similar vulnerability to most toxicants, except for those that require a very specific target, metabolism or mechanism present only in specific cell types. The majority of chemicals triggers "general cytotoxicity" in any cell at similar concentrations. We hypothesize that cells differ less in their vulnerability to a given toxicant than in their resilience (coping with the "hit"). In many cases, cells do not return to the naive state after a toxic insult. The phenomena of "pre-conditioning", "tolerance" and "hormesis" describe this for low-dose exposures to toxicants that render the cell more resistant to subsequent hits. The defense and resilience programs include epigenetic changes that leave a "memory/scar" - an alteration as a consequence of the stress the cell has experienced. These memories might have long-term consequences, both positive (resistance) and negative, that contribute to chronic and delayed manifestations of hazard and, ultimately, disease. This article calls for more systematic analyses of how cells cope with toxic perturbations in the long-term after stressor withdrawal. A technical prerequisite for these are stable (organotypic) cultures and a characterization of stress response molecular networks. PMID:26536287

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

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

  4. Evaluation of [sup 99]Tc[sup m] nonspecific polyclonal IgG in the detection of rejection in a single lung transplant canine model

    Larcos, G.; McLarty, A.J.; McGregor, C.G.A.; Brown, M.L.; Hung, J.C.; O' Connor, M.K.; Tazelaar, H.D. (Mayo Clinic, Rochester, MN (United States))

    1993-01-01

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

  5. Electronic beam computer tomography and transthoracical echocardiography in postoperative after-treatment after orthoheart transplantation, clinical study before, during and after rejection therapy

    Nine pacemaker-stimulated patients with mild acute rejection were examined before, during, one week and six weeks (where the biopsy showed no rejection) after rejection therapy (methylprednisolon 1000 mg for three) with transthoracical echocardiography and electronic beam computer tomography (EBT). Ten patients with mild acute rejection without pacemaker stimulation were compared with the stimulated patients. The ejection fraction (EF) increased during therapy and decreased one week after therapy significantly in the stimulated, slightly in the control group. There were no echocardiographic parameters (EF, left and right ventricular diameters, wall thickness, flow and pressure above aortic and pulmonary valves) which showed significant differences before and six weeks after therapy. The EBT showed a significant decrease of left ventricular wall thickness and left ventricular mass. Transthoracical echocardiography seems to be no predicative method in the diagnosis mild acute heart allograft rejection. EBT could be a practicable noninvasive method to state acute heart allograft rejections. The effect of the methylprednisolone therapy could be associated with rejection. (author)

  6. Evaluation of the 99mTc-IOR t3 as a radiotracer of the rejection of the renal transplant

    A formulation of freeze-dried kit with ior t3 (anti-CD3) monoclonal antibody (MoAb) is presented. Once labelled with 99mTc purity higher than 95.0 % was reached. HPLC showed a low proportion of aggregates and fragments. A clinical trial is made with patients without clinical signs of renal graft rejection by means of 99mTc -ior t3. Preliminary results (n=5) showed a rapid and active uptake in the kidney when an acute graft rejection is present. Acute tubular necrosis and other renal complications showed lower concentrations of the radiopharmaceuticals

  7. Structural Decoupling and Disturbance Rejection in a Distillation Column

    Bahar, Mehrdad; Jantzen, Jan; Commault, C.;

    1996-01-01

    Introduction, distillation column model, input-output decoupling, disturbance rejection, concluding remarks, references.......Introduction, distillation column model, input-output decoupling, disturbance rejection, concluding remarks, references....

  8. 他克莫司胶囊和缓释胶囊预防肝移植急性排斥反应的效果和安全性%A randomized trial on the efficacy and safety of Advagraf vs tacrolimus in prevention of acute liver allograft rejection

    栗光明; 冷希圣; 郑树森; 刘永锋; 朱志军; 夏强; 周俭; 傅志仁; 黄磊; 朱继业

    2011-01-01

    in the experimental group and the control group, separately. The average age of experimental group and control group was 46 ± 10 and 49 ± 9, respectively. Patients in experimental group received Advagraf, once daily, and the dose was adjusted according to the drug concentration,and the drug concentration was between 2 to 10 μg/L. The control group given tacrolimus, twice daily, and the drug concentration was between 2 to 10 μg/L. Results The incidence of acute rejection reaction was 1.20 % and 1.18 % respectively in experimental group and control group, and the 95 %confidence interval was -3.25% ~3.31 % and -3.26% ~ 3.34 %, individually. There was 1 case of acute rejection reaction in experimental group and control group, respectively. The patient and organ survival rate was 100%. Sixteen adverse events occurred in 15 patients (17.65 %) of the experimental group, and 10 adverse events occurred in 10 patients (11.63 %) of control group. Severe adverse events relating to the test drug in experimental group occurred in 4 patients (4. 71 %). and 2 patients (2. 33) in control group.Conclision Clinical trials indicated that Advagraf has efficacy and safety profiles similar to those of tacrolimus. The drug is safe and may improve patient compliance.

  9. 抗MICA抗体的产生途径及其对肾移植后急性排斥反应治疗效果的影响%Anti-MICA antibodies: production path and impact on therapeutic efficacy after renal transplantation with acute rejection

    于立新; 刘如敏; 罗敏; 肖露露; 付绍杰; 王亦斌; 张新科

    2012-01-01

    目的 探讨抗多态性主要组织相容性复合体Ⅰ类相关链A(MICA)抗体的产生途径及其对肾移植后急性排斥反应(AR)治疗效果的影响.方法 随机抽取等待肾移植者157例,采用Luminex200液相芯片分析技术检测抗MICA抗体及其特异性,并采集临床资料,分析抗MICA抗体的产生途径及其免疫球蛋白类型,进而探讨IgM型抗MICA抗体与IgM和IgG复合型抗MICA抗体对肾移植后急性排斥反应(AR)发生率和治疗效果的影响.结果 157例中,既往有输血、妊娠、移植史者68例,移植前抗MICA抗体阳性者19例(27.9%);既往没有致敏经历者89例,移植前抗MICA抗体阳性者26例(29.2%),二者间抗MICA抗体阳性率的差异无统计学意义(P>0.05).抗MICA抗体阳性者45例,其中26例(57.8%)既往无致敏经历,其抗MICA抗体类型为IgM;另19例(42.2%)有已知的一种或多种致敏经历,其抗MICA抗体类型为IgG和IgM复合型.抗MICA抗体阳性的45例,有38例接受了肾移植,其中22例IgM型抗MICA抗体者,有7例(31.8%)发生AR,经甲泼尼龙冲击治疗均获得逆转,另16例IgM和IgG复合型抗MICA抗体者亦有7例(43.8%)发生AR,经甲泼尼龙等治疗,3例(42.9%)逆转,4例移植肾功能丧失;两种免疫球蛋白类型抗MICA抗体阳性者间肾移植后AR发生率的差异无统计学意义(P>0.05),但AR逆转率的差异有统计学意义(P<0.05).结论 对于无致敏史者其抗MICA抗体的产生可能存在经典的“天然抗体”的产生途径,其免疫球蛋白类型为IgM,肾移植后若发生AR,治疗转归较好;而对于移植前预存IgG和IgM复合型抗MICA抗体者,因其AR治疗的转归不佳,需予以足够重视.%Objective To investigate the production path of major histocompatibility complex class Ⅰ chain-related gene A(MICA) antibodies and the impact on the therapeutic efficacy after acute rejection in renal transplantation recipients.Methods Luminex flow cytometry was used to

  10. Peer acceptance/rejection and academic achievement

    Spasenović Vera Z.

    2003-01-01

    Considerations of the nature and role of peer relations in child development indicate that peer interaction is an important factor in developing social and cognitive competences. Peer relations not only influence current but also subsequent academic, behavioral and emotional development. Accepted students more often display better academic achievement, whereas the status of rejection is coupled with academic difficulties and lower academic achievement. Peer rejection is a relatively stable ch...

  11. Experimental Quantum Error Rejection for Quantum Communication

    Chen, Yu-Ao; Zhang, An-Ning; Zhao, Zhi; Zhou, Xiao-Qi; Pan, Jian-Wei

    2005-01-01

    We report an experimental realization of bit-flip error rejection for error-free transfer of quantum information through a noisy quantum channel. In the experiment, an unknown state to be transmitted is encoded into a two-photon entangled state, which is then sent through an engineered noisy quantum channel. At the final stage, the unknown state is decoded by a quantum parity measurement, successfully rejecting the erroneous transmission over the noisy quantum channel.

  12. Corneal Graft Rejection: Incidence and Risk Factors

    Alireza Baradaran-Rafii

    2008-12-01

    Full Text Available

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

  13. First-in-Human Study of the Safety and Efficacy of TOL101 Induction to Prevent Kidney Transplant Rejection

    Flechner, S. M.; Mulgoankar, S.; Melton, L. B.; Waid, T. H.; Agarwal, A.; Miller, S. D.; Fokta, F.; Getts, M. T.; Frederick, T. J.; Herrman, J. J.; Puisis, J. P.; O’Toole, L.; Sung, R.; Shihab, F.; Wiseman, A. C.; Getts, D. R.

    2015-01-01

    TOL101 is a murine IgM mAb targeting the αβ TCR. Unlike other T cell targets, the αβ TCR has no known intracellular signaling domains and may provide a nonmitogenic target for T cell inactivation. We report the 6-month Phase 2 trial data testing TOL101 in kidney transplantation. The study was designed to identify a dose that resulted in significant CD3 T cell modulation (<25 T cell/mm3), to examine the safety and tolerability of TOL101 and to obtain preliminary efficacy information. Thirty-six patients were enrolled and given 5–10 daily doses of TOL101; 33 patients completed dosing, while three discontinued after two doses due to a self-limiting urticarial rash. Infusion adjustments, antihistamines, steroids and dose escalation of TOL101 reduced the incidence of the rash. Doses of TOL101 above 28mg resulted in prolonged CD3 modulation, with rapid recovery observed 7 days after therapy cessation. There were no cases of patient or graft loss. Few significant adverse events were reported, with one nosocomial pneumonia. There were five biopsy-confirmed acute cellular rejections (13.9%); however, no donor-specific antibodies were detected. Overall TOL101 was well-tolerated, supporting continued clinical development using the dose escalating 21– 28–42–42–42mg regimen. PMID:24751150

  14. Image rejects in general direct digital radiography

    The number of rejected images is an indicator of image quality and unnecessary imaging at a radiology department. Image reject analysis was frequent in the film era, but comparably few and small studies have been published after converting to digital radiography. One reason may be a belief that rejects have been eliminated with digitalization. To measure the extension of deleted images in direct digital radiography (DR), in order to assess the rates of rejects and unnecessary imaging and to analyze reasons for deletions, in order to improve the radiological services. All exposed images at two direct digital laboratories at a hospital in Norway were reviewed in January 2014. Type of examination, number of exposed images, and number of deleted images were registered. Each deleted image was analyzed separately and the reason for deleting the image was recorded. Out of 5417 exposed images, 596 were deleted, giving a deletion rate of 11%. A total of 51.3% were deleted due to positioning errors and 31.0% due to error in centering. The examinations with the highest percentage of deleted images were the knee, hip, and ankle, 20.6%, 18.5%, and 13.8% respectively. The reject rate is at least as high as the deletion rate and is comparable with previous film-based imaging systems. The reasons for rejection are quite different in digital systems. This falsifies the hypothesis that digitalization would eliminates rejects. A deleted image does not contribute to diagnostics, and therefore is an unnecessary image. Hence, the high rates of deleted images have implications for management, training, education, as well as for quality

  15. Micro and nanoparticle drug delivery systems for preventing allotransplant rejection.

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

    2015-09-01

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

  16. Treatment of Antibody-Mediated Rejection in Kidney Transplantation

    Magdalena Durlik

    2013-07-01

    Full Text Available Antibody-mediated rejection (AMR is a relatively rare but severe complication in kidney transplantation associated with increased risk of graft loss. Diagnosis of acute and chronic AMR is based on typical histological hallmarks, deposition of C4d in peritubular capillaries and presence of donor-specific antibodies (DSA. Many novel and attractive treatment options have become available in recent years: antibody removal and production inhibition (plasmapheresis, IVIg, B cell depletion (rituximab, plasma cell depletion and apoptosis (bortezomib, and complement activation inhibition (eculizumab. Standard therapy is based on PP and IVIg. Preliminary results with new agents are encouraging but require randomised clinical trials and long-term follow-up.

  17. CARDIAC TRANSPLANT REJECTION AND NON-INVASIVE COMON CAROTID ARTERY WALL FUNCTIONAL INDICES

    A. O. Shevchenko

    2015-01-01

    Full Text Available Allograft rejection would entail an increase in certain blood biomarkers and active substances derived from activated inflammatory cells which could influence entire vascular endothelial function and deteriorate arterial wall stiffness. We propose that carotid wall functional indices measured with non-invasive ultrasound could we valuable markers of the subclinical cardiac allograft rejection. Aim. Our goal was to analyze the clinical utility of functional common carotid wall (CCW variables measured with high-resolution Doppler ultrasound as a non-invasive screening tool for allograft rejection in cardiac transplant patients (pts. Methods. One hundred and seventy one pts included 93 cardiac recipients, 30 dilated cardiomyopathy waiting list pts, and 48 stable coronary artery disease (SCAD pts without decompensated heart failure were included. Along with resistive index (Ri, pulsative index (Pi, and CCW intima-media thickness (IMT, CCW rigidity index (iRIG was estimated using empirical equation. Non-invasive evaluation was performed in cardiac transplant recipients prior the endomyo- cardial biopsy. Results. Neither of Ri, Pi, or CCW IMT were different in studied subgroups. iRIG was signifi- cantly lower in SCAD pts when compared to the dilated cardiomyopathy subgroup. The later had similar values with cardiac transplant recipients without rejection. Antibody-mediated and cellular rejection were found in 22 (23.7% and 17 (18.3% cardiac recipients, respectively. Mean iRIG in pts without rejection was significantly lower in comparison to antibody-mediated rejection and cell-mediated (5514.7 ± 2404.0 vs 11856.1 ± 6643.5 and 16071.9 ± 10029.1 cm/sec2, respectively, p = 0.001. Area under ROC for iRIG was 0.90 ± 0.03 units2. Analysis showed that iRIG values above estimated treshold 7172 cm/sec2 suggested relative risk of any type of rejection 17.7 (95%CI = 6.3–49.9 sensitivity 80.5%, specificity – 81.1%, negative predictive value – 84

  18. Novel Multivariate Methods for Integration of Genomics and Proteomics Data: Applications in a Kidney Transplant Rejection Study

    Günther, Oliver P.; Shin, Heesun; Ng, Raymond T.; McMaster, W. Robert; McManus, Bruce M.; Keown, Paul A.; Tebbutt, Scott. J.

    2014-01-01

    Abstract Multi-omics research is a key ingredient of data-intensive life sciences research, permitting measurement of biological molecules at different functional levels in the same individual. For a complete picture at the biological systems level, appropriate statistical techniques must however be developed to integrate different ‘omics’ data sets (e.g., genomics and proteomics). We report here multivariate projection-based analyses approaches to genomics and proteomics data sets, using the case study of and applications to observations in kidney transplant patients who experienced an acute rejection event (n=20) versus non-rejecting controls (n=20). In this data sets, we show how these novel methodologies might serve as promising tools for dimension reduction and selection of relevant features for different analytical frameworks. Unsupervised analyses highlighted the importance of post transplant time-of-rejection, while supervised analyses identified gene and protein signatures that together predicted rejection status with little time effect. The selected genes are part of biological pathways that are representative of immune responses. Gene enrichment profiles revealed increases in innate immune responses and neutrophil activities and a depletion of T lymphocyte related processes in rejection samples as compared to controls. In all, this article offers candidate biomarkers for future detection and monitoring of acute kidney transplant rejection, as well as ways forward for methodological advances to better harness multi-omics data sets. PMID:25387159

  19. Belatacept prophylaxis against organ rejection in adult kidney-transplant recipients.

    Del Bello, Arnaud; Marion, Olivier; Milongo, David; Rostaing, Lionel; Kamar, Nassim

    2016-02-01

    End-stage renal disease is a major health problem worldwide, with kidney transplantation being the treatment of choice. Calcineurin inhibitors are still the cornerstone of immunosuppressive therapy. However, they have well-known nephrotoxic affects and increase the risk of cardiovascular disease and cancer. In contrast, belatacept is a biological immunosuppressive agent that inhibits the T-cell co-stimulation. It is approved by the US Food and Drug Administration and the European Medicine Agency for use in adult kidney-transplant recipients to prevent acute rejection. Developmental studies show that belatacept is as efficient as calcineurin inhibitors at preventing acute rejection. In addition, kidney function is better and cardiovascular risk factors are reduced in patients given belatacept. Herein, the authors review the published evidence concerning the efficacy and safety of belatacept and discuss its potential specific indications. PMID:26691282

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

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

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

  1. Integrin antagonists prevent costimulatory blockade-resistant transplant rejection by CD8+ memory T cells

    Kitchens, W. H.; Haridas, D.; Wagener, M. E.; Song, M.; Kirk, A. D.; Larsen, C. P.; Ford, M. L.

    2012-01-01

    The success of belatacept in late-stage clinical trials inaugurates the arrival of a new class of immunosuppressants based on costimulatory blockade, an immunosuppression strategy that disrupts essential signals required for alloreactive T cell activation. Despite having improved renal function, kidney transplant recipients treated with belatacept experienced increased rates of acute rejection. This finding has renewed focus on costimulatory blockade-resistant rejection and specifically the role of alloreactive memory T cells in mediating this resistance. To study mechanisms of costimulatory blockade-resistant rejection and enhance the clinical efficacy of costimulatory blockade, we developed an experimental transplant system that models a donor-specific memory CD8+ T cell response. After confirming that graft-specific memory T cells mediate costimulatory blockade-resistant rejection, we characterized the role of integrins in this rejection. The resistance of memory T cells to costimulatory blockade was abrogated when costimulatory blockade was coupled with either anti-VLA-4 or anti-LFA-1. Mechanistic studies revealed that in the presence of costimulatory blockade, anti-VLA-4 impaired T cell trafficking to the graft but not memory T cell recall effector function, whereas anti-LFA-1 attenuated both trafficking and memory recall effector function. As antagonists against these integrins are clinically approved, these findings may have significant translational potential for future clinical transplant trials. PMID:21942986

  2. Acute Renal Failure - A Serious Complication in Patients After Kidney Transplantation.

    Basta-Jovanovic, G; Bogdanovic, Lj; Radunovic, M; Prostran, M; Naumovic, R; Simic-Ogrizovic, S; Radojevic-Skodric, S

    2016-01-01

    Free radical-mediated injury releases proinflammatory cytokines and activates innate immunity. It has been suggested that the early innate response and the ischemic tissue damage play roles in the development of adaptive responses, which may lead to acute kidney rejection. Various durations of hypothermic kidney storage before transplantation add to ischemic tissue damage. The final stage of ischemic injury occurs during reperfusion that develops hours or days after the initial insult. Repair and regeneration processes occur together with cellular apoptosis, autophagy and necrosis and a favorable outcome is expected if regeneration prevails. Along the entire transplantation time course, there is a great demand for novel immune and nonimmune injury biomarkers. The use of these markers can be of great help in the monitoring of kidney injury in potential kidney donors, where acute kidney damage can be overlooked, in predicting acute transplant dysfunction during the early post-transplant periods, or in predicting chronic changes in long term followup. Numerous investigations have demonstrated that biomarkers that have the highest predictive value in acute kidney injury include NGAL, Cystatin C, KIM-1, IL-18, and L-FABP. Most investigations show that the ideal biomarker to fulfill all the needs in renal transplant has not been identified yet. Although, in many animal models, new biomarkers are emerging for predicting acute and chronic allograft damage, in human allograft analysis they are still not routinely accepted and renal biopsy still remains the gold standard. PMID:27498898

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

    A. G. Kupriyanova

    2012-01-01

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

  4. Peripheral blood T Regulatory cell counts may not predict transplant rejection

    Feng Li; Zhang Jie; Zhang Chuntao; Shan Juan; Huang Yuchuan; Li Shengfu; Li Youping

    2010-01-01

    Abstract Background Recent evidence shows that allograft survival rates show a positive correlation with the number of circulating T regulatory cells (Tregs). This study investigated both the number and the cytokine profiles exhibited by Foxp3+ Tregs in blood, spleen and lymph nodes of Lewis rat recipients of BN rat cardiac allografts after a single-dose of Rapamycin (RAPA). Results Rats were divided into three groups: control group (containing healthy control and acute rejection group), and ...

  5. Indium (111In)-labelled platelets in the diagnosis of renal transplant rejection: preliminary findings

    Eleven patients with recent kidney transplants have undergone serial pelvic imaging after autologous platelet labelling with indium-111. Rejection was accompanied by marked platelet deposition in the graft, whereas acute tubular necrosis was characterized by minimal platelet accumulation. The method has been quantified by comparing counts over the graft to counts from a similar area on the opposite site, and appears to distinguish between the two main causes of renal failure after transplantation. In addition, complications of transplant surgery may be demonstrated. (author)

  6. Factors associated with rejection of renal transplant patients in the Emergency Department

    Erkan GOKSU; Ozlem YIGIT; Oktay ERAY; Ayse GOZLUKAYA; Cenker EKEN

    2010-01-01

    Objective: Renal transplantation is the most effective treatment for the end-stage kidney disease. Increased number of renal transplant patients lead to a rise in the acute presentations of these patients to emergency departments (EDs) in recent years. The most important problem for these patients is ‘rejection’. We aimed to determine the factors to predict a possible rejection in patients with kidney transplantation in our study. Methods: This retrospective case control study was conducted i...

  7. High Mean Fluorescence Intensity Donor-Specific Anti-HLA Antibodies Associated With Chronic Rejection Postliver Transplant

    O’Leary, J. G.; Kaneku, H.; Susskind, B. M.; Jennings, L. W.; Neri, M. A.; Davis, G. L.; Klintmalm, G. B.; Terasaki, P. I.

    2015-01-01

    In contrast to kidney transplantation where donorspecific anti-HLA antibodies (DSA) negatively impact graft survival, correlation of DSA with clinical outcomes in patients after orthotopic liver transplantation (OLT) has not been clearly established. We hypothesized that DSA are present in patients who develop chronic rejection after OLT. Prospectively collected serial serum samples on 39 primary OLT patients with biopsy-proven chronic rejection and 39 comparator patients were blinded and analyzed for DSA using LABScreen single antigen beads test, where a 1000 mean fluorescence value was considered positive. In study patients, the median graft survival was 15 months, 74% received ≥ one retransplant, 20% remain alive and 87% had ≥ one episode of acute rejection. This is in contrast to comparator patients where 69% remain alive, and no patient needed retransplant or experienced rejection. Thirty-six chronic rejection patients (92%) and 24 (61%) comparator patients had DSA (p = 0.003). Chronic rejection versus comparator patients had higher mean fluorescence intensity (MFI) DSA. Although a further study with larger numbers of patients is needed to identify clinically significant thresholds, there is an association of high-MFI DSA with chronic rejection after OLT. PMID:21672151

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

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

    2016-11-01

    This study investigates abuse and rejection sensitivity as important correlates of risky sexual behavior in the context of substance use. Victims of abuse may experience heightened sensitivity to acute social rejection and consequently engage in risky sexual behavior in an attempt to restore belonging. Data were collected from 258 patients at a substance use treatment facility in Washington, D.C. Participants' history of abuse and risky sexual behavior were assessed via self-report. To test the mediating role of rejection sensitivity, participants completed a social rejection task (Cyberball) and responded to a questionnaire assessing their reaction to the rejection experience. General risk-taking propensity was assessed using a computerized lab measure. Abuse was associated with increased rejection sensitivity (B=0.124, SE=0.040, p=0.002), which was in turn associated with increased risky sex (B=0.06, SE=0.028, p=0.03) (indirect effect=0.0075, SE=0.0043; 95% CI [0.0006, 0.0178]), but not with other indices of risk-taking. These findings suggest that rejection sensitivity may be an important mechanism underlying the relationship between abuse and risky sexual behavior among substance users. These effects do not extend to other risk behaviors, supporting the notion that risky sex associated with abuse represents a means to interpersonal connection rather than a general tendency toward self-defeating behavior. PMID:27344009

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

    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

  10. Video auditing techniques for breaker reject

    Jenkins, B.M.; Corke, P.I.; O`Brien, G.D.; Waugh, J.M. [CSIRO (Australia). Division of Minerals

    1998-12-31

    Rotary breakers are used by many Australian coal mines to reduce the topsize of run of mine (ROM) coal to a size that can be handled by the processing plant. Coal that does not break to the designated topsize therefore passes out with the rock as breaker rejects. The degree of coal loss can be assessed manually by stop belt auditing of the reject belt, but this method is impractical for long-term monitoring of breaker rejects and breaker performance. Case studies of several open cut coal mines in the Bowen Basin of Central Queensland were made to determine the extent of the problem. The results indicated instances where significant losses did occur, but it was not possible to make an accurate estimate of the total value of the losses. This paper covers work undertaken to develop new auditing techniques for qualitative, quantitative and continuous monitoring of reject belt material which uses relatively low-cost equipment and mature technology. Initial work has concentrated on developing video surveillance techniques suitable for the range of environmental conditions typically encountered in the field. Multi-media methods are being developed for qualitative data presentation, and image analysis techniques are being investigated to extract basic quantitative information from video sequences, such as particle size and shape. Future work includes development of automatic methods using machine vision for 100% on-line inspection. The main attraction of the methodology being adopted is the potential to easily adapt the techniques to diagnostic and control functions. In situations where significant losses occur, this approach could open up many possibilities for reducing coal rejection or allowing its recovery from the rejects stream to improve productivity. 12 refs., 4 figs., 1 tab.

  11. Large Solar-Rejection Filter

    Roberts, William; Sheikh, David; Patrick, Brian

    2007-01-01

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

  12. Radiation therapy for renal transplant rejection reactions

    Forty-four renal transplant patients were given radiation therapy for severe rejection phenomena. The 29 patients who had only one course of irradiation had a 52.3% successful function rate. Fifteen patients received from two to four courses of irradiation with an ultimate 60% rate of sustained function. Fifty patients who received only steroid and other medical management but no irradiation had a 60% rate of successful renal function. In the irradiation group, no patient whose creatinine level did not respond to radiation therapy maintained a functioning kidney. The data indicate that the overall successful function rate is maintained by radiation therapy in patients who show severe allograft rejection phenomena

  13. Radiation therapy for renal transplant rejection reactions

    Peeples, W.J.; Wombolt, D.G.; El-Mahdi, A.M.; Turalba, C.I.

    1982-01-01

    Forty-four renal transplant patients were given radiation therapy for severe rejection phenomena. The 29 patients who had only one course of irradiation had a 52.3% successful function rate. Fifteen patients received from two to four courses of irradiation with an ultimate 60% rate of sustained function. Fifty patients who received only steroid and other medical management but no irradiation had a 60% rate of successful renal function. In the irradiation group, no patient whose creatinine level did not respond to radiation therapy maintained a functioning kidney. The data indicate that the overall successful function rate is maintained by radiation therapy in patients who show severe allograft rejection phenomena.

  14. On Multiple Hypothesis Testing with Rejection Option

    Grigoryan, Naira; Voloshynovskiy, Svyatoslav; Koval, Oleksiy

    2011-01-01

    We extend existing results on multiple hypothesis testing (HT) in view of rejection option. The model has many different applications. Errors in testing of M hypotheses regarding the source distribution with an option of rejecting all those hypotheses are considered. The source is discrete and arbitrarily varying (AVS). The tradeoffs among error probability exponents/reliabilities are investigated and the optimal decision strategies are outlined. Then the main result is specialized for discrete memoryless sources (DMS) and studied further. Geometric interpretations of the optimal decision schemes are given for the current and known bounds in multi-HT for AVS.

  15. Solar dynamic space power system heat rejection

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

    1986-01-01

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

  16. Antimyosin imaging in cardiac transplant rejection

    Johnson, L.L.; Cannon, P.J. (Department of Medicine, College of Physicians and Surgeons, Columbia University, New York (United States))

    1991-09-01

    Fab fragments of antibodies specific for cardiac myosin have been labeled with indium-111 and injected intravenously into animals and into patients with heart transplants. The antibodies, developed by Khaw, Haber, and co-workers, localize in cardiac myocytes that have been damaged irreversibly by ischemia, myocarditis, or the rejection process. After clearance of the labeled antibody from the cardiac blood pool, planar imaging or single photon emission computed tomography is performed. Scintigrams reveal the uptake of the labeled antimyosin in areas of myocardium undergoing transplant rejection. In animal studies, the degree of antimyosin uptake appears to correlate significantly with the degree of rejection assessed at necropsy. In patients, the correlation between scans and pathologic findings from endomyocardial biopsy is not as good, possibly because of sampling error in the endomyocardial biopsy technique. The scan results at 1 year correlate with either late complications (positive) or benign course (negative). Current limitations of the method include slow blood clearance, long half-life of indium-111, and hepatic uptake. Overcoming these limitations represents a direction for current research. It is possible that from these efforts a noninvasive approach to the diagnosis and evaluation of cardiac transplantation may evolve that will decrease the number of endomyocardial biopsies required to evaluate rejection. This would be particularly useful in infants and children. 31 references.

  17. Local graft irradiation in renal transplant rejection

    From 1977 to 1988, of 142 renal transplantations, seven recipients (4.9%) received local graft irradiation following rejective reaction refractory to antirejection medical managements. Concurrent with the administration of pulsed high dose methylprednisolone and other antirejection medical managements, the graft was irradiated with a total dose of 6.0 Gy-150 cGy per fraction every other day at the midplane of the graft using two opposing portals of 4MX Linac. The fields were defined by palpation and echography. All patients had improvements in serum creatinine on the 10th day after beginning the irradiation. Four patients with peripheral lymphocytosis during the irradiation combined with pulsed high dose methylprednisolone improved in renal functions. On the other hand, out of 3 patients with lymphcytopenic changes, in two the transplanted graft was removed due to deteriorations, and the other patient is currently suffering from chronic rejection. Local graft irradiation can be useful in maintaining a rejective graft and reversing its functions in some patients whose rejective reaction failed to respond to the antirejection medical managements. (author)

  18. Local graft irradiation in renal transplant rejection

    Kawamura, Masashi; Kataoka, Masaaki; Itoh, Hisao (Ehime Univ., Matsuyama (Japan). School of Medicine)

    1990-04-01

    From 1977 to 1988, of 142 renal transplantations, seven recipients (4.9%) received local graft irradiation following rejective reaction refractory to antirejection medical managements. Concurrent with the administration of pulsed high dose methylprednisolone and other antirejection medical managements, the graft was irradiated with a total dose of 6.0 Gy-150 cGy per fraction every other day at the midplane of the graft using two opposing portals of 4MX Linac. The fields were defined by palpation and echography. All patients had improvements in serum creatinine on the 10th day after beginning the irradiation. Four patients with peripheral lymphocytosis during the irradiation combined with pulsed high dose methylprednisolone improved in renal functions. On the other hand, out of 3 patients with lymphcytopenic changes, in two the transplanted graft was removed due to deteriorations, and the other patient is currently suffering from chronic rejection. Local graft irradiation can be useful in maintaining a rejective graft and reversing its functions in some patients whose rejective reaction failed to respond to the antirejection medical managements. (author).

  19. Antimyosin imaging in cardiac transplant rejection

    Fab fragments of antibodies specific for cardiac myosin have been labeled with indium-111 and injected intravenously into animals and into patients with heart transplants. The antibodies, developed by Khaw, Haber, and co-workers, localize in cardiac myocytes that have been damaged irreversibly by ischemia, myocarditis, or the rejection process. After clearance of the labeled antibody from the cardiac blood pool, planar imaging or single photon emission computed tomography is performed. Scintigrams reveal the uptake of the labeled antimyosin in areas of myocardium undergoing transplant rejection. In animal studies, the degree of antimyosin uptake appears to correlate significantly with the degree of rejection assessed at necropsy. In patients, the correlation between scans and pathologic findings from endomyocardial biopsy is not as good, possibly because of sampling error in the endomyocardial biopsy technique. The scan results at 1 year correlate with either late complications (positive) or benign course (negative). Current limitations of the method include slow blood clearance, long half-life of indium-111, and hepatic uptake. Overcoming these limitations represents a direction for current research. It is possible that from these efforts a noninvasive approach to the diagnosis and evaluation of cardiac transplantation may evolve that will decrease the number of endomyocardial biopsies required to evaluate rejection. This would be particularly useful in infants and children. 31 references

  20. Waste heat rejection from geothermal power stations

    Robertson, R.C.

    1978-12-01

    This study of waste heat rejection from geothermal power stations is concerned only with the heat rejected from the power cycle. The heat contained in reinjected or otherwise discharged geothermal fluids is not included with the waste heat considered here. The heat contained in the underflow from the flashtanks in such systems is not considered as part of the heat rejected from the power cycle. By following this definition of the waste heat to be rejected, various methods of waste heat dissipation are discussed without regard for the particular arrangement to obtain heat from the geothermal source. Recent conceptual design studies made for 50-MW(e) geothermal power stations at Heber and Niland, California, are of particular interst. The former uses a flashed-steam system and the latter a binary cycle that uses isopentane. In last-quarter 1976 dollars, the total estimated capital costs were about $750/kW and production costs about 50 mills/kWhr. If wet/dry towers were used to conserve 50% of the water evaporation at Heber, production costs would be about 65 mills/kWhr.

  1. Partial interference subspace rejection in CDMA systems

    Hansen, Henrik; Affes, Sofiene; Mewelstein, Paul

    2001-01-01

    Previously presented interference subspace rejection (ISR) proposed a family of new efficient multiuser detectors for CDMA. We reconsider in this paper the modes of ISR using decision feedback (DF). DF modes share similarities with parallel interference cancellation (PIC) but attempt to cancel...

  2. Development of enhanced sulfur rejection processes

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

    1996-03-01

    Research at Virginia Tech led to the development of two complementary concepts for improving the removal of inorganic sulfur from many eastern U.S. coals. These concepts are referred to as Electrochemically Enhanced Sulfur Rejection (EESR) and Polymer Enhanced Sulfur Rejection (PESR) processes. The EESR process uses electrochemical techniques to suppress the formation of hydrophobic oxidation products believed to be responsible for the floatability of coal pyrite. The PESR process uses polymeric reagents that react with pyrite and convert floatable middlings, i.e., composite particles composed of pyrite with coal inclusions, into hydrophilic particles. These new pyritic-sulfur rejection processes do not require significant modifications to existing coal preparation facilities, thereby enhancing their adoptability by the coal industry. It is believed that these processes can be used simultaneously to maximize the rejection of both well-liberated pyrite and composite coal-pyrite particles. The project was initiated on October 1, 1992 and all technical work has been completed. This report is based on the research carried out under Tasks 2-7 described in the project proposal. These tasks include Characterization, Electrochemical Studies, In Situ Monitoring of Reagent Adsorption on Pyrite, Bench Scale Testing of the EESR Process, Bench Scale Testing of the PESR Process, and Modeling and Simulation.

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

    V. N. Poptsov

    2015-01-01

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

  4. Elevated ST2 Distinguishes Incidences of Pediatric Heart and Small Bowel Transplant Rejection.

    Mathews, L R; Lott, J M; Isse, K; Lesniak, A; Landsittel, D; Demetris, A J; Sun, Y; Mercer, D F; Webber, S A; Zeevi, A; Fischer, R T; Feingold, B; Turnquist, H R

    2016-03-01

    Elevated serum soluble (s) suppressor of tumorigenicity-2 is observed during cardiovascular and inflammatory bowel diseases. To ascertain whether modulated ST2 levels signify heart (HTx) or small bowel transplant (SBTx) rejection, we quantified sST2 in serially obtained pediatric HTx (n = 41) and SBTx recipient (n = 18) sera. At times of biopsy-diagnosed HTx rejection (cellular and/or antibody-mediated), serum sST2 was elevated compared to rejection-free time points (1714 ± 329 vs. 546.5 ± 141.6 pg/mL; p = 0.0002). SBTx recipients also displayed increased serum sST2 during incidences of rejection (7536 ± 1561 vs. 2662 ± 543.8 pg/mL; p = 0.0347). Receiver operator characteristic (ROC) analysis showed that serum sST2 > 600 pg/mL could discriminate time points of HTx rejection and nonrejection (area under the curve [AUC] = 0.724 ± 0.053; p = 0.0003). ROC analysis of SBTx measures revealed a similar discriminative capacity (AUC = 0.6921 ± 0.0820; p = 0.0349). Quantitative evaluation of both HTx and SBTx biopsies revealed that rejection significantly increased allograft ST2 expression. Pathway and Network Analysis of biopsy data pinpointed ST2 in the dominant pathway modulated by rejection and predicted tumor necrosis factor-α and IL-1β as upstream activators. In total, our data indicate that alloimmune-associated pro-inflammatory cytokines increase ST2 during rejection. They also demonstrate that routine serum sST2 quantification, potentially combined with other biomarkers, should be investigated further to aid in the noninvasive diagnosis of rejection. PMID:26663613

  5. 75 FR 32490 - Issues in the Development of Medical Products for the Prophylaxis and/or Treatment of Acute...

    2010-06-08

    ... Prophylaxis and/or Treatment of Acute Antibody Mediated Rejection in Kidney Transplant Recipients; Public... prophylaxis and/or treatment of acute antibody mediated rejection (AMR) in kidney transplant recipients. This..., academia, and industry on various aspects of development of medical products for prophylaxis...

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

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

    2016-07-01

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

  7. Long-term efficacy of atorvastatin in allograft rejection following renal transplantation: A randomized clinical trial

    Mohammad A Amirzargar

    2015-01-01

    Full Text Available Statins are a class of drug that can efficiently reduce the level of low-density lipoprotein (LDL as well as increase the LDL receptors. Several non-lipid-lowering effects of this type of drug have been described. It is reported that they have an influence in preventing graft rejection, especially of the acute type. In this study, patients with end-stage renal disease and candidates for kidney transplantation were divided into two groups. Group A (intervention group received atorvastatin for two weeks prior to their transplant surgery while group B (control group received placebo. The lipid profile was tested (triglycerides, cholesterol, LDL in all patients two weeks before the transplantation. After transplantation, drug use was stopped. We also checked the LDL serum levels in patients with raised lipid levels (LDL >100 every two weeks. After this period, the serum lipid levels were checked monthly up to six months. Hyperlipidemia, when present, was controlled by fibrates. Concerning the rejection episodes, there was no significant difference between the two groups. In group A (13 men and nine women, three (14.3% cases of rejection were observed whereas four (21.3% cases of rejection were seen in group B (11 men and 10 women (P = 0.5. Within group A, five (22.7% cases of delayed graft function were found while four (19% similar cases were observed in group B (P = 0.7. There was no statistically significant difference concerning delayed graft function between the two groups. Despite all the mechanisms attributed to the probable anti-rejection properties of statins, we found no significant correlation with the administration of these drugs before transplantation and the protection against graft rejection episodes.

  8. The nitric oxide in ischemia-reperfusion injury and acute rejection of rat intestinal transplantation%一氧化氮在大鼠小肠移植缺血再灌注损伤和急性排斥反应中的作用

    李晓林; 邹小明; 李刚; 宋茂力; 聂刚; 姜浩

    2012-01-01

    目的 探讨一氧化氮(NO)在大鼠小肠移植缺血再灌注损伤(IRI)和急性排斥反应(AR)中作用.方法 建立同种大鼠原位小肠移植模型,采用随机数字表法将受鼠分为4组.移植对照组、左旋精氨酸(L-Arg)组、左旋硝基精氨酸甲酯(L-NAME)Ⅰ组(Ⅰ组)和L-NAMEⅡ组(Ⅱ组)受鼠于手术当天开始分别每天给予生理盐水、L-Arg 150 mg·kg-1 ·d-1、L-NAME 4和8 mg·kg-1·d-1.术后观察各组受鼠的存活时间,行HE染色观察移植小肠的组织病理学改变,采用免疫组织化学法观察移植小肠一氧化氮合酶(NOS)的活性,以及检测血糖吸收功能和血清NO浓度.结果 移植对照组、L-Arg组、Ⅰ组及Ⅱ组受鼠的存活时间分别为(11.7±1.2)d、(10.2±1.0)d、(12.3±1.5)d和(17.3±1.9)d,Ⅱ组受鼠的存活时间明显延长(P<0.01).与移植对照组相比,L-Arg组和Ⅰ组IRI的Park评分下降,IRI减轻;Ⅱ组Park评分显著升高(P<0.01),IRI加重,但AR明显减轻.与移植对照组相比,IRI期间,Ⅰ组iNOS染色减弱,Ⅱ组iNOS和nNOS染色均减弱;AR期间,Ⅱ组iNOS染色明显减弱.各组血清NO浓度于再灌注后30min逐渐升高.与移植对照组相比,Ⅱ组血 NO浓度的升高延缓.与移植对照组相比,L-Arg组血糖吸收值于再灌注30 min至术后3d明显增高(P<0.01);Ⅰ组和Ⅱ组血糖吸收值术后处于较低水平.结论 NO在大鼠小肠移植IRI中起到了细胞毒和细胞保护的双重作用;在AR中加重了组织损伤.术后早期补充L-Arg可促进移植肠管对糖类的吸收.%Objective To evaluate the role of nitric oxide (NO) in ischemia reperfusion injury (IRI) and acute rejection (AR) of intestinal transplantation in rats.Methods The rat orthotopic intestinal transplantation was performed. Animals were assigned to the following 4 groups with random methods:transplant control group,L-arginine (L-Arg) group,NG-Nitro-L-arginine methyl ester (L-NAME) Ⅰ group (group Ⅰ ) and L-NAME Ⅱ group

  9. Chronic allograft rejection: A significant hurdle to transplant success

    Malgorzata Kloc; Ghobrial, Rafik M.

    2014-01-01

    The state-of-the-art immunosuppression drugs do not ensure indefinite transplant survival, and most transplants are continuously lost to chronic rejection even years posttransplantation. This form of rejection is responsible for long-term failure of transplanted organs. The mechanisms involved in development of chronic rejection are not well-understood. One of the main features of chronic rejection is progressive luminal narrowing of graft vessels, which results in compromised blood flow, isc...

  10. Rejection Pathways in Heart Transplant Recipients

    Besouw, Nicole

    1999-01-01

    textabstractSince the beginning of this century experimental heart transplantations in animal studies were performed.' These studies were started in Rotterdam in the seventies to compare heterotopic and orthotopic heart transplantations, and to study the process of chronic rejection. The history of the first human heart transplantation started in South-Africa and it was carried out by Barnard in 1967. Several cardiac surgeons around the world initiated new transplantation programmes. However,...

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

    Reschen ME

    2014-09-01

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

  12. Two cases of hepatobiliary scintigraphy of liver transplantation in rejection

    Kanegawa, Kimio; Nishiyama, Syouji; Muraji, Toshihiro (Kobe Children' s Hospital, Hyogo (Japan)); Ishii, Kazunari; Kouno, Michio

    1992-04-01

    We report two patients with liver transplantation who underwent hepatobiliary scintigraphy in rejection. In the first patient, hepatobiliary scintigraphy showed dilatation of bile duct but it showed good clearance from the liver. In the second patient, hepatobiliary scintigraphy showed delayed clearance from the liver. Both patients recovered from rejection. There were four main complications, including vascular and biliary abnormality, infection, and rejection, after liver transplantation. Hepatobiliary scintigraphy showed almost the same findings except for biliary complication, so it was difficult to distinguish between infection and rejection. But hepatobiliary scintigraphy may be useful to evaluate transplanted liver function in rejection. (author).

  13. Two cases of hepatobiliary scintigraphy of liver transplantation in rejection

    We report two patients with liver transplantation who underwent hepatobiliary scintigraphy in rejection. In the first patient, hepatobiliary scintigraphy showed dilatation of bile duct but it showed good clearance from the liver. In the second patient, hepatobiliary scintigraphy showed delayed clearance from the liver. Both patients recovered from rejection. There were four main complications, including vascular and biliary abnormality, infection, and rejection, after liver transplantation. Hepatobiliary scintigraphy showed almost the same findings except for biliary complication, so it was difficult to distinguish between infection and rejection. But hepatobiliary scintigraphy may be useful to evaluate transplanted liver function in rejection. (author)

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

    Flynn, Edward R. [Senior Scientific, 11109 Country Club NE, Albuquerque, NM 87111 (United States)]. E-mail: seniorsci@nmia.com; Bryant, H.C. [Senior Scientific, 11109 Country Club NE, Albuquerque, NM 87111 (United States); Department of Physics and Astronomy, University of New Mexico, Albuquerque, NM 87131 (United States); Bergemann, Christian [Chemicell GmbH, Berlin (Germany); Larson, Richard S. [Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131 (United States); Lovato, Debbie [Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131 (United States); Sergatskov, Dmitri A. [Senior Scientific, 11109 Country Club NE, Albuquerque, NM 87111 (United States)

    2007-04-15

    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{sup 5} cells, can provide early warning of impending transplant rejection and monitor immune-suppressive chemotherapy.

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

    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.

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

    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, 105 cells, can provide early warning of impending transplant rejection and monitor immune-suppressive chemotherapy

  17. Oedipal shame, rejection, and adolescent development.

    Caparrotta, Luigi

    2003-12-01

    The definition of oedipal shame, dramatized in Sophocles' tragedy, is the painful affect resulting from accepting the reality of one's origins. A clinical example focusing on shame arising from adoption links oedipal shame to the theme of rejection. Furthermore, in adolescence the revival of the oedipal conflict may reactivate oedipal shame in which unconscious idealized fantasies of personal perfection and the object carried over from childhood have to be renegotiated. This process, illustrated by two clinical vignettes, may reveal entrenched masochistic defenses. An examination of a final scene from a film underscores the significance of oedipal shame in clinical practice. PMID:14703298

  18. USA: California rejects mandatory GMO labelling

    Paull, John

    2012-01-01

    Buying organic remains the best strategy for US consumers to avoid eating GM food. The voters of California have rejected the proposal to label GMO food. The proposition was narrowly lost, 47% to 53% (4,326,770 ‘Yes’ votes vs. 4,884,961 ‘No’ votes). Proposition 47 was supported by the organic sector but opposed by a coalition of GMO companies and US multinational food companies. Californians were invited to vote into law ‘The California Right to Know Genetically Engineered Food Act’. Section ...

  19. Solar Rejection Filter for Large Telescopes

    Hemmati, Hamid; Lesh, James

    2009-01-01

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

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

    Kathryn J. Lindley

    2012-01-01

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

  1. Uremic escape of renal allograft rejection

    It is demonstrated in rats that, in the presence of early postoperative severe but transient uremia, the survival of first set Brown-Norway (BN) renal allografts in Lewis (LEW) recipients is at least three times prolonged when compared to non-uremic controls. This phenomenon is called 'uremic escape of renal allograft rejection'. By means of lethal X-irradiation of donors of BN kidneys transplanted into transiently uremic and non-uremic LEW recipients, the presence of passenger lymphocyte immunocompetence is demonstrated to be obilgatory for this phenomenon to occur. As a result of mobile passenger lymphocyte immunocompetence, a graft-versus-host (GVH) reaction is elicited in the spleens of LEW recipients of BN kidneys which amplifies the host response. The splenomegaly observed in LEW recipients of BN kidneys is caused not only by this GVH reaction, which is shown to be exquisitely sensitive to even mild uremia. It is also contributed to by a proliferative response of the host against the graft (which latter response is equated with an in vivo equivalent of a unilateral mixed lymphocyte reaction (MLR)), since the reduction in spleen weights caused by abrogation of mobile passenger lymphocyte immunocompetence brought about by lethal donor X-irradiation is increased significantly by early postoperative severe but transient uremia. It is concluded that in uremic escape of renal allograft rejection both reactions are suppressed by uremia during the early post-operative period. (Auth.)

  2. Graft rejection after hematopoietic cell transplantation with nonmyeloablative conditioning.

    Masmas, Tania N; Petersen, Søren L; Madsen, Hans O; Ryder, Lars P; Kornblit, Brian; Svejgaard, Arne; Andersen, Pernille; Dickmeiss, Ebbe; Vindeløv, Lars L

    2008-07-01

    Graft rejection after hematopoietic cell transplantation (HCT) with nonmyeloablative conditioning is a rare but serious clinical problem. Graft rejection and salvage therapy in eight patients in a retrospective analysis of 124 consecutive patients is reported. The patients were conditioned with low-dose fludarabine and total body irradiation (TBI). The association of pretransplantation risk factors with rejection and the effect of chimerism and graft-versus-host disease on rejection were analyzed. Overall survival (OS) and progression free survival (PFS) were compared between patients with and without rejection. Retransplantation was performed with increased TBI conditioning for all patients, and with increased mycophenolate mofetil doses for recipients with HLA-identical sibling donors. No known pretransplantation risk factors were confirmed in this study. Rejection episodes were unevenly distributed over time. The storage temperature of the apheresis products was identified as a risk factor for rejection. Storage of the apheresis products at 5 degrees C diminished the risk of rejection. Low donor T cell chimerism at Day +14 significantly increased the risk of rejection. Seven patients were retransplanted. All but one engrafted successfully, but with decreased OS and PFS. Two patients received pentostatin infusion prior to donor lymphocyte infusions in unsuccessful attempts at reversing rejection. Storage temperature and donor chimerism had a significant effect on rejection. Following rejection, patients are at greater risk of dying from infections and progression/relapse of their malignancy. Retransplantation is feasible and well tolerated after HCT with nonmyeloablative conditioning and should be performed without delay in patients with imminent and manifest graft rejection. PMID:18383319

  3. Acute Bronchitis

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

  4. The innate immune response in ischemic acute kidney injury

    Jang, Hye Ryoun; Rabb, Hamid

    2008-01-01

    Kidney ischemia reperfusion injury is a major cause of morbidity in both allograft and native kidneys. Ischemia reperfusion-induced acute kidney injury is characterized by early, allo-antigen independent inflammation. Major components of the innate immune system are activated and participate in the pathogenesis of acute kidney injury, plus prime the allograft kidney for rejection. Soluble members of innate immunity implicated in acute kidney injury include the complement system, cytokines, an...

  5. Noninvasive monitoring of mouse renal allograft rejection using micro-CT

    Hou, Jiangang; Fujino, Masayuki; Cai, Songjie; Ding, Qiang; Li, Xiao-Kang

    2015-01-01

    Purpose Acute renal graft rejection can only be definitively diagnosed by renal biopsy. However, biopsies carry a risk of renal transplant injury and loss. Micro-CT is widely used in preclinical studies of small animals. Here, we propose micro-CT could noninvasively monitor and evaluate renal location and function in a mouse kidney transplant model. Methods Orthotopic kidney transplantation was performed in a BALB/c -to- C57BL/6j or C57BL/6j-to- C57BL/6j mouse model. After optimizing imaging ...

  6. Nanoparticle Enhanced MRI Scanning to Detect Cellular Inflammation in Experimental Chronic Renal Allograft Rejection

    S. R. Alam

    2015-01-01

    Full Text Available Objectives. We investigated whether ultrasmall paramagnetic particles of iron oxide- (USPIO- enhanced magnetic resonance imaging (MRI can detect experimental chronic allograft damage in a murine renal allograft model. Materials and Methods. Two cohorts of mice underwent renal transplantation with either a syngeneic isograft or allograft kidney. MRI scanning was performed prior to and 48 hours after USPIO infusion using T2∗-weighted protocols. R2∗ values were calculated to indicate the degree of USPIO uptake. Native kidneys and skeletal muscle were imaged as reference tissues and renal explants analysed by histology and electron microscopy. Results. R2∗ values in the allograft group were higher compared to the isograft group when indexed to native kidney (median 1.24 (interquartile range: 1.12 to 1.36 versus 0.96 (0.92 to 1.04, P<0.01. R2∗ values were also higher in the allograft transplant when indexed to skeletal muscle (6.24 (5.63 to 13.51 compared to native kidney (2.91 (1.11 to 6.46 P<0.05. Increased R2∗ signal in kidney allograft was associated with macrophage and iron staining on histology. USPIO were identified within tissue resident macrophages on electron microscopy. Conclusion. USPIO-enhanced MRI identifies macrophage.

  7. Multivisceral transplantation in pigs: a clinicopathological analysis of tissue rejection.

    Mitsuoka,Shintaro

    1995-10-01

    Full Text Available In this study, we established the surgical procedure and postoperative care of multivisceral transplantation (MVTX in pigs, and examined the functional changes and rejection pattern of transplanted organs in MVTX. Twenty-two MVTXs were performed without immunosuppression, and nine cases (41% that survived for 5 days or more after MVTX were used for evaluation. Rejection in grafts including the liver, pancreas, and gastrointestinal tract were assessed histopathologically. On day 5 after transplantation, the duodenum and small bowel already showed signs of mild rejection. On the other hand, in the liver, pancreas and stomach, rejection occurred later and was still mild on day 16. Hepatic rejection in MVTX appeared to occur later than in simple liver transplantation (LTX. These results showed that the susceptibility to rejection of individual visceral organs varies.

  8. The Rejection-Rage Contingency in Borderline Personality Disorder

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

    2011-01-01

    Though longstanding clinical observation reflected in the DSM-IV suggests that the rage characteristic of borderline personality disorder (BPD) often appears in response to perceived rejection, the role of perceived rejection in triggering rage in BPD has never been empirically tested. Extending basic personality research on rejection sensitivity to a clinical sample, a priming-pronunciation experiment and a 21-day experience-sampling diary examined the contingent relationship between perceived rejection and rage in participants diagnosed with BPD compared to healthy controls. Despite the differences in these two assessment methods, the indices of rejection-contingent rage that they produced were both elevated in the BPD group, and were strongly interrelated. They provide corroborating evidence that reactions to perceived rejection significantly explain the rage seen in BPD. PMID:21500875

  9. Regulatory Allospecific T Cell Clones Abrogate Chronic Allograft Rejection

    Waaga-Gasser, Ana Maria; Grimm, Martin R.; Lutz, Jens; Lange, Volkmar; Lenhard, Susanne M.; Aviles, Beatriz; Kist-van Holthe, Joana E; Lebedeva, Tatiana; Samsonov, Dimitry; Meyer, Detlef; Hancock, Wayne W.; Heemann, Uwe; Gasser, Martin; Chandraker, Anil

    2009-01-01

    True alloantigen-specific tolerance is the ultimate goal of solid organ transplantation, eliminating the need for long-term immunosuppression. Recent evidence suggests that Th1-derived cytokines are associated with rejection and Th2-derived cytokines with long-term allograft survival, but the roles of these subsets in rejection and tolerance are incompletely understood. Here, we analyzed the functional and regulatory capacities of T cell clones derived from tolerant and rejecting rats (Wistar...

  10. The private rejection of unfair offers and emotional commitment

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

    2009-01-01

    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 responde...

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

    Lifang Zhu

    2015-01-01

    The rejection of organic micropollutants, including three polycyclic aromatic hydrocarbons (PAHs) and three phthalic acid esters (PAEs), by clean and fouled nanofiltration membranes was investigated in the present study. The rejection of organic micropollutants by clean NF90 membranes varied from 87.9 to more than 99.9%, while that of NF270 membranes ranged from 32.1 to 92.3%. Clear time-dependence was observed for the rejection of hydrophobic micropollutants, which was attributed to the adso...

  12. Community rejection following sexual assault as ‘forced migration’

    AJ Morgen

    2013-01-01

    When women are banished from their communities following sexual assault, this rejection should be considered an act of forced migration by the administrators of truth commission reparations programmes.

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

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

    2015-01-01

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

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

    Dua Harminder

    1999-01-01

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

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

    2014-01-01

    Background The major challenge in ABO-incompatible transplantation is to minimize antibody-mediated rejection. Effective reduction of the anti-ABO blood group antibodies at the time of transplantation has made ABO-incompatible kidney transplantation a growing practice in our hospital and in centers worldwide. ABO antibodies result from contact with A- and B-like antigens in the intestines via nutrients and bacteria. We demonstrate a patient with fulminant antibody-mediated rejection late after ABO-incompatible kidney transplantation, whose anti-A antibody titers rose dramatically following Serratia marcescens sepsis. Case presentation A 58-year-old woman underwent an ABO-incompatible kidney transplantation for end-stage renal disease secondary to autosomal dominant polycystic kidney disease. It concerned a blood group A1 to O donation. Pre-desensitization titers were 64 for anti-blood group A IgM and 32 for anti-blood group A IgG titers. Desensitization treatment consisted of rituximab, tacrolimus, mycophenolate mofetil, corticosteroids, immunoadsorption and intravenous immunoglobulines. She was readmitted to our hospital 11 weeks after transplantation for S. marcescens urosepsis. Her anti-A IgM titer rose to >5000 and she developed a fulminant antibody-mediated rejection. We hypothesized that the (overwhelming) presence in the blood of S. marcescens stimulated anti-A antibody formation, as S. marcescens might share epitopes with blood group A antigen. Unfortunately we could not demonstrate interaction between blood group A and S. marcescens in incubation experiments. Conclusion Two features of this post-transplant course are remarkably different from other reports of acute rejection in ABO-incompatible kidney transplantation: first, the late occurrence 12 weeks after kidney transplantation and second, the very high anti-A IgM titers (>5000), suggesting recent boosting of anti-A antibody formation by S. marcescens. PMID:24517251

  16. Circulating Cell-Free DNA Enables Noninvasive Diagnosis of Heart Transplant Rejection

    De Vlaminck, Iwijn; Valantine, Hannah A.; Snyder, Thomas M.; Strehl, Calvin; Cohen, Garrett; Luikart, Helen; Neff, Norma F.; Okamoto, Jennifer; Bernstein, Daniel; Weisshaar, Dana; Quake, Stephen R.; Khush, Kiran K.

    2014-01-01

    Monitoring allograft health is an important component of posttransplant therapy. Endomyocardial biopsy is the current gold standard for cardiac allograft monitoring but is an expensive and invasive procedure. Proof of principle of a universal, noninvasive diagnostic method based on high-throughput screening of circulating cell-free donor-derived DNA (cfdDNA) was recently demonstrated in a small retrospective cohort. We present the results of a prospective cohort study (65 patients, 565 samples) that tested the utility of cfdDNA in measuring acute rejection after heart transplantation. Circulating cell-free DNA was purified from plasma and sequenced (mean depth, 1.2 giga–base pairs) to quantify the fraction of cfdDNA. Through a comparison with endomyocardial biopsy results, we demonstrate that cfdDNA enables diagnosis of acute rejection after heart transplantation, with an area under the receiver operating characteristic curve of 0.83 and sensitivity and specificity that are comparable to the intrinsic performance of the biopsy itself. This noninvasive genome transplant dynamics approach is a powerful and informative method for routine monitoring of allograft health without incurring the risk, discomfort, and expense of an invasive biopsy. PMID:24944192

  17. Perturbations in the Urinary Exosome in Transplant Rejection

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

    2015-01-01

    Background: Urine exosomes are small vesicles exocytosed into the urine by all renal epithelial cell types under normal physiologic and disease states. Urine exosomal proteins may mirror disease specific proteome perturbations in kidney injury. Analysis methodologies for the exosomal fraction of the urinary proteome were developed for comparing the urinary exosomal fraction versus unfractionated proteome for biomarker discovery. Methods: Urine exosomes were isolated by centrifugal filtration of urine samples collected from kidney transplant patients with and without acute rejection (AR), which were biopsy matched. The proteomes of unfractionated whole urine (Uw) and urine exosomes (Ue) underwent mass spectroscopy-based quantitative proteomics analysis. The proteome data were analyzed for significant differential protein abundances in AR. Results: A total of 1018 proteins were identified in Uw and 349 proteins in Ue. Two hundred seventy-nine overlapped between the two urinary compartments and 70 proteins were unique to the Ue compartment. Of 349 exosomal proteins identified from transplant patients, 220 had not been previously identified in the normal Ue fraction. Eleven Ue proteins, functionally involved in an inflammatory and stress response, were more abundant in urine samples from patients with AR, three of which are exclusive to the Ue fraction. Ue AR-specific biomarkers (1) were also detected in Uw, but since they were observed at significantly lower abundances in Uw, they were not significant for AR in Uw. Conclusion: A rapid urinary exosome isolation method and quantitative measurement of enriched Ue proteins was applied. Perturbed proteins in the exosomal compartment of urine collected from kidney transplant patients were specific to inflammatory responses, and were not observed in the Ue fraction from normal healthy subjects. Ue-specific protein alterations in renal disease provide potential mechanistic insights and offer a unique panel of sensitive

  18. Detection and measurement of tubulitis in renal allograft rejection

    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.

  19. Heterosexual Rejection and Mate Choice: A Sociometer Perspective

    Lin eZHANG

    2015-12-01

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

  20. 48 CFR 1419.505 - Rejecting Small Business Administration recommendations.

    2010-10-01

    ... Rejecting Small Business Administration recommendations. (a) A written justification in support of the CO's... 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...

  1. 48 CFR 19.505 - Rejecting Small Business Administration recommendations.

    2010-10-01

    ... Small Business Administration recommendations. (a) If the contracting officer rejects a recommendation... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Rejecting Small Business Administration recommendations. 19.505 Section 19.505 Federal Acquisition Regulations System FEDERAL...

  2. 48 CFR 219.505 - Rejecting Small Business Administration recommendations.

    2010-10-01

    ...-Asides for Small Business 219.505 Rejecting Small Business Administration recommendations. (b) The... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Rejecting Small Business Administration recommendations. 219.505 Section 219.505 Federal Acquisition Regulations System...

  3. 48 CFR 2919.505 - Rejecting Small Business Administration recommendations.

    2010-10-01

    ... Small Business 2919.505 Rejecting Small Business Administration recommendations. When the SBA... 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...

  4. Family Rejection Triples Risk for Suicide Attempts by Transgender People

    ... contact with their child; there were incidents of domestic violence; children cut off communication; or parents or siblings stopped communicating with the person. In the case of "high" level rejection, the ... study found. A high level of family rejection was tied to a two and a ...

  5. Molecular phenotyping of T cell-mediated rejection

    Chong, Anita S.; Perkins, David L.

    2014-01-01

    A new study has reported a molecular signature of T cell-mediated rejection in human kidney transplant biopsy samples that is enriched for effector T cells, interferon-γ and macrophages. Inhibitors of T cell activation, such as CTLA4 and PDL1, were also prominent, raising the possibility that these immunological constrains could be harnessed by therapies for treating rejection.

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

    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…

  7. Immunological tolerance and tumor rejection in embryo-aggregated chimeric mice – Lessons for tumor immunity

    Rejection of transplanted tumors by the immune system is a rare event in syngeneic hosts, and is considered to be dependent on the local interaction of defensive immune reactions and tumor tolerance mechanisms. Here, we have enlisted the aid of a unique set of embryo-aggregated lineage chimeric mice derived from C57/BL6 and FVB donors to study the interplay between local and systemic tumor immunity and tolerance in rejection of mouse B16 melanoma cells, syngeneic to the C57/BL6 donor strain. Two variants of embryo-aggregated chimeric mice with either variable or no contribution of C57-derived cells to their skin were generated by the fusion of different ratios of morula stage blastomers. Chimeric mice were analyzed for s.c. growth of B16 tumors in comparison to their respective donor strains as well as normal F1 hybrids, and the relative frequencies of cellular components of the immune system by FACS analysis of peripheral blood or lymph node cells. B16 tumors grew significantly faster in mice with full chimerism in their skin as compared to syngeneic C57 or semi-syngeneic C57 × FVB F1 hosts. In contrast, s.c. tumor growth was either absent or significantly reduced in chimeric mice lacking C57-derived cells in their skin, but tolerant to C57 tissue in other organs. Comparison of the relative frequencies of various immune cells in the periphery via FACS-analysis did not reveal any significant differences between the two types of chimeric mice with respect to their donor strains. Our data suggest a complex interplay between mechanisms of local peripheral tolerance and innate antitumor mechanisms possibly involving NK cell allorecognition as a basis for the differential growth or rejection of B16 tumors in these unique chimeric mice, which we suggest to constitute a valuable new model system for the study of immune-mediated tumor rejection

  8. Uptake of myocardial imaging agents by rejected hearts

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

  9. Graft rejection after hematopoietic cell transplantation with nonmyeloablative conditioning

    Masmas, T.N.; Petersen, S.L.; Madsen, H.O.; Ryder, L.P.; Kornblit, B.; Svejgaard, A.; Andersen, P.; Dickmeiss, E.; Vindelov, L.L.

    2008-01-01

    Graft rejection after hematopoietic cell transplantation (HCT) with nonmyeloablative conditioning is a rare but serious clinical problem. Graft rejection and salvage therapy in eight patients in a retrospective analysis of 124 consecutive patients is reported. The patients were conditioned with low......-dose fludarabine and total body irradiation (TBI). The association of pretransplantation risk factors with rejection and the effect of chimerism and graft-versus-host disease on rejection were analyzed. Overall survival (OS) and progression free survival (PFS) were compared between patients with and without......, patients are at greater risk of dying from infections and progression/relapse of their malignancy. Retransplantation is feasible and well tolerated after HCT with nonmyeloablative conditioning and should be performed without delay in patients with imminent and manifest graft rejection Udgivelsesdato: 2008/7...

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

    Gustafson, Eric; Carlson, Albert W.

    1987-01-01

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

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

    Valladares Linares, Rodrigo

    2011-12-01

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

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

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

    2011-12-15

    As forward osmosis (FO) gains attention as an efficient technology to improve wastewater reclamation processes, it is fundamental to determine the influence of fouling in the rejection of emerging contaminants (micropollutants). This study focuses on the rejection of 13 selected micropollutants, spiked in a secondary wastewater effluent, by a FO membrane, using Red Sea water as draw solution (DS), differentiating the effects on the rejection caused by a clean and fouled membrane. The resulting effluent was then desalinated at low pressure with a reverse osmosis (RO) membrane, to produce a high quality permeate and determine the rejection with a coupled forward osmosis - low pressure reverse osmosis (FO-LPRO) system. When considering only FO with a clean membrane, the rejection of the hydrophilic neutral compounds was between 48.6% and 84.7%, for the hydrophobic neutrals the rejection ranged from 40.0% to 87.5%, and for the ionic compounds the rejections were between 92.9% and 96.5%. With a fouled membrane, the rejections were between 44.6% and 95.2%, 48.7%-91.5% and 96.9%-98.6%, respectively. These results suggest that, except for the hydrophilic neutral compounds, the rejection of the micropollutants is increased by the presence of a fouling layer, possibly due to the higher hydrophilicity of the FO fouled membrane compared to the clean one, the increased adsorption capacity of hydrophilic compounds and reduced mass transport capacity, membrane swelling, and the higher negative charge of the membrane surface, related to the foulants composition, mainly NOM acids (carboxylic radicals) and polysaccharides or polysaccharide-like substances. However, when coupled with RO, the rejections in both cases increased above 96%. The coupled FO-LPRO system was an effective double barrier against the selected micropollutants. PMID:22055122

  13. Alpha Background Rejection in Bolometer Detectors

    Deporzio, Nicholas

    2016-03-01

    This study presents the modification of bolometer detectors used in particle searches to veto or otherwise reject alpha radiation background and the statistical advantages of doing so. Several techniques are presented in detail - plastic film scintillator vetoes, metallic film ionization vetoes, and scintillating bolometer vetoes. Plastic scintillator films are cooled to bolometer temperatures and bombarded with 1.4MeV to 6.0MeV alpha particles representative of documented detector background. Photomultipliers detect this scintillation light and produce a veto signal. Layered metallic films of a primary metal, dielectric, and secondary metal, such as gold-polyethylene-gold films, are cooled to milli-kelvin temperatures and biased to produce a current signal veto when incident 1.4MeV to 6.0MeV alpha particles ionize conduction paths through the film. Modified Zinc Molybdate Bolometers are used to produce scintillation light when stimulated by alpha background. Calibration of veto signal to background energy is presented. Results are used to quantify the statistical impact of such modifications on bolometer searches.

  14. Solar gains and thermal rejects by ventilation

    Data recorded between September 1983 and February 1985 were analyzed in detail and the main results are as follows: • Solar radiation covers a large fraction of the daily heat load : in local climatic conditions, between October and June, solar energy provided for nearly 40 % of the heat load of the greenhouse. This amount represents 32 % of the incident radiation. • Thermal excesses that were ventilated during overheating periods (Tint > 24 °C) represent 37 % of the incident solar energy. However, due to the seasonal phase differences between the thermal need and the incident solar power, only half of these rejects could potentially be saved by a short term storage system. • A method was developed for determining the monthy net auxiliary consumption of the greenhouse. Solar gains were evaluated by means of a monthly utilization factor (ratio of the solar energy used divided by the absorbed solar energy in the greenhouse). This factor has been experimentally fitted to a function of the gain load ratio (ratio of absorbed solar energy divided by the daytime heat load). The above representation appears to be valid for any type of climate or greenhouse. • The model also takes into account the effect of wind and radiative heat losses to the sky and calculates the net auxiliary requirements within less than 10%. (author)

  15. Ferrite grade iron oxides from ore rejects

    K S Rane; V M S Verenkar; P Y Sawant

    2001-06-01

    Iron oxyhydroxides and hydroxides were synthesized from chemically beneficiated high SiO2/Al2O3 low-grade iron ore (57.49% Fe2O3) rejects and heated to get iron oxides of 96–99.73% purity. The infrared band positions, isothermal weight loss and thermogravimetric and chemical analysis established the chemical formulas of iron-oxyhydroxides as -FeOOH.0.3H2O; -FeOOH.0.2H2O and amorphous FeOOH. The thermal products of all these were -Fe2O3 excepting that of -FeOOH.0.3H2O which gave mainly -Fe2O3 and some admixture of -Fe2O3. The hydrazinated iron hydroxides and oxyhydroxides, on the other hand, decomposed autocatalytically to mainly -Fe2O3. Hydrazine method modifies the thermal decomposition path of the hydroxides. The saturation magnetization, s, values were found to be in the range 60–71 emu g–1 which are close to the reported values for -Fe2O3. Mechanism of the -Fe2O3 formation by hydrazine method is discussed.

  16. Subclinical Rejection in Renal Transplantation: Reappraised.

    Mehta, Rajil; Sood, Puneet; Hariharan, Sundaram

    2016-08-01

    Short-term outcomes in renal transplantation have improved significantly in the past few years. However, the improvement in long-term outcomes has been modest. The reasons for graft failure beyond the first year of transplantation have been attributed to several different factors. We believe that subclinical rejection (SCR) may be 1 of the factors that contribute to graft loss in the long run. We also believe that there are data to suggest that SCR leads to progressive fibrosis and loss of graft function. This has been demonstrated even in patients who have mild degrees of subclinical inflammation. This review outlines the major studies that have been published on this important topic. It also outlines potential risk factors for the development of SCR. The current approach and diagnostic methods are discussed as well as their pros and cons. Newer noninvasive methods of diagnosis as well as molecular diagnostics and their merits and shortcomings are also discussed in some depth. Thus, the proposed state of the art review on SCR will create a renewed interest at all levels including transplant clinicians, transplant researchers, pharmaceutical industries as well as regulatory organizations. PMID:26985747

  17. Alpha Background Rejection in Bolometer Detectors

    Deporzio, Nicholas; Cuore Collaboration

    This study presents the modification of bolometer detectors used in particle searches to veto or otherwise reject alpha radiation background and the statistical advantages of doing so. Several techniques are presented in detail - plastic film scintillator vetoes, metallic film ionization vetoes, and Cherenkov radiation vetoes. Plastic scintillator films are cooled to bolometer temperatures and bombarded with 1.4MeV to 6.0MeV alpha particles representative of documented detector background. Quantum dot based liquid scintillator is similarly bombarded to produce a background induced scintillation light. Photomultipliers detect this scintillation light and produce a veto signal. Layered metallic films of a primary metal, dielectric, and secondary metal, such as gold-polyethylene-gold films, are cooled to milli-kelvin temperatures and biased to produce a current signal veto when incident 1.4MeV to 6.0MeV alpha particles ionize conduction paths through the film. Calibration of veto signal to background energy is presented. These findings are extrapolated to quantify the statistical impact of such modifications to bolometer searches. Effects of these techniques on experiment duration and signal-background ratio are discussed.

  18. Background Assay and Rejection in DRIFT

    Brack, Jeff; Dorofeev, Alexei; Ezeribe, Anthony; Gauvreau, Jean-Luc; Gold, Michael; Harton, John; Lafler, Randy; Lauer, Robert; Lee, Eric R; Loomba, Dinesh; Matthews, John; Miller, Eric H; Monte, Alissa; Murphy, Alex; Paling, Sean; Phan, Nguyen; Sadler, Steve; Scarff, Andrew; Snowden-Ifft, Daniel; Spooner, Neil; Telfer, Sam; Walker, Daniel; Williams, Matt; Yuriev, Leonid

    2014-01-01

    The DRIFT-IId dark matter detector is a m$^3$-scale low-pressure TPC with directional sensitivity to WIMP-induced nuclear recoils. Its primary backgrounds were due to alpha decays from contamination on the central cathode. Efforts to reduce these backgrounds led to replacing the 20 \\mu m wire central cathode with one constructed from 0.9 \\mu m aluminized mylar, which is almost totally transparent to alpha particles. Detailed modeling of the nature and origin of the remaining backgrounds led to an in-situ, ppt-sensitive assay of alpha decay backgrounds from the central cathode. This led to further improvements in the thin-film cathode resulting in over 2 orders of magnitude reduction in backgrounds compared to the wire cathode. Finally, the addition of O$_2$ to CS$_2$ gas was found to produce multiple species of electronegative charge carriers, providing a method to determine the absolute position of nuclear recoils and reject all known remaining backgrounds while retaining a high efficiency for nuclear recoil...

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

    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. PMID:22799588

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

    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…

  1. Acute Pancreatitis and Pregnancy

    ... Acute Pancreatitis > Acute Pancreatitis and Pregnancy test Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is ... of acute pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for ...

  2. The cell cycle and acute kidney injury

    Price, Peter M.; Safirstein, Robert L.; Megyesi, Judit

    2009-01-01

    Acute kidney injury (AKI) activates pathways of cell death and cell proliferation. Although seemingly discrete and unrelated mechanisms, these pathways can now be shown to be connected and even to be controlled by similar pathways. The dependence of the severity of renal-cell injury on cell cycle pathways can be used to control and perhaps to prevent acute kidney injury. This review is written to address the correlation between cellular life and death in kidney tubules, especially in acute ki...

  3. Modelling cellular behaviour

    Endy, Drew; Brent, Roger

    2001-01-01

    Representations of cellular processes that can be used to compute their future behaviour would be of general scientific and practical value. But past attempts to construct such representations have been disappointing. This is now changing. Increases in biological understanding combined with advances in computational methods and in computer power make it possible to foresee construction of useful and predictive simulations of cellular processes.

  4. Evaluation of changes of mean parenchymal transit time and de convoluted curve in actual rejected transplanted kidney by Tc-99m-DTPA

    Precise diagnosis of complication after renal transplantation is necessary for treatment decision making. Acute rejection is one of the most serious but treatable complications. It is well known that mean parenchymal transit time (MPTT) arises with decreased function of Kidneys. In this study we evaluated changes of MPTT and de convoluted curve to asses the diagnostic value of these parameters rejection. This investigation was carried out on 27 complicated transplanted kidneys (11 cases with acute rejection - A R- and 16 cases with other complication-O C-) and 13 normal grafts by Tc-99-DTPA scintigraphy. MPPT, the time of 20% (T 20) and %80 (T 80) of curve pla tue as well as the ratio of T 20/T 80 were calculated according to de convoluted curve. In normal grafts Matt was 2.03+0.54 which arise d in A R (4.05+0.2), P0.1) between Ar and O C, however, the ratio of T 20/T 80 was higher in A R compared to O C (2.41+0.23 versus 1.77+0.27, P<0.001). With consideration of 2.1 as T 20. T 80 threshold, sensitivity and accuracy values for diagnosis of A R were 90%, 87% and 89% respectively. MPTT is a sensitive parameter to diagnosis of complicated transplanted kidney, but with calculation of T 20/T 80, we can obtain an accurate parameter for diagnosis for of acute rejection

  5. Bronchitis - acute

    ... sharing features on this page, please enable JavaScript. Acute bronchitis is swelling and inflammation in the main passages ... present only for a short time. Causes When acute bronchitis occurs, it almost always comes after having a ...

  6. Bronchitis - acute

    Acute bronchitis is swelling and inflammation in the main passages that carry air to the lungs. The swelling narrows ... makes it harder to breathe. Another symptom of bronchitis is a cough. Acute means the symptoms have ...

  7. Acute Bronchitis

    Bronchitis is an inflammation of the bronchial tubes, the airways that carry air to your lungs. It ... chest tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis ...

  8. Detection of cardiac transplant rejection with radiolabeled lymphocytes

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

  9. Detection of cardiac transplant rejection with radiolabeled lymphocytes. [Rats

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

    1982-03-01

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

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

    Lifang Zhu

    2015-01-01

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

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

    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.

  12. Acute pancreatitis

    Bo-Guang Fan; Åke Andrén-Sandberg

    2010-01-01

    Background : Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims : The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods : We reviewed the English-language literature (Medline) addressing pancreatitis. Results : Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingest...

  13. Acute pancreatitis

    Bo-Guang Fan; Åke Andrén-Sandberg

    2010-01-01

    Background: Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims: The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods: We reviewed the English-language literature (Medline) addressing pancreatitis. Results: Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion....

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

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

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

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

    1989-09-01

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

  16. SCHEDULING WITH REJECTION AND NON-IDENTICAL JOB ARRIVALS

    Zhigang CAO; Yuzhong ZHANG

    2007-01-01

    In this paper, we address the scheduling problem with rejection and non-identical job arrivals, in which we may choose not to process certain jobs and each rejected job incurs a penalty.Our goal is to minimize the sum of the total penalties of the rejected jobs and the maximum completion time of the processed ones. For the off-line variant, we prove its NP-hardness and present a PTAS, and for the on-line special case with two job arrivals, we design a best possible algorithm with competitive ratio (√5+1)/2.

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

    Guinn, David; Burgermeister, Diane M

    2016-01-01

    A retrospective review of medical records was proposed to examine mental health staff compliance with documentation of a suicide assessment tool according to institutional policy on suicide screening within a U.S. correctional facility. A shift in focus was necessary when the proposed study was rejected by the institutional review board. Reasons for the rejection included low perceived benefit versus greater risk to the correctional facility and the need for prisoner informed consent, albeit the design was a retrospective medical record review. Because of this rejection, ethical issues in the prevention of suicide in prisons were examined with implications for the forensic nurse leading quality improvement initiatives. PMID:26910268

  18. Heterogeneous cellular networks

    Hu, Rose Qingyang

    2013-01-01

    A timely publication providing coverage of radio resource management, mobility management and standardization in heterogeneous cellular networks The topic of heterogeneous cellular networks has gained momentum in industry and the research community, attracting the attention of standardization bodies such as 3GPP LTE and IEEE 802.16j, whose objectives are looking into increasing the capacity and coverage of the cellular networks. This book focuses on recent progresses,  covering the related topics including scenarios of heterogeneous network deployment, interference management i

  19. Cellular Reflectarray Antenna

    Romanofsky, Robert R.

    2010-01-01

    The cellular reflectarray antenna is intended to replace conventional parabolic reflectors that must be physically aligned with a particular satellite in geostationary orbit. These arrays are designed for specified geographical locations, defined by latitude and longitude, each called a "cell." A particular cell occupies nominally 1,500 square miles (3,885 sq. km), but this varies according to latitude and longitude. The cellular reflectarray antenna designed for a particular cell is simply positioned to align with magnetic North, and the antenna surface is level (parallel to the ground). A given cellular reflectarray antenna will not operate in any other cell.

  20. Acute pancreatitis

    Bo-Guang Fan

    2010-05-01

    Full Text Available Background: Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims: The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods: We reviewed the English-language literature (Medline addressing pancreatitis. Results: Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions: Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  1. Acute pancreatitis

    Bo-Guang Fan

    2010-01-01

    Full Text Available Background : Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims : The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods : We reviewed the English-language literature (Medline addressing pancreatitis. Results : Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions : Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  2. Non-clairvoyant weighted flow time scheduling with rejection penalty

    Chan, Ho-Leung; Chan, Sze-Hang; Lam, Tak-Wah;

    2012-01-01

    This paper initiates the study of online scheduling with rejection penalty in the non-clairvoyant setting, i.e., the size (processing time) of a job is not assumed to be known at its release time. In the rejection penalty model, jobs can be rejected with a penalty, and the user cost of a job is...... defined as the weighted flow time of the job plus the penalty if it is rejected before completion. Previous work on minimizing the total user cost focused on the clairvoyant single-processor setting [BBC+03,CLL11] and has produced O(1)-competitive online algorithm for jobs with arbitrary weights and...... results assume a processor running at a fixed speed. This paper shows more interesting results on extending the above study to the dynamic speed scaling model, where the processor can vary the speed dynamically and the rate of energy consumption is an arbitrary increasing function of speed. A scheduling...

  3. Hyperacute Rejection of a Living Unrelated Kidney Graft

    Dietlind Tittelbach-Helmrich

    2014-01-01

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

  4. Community rejection following sexual assault as ‘forced migration’

    AJ Morgen

    2013-09-01

    Full Text Available When women are banished from their communities following sexual assault, this rejection should be considered an act of forced migration by the administrators of truth commission reparations programmes.

  5. The sequential rejection principle of familywise error control

    Goeman, Jelle J.; Solari, Aldo

    2012-01-01

    Closed testing and partitioning are recognized as fundamental principles of familywise error control. In this paper, we argue that sequential rejection can be considered equally fundamental as a general principle of multiple testing. We present a general sequentially rejective multiple testing procedure and show that many well-known familywise error controlling methods can be constructed as special cases of this procedure, among which are the procedures of Holm, Shaffer and Hochberg, parallel...

  6. Experimental diabetes exacerbates skin transplant rejection in rats

    Flávio Pola dos Reis; Angelo Sementilli; Antonio Ricardo de Toledo Gagliardi

    2013-01-01

    PURPOSE: To investigate the effect of chronic experimental diabetes on skin allografts in rats as a simple model that could clarify some basic aspects and mechanisms involved in transplant rejection in diabetes compared to normal animals. METHODS: Skin grafting was performed with fragments of tail skin from sex matched non diabetic Wistar rats engrafted onto the thoracic area of diabetic and non diabetic recipients. Grafts were scored for rejection every other day and were removed on day 14. ...

  7. Liver Transplant Rejection: Angiographic Findings in 35 Patients

    White, Robert M.; Zajko, Albert B.; Demetris, A Jake; Bron, Klaus M.; DEKKER, ANDREW; Starzl, Thomas E.

    1987-01-01

    Rejection, the leading cause of liver allograft dysfunction, is usually detected by liver biopsy. The purpose of this study was to determine if there are angiographic findings that correlate with this posttransplantation complication. In a retrospective study, the angiograms of 35 patients with histologically proven allograft rejection were reviewed. The examinations were done because of suspected posttransplantation vascular complications. Abnormal hepatic arteriograms were observed in 30 (8...

  8. Main feed water pump NPSH control during load rejection transient

    The paper introduces the damage to the Main feed water pump because of pump cavitation, analysis the disadvantaged impact of pressure reducing during load rejection transient condition, and the characteristic for Main feedwater pump NPSH during load rejection transient condition; summarizes the characteristics of Main feedwater pump NPSH comparing to NPQJVC. What's more, this paper has a lot for commissioning and running the Main feedwater pump. (author)

  9. On Properties of Update Sequences Based on Causal Rejection

    Eiter, T.; Fink, M; Sabbatini, G; Tompits, H.

    2001-01-01

    We consider an approach to update nonmonotonic knowledge bases represented as extended logic programs under answer set semantics. New information is incorporated into the current knowledge base subject to a causal rejection principle enforcing that, in case of conflicts, more recent rules are preferred and older rules are overridden. Such a rejection principle is also exploited in other approaches to update logic programs, e.g., in dynamic logic programming by Alferes et al. We give a thoroug...

  10. Performance Evaluation of Air-Based Heat Rejection Systems

    Hannes Fugmann; Björn Nienborg; Gregor Trommler; Antoine Dalibard; Lena Schnabel

    2015-01-01

    On the basis of the Number of Transfer Units (NTU) method a functional relation between electric power for fans/pumps and effectiveness in dry coolers and wet cooling towers is developed. Based on this relation, a graphical presentation method of monitoring and simulation data of heat rejection units is introduced. The functional relation allows evaluating the thermodynamic performance of differently sized heat rejection units and comparing performance among them. The method is used to evalua...

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

    Chew, F S

    1991-03-01

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

  12. Experimental quantum error rejection for long-distance quantum communication

    Full text: We report an experimental realization of bit-flip error rejection for error-free transfer of quantum information through a noisy quantum channel. In the experiment, an unknown state to be transmitted is encoded into a two- photon entangled state, which is then sent through the engineered noisy quantum channel. At the final stage, the unknown state was decoded by a quantum parity measurement, successfully rejecting the erroneous transmission over the noisy quantum channel. (author)

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

    Trentacosta, Christopher J.; Shaw, Daniel S.

    2007-01-01

    The present study examined relations among maternal psychological resources, rejecting parenting, and early adolescent antisocial behavior in a sample of 231 low-income mothers and their sons with longitudinal assessments from age 18 months to 12 years. The maternal resources examined were age at first birth, aggressive personality, and empathy. Each of the maternal resources predicted rejecting parenting during early childhood in structural equation models that controlled for toddler difficu...

  14. Choice, Rejection, and Elaboration on Preference-Inconsistent Alternatives

    Juliano Laran; Keith Wilcox

    2011-01-01

    Previous research has demonstrated that rejecting product alternatives (i.e., choosing which alternatives to give up) may cause preference reversals compared to choosing alternatives. We provide an investigation into the psychological processes underlying this phenomenon. These preference reversals can be caused by increased elaboration on the features of preference-inconsistent alternatives when people reject alternatives. When these features are appealing, increased elaboration increases pr...

  15. The Pathology of Lung Allograft Rejection: A Concise Review

    Anja Roden; Henry Tazelaar

    2012-01-01

    Lung transplantations in humans have been performed for almost 50 years. However, allograft rejection, non-rejection diseases such as harvest/reperfusion injury, infection, drug toxicity, post-transplant lymphoproliferative diseases, and recurrent disease are still significant complications. Although the clinical impression might suggest the possibility of any of these conditions, tissue diagnosis is usually necessary to establish a definitive diagnosis. This article mainly focuses on reviewi...

  16. Cellular oncogenes in neoplasia.

    Chan, V T; McGee, J O

    1987-01-01

    In recent years cellular homologues of many viral oncogenes have been identified. As these genes are partially homologous to viral oncogenes and are activated in some tumour cell lines they are termed "proto-oncogenes". In tumour cell lines proto-oncogenes are activated by either quantitative or qualitative changes in gene structure: activation of these genes was originally thought to be a necessary primary event in carcinogenesis, but activated cellular oncogenes, unlike viral oncogenes, do ...

  17. Cellular Cardiomyoplasty: Clinical Application

    Chachques, J. (J.); Acar, C; J. Herreros; Trainini, J. (Jorge); Prosper, F.; D’Attellis, N. (N.); Fabiani, J. N.; Carpentier, A

    2004-01-01

    Myocardial regeneration can be induced with the implantation of a variety of myogenic and angiogenic cell types. More than 150 patients have been treated with cellular cardiomyoplasty worldwide, 18 patients have been treated by our group. Cellular cardiomyoplasty seems to reduce the size and fibrosis of infarct scars, limit postischemic remodelling, and restore regional myocardial contractility. Techniques for skeletal myoblasts culture and ex vivo expansion using auto...

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

    Valladares Linares, Rodrigo

    2014-07-17

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

  19. A novel noninvasive method to detect rejection after heart transplantation

    Jun Hu

    2012-12-01

    Full Text Available Prompt and accurate detection of rejection prior to pathological changes after organ transplantation is vital for monitoring rejections. Although biopsy remains the current gold standard for rejection diagnosis, it is an invasive method and cannot be repeated daily. Thus, noninvasive monitoring methods are needed. In this study, by introducing an IL-2 neutralizing monoclonal antibody (IL-2 N-mAb and immunosuppressants into the culture with the presence of specific stimulators and activated lymphocytes, an activated lymphocyte-specific assay (ALSA system was established to detect the specific activated lymphocytes. This assay demonstrated that the suppression in the ALSA test was closely related to the existence of specific activated lymphocytes. The ALSA test was applied to 47 heart graft recipients and the proliferation of activated lymphocytes from all rejection recipients proven by endomyocardial biopsies was found to be inhibited by spleen cells from the corresponding donors, suggesting that this suppression could reflect the existence of activated lymphocytes against donor antigens, and thus the rejection of a heart graft. The sensitivity of the ALSA test in these 47 heart graft recipients was 100%; however, the specificity was only 37.5%. It was also demonstrated that IL-2 N-mAb was indispensible, and the proper culture time courses and concentrations of stimulators were essential for the ALSA test. This preliminary study with 47 grafts revealed that the ALSA test was a promising noninvasive tool, which could be used in vitro to assist with the diagnosis of rejection post-heart transplantation.

  20. The private rejection of unfair offers and emotional commitment.

    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. PMID:19564602