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Sample records for acute cellular rejection

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

    Science.gov (United States)

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

    2016-03-01

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

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

    DEFF Research Database (Denmark)

    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...

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

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

    2016-03-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    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.)

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

    Science.gov (United States)

    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

  8. Urinary granzyme A mRNA is a biomarker to diagnose subclinical and acute cellular rejection in kidney transplant recipients

    NARCIS (Netherlands)

    S.M. Ham; K.M. Heutinck; T. Jorritsma; F.J. Bemelman; M.C.M. Strik; W. Vos; J.J.F. Muris; S. Florquin; R.J.M. ten Berge; A.T. Rowshani

    2010-01-01

    The distinction between T-cell-mediated rejection (TCMR) and other causes of kidney transplant dysfunction such as tubular necrosis requires biopsy. Subclinical rejection (SCR), an established risk factor for chronic allograft dysfunction, can only be diagnosed by protocol biopsy. A specific non-inv

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

    NARCIS (Netherlands)

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

    2002-01-01

    OBJECTIVE: To assess whether diastolic graft function is influenced by intragraft interleukin 2 (IL-2) messenger RNA (mRNA) expression in rejecting cardiac allografts. DESIGN: 16 recipients of cardiac allografts were monitored during the first three months after transplantation. The presence of IL-2

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

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    Elena Crespo

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

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

    Science.gov (United States)

    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

  12. Monitoring of Acute Rejection after Orthotopic Heart Tranplantation

    Institute of Scientific and Technical Information of China (English)

    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.

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

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    L. V. Shkalova

    2011-01-01

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

  14. CURRENT VIEW ON MORPHOLOGY OF ACUTE REJECTION IN LIVER TRANSPLANTATION

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    L.V. Shkalova

    2012-01-01

    Full Text Available We present a scientific literature data analysis of morphological features and severity criteria of the liver allograft acute rejection during last 20 years. Modern conception was given about the role of immunological mechanisms in the de- velopment of liver graft acute rejection. We describe roles of different cell types in the destructive immune response during liver allograft acute rejection. Advantages and disadvantages of Banff-classifications 1995, 1997 are discussed as well as the necessity of grading the acute rejection as early and late. We propose clinico-morphological correlations in liver allograft acute rejection

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

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

    2012-05-01

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

  16. Predicting outcome of acute kidney transplant rejection using

    NARCIS (Netherlands)

    Rekers, Niels Vincent

    2014-01-01

    Acute kidney transplant rejection is an important risk factors for adverse graft outcome. Once diagnosed, it remains difficult to predict the risk of graft loss and the response to anti-rejection treatment. The aim of this thesis was to identify biomarkers during acute rejection, which predict the r

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

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    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. Spontaneous restoration of transplantation tolerance after acute rejection

    OpenAIRE

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

    2015-01-01

    Transplantation is a cure for end-stage organ failure but, in the absence of pharmacological immunosuppression, allogeneic organs are acutely rejected. Such rejection invariably results in allosensitization and accelerated rejection of secondary donor-matched grafts. Transplantation tolerance can be induced in animals and a subset of humans, and enables long-term acceptance of allografts without maintenance immunosuppression. However, graft rejection can occur long after a state of transplant...

  20. Acute Rejection after Human Renal Transplantation

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    Ana Roussoulières

    2007-01-01

    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.

  1. Acute rejection episodes after kidney transplantation

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    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.

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

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    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

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

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

    2015-04-01

    The aim of the study was to evaluate the long-term influence of repeated acute cellular rejections on left ventricular longitudinal deformation in heart transplantation (HTX) patients. One hundred and seventy-eight HTX patients were included in the study. Rejections were classified according to the International Society of Heart and Lung Transplantation (ISHLT) classification (0R-3R). Patients were divided into three groups according to rejection scores (RSs). Group 1: longitudinal strain (GLS) comparing to rejection groups (GLS group 1: -16.8 ± 2.4 (%); GLS group 2: -15.9 ± 3.3 (%); GLS group 3: -14.5 ± 2.9 (%), P = 0.0003). After excluding patients with LVEF cardiac rejections lead to impaired graft function as detected by decreasing magnitude of GLS. In contrast, traditional systolic graft function surveillance by LVEF did not correlate to rejection burden.

  4. Spontaneous restoration of transplantation tolerance after acute rejection.

    Science.gov (United States)

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

    2015-01-01

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

  5. Acute renal transplant rejections: A single center experience

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    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.

  6. Gene Expression Profiling on Acute Rejected Transplant Kidneys with Microarray

    Institute of Scientific and Technical Information of China (English)

    Deping LI; Kang WANG; Yong DAI; Tianyu LV

    2008-01-01

    To investigate the gene expression profiles in acute allograft rejection of renal trans- plantation, and identify the markers for the early diagnosis of acute rejection, heterotopic kidney transplantation was performed by using F344 or Lewis donors and Lewis recipients. No immunosup- pressant was used. Renal grafts were harvested on days 3, 7, and 14. A commercial microarray was used to measure gene expression levels in day-7 grafts. The expression levels of 48 genes were up-regulated in the allograft in comparison with the isograft control, and interferon-y-induced GTPase gene was most significantly up-regulated in allografts. It is concluded that a variety of pathways are involved in organ transplant rejection which is dynamic and non-balanced. IFN-inducible genes, such as IGTP, may play an important role in the rejection. A lot of important factors involved in acute re- jection are unnecessary but sufficient conditions for the rejection. We are led to conclude that it is virtually impossible to make an early diagnosis based on a single gene marker, but it could he achieved on the basis of a set of markers.

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

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    Norsworthy Kelly J

    2009-06-01

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

  8. CD4+ T Lymphocytes are Not Necessary for the Acute Rejection of Vascularized Mouse Lung Transplants

    OpenAIRE

    Gelman, Andrew E.; Okazaki, Mikio; Lai, Jiaming; Kornfeld, Christopher G.; Kreisel, Friederike H.; Richardson, Steven B.; Sugimoto, Seiichiro; Tietjens, Jeremy R.; Patterson, G. Alexander; Krupnick, Alexander S.; Kreisel, Daniel

    2008-01-01

    Acute rejection continues to present a major obstacle to successful lung transplantation. While CD4+ T lymphocytes are critical for the rejection of some solid organ grafts the role of CD4+ T cells in the rejection of lung allografts is largely unknown. In this study we demonstrate in a novel model of orthotopic vascularized mouse lung transplantation that acute rejection of lung allografts is independent of CD4+ T cell-mediated allorecognition pathways. CD4+ T cell-independent rejection occu...

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    DEFF Research Database (Denmark)

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

    1993-01-01

    Transplantation has become an accepted treatment of many cardiac end-stage diseases. Acute cellular rejection accounts for 15% to 20% of all graft failures. The first grading system of acute cellular rejection, the Stanford Classification, was introduced in 1979, and since then many other grading...... systems have evolved. Most recently, the International Grading System was introduced in The Journal of Heart and Lung Transplantation. In this study the interobserver reproducibility of both the Stanford Classification and the International Grading System is evaluated using Kappa statistics. Three...... observers evaluated 168 endomyocardial biopsy specimens according to the Stanford Classification and 100 endomyocardial biopsy specimens according to the International Grading System. The evaluation was carried out blindly. Kappa values of 54.1% and 51.5%, respectively, were obtained, both significantly...

  12. Expression of Cytokines in Acute Heart Transplantation Rejection

    Institute of Scientific and Technical Information of China (English)

    XIA Jiahong; XU Lei; YANG Chenyuan

    2006-01-01

    The expression and changes of local cytokines network were detected in heart transplantation in rats, so as to determine the role of cytokines in the acute rejection of rats of heart transplantation. Allografts were divided into 4 groups (n=12 in each group): group A (control), group B (IL-2 monoclonal antibody-treated), group C (CsA-treated) and group D (IL-2 monoclonal antibody+CsA-treated). Hearts from DA rats were transplanted into a cervical location in Wistar recipients. The local expression of IL-1β, IL-2, CD25, IL-4, IL-5, IL-6, IL-10, TNFα and INFγ was detected at day 1, 3, 5, 7, 9, 11 and 14 by reverse transcription polymerase chain reaction. The results showed that the survival time of allografts was 8.3±1.7, 29.2±7.1 (P<0.05), 26.4±5.7 (P<0.05) and 55.0±10.6 (P<0.01) days respectively in groups A, B, C and D. The expression of IL-1β, IL-4, IL-10and IFNγ was up-regulated, and that of IL-2, CD25, IL-5, IL-6 and TNFα was significantly inhibited in group A; The expression of IL-1β, IL-5, IL-6, IL-10 and IFNγ was up-regulated, and that of IL-2,IL-4 and TNFα was significantly down-regulated in group B; The expression of IL-1β, IL-2, CD25,IL-5, TNFα and IFNγ was up-regulated, and that of IL-4, IL-6 and IL-10 was significantly down-regulated in group C; The expression of IL-14, Il-5, IL-6 and Il-10 was up-regulated, and that of IL-1β, IL-2, CD25, TNFα and IFNγ was significantly down-regulated in group D. In conclusion,cytokines play an important role in the development of acute transplantation rejection. Different cytokines play different roles in different local environments.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Impact of acute rejection episodes on long-term renal allograft survival

    Institute of Scientific and Technical Information of China (English)

    吴建永; 陈江华; 王逸民; 张建国; 朱琮; 寿张飞; 王苏娅; 张萍; 黄洪锋; 何强

    2003-01-01

    Objective To assess the impact of the number, and time of acute rejection (AR) and outcome of anti-rejection therapy on the long-term survival of renal allografts and the relative risk factors. Methods The Kaplan-Meier analysis and log-rank test were used to calculate the survival rates of patients and grafts in no acute rejection group (NAR, 895 patients), 1 rejection episode group (1AR, 183), 2 and more than 2 rejection episodes group (2AR, 17), acute rejection group [AR (1AR+2AR), 200], early acute rejection group (within 90 days after transplantation, EAR, 125), late acute rejection group (91 days later, LAR, 58), completely AR reversed group (CAR, 105), and incompletely AR reversed group (IAR, 68). The relative risk factors were analyzed by the Cox proportional hazards regression. Results The 5- and 10-year survival rates of renal allografts were 75.4% and 17.1% in AR and 93.2% and 86.5% in the NAR group (P<0.0001). The long-term graft survival was much lower in the 2AR group than in the NAR or 1AR groups (P<0.0001 and P=0.002, respectively). It was similar in either the NAR or CAR groups (P=0.31), but it was significantly lower (P<0.0001) in the IAR group. Multivariate Cox regression analysis revealed that the outcome of anti-rejection therapy is an important risk factor affecting the long-term survival of allografts.Conclusions AR is significantly associated with poor long-term survival of renal allografts. But the long-term graft survival of patients with one acute rejection but completely reversed is not significantly different from that of patients without acute rejection.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  16. Programmed death 1 mRNA in peripheral blood as biomarker of acute renal allograft rejection

    Institute of Scientific and Technical Information of China (English)

    WANG Ya-wen; WANG Zhen; SHI Bing-yi

    2011-01-01

    Background Invasive kidney biopsy is a priority diagnostic method for the acute rejection after renal transplantation for the past decades. However, no effective and noninvasive assay for predicting the severity of acute rejection is in wide use at present. This study was designed to investigate the predictive value of programmed death 1 (PD-1) mRNA for acute rejection after renal transplantation with real-time reverse transcriptase polymerase chain reaction (RT-PCR). A noninvasive diagnostic method has been expected to replace the tranditional kidney biopsy for the diagnosis of acute rejection and prediction of the outcome after kidney transplantation.Methods The whole blood samples from 19 subjects with acute rejection, 20 subjects with delayed graft function (DGF)and 21 subjects with stable recipients after kidney transplantation in a single kidney transplantation center between 2006 and 2009 were collected. The messenger RNA (mRNA) of PD-1 was analyzed with real-time RT-PCR. The associations of PD-1 mRNA levels with acute rejection and disease severity were investigated.Results The log-transformed ratio of PD-1 mRNA to GAPDH mRNA was higher in peripheral blood mononuclear cell (PBMC) from the group with acute rejection (4.52±1.1) than that from the group with DGF (1.12±0.6) or the group with normal biopsy results (0.7±0.4) (P <0.01, by the Kruskal-Wallis test). PD-1 mRNA levels were correlated with serum creatinine levels measured at the time of biopsy in the acute rejection group (Spearman's correlation coefficient, r=0.81,P=0.03), but not in the group with DGF or the group with normal biopsy results. PD-1 mRNA levels identified subjects at risk for graft failure within six months after the incident episode of acute rejection.Conclusions Our data suggest that PD-1 status may be a new predictor of acute rejection and the levels of PD-1mRNA in whole blood cells may positively correlate with the severity of acute rejection after renal transplantation

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

    NARCIS (Netherlands)

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

    1997-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    OpenAIRE

    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...

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

    NARCIS (Netherlands)

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

    1995-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Gyeh Yon; Lee, M. H.; Son, K. M.; Shin, K. S.; Park, Y. H. [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1990-12-15

    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%)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Neves, L A [Universidade Estadual Paulista, IGCE, DEMAC, Rio Claro, SP (Brazil); Oliveira, F R; Peres, F A [Faculdade de Tecnologia de Sao Jose do Rio Preto, Sao Jose do Rio Preto, SP (Brazil); Moreira, R D; Moriel, A R; De Godoy, M F [Faculdade de Medicina de Sao Jose do Rio Preto, FAMERP, Sao Jose do Rio Preto, SP (Brazil); Murta Junior, L O, E-mail: laneves@rc.unesp.br [Universidade de Sao Paulo, FFCLRP, Depto Computacao e Matematica, Ribeirao Preto (Brazil)

    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.

  4. Diagnosis and Treatment of Pancreas Rejection

    OpenAIRE

    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...

  5. The Characteristics of Acute Rejection after Limb Allotransplantation in Rats-An Experimental Study

    Institute of Scientific and Technical Information of China (English)

    康皓; 洪光祥; 王发斌; 陈振兵; 黄启顺; 翁雨雄

    2003-01-01

    To study the characteristics of acute rejection after limb allotransplantation, 29 male Sprague-Dawley rats were randomly divided into 2 groups, with 15 rats in control group and 14 rats in experimental group. Each rat in control group underwent limb replantation. Each rat in experimental group received limb transplantation from Wistar rat. No immnosuppressive drugs were used after operation. The circulation of the transplanted limb, time and signs of rejection, histopathological changes in the tissues of the limb graft when rejected and survival time of limb grafts were evaluated. In the control group, no signs of rejection were observed, the circulation of each replanted limb was normal, it could survive for a longer time. The experimental group showed clinical signs of rejection (sub dermal edema and erythema) after a mean time of 3. 36±1.15 days, and the mean survival time of the allografts was only 7±0.78 days. Histopathological examination showed most violent rejection reaction in skin. It is concluded that with Wistar-to-SD limb transplantation without use of immunosuppression, rejection of the grafts would occur after a mean time of 3.36 ±1.15days; the earliest signs of rejection were edema and erythema of the skin, skin being the most representative component of limb graft rejection.

  6. Characterization of Acute Renal Allograft Rejection by Human Serum Proteomic Analysis

    Institute of Scientific and Technical Information of China (English)

    Ying GAO; Ke WU; Yi XU; Hongmin ZHOU; Wentao HE; Weina ZHANG; Lanjun CAI; Xingguang LIN; Zemin FANG; Zhenlong LUO; Hui GUO; Zhonghua CHEN

    2009-01-01

    To identify acute renal allograft rejection biomarkers in human serum, two-dimensional differential in-gel electrophoresis (2-D DIGE) and reversed phase high-performance liquid chromatog-raphy (RP-HPLC) followed by electrospray ionization mass spectrometry (ESI-MS) were used. Serum samples from renal allograft patients and normal volunteers were divided into three groups: acute rejec-tion (AR), stable renal function (SRF) and normal volunteer (N). Serum samples were firstly processed using Multiple Affinity Removal Column to selectively remove the highest abundance proteins. Differ-entially expressed proteins were analyzed using 2-D DIGE. These differential protein spots were ex-cised, digested by trypsin, and identified by RP-HPLC-ESI/MS. Twenty-two differentially expressed proteins were identified in serum from AR group. These proteins included complement C9 precursor,apolipoprotein A-Ⅳ precursor, vitamin D-binding protein precursor, beta-2-glycoprotein 1 precursor,etc. Vitamin D-binding protein, one of these proteins, was confirmed by ELISA in the independent set of serum samples. In conclusion, the differentially expressed proteins as serum biomarker candidates may provide the basis of acute rejection noninvasive diagnosis. Confirmed vitamin D-binding protein may be one of serum biomarkers of acute rejection. Furthermore, it may provide great insights into un-derstanding the mechanisms and potential treatment strategy of acute rejection.

  7. Immunologic role of nitric oxide in acute rejection of golden hamster to rat liver xenotransplantation

    Institute of Scientific and Technical Information of China (English)

    Tong-Jin Diao; Tong-Ye Yuan; You-Lin Li

    2002-01-01

    AIM: To evaluate the immunologic role and expressionsignificances of nitric oxide(NO), nitric oxide synthase(NOS),and its isoenzyme in acute rejection to liverxenografts from golden hamster in rat.METHODS: Liver transplantations were randomlydivided into five groups(n=6-9):isografts (group I );xenografts (groupⅡ); xenografts plus cyclosporinetreatment (group Ⅲ), xenografts pluscyclophosphamide treatment combined withsplenectomy (group Ⅳ), and xenografts usingcyclophosphamide in combination with splenectomy(group Ⅳ) and xenografts using splenectomy inaddition to cyclophosphamide and cyclosporinetreatments(group V) .The levels of ALT, TNF- α, andnitric oxide production(NOx) in serum of reciprentswere examined,and expressions of type Ⅱ (iNOS) andtypeⅢ (cNOS) nitric oxide synthase(NOS)-inducibleNOS(iNOS) and constitutive NOS(cNOS) wereobserved by NADPH diaphorase histochemical andimmunohistochemical staining.RESULTS: The level of serum ALT, activity of serumTNF-α and systemic levels of NO metabolite in groupsⅡand Ⅳ were higher than those of groups Ⅰ andy(serum ALT, 2416±475, 2540±82.5) nkat. L-1 vs(556.8±43.5, 677.30±38.2 ) nkat. L-1, P<0.01;(serum TNF-α, 353.5±16.1,444.6±28.1) ng.L-1 vs38.5±5.2, 52.0±5.7) ng.L-1, P<0.01; (serum NOx514.6 ± 18.1, 336.0 ± 43.0 )nmol.g-1, vs 26.1 ± 5.7, 27.7±6.0) nmol.g-1, P<0.01.Cyclosporine in group Ⅲcan repress the cellular immune response and thesynthesis of nitric oxide and the expression of NOsynthase,but not prolong the liver xenograftsurvival.The over-expression of NOS, iNOS and cNOSin liver xenograft rejection in groups Ⅱand Ⅳ weredetected by NADPH diaphorase histochemical andimmunohistochemical staining.CONCLUSION: The degrees of acute rejection can beeffectively repressed in golden hamster to rat liverxenografts with splenectomy and cyclosporine. Nitricoxide metabolites, and nitric oxide synthase and itsisoenzymes,above all inducible NOS (iNOS) can beused as potential diagnostic

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

    Science.gov (United States)

    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

  9. Power doppler sonography in early renal transplantation: Does it differentiate acute graft rejection from acute tubular necrosis?

    Directory of Open Access Journals (Sweden)

    Haytham M Shebel

    2014-01-01

    Full Text Available To evaluate the role of power Doppler in the identification and differentiation bet-ween acute renal transplant rejection and acute tubular necrosis (ATN, we studied 67 live donor renal transplant recipients. All patients were examined by spectral and power Doppler sono-graphy. Assessment of cortical perfusion (CP by power Doppler was subjective, using our grading score system: P0 (normal CP; homogenous cortical blush extending to the capsule, P1 (reduced CP; cortical vascular cut-off at interlobular level, P2 (markedly reduced CP; scattered cortical color flow at the interlobar level. Renal biopsies were performed during acute graft dysfunction. Pathological diagnoses were based on Banff classification 1997. The Mann- Whitney test was used to test the difference between CP grades with respect to serum creatinine (SCr, and resistive index (RI. For 38 episodes of acute graft rejection grade I, power Doppler showed that CP was P1 and RI ranging from 0.78 to 0.89. For 21 episodes of acute graft rejection grade II, power Doppler showed that CP was P1, with RI ranging from 0.88 to >1. Only one case of grade III rejection had a CP of P2. Twelve biopsies of ATN had CP of P0 and RI ranging from 0.80 to 0.89 There was a statistically significant correlation between CP grading and SCr (P <0.01 as well as between CP grading and RI (P <0.05. CP grading had a higher sensitivity in the detection of early acute rejection compared with RI and cross-sectional area measurements. We conclude that power Doppler is a non-invasive sensitive technique that may help in the detection and differentiation between acute renal transplant rejection and ATN, particularly in the early post-transplantation period.

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

    Directory of Open Access Journals (Sweden)

    Priscila Cilene León Bueno de Camargo

    2014-08-01

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

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

    Science.gov (United States)

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

    2014-01-01

    Our objective was to determine the levels of lactate dehydrogenase, IL-6, IL-8, and VEGF, as well as the total and differential cell counts, in the pleural fluid of lung transplant recipients, correlating those levels with the occurrence and severity of rejection. We analyzed pleural fluid samples collected from 18 patients at various time points (up to postoperative day 4). The levels of IL-6, IL-8, and VEGF tended to elevate in parallel with increases in the severity of rejection. Our results suggest that these levels are markers of acute graft rejection in lung transplant recipients. PMID:25210966

  12. OX40 mRNA in peripheral blood as a biomarker of acute renal allograft rejection

    Institute of Scientific and Technical Information of China (English)

    WANG Yu-liang; FU Ying-xin; ZHU Zhi-jun; WANG Hui; SHEN Zhong-yang

    2012-01-01

    Background Acute rejection remains an important cause of renal allograft dysfunction and the need for accurate diagnosis is essential to successfully treat transplant recipients.The purpose of this study was to determine the costimulatory molecules OX40 and OX40L messenger RNA (mRNA) levels in peripheral blood mononuclear cells (PBMCs) to predict acute renal transplant rejection.Methods The whole blood samples from 20 recipients with biopsy-confirmed acute rejection (rejection group),20 recipients with stable graft function and normal biopsy results (stable group) after kidney transplantation,and 20 healthy volunteers (control group) were collected.The mRNA levels of OX40 and OX40L were analyzed with TaqMan real-time reverse transcriptase polymerase chain reaction (RT-PCR).The association of OX40 and OX40L mRNA levels with disease severity was investigated.Results There was no significant difference of OX40,OX40L mRNA levels in PBMCs between the stable group and control group (P>0.05).The levels of OX40 and OX40L mRNA were significantly higher in the rejection group than in the control group (P<0.01 and P<0.05,respectively).Non-significantly higher OX40L mRNA and significantly higher OX40 mRNA in PBMCs were observed in subjects in the rejection group compared with the stable group (P >0.05 and P <0.01,respectively).Receiver operating characteristic (ROC) curve analysis demonstrated that OX40 mRNA levels could discriminate recipients who subsequently suffered acute allograft rejection (area under the curve,0.908).OX40 and OX40L mRNA levels did not significantly correlate with serum creatinine levels in the rejection group (P >0.05).Levels of OX40 mRNA after anti-rejection therapy were lower than those at the time of protocol biopsy in the rejection group (P<0.05).Conclusion Our data suggest that measurement of OX40 mRNA levels after transplant might offer a noninvasive means for recognizing recipients at risk of acute renal allograft rejection.

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

    Directory of Open Access Journals (Sweden)

    Li Li

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

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

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    Kim, Eun Kyung; Kim, Myeong Jin; Lee, Jong Tae; Yoo, Hyung Sik; Kim, Ki Whang; Park, Ki Ill; Chung, Hyun Joo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1995-12-15

    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

  15. Identification of the candidate genes associated with cellular rejection in pig-to-human xenotransplantation

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    To identify the genes associated with cellular rejection in pig-to-human xenotransplantation, the suppression subtractive hybridization (SSH) was used in screening the up-regulated genes from a co-culture of human peripheral blood mononuclear cells (PBMCs) and porcine vascular endothelial cell line PIEC. The up-regulated cDNAs were cloned into pGEM-T Easy vector and then sequenced. Nucleic acid homology searches were performed using the BLAST program. A subtracted cDNA library including about 300 clones with the expected up-regulated genes was obtained. Twenty-four of these clones were analyzed by sequencing and homology comparison was made. These clones represent the genes of human perforin (PRF1), proteasome, lymphocyte specific interferon regulatory factor/interferon regulatory factor 4 (LSIRF/IRF 4), muscleblind-like (MBNL) protein and a porcine expressed sequence tag (EST) which has 81% homology with human oxidative-stress responsive 1 (OSR 1). These genes might be the candidate genes which are associated with cellular rejection in pig-to-human xenotransplantation.

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

    Science.gov (United States)

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

    2014-01-01

    Acute skin rejection in vascularized composite allotransplantation (VCA) is the major obstacle for wider adoption in clinical practice. This study utilized computational modeling to identify biomarkers for diagnosis and targets for treatment of skin rejection. Protein levels of 14 inflammatory mediators in skin and muscle biopsies from syngeneic grafts [n = 10], allogeneic transplants without immunosuppression [n = 10] and allografts treated with tacrolimus [n = 10] were assessed by multiplexed analysis technology. Hierarchical Clustering Analysis, Principal Component Analysis, Random Forest Classification and Multinomial Logistic Regression models were used to segregate experimental groups. Based on Random Forest Classification, Multinomial Logistic Regression and Hierarchical Clustering Analysis models, IL-4, TNF-α and IL-12p70 were the best predictors of skin rejection and identified rejection well in advance of histopathological alterations. TNF-α and IL-12p70 were the best predictors of muscle rejection and also preceded histopathological alterations. Principal Component Analysis identified IL-1α, IL-18, IL-1β, and IL-4 as principal drivers of transplant rejection. Thus, inflammatory patterns associated with rejection are specific for the individual tissue and may be superior for early detection and targeted treatment of rejection. PMID:24926998

  17. VITAL COMPUTER MORPHOMETRY OF LIMPHOCYTES IN DIAGNOSIS OF ACUTE RENAL ALLOGRAFT REJECTION

    Directory of Open Access Journals (Sweden)

    A. V. Vatazin

    2009-01-01

    Full Text Available The article focuses on the results of the investigation of peripheral blood lymphocyte morphofunctional status in healthy volunteers and renal allograft recipients for early postoperative period. Working out noninvasive tests for diagnosis of acute renal allograft rejection based on the measuring of cell morphometric parameters by method of coherent phase microscopy (CPM. It was found out that the lymphocyte phase height was proportional cell image density and its geometrical thickness. Our results showed that the variations of immunocompetent cell morphometric indicants can be in advance the dynamics of blood creatine increasing and answer for early criteria of acute renal allograft rejection

  18. Differentiation between renal allograft rejection and acute tubular necrosis by renal scan

    Energy Technology Data Exchange (ETDEWEB)

    Delmonico, F.L.; McKusick, K.A.; Cosimi, A.B.; Russell, P.S.

    1977-04-01

    The usefulness of the renal scan in diagnosing technical complications in the transplant patient is well established. However, the ability of the renal scan to differentiate between acute rejection and acute tubular necrosis has remained uncertain. We have evaluated the effectiveness of the /sup 99m/Tc DTPA computer-derived time-activity curve of renal cortical perfusion, as well as data obtained from scintillation camera images, in making such diagnoses. Fifteen patients with a clinical diagnosis of either acute rejection or acute tubular necrosis, or both, were studied retrospectively. Technetium scan diagnoses did not agree with the clinical assessment in nine of the patients. Thus selection of a course of treatment should not be based on data obtained from the scan alone.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Science.gov (United States)

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

    2013-10-21

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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    NARCIS (Netherlands)

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

    1993-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    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

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2015-02-01

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

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

    Institute of Scientific and Technical Information of China (English)

    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

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

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

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

    1994-09-15

    During posttransplant acute renal failure (ARF), the diagnosis of allograft rejection constitutes a major problem. We evaluated the value of Doppler ultrasonography in identifying grafts at risk of rejection during ARF. In 184 recipients of a renal allograft, Doppler examinations were performed on the first and fifth postoperative day. Doppler spectra were quantitatively analyzed with a user-written computer program. Doppler findings were not used in clinical decision making. ARF was defined as a diuresis cadaveric grafts (n = 123), while living related donor grafts (n = 20) showed a lower RI (0.55 +/- 0.07; P 4 days (n = 24), RI was not significantly different (0.63 +/- 0.07 vs. 0.68 +/- 0.15; NS). However, the acceleration time of the systolic deflection of the spectrum waveform (Tmax) was shorter in grafts with ARF > 4 days (86 +/- 47 msec vs. 128 +/- 39 msec; P 4 days (n = 24) showed a Tmax or = 90 msec, only 2 rejections occurred (negative predictive value, 13/15 = 87%). For the RI (> 0.85), positive predictive value was 4/5 = 80% and negative predictive value (RI identification of patients at risk for rejection and in the timing of allograft biopsy during ARF. Persistently short Tmax values on the fifth day after transplantation perform better in identifying grafts at risk of rejection than high RI values.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    International Nuclear Information System (INIS)

    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)

  13. Distinct histologic patterns of acute, prolonged, and chronic rejection in vascularized rat pancreas allografts.

    OpenAIRE

    Steiniger, B; Klempnauer, J

    1986-01-01

    In a model of pancreas whole organ transplantation in streptozotocin diabetic rats distinct histologic patterns of acute, prolonged and chronic rejection were defined by light microscopy. Allotransplantation between major histocompatibility complex (MHC) congenic and recombinant rat strains allowed an immunogenetic analysis of the effect of defined histocompatibility antigens on graft morphology. The impact of surgical techniques with preserved and suppressed exocrine secretion on graft histo...

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

    Science.gov (United States)

    Gupta, Pallav; Sharma, Amit; Khullar, Dinesh

    2014-08-01

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

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

    International Nuclear Information System (INIS)

    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)

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

    NARCIS (Netherlands)

    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

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

    Directory of Open Access Journals (Sweden)

    Stefan Reuter

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

  18. CONVERSION TO TACROLIMUS IN PATIENTS WITH LATE ACUTE AND CHRONIC REJECTION OF TRANSPLANTED KIDNEY

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    E. S. Stolyarevich

    2011-01-01

    Full Text Available Tасrolimus (Tac has been used for rescuing of renal allografts from refractory rejection that occurred during treatment with conventional cyclosporine A (CsA mostly in the early posttransplant period. Less is known about effect of Tac in cases of late acute rejection. Aim of the study was to examine the long-term effects of switching from CyA-based therapy to Tac-based therapy versus continuation of CsA in renal transplant patients with acute rejection occurred 3 month after transplantation or later. In this comparative prospective clinical study 176 patients experiencing a late biopsy-proven acute or active chronic rejection were followed-up for up to 6 months. 61 pati- ents were converted from a CуA-based therapy to the Tac one; in 115 patients CsA-based therapy was continued. During the first month after the rejection episode the median serum creatinine concentration had decreased in both groups (from 0.27 (0.18; 0.4 to 0.25 (0.16; 0.41 mmol/l in the CsA group and from 0.25 (0.18; 0.3 to 0.18 (0.14; 0.25 mmol/l in the Tac group. During the follow-up graft function remained stable in the Tac group 0,17 (0,14; 0,3 mmol/l, while in the CsA group a trend to progression of graft failure was observed 0.33 (0.19; 0.8 mmol/l. The 3-year Kaplan-Meier estimates for graft loss were 57,1% (Tac and 40,9% (CsA, respectively (р < 0.01. Conclusion: early switch from the CsA- to the Tac-based therapy after a late biopsy-confirmed rejection resulted in a significant improvement in the clinical output in renal graft recipients compared to patients for whom the CyA therapy was continued. 

  19. New approaches to the management of acute and chronic cardiac allograft rejection

    Energy Technology Data Exchange (ETDEWEB)

    Isobe, Mitsuaki; Suzuki, Jun-ichi [Shinshu Univ., Matsumoto, Nagano (Japan). School of Medicine

    1998-05-01

    There are still many problems to be faced in the field of heart transplantation. Acute and chronic rejection are still the major medical obstacles. In this review, we describe recent research in this field undertaken in our laboratory. The induced intercellular adhesion molecule-1 (ICAM-1) and MHC class II antigen resulting from rejection can be visualized in vivo by radioimmunoscintigraphy. This non-invasive method is sensitive for detecting early rejection and allows quantitative assessment of rejection. Short-term administration of monoclonal antibodies to ICAM-1 and leukocyte function-associated antigen-1 (LFA-1) results in an indefinite acceptance of cardiac allografts by induction of antigen-specific tolerance, as evidenced by acceptance of the secondary skin allografts. The characteristics and possible mechanisms of this tolerance induction are discussed. Immunohistopathologic features of graft coronary arteriopathy are shown. Adhesion molecules, cytokines, and growth factors are associated with intimal hyperplasia and phenotypic transformation of smooth muscle cells in the allograft coronary arteries. Dramatic reduction in this intimal hyperplasia was demonstrated by antisense gene therapy targeting cyclin-dependent kinase 2 kinase. We hope that these investigations will contribute to the improvement of the management of patients who undergo heart transplantation. (author). 117 refs.

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

    Science.gov (United States)

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

    2012-02-01

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

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

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    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.

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

    Science.gov (United States)

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

    2014-07-01

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

  3. Using intramyocardial electrograms combined with other noninvasive methods for monitoring acute rejection following human heart transplantation

    Institute of Scientific and Technical Information of China (English)

    JIA Yi-xin; MENG Xu; SUN Ling-bo; HAN Jie; CHEN Yang-tian

    2009-01-01

    Background Acute allograft rejection in heart transplantation remains as one of the major complications. Obligatory graft surveillance is still achieved with the invasive and expensive endomyocardial biopsy (EMB). Our study aimed to study the use of intramyocardial electrograms combined with other noninvasive methods for the monitoring of acute rejection after human heart transplantation. Methods Permanent pacemakers were implanted in 58 patients undergoing heart transplantations. Intramyocardial electrograms (IMEG) were recorded periodically and the results were compared with those from EMBs. The R wave amplitude of the IMEG was used as the index value, the average R wave amplitude at the third week following transplantation was considered as the baseline, and a reduction of >20% compared with the baseline was regarded as a positive result. EMB was performed in cases of positive IMEG results and also at other times. Other noninvasive methods were used to help the diagnosis. Acute rejection (AR) was defined as international Society of Heart-Lung Transplantation grade Ilia or higher.Results We obtained 1231 IMEG records and 127 EMBs. Of the total 127 EMBs, 53 were positive, in which there were 42 IMEG positive results and 11 negative, while in the rest 74 negative EMBs, there were 9 IMEG positive results and 65 negative. The sensitivity of IMEG for the diagnosis of AR was 79.2%, and the specificity was 87.8%. The positive predictive value was 82.4% and the negative predictive value was 85.5%. Of the total of 1231 IMEG records, 51 were positive and 1180 were negative. Excluding 11 proved by EMB to be false negative, if the other 1169 were considered as no evidence of rejection, through the other noninvasive methods, AR diagnosed by this noninvasive monitoring strategy, the sensitivity was 79.2%, and the specificity was 99.2%. The positive predictive value was 82.4% and the negative predictive value was 99.1%. Conclusions IMEG can be used as a noninvasive method for

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

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    Atkins, H.L.; Oster, Z.H.; Anaise, D.; Wein, S.; Waltzer, W.; Gonder, A.; Cooch, E.; Rapaport, F.T.

    1985-05-01

    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.

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

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    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

    International Nuclear Information System (INIS)

    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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-04-10

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

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

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    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.

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

    Science.gov (United States)

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

    2005-03-01

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

  11. The imbalance of helper T lymphocytes and cytotoxic T lymphocytes in acute renal transplantation rejection

    Institute of Scientific and Technical Information of China (English)

    YAN JIANG; ZHI QIN TANG; LIN PENG; YU LIANG WANG; ZHI PING WANG

    2007-01-01

    To investigate the imbalance state of helper T lymphocytes (Th) and cytotoxic T lymphocytes (Tc) and the roles of Th1/Th2/Th3 and Tc1/Tc2 cells in renal transplantation rejection, the percentages of these cells in peripheral blood of 24 cases of renal transplantation recipients with acute rejection and the dynamic changes of the CD4/CD8 ratio were determined by flow cytometry analysis,while 30 cases of healthy individuals were set up as controls. In these healthy controls, the percentages of the Th1, Th2 and Th3 cells were (10.45±8.15)%, (5.05±4.15)% and (3.90±3.21)%,and those of Tc1 and Tc2 cells were (9.83±7.03)% and (4.51±2.17)%, respectively. However,the percentages of Th1 and Tc1 cells in peripheral blood of the stable recipients after transplantation were (7.29±5.62)% and (7.04±5.15)%, showing definite reduction, while those of Th2, Th3and Tc2 cells showed significant increase, (6.34±5.67)%, (4.94±4.14) % and ( 6.86 ±4.42) %, respectively. In case of recipients with acute rejection, the percentages of Th1 and Tc1 cells appeared to be (18.55±13.21)% and (15.84±11.72)%, also showing significant increase, but those of Th2,Th3 and Tc2 cells appeared to be reduced, (4.19±3.62)%, (3.02±2.83)% and (3.88±1.63) %, respectively. Significant differences could be detected among these three groups (P <0.05). The CD4/CD8 ratio in cases with acute rejection was higher than those of stable recipients (2.24±0.59 vs 1.95±0.45), but that of the stable recipients and healthy controls (1.98±0.31 )showed no any significant difference. From the above observation, it is evident that imbalance between Th1, Th2 and Th3 with Te1 and Tc2 cells may exist after renal transplantation and probably, the immune imbalance may be induced through the secretion of cytokines INF-γ by Th1 or Te1 cells , I1-4 by Th2 and Tc2 cells and TGF-β by Th3.

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

    OpenAIRE

    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) ...

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

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    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

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

    Science.gov (United States)

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

    2015-09-01

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

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

    Science.gov (United States)

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

    2012-10-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    BACKGROUND: Regardless of the extensive worldwide use of calcineurin inhibitors, little is known about the behavior of calcineurin phosphatase (CaN) during acute allograft rejection. The aim of this study was to investigate the temporal profile of CaN during acute allograft rejection and reveal...... 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...

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

    Directory of Open Access Journals (Sweden)

    A.V Trailin

    2009-01-01

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

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

    KAUST Repository

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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. High or low dose steroid therapy for acute renal transplant rejection after prophylactic OKT3 treatment: a prospective randomized study.

    Science.gov (United States)

    De Backer, D; Abramowicz, D; Goldman, M; De Pauw, L; Viseur, P; Vanherweghem, J L; Kinnaert, P; Vereerstraeten, P

    1992-01-01

    In this prospective randomized study, acute renal transplant rejections occurring in patients who received prophylactic OKT3 therapy were treated with either 3 pulses of 8 mg/kg methylprednisolone (MPS) in an alternate-day regimen (total dose 25 mg/kg in 1 week, H group, n = 24) or 5 daily pulses of 3 mg/kg MPS (total dose 17 mg/kg, L group, n = 22). Acute rejection was proven by biopsy in more than 85% of cases in both groups. No difference was observed in rejection reversal (H 88%, L 91%), graft losses in the following 3 months (H 11%, L 4%) or the time evolution of the serum creatinine levels. The number (H 14, L 21) as well as the nature and severity of infections were similar in both groups. Only one death occurred in a patient who received OKT3 rescue therapy for corticoresistant rejections and developed Epstein-Barr virus (EBV)-related lymphoma. In conclusion, low dose MPS pulses appear as effective and safe as a higher dose to reverse acute rejection occurring after OKT3 prophylaxis. Thus, we favour the use of the low dose regimen in these patients. PMID:14621839

  4. Effect of 1,25-dihydroxyvitamin D3 on preventing allograft from acute rejection following rat orthotoic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Ai-Bin Zhang; Shu-Sen Zheng; Chang-Ku Jia; Yan Wang

    2003-01-01

    AIM: To study the mechanism and the preventive role of 1,25-dihydroxyvitamin D3 in acute rejection following orthotopic liver transplantation.METHODS: Rats were randomly divided as donors or recipients for orthotopic liver allotransplantation model. Four groups were designed in the study, Group Ⅰ: syngenic control (Wistar to Wistar); Group Ⅱ: acute rejection (SD to Wistar);Group Ⅲ: acute rejection treated with cyclosporine A, and Group Ⅳ: acute rejection treated with 1,25-(OH)2D3. Liver function, rejection activity index and mRNA of IFN-γ, IL-10intragraft in recipients were measured on day t, 5, 7, 15,30 posttransplant for assessing graft function, severity of acute rejection and immune state of recipients.RESULTS: Survival time of recipients in Group Ⅳ was significantly prolonged (4/6 recipients survived for over 100days. vs Group Ⅱ, P<0.001; vs Group Ⅲ, P>0.05). After treatment with 1,25-(OH)2 D3, mean value of all the assay tested on each experimental time was compared, liver function in group Ⅳ was significantly improved (AST 127±41U/L-360±104 U/L, BIL 13±5 mmol/1-38±11 mmol/l; vs Group Ⅱ, P<0.05; vs Group Ⅲ, P>0.05. Rejection activity index was significantly decreased (0-3.3±1.6; vsGroup Ⅱ, P<0.05;vsGroup Ⅲ, P>0.05). Level of hepatic IFN-γ, mRNA in group Ⅳ was decreased, while level of hepatic IL-10 mRNA was increased (vs Group Ⅱ, P<0.05; vs Group Ⅲ, P>0.05).CONCLUSION: Our results indicated that 1,25-(OH)2D3induced the secretion of cytokine toward to Th2 type, which would alleviate acute rejection, protect liver function and prolong survival of recipient after orthotopic liver transplantation.

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

    Science.gov (United States)

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

    2015-01-01

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

  6. Correlation of CD95 and soluble CD95 expression with acute rejection status of liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Yu-Liang Wang; Yan-Yan Zhang; Guang Li; Zhi-Qin Tang; Yan-Li Zhou; Zhi-Jun Zhu; Zhi Yao

    2005-01-01

    AIM: To analyze the expression levels of soluble form of CD95, CD95 ligand (sCD95 and sCD95L, respectively) in plasma and CD95 expression on CD3+ cells in livertransplanted recipients with acute rejection (AR).METHODS: Peripheral blood mononuclear cells (PBMCs)were isolated from 30 clinically liver transplanted recipients.CD95 expression on CD3+ cells was quantitatively measured by two-color fluorescence activated cell sorter (FACS)analysis. Lymphocyte surface phenotypes of CD4, CD8,CD16 and CD55 were determined by flow cytometry.Plasma levels of sCD95 and sCD95L were detected byEnzyme Linked-Immuno-Sorbent Assay (ELISA). The results were compared with that from normal healthy volunteers (n = 15 individuals).RESULTS: FACS analysis showed that CD95 expression on CD3+ T cells was significantly increased in liver transplanted recipients with AR compared to that in stable recipients without rejection and infection or healthy individuals who did not undergo transplantation (18 676.93±11 588.34/molecule,6 848.20±1712.96/molecule, 6 418.01±2 001.95/molecule,respectively, P<0.01). Whereas no significant difference was seen between liver-transplanted stable recipients and healthy individuals. Furthermore, no significant differences were detected between each group with CD4/CD8 ratio or the percentage of CD16+56+ cells. Plasma levels of sCD95were significantly higher in transplanted recipients with AR compered to that in stable recipients or healthy individuals (391.88±196.00, 201.37±30.30, 148.83±58.25 pg/mL,respectively, P<0.01). In contrast, the plasma levels ofsCD95L in liver- transplanted recipients were not significantlydifferent from that in healthy individuals.CONCLUSION: The present results indicate that the increased CD95 expression on CD3+ cells and the increased levels of sCD95 in plasma may modify the immunological situation of the recipients after transplantation or represent the ongoing graft rejection.

  7. Suppression of acute rejective response following orthotopic liver transplantation in experimental rats infected with Echinococcus multilocularis

    Institute of Scientific and Technical Information of China (English)

    LI Tao; ZHAO Jin-ming; ZHANG Yan; PAI Zu-la; ZHANG Wei; Tuxun Tuer-hongjiang; BAI Lei; WU Jiang; WEN Hao

    2011-01-01

    Background Hepatic alveolar echinococcosis (AE) is a parasitic disease in humans and caused by the Echinococcus multilocularis (Em). Orthotopic liver transplantation (OLT) may be the only effective treatment for end-stage hepatic AE. However, in some AE patients, extrahepatic Em can not be completely eliminated after OLT. We aimed to study whether the immunological changes caused by Em evasion may influence the rejective response.Methods Rat modles of AE were established by injecting the Em suspension into abdomen of Brown Norway (BN) rats.Three months later, in the experimental group, the liver was transplanted from Lewis (LEW) rats to Em-infected BN rats.In the control group, transplantation was from LEW rats to healthy BN rats. Liver tissue and peripheral blood (PB)samples were collected on days 1, 3, 5, and 7 after OLT. Liver tissue was analyzed after hematoxylin and eosin (H&E)staining; numbers of CD4, CD8, and CD28 on peripheral blood cells were detected by flow cytometry; and expression of the chemokine fractalkine (Fkn) was detected by reverse transcription PCR (RT-PCR). Interleukin-10 (IL-10) was measured in the serum by enzyme-linked immunosorbent assay (ELISA). In every group, eight BN rats were retained for observing survival time.Results The survival times of recipients in the experimental group were prolonged compared with those in the control group. The rejective response occurred later and was milder in the experimental group, percentage of CD4, CD8, CD28 T-cells and Fkn mRNA expression were lower in the experimental group. While the serum IL-10 levels were higher in the experimental group than those in the control group.Conclusions Acute rejective response after OLT was attenuated in the rats with Em infection, and the recipients survival time was prolonged. Em may play a role in this process by elevating IL-10 secretion, decreasing the effector T cells, inhibiting the expression of Fkn, which lead to reduce the inflammatory cells infiltration into

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  9. Cellular basis of allograft rejection in vivo. III. Restoration of first-set rejection of heart grafts by T helper cells in irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Hall, B.M.; de Saxe, I.; Dorsch, S.E.

    1983-12-01

    An adoptive transfer model was used to examine the subpopulations of lymphocytes required to effect first-set rejection of directly vascularized heart allografts. PVG heart grafts are not rejected in irradiated DA hosts for at least 50 days. The adoptive transfer of 5 X 10(7) syngeneic lymph node cells (LNC) restores rejection to 14.4 +/- 2.4 days (mean +/- SD). Subpopulations of LNC, were separated by an indirect ''panning'' technique using the mouse antirat monoclonal antibodies W3/13, MRC OX8, or W3/25 to deplete the unwanted subsets of cells. Each subpopulation was tested, in a number equivalent to the number present in 5 X 10(7) normal LNC, for its ability to cause the rejection of heart grafts. Whole T cells (W3/13+) or helper/inducer T cells (W3/25+) restored graft rejection to 16.4 +/- 3.8 d and 16.0 +/- 2.4 days, respectively. Neither cytotoxic/suppressor T cells (MRC OX8+) nor B cells (Ig+) restored rejection. Indirect immunoperoxidase stains of the grafts showed that although W3/25+ cells predominated in the rejected tissue, MRC OX8+ cells were also present even in grafts from rats restored with inocula that contained less than 1% MRC OX8+ cells. Examination of lymphoid tissues suggested that the MRC OX8+ cells might be of host origin. By the time the grafts were rejected in irradiated hosts, significant thymic regeneration had occurred and there were large numbers of MRC OX8+ cells present in the thymus, as well as some in lymph nodes and spleen.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Anaise, D.; Oster, Z.H.; Atkins, H.L.; Arnold, A.N.; Weis, S.; Waltzer, W.C.; Rapaport, F.T.

    1986-11-01

    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.

  13. Celecoxib plays a multiple role to peripheral blood lymphocytes and allografts in acute rejection in rats after cardiac transplantation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xue-feng; ZHANG Fan; LIU Hong-yu; SUN Guo-dong; LIU Zong-hong; L(U) Hang; CHI Chao; LI Chun-yu

    2009-01-01

    Background Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is a non-steroidal anti-inflammatory drug used as an adjuvant to sensitize cancer cells to apoptosis. However, in rats suffering from acute rejection, celecoxib reduced apoptosis of myocardial cells. We hypothesize that celecoxib reduces myocardial apoptosis either by inducing apoptosis in peripheral blood lymphocytes (PBLs) or by altering the percentage of CD4+ and CD8+ lymphocytes. Methods After cardiac transplantation, rats were administered intragastrically with celecoxib (50 mg/kg per day) for 3, 5 or 7 days, at which time the graft was excised and evaluated for organ rejection. In addition, PBLs were isolated from the blood to determine PBLs apoptosis, and the percentage of CD4+ and CD8+ lymphocytes. Results Celecoxib induced PBLs apoptosis in 3 days, but protected the cells from apoptosis at 5 and 7 days. Also, the percentage of CD4+ lymphocytes decreased only at 3 days, but a reduction in the percentage of CD8+ lymphocytes was not seen until 7 days after the transplant surgery. Celecoxib only decreased acute rejection at 5 days, with no discernible difference in rejection after 3 and 7 days. Conclusions The results suggested that celecoxib displayed a multiple physiological function in a time-dependent manner.

  14. Forkhead box protein 3 mRNA expression in the peripheral blood of kidney-transplant recipients with acute rejection

    Institute of Scientific and Technical Information of China (English)

    WANG Wei; LI Xiao-bei; YANG Xiao-yong; ZHANG Xiao-dong

    2011-01-01

    Background Regulatory T cells (Tregs) are immunologically and clinically interesting not least because of the important role they play in allograft rejection. Likewise, expression of the transcription factor forkhead box protein 3 (FOXP3), detected in transplant biopsies, is also of interest because of its role in the development of regulatory T cells. In this study, we Investigated the relationship between FoxP3 mRNA expression and acute organ rejection in kidney-transplant recipients.Methods In this prospective study, FoxP3 mRNA expression levels in peripheral blood samples from 10 recipients of living relative-donor kidney transplants were measured before transplantation as well as at the 14th and 90th days post-transplantation. In addition, 46 first-time kidney-transplant recipients participated in a cross-sectional study, with 28 patients classified as having acute organ rejection; whilst the remaining 18 patients had functionally stable allografts. FoxP3 mRNA expression levels in peripheral blood samples were compared between these two different groups.Results Before transplantation mean FoxP3 mRNA levels vs. GADPH mRNA levels (lg(FoxP3 mRNA/GADPH mRNA)) in the 10 recipients were 1.11±0.67. The mean FoxP3 mRNA expression levels measured at 14th and 90th days post-transplantation were significantly higher than before transplantation (1.69±0.38, P=0.03; 1.44±0.21, P=0.04, respectively). Additionally, the mean FoxP3 mRNA levels vs. GADPH mRNA expression levels (lg(FoxP3 mRNA/GADPH mRNA)) were significantly higher in recipients suffering acute rejection compared with those with stable allografts (1.77±0.61 and 1.43±0.27, respectively, P=0.03).Conclusions After kidney transplantation, FoxP3 mRNA levels were found to increase in the peripheral blood of all recipients. Considerably higher FoxP3 mRNA levels were observed in recipients suffering acute rejection. These results suggest that FoxP3 mRNA levels in peripheral blood samples can be used as a diagnostic

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

    Directory of Open Access Journals (Sweden)

    Dai Yong

    2008-01-01

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

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

    International Nuclear Information System (INIS)

    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)

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

    OpenAIRE

    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...

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

    Institute of Scientific and Technical Information of China (English)

    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.

  19. Spontaneous resolution of acute rejection and tolerance induction with IL-2 fusion protein in vascularized composite allotransplantation.

    Science.gov (United States)

    Jindal, R; Unadkat, J; Zhang, W; Zhang, D; Ng, T W; Wang, Y; Jiang, J; Lakkis, F; Rubin, P; Lee, W P A; Gorantla, V S; Zheng, X X

    2015-05-01

    Vascularized composite allotransplantation (VCA) has emerged as a treatment option for treating nonlife-threatening conditions. Therefore, in order to make VCA a safe reconstruction option, there is a need to minimize immunosuppression, develop tolerance-inducing strategies and elucidate the mechanisms of VCA rejection and tolerance. In this study we explored the effects of hIL-2/Fc (a long-lasting human IL-2 fusion protein), in combination with antilymphocyte serum (ALS) and short-term cyclosporine A (CsA), on graft survival, regulatory T cell (Treg) proliferation and tolerance induction in a rat hind-limb transplant model. We demonstrate that hIL-2/Fc therapy tips the immune balance, increasing Treg proliferation and suppressing effector T cells, and permits VCA tolerance as demonstrated by long-term allograft survival and donor-antigen acceptance. Moreover, we observe two distinct types of acute rejection (AR), progressive and reversible, within hIL-2/Fc plus ALS and CsA treated recipients. Our study shows differential gene expression profiles of FoxP3 versus GzmB, Prf1 or interferon-γ in these two types of AR, with reversible rejection demonstrating higher Treg to Teff gene expression. This correlation of gene expression profile at the first clinical sign of AR with VCA outcomes can provide the basis for further inquiry into the mechanistic aspects of VCA rejection and future drug targets. PMID:25676865

  20. Cutting Edge: Acute Lung Allograft Rejection Is Independent of Secondary Lymphoid Organs1

    OpenAIRE

    Gelman, Andrew E.; Li, Wenjun; Richardson, Steven B.; Zinselmeyer, Bernd H.; Lai, Jiaming; Okazaki, Mikio; Kornfeld, Christopher G.; Kreisel, Friederike H.; Sugimoto, Seiichiro; Tietjens, Jeremy R.; Dempster, John; Patterson, G. Alexander; Krupnick, Alexander S.; Miller, Mark J.; Kreisel, Daniel

    2009-01-01

    It is the prevailing view that adaptive immune responses are initiated in secondary lymphoid organs. Studies using alymphoplastic mice have shown that secondary lymphoid organs are essential to initiate allograft rejection of skin, heart, and small bowel. The high immunogenicity of lungs is well recognized and allograft rejection remains a major contributing factor to poor outcomes after lung transplantation. We show in this study that alloreactive T cells are initially primed within lung all...

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Thomas H Waid

    2009-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Junichiro Sageshima

    2009-06-01

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

  4. Use of PCR and PCR-SSP for detection of urinary donor-origin DNA in renal tran splant recipients with acute rejection

    Institute of Scientific and Technical Information of China (English)

    张志宏; 大河内信弘; 岗崎肇; 郭应禄

    2003-01-01

    Objective To analyze the urine of renal recipients for the presence of donor DNA in an attempt to establish an alternative diagnostic means of acute rejection.Methods Sixty-four renal transplant recipients were examined. Thirty-seven were norma lafter transplantation, while 22 others developed acute rejection, based on ser um creatinine levels and/or needle biopsy findings of the graft. Five developed drug-induced renal dysfunction. In female recipients with a male graft, we ex amined urine for the presence of Y chromosome (SRY and DYZ-1) and in recipients receiving an HLA mismatched graft, we looked for HLA-DR gene (DRB1) using PCR .Results Among the 14 female recipients with male grafts demonstrating stable renal function, only one was positive for SRY and DYZ-1 on the Y chromosome. However, SRY and DYZ-1 were found in the urine of four female patients with acute rejection , but these DNA fragments were not detected in 3 of the 4 after anti-rejection therap y. The last patient was referred to hemodialysis. Of 23 recipients of a graft from HLA mismatch donors with stable renal function, DRB1 was negative in 21 (91 %). Of 18 patients with acute rejection, DRB1 was positive in 16 (89%) and nega tive in 2. These DNA fragments were no longer found in 13 patients after anti -rejection therapy. In all patients with drug induced renal dysfunction, donor -derived DNA was negative.Conclusions Presence of door specific DNA in the urine of the recipient is strongly associat ed with acute rejection. Analysis of DNA derived from donor cells in urine was an effective and accurate method for the diagnosis of acute rejection of a renal transplant.

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

    NARCIS (Netherlands)

    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

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

    NARCIS (Netherlands)

    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

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

    Science.gov (United States)

    Sticová, Eva; Honsová, Eva

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Fabricio Ferreira Coelho

    2003-01-01

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

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

    Science.gov (United States)

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

    2014-11-01

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

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

    Science.gov (United States)

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

    2012-09-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Burç Dedeoglu

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

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

    Institute of Scientific and Technical Information of China (English)

    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

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

    LENUS (Irish Health Repository)

    O'Seaghdha, C M

    2011-04-06

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

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    DEFF Research Database (Denmark)

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

    1999-01-01

    Background: A widely held view is that any increase in the potency of an immunosuppressive agent will lead to an increase in infection and malignancy, such as life-threatening Epstein-Barr virus (EBV) induced posttransplant lymphoproliferative disorders (PTLD), We tested this paradigm by studying......: (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...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

    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...

  1. Antibodies: Immunoconjugates and autologous cellular therapy in acute lymphoblastic leukemia.

    Science.gov (United States)

    Advani, Anjali

    2015-01-01

    Using a case study of a 57-year-old man with relapsed/refractory precursor-B (pre-B) acute lymphoblastic leukemia (ALL), this review discusses treatment with immunoconjugates and autologous therapy in acute ALL. Three therapies--blinatumomab, inotuzumab, and CAR T cells--are considered here, each with advantages in specific clinical situations. These therapies represent some of the exciting advances that have been made in the treatment of ALL over the last several years.

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

    Directory of Open Access Journals (Sweden)

    Silke Roedder

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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Tor Skibsted Clemmensen

    2014-01-01

    Full Text Available This case displays limited utility of left ventricular ejection fraction to detect acute graft failure due to microvascular vasculopathy and suspected humoral rejection. Despite severe and progressive graft failure, clinically and by right heart catheterizations, left ventricular ejection fraction 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 routine monitoring of graft function by global longitudinal strain as supplement to routine left ventricular ejection fraction and diastolic Doppler measurements.

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

    Science.gov (United States)

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

    2014-08-01

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

  6. 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

    OpenAIRE

    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...

  7. Diagnosis and treatment of acute rejection in the first case of human living-related small bowel transplantation with a long-term survival in China

    Institute of Scientific and Technical Information of China (English)

    Wei-Liang Song; Wei-Zhong Wang; Guo-Sheng Wu; Meng-Bin Li; Ji-Peng Li; Gang Ji; Guang-Long Dond; Hong-Wei Zhang

    2005-01-01

    AIM: To report the comprehensive diagnosis and treatment of acute rejection in the first case of living-related small bowel transplantation with a long-term survival in China.METHODS: A 18-year-old boy with short gut syndrome underwent living-related small bowel transplantation, with the graft taken from his father (44-year old). A segment of 150-cm distal small bowel was resected from the donor. The ilea-colic artery and vein from the donor were anastomosed to the infrarenal aorta and vena cava of the recipient respectively. The intestinal continuity was restored with an end-to-end anastomosis between the recipient jejunum and donor ileum, and the distal end was fistulized. FK506, MMF and prednisone were initially used for post-transplant immunosuppression. Endoscopic observation and mucosal biopsies of the graft were carried out through the terminal ileum enterostomy; serum was collected to detect the levels of IL-2R, IL-4, IL-6 and IL-8.The change of the graft secretion and absorption was observed.RESULTS: Acute rejection was diagnosed promptly and cured. The patient was in good health, 5 years after livingrelated small bowel transplantation.CONCLUSION: The correct diagnosis and treatment of acute rejection are the key to the long-term survival after living-related small bowel transplantation.

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

    Directory of Open Access Journals (Sweden)

    Zhou J

    2014-12-01

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

  9. Cytokine production during the inhibition of acute vascular rejection in a concordant hamster-to-rat cardiac xenotransplantation model

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiao-gang; L(U) Yi; WANG Bo; LI Hui; YU Liang; LIU Chang; WU Zheng; LIU Xue-min

    2007-01-01

    Background The aim of the current study was to investigate the role of interleukin (IL)-2, interferon (IFN)-γ, IL-4 and IL-10 in a concordant hamster-to-rat cardiac xenotransplantation model. Methods A hamster-to-rat cardiac transplantation was performed using SD rats as recipients of Golden Syrian hamster hearts. A total of 60 SD rats were divided into four groups and treated as follows: control group (n=15); splenectomy group (n=15); CsA group (n=15); CsA + splenectomy group (n=15). Levels of IL-2, IFN-γ, IL-4 and IL-10 were measured by enzyme linked immunosorbent assay (ELISA). Sera were harvested at different time points in each group: day 1, and 3 as well as the day the xenograft stopped beating in the control group and CsA group; day 1, 3, 7, 14 and 30 in the splenectomy group and CsA+splenectomy group. The expression of P-selectin and intercellular adhesion molecule-1 (ICAM-1) was examined by immunohistochemical analysis of the xenograft after cardiac xenotransplantation. Results Serum levels of IL-2 and IFN-γ were upregulated in untreated (day 3) and splenectomy-treated animals (day 7) compared to CsA + splenectomy treated animals (day 7). IL-10 was upregulated in long-term survival recipients following splenectomy + CsA. Neither P-selectin nor ICAM-1 expression was detected in long-term survival xenografts. Conclusions Serum IL-2 and IFN-γ were elevated following acute vascular rejection. Serum IL-10 was correlated to immunosuppression and protective effects in long-term survival rats following concordant cardiac xenotransplantation.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2009-09-01

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

  12. Disturbance Rejection

    OpenAIRE

    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

  13. Chronic alloantibody mediated rejection

    OpenAIRE

    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...

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

    Institute of Scientific and Technical Information of China (English)

    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

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

    OpenAIRE

    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 ...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    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 future...... indicating a narrow therapeutic window for induction of tolerance by specifically targeting T-cells. The results also indirectly indicate that Tregs early after transplantation could have an impact on the long-term outcome. © 2014 Elsevier B.V....

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

    Directory of Open Access Journals (Sweden)

    Christopher Vollmers

    2015-10-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  20. Rejecting Change

    Institute of Scientific and Technical Information of China (English)

    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

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

    Science.gov (United States)

    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

  2. Intravenous immunoglobulin therapy for acute humoral rejection of kidney transplants%静脉注射人免疫球蛋白治疗肾移植后急性体液性排斥反应

    Institute of Scientific and Technical Information of China (English)

    翁国斌; 祁洪刚; 唐莉; 翁锡君; 姜继光; 姚许平

    2009-01-01

    Objective To explore the clinical effectiveness intravenous immunoglobulin therapy for kidney transplant recipients with acute humoral rejection of the clinical effects.Methods From January 2005 to December 2007,252 cases received kidney transplantation,and according to the standard of Banff,there were 16 cases of acute humoral rejection(3 cases of grade I,9 cases of grade Ⅱ,and 4 cases of grade Ⅲ).Tacrolimus,mycophenolate mofetil and corticosteroids were used to prevent rejection,16 AHR patients were treated with intravenous immunoglobulin(IVIG)treatment,20 g/d for 3 d.12 patients whose AHR occurred withing 1 month delayed graft function,so they had hemodialysis transition,amd 1 case of them had plasma exchange treatment.The reversal of AHR and the changes in humoral and cellular immunity of recipients were observed.Results 13 cases was reversed and 3 cases had nephrectomy.After treatment,the differents of reduction level in HLA-I and HLA-Ⅱantibody was not obvious(P>0.05).The IgG level was increased from(7.3±1.5)g/L to (18.3±3.6)g/L,significantly(P0.05);IgG水平明显上升,由(7.3±1.5)g/L升至(18.3±3.6)g/L(P<0.01);补体C3和C4水平分别为0.3±0.2)g/L和(0.1±0.1)g/L,较治疗前显著降低(P<0.01).IVIG治疗过程中,2例患者出现胸闷及体温升高,对症治疗后好转,患者治疗前后的肝功能均无显著变化.结论 IVIG对肾移植术后AHR的早期治疗有一定的效果,其机制可能与抗体封闭及对患者的体液免疫和细胞免疫的调节有关.

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

    Science.gov (United States)

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

    2000-11-01

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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    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...

  5. Autophagy in allografts rejection: A new direction?

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    Silke Roedder

    2014-11-01

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

  9. Effect of nifedipine on renal transplant rejection.

    Science.gov (United States)

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

    1993-10-01

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

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

    OpenAIRE

    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...

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Yingzi Ming

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

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

    Science.gov (United States)

    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

  14. LATE RENAL GRAFT REJECTION: PATHOLOGY AND PROGNOSIS

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    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

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

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    Witt CA

    2014-10-01

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

  16. Renal allograft rejection: sonography and scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Singh, A.; Cohen, W.N.

    1980-07-01

    A total of 30 renal allograft patients who had sonographic B scanning and radionuclide studies of the transplant was studied as to whether: (1) the allograft rejection was associated with any consistent and reliable sonographic features and (2) the sonograms complemented the radionuclide studies. Focal areas of decreased parenchymal echogenicity were the most striking and consistent sonographic finding in chymal echogenicity were the most striking and consistens sonographic finding in allograft rejection. This was observed in most of the patients exhibiting moderate or severe rejection, but was frequently absent with mild rejection. Areas of decreased parenchymal echogenicity were not seen during episodes of acute tubular necrosis. Therefore, sonography showing zones of decreased parenchymal echogenicity was complementary to radionuclide studies in the diagnosis of allograft rejection versus acute tubular necrosis. Corticomedullary demarcation was difficult to interpret because of technical variables, and was inconsistently related to rejection in this series.

  17. Cellular localization of uranium in the renal proximal tubules during acute renal uranium toxicity.

    Science.gov (United States)

    Homma-Takeda, Shino; Kitahara, Keisuke; Suzuki, Kyoko; Blyth, Benjamin J; Suya, Noriyoshi; Konishi, Teruaki; Terada, Yasuko; Shimada, Yoshiya

    2015-12-01

    Renal toxicity is a hallmark of uranium exposure, with uranium accumulating specifically in the S3 segment of the proximal tubules causing tubular damage. As the distribution, concentration and dynamics of accumulated uranium at the cellular level is not well understood, here, we report on high-resolution quantitative in situ measurements by high-energy synchrotron radiation X-ray fluorescence analysis in renal sections from a rat model of uranium-induced acute renal toxicity. One day after subcutaneous administration of uranium acetate to male Wistar rats at a dose of 0.5 mg uranium kg(-1) body weight, uranium concentration in the S3 segment of the proximal tubules was 64.9 ± 18.2 µg g(-1) , sevenfold higher than the mean renal uranium concentration (9.7 ± 2.4 µg g(-1) ). Uranium distributed into the epithelium of the S3 segment of the proximal tubules and highly concentrated uranium (50-fold above mean renal concentration) in micro-regions was found near the nuclei. These uranium levels were maintained up to 8 days post-administration, despite more rapid reductions in mean renal concentration. Two weeks after uranium administration, damaged areas were filled with regenerating tubules and morphological signs of tissue recovery, but areas of high uranium concentration (100-fold above mean renal concentration) were still found in the epithelium of regenerating tubules. These data indicate that site-specific accumulation of uranium in micro-regions of the S3 segment of the proximal tubules and retention of uranium in concentrated areas during recovery are characteristics of uranium behavior in the kidney.

  18. Split Rejection in Vascularized Composite Allotransplantation

    OpenAIRE

    Sinha, Indranil; Pomahac, Bohdan

    2013-01-01

    Introduction: Graft monitoring following vascularized composite allotransplantation (VCA) relies primarily on serial skin biopsy. However, given that VCA comprised multiple tissue types, skin biopsy may not accurately reflect rejection in other transplanted tissue. Methods: A review of the literature on episodes of both acute and chronic rejection following VCA was completed. Special attention was given to how these patients were monitored for rejection and whether skin biopsy accurately refl...

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

    Science.gov (United States)

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

    2013-11-01

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

  20. The diagnostic significance of urine chemokines in acute renal allograft rejection%尿液趋化因子检测在移植肾急性排斥反应中的诊断意义

    Institute of Scientific and Technical Information of China (English)

    陈瑜; 王立明

    2013-01-01

    急性排斥反应是肾移植术后的最主要的并发症,也是导致移植肾失功最重要的危险因素之一.早期、无创预测急性排斥反应的发生是目前移植领域研究的趋势.尿液作为移植肾的直接产物,其中的成分有效反映了移植肾的情况.趋化因子作为细胞因子的一种,其与受体的相互作用是淋巴细胞发生定向迁徙和募集的重要条件,在炎症浸润、细胞迁移、移植排斥反应中起重要的作用.因此,检测尿液中趋化因子水平对移植肾急性排斥反应的早期诊断和监测疗效有十分重要的意义.%Acute rejection is not only the most common complication after renal transplantation,but also one of the most important risk factors for renal allograft dysfunction.The early,non-invasive prediction of acute rejection is the trend of transplant clinical research.Urine is the direct product of the transplanted kidney,in which the ingredients reflect the graft function.As a kind of cytokines,chemokines interactions with the receptors are important condition for directional migration and recruitment of lymphocytes and play an important role in the inflammatory infiltration,cell migration and transplant rejection reactions.Therefore,the detection of urine chemokine level has great significance for early diagnosis of acute renal allograft rejection and monitoring the efficacy of treatment.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    International Nuclear Information System (INIS)

    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. Significance of MICA antibody monitoring in management of acute and chronic rejection af-ter renal transplantation%MICA抗体监测在肾移植术后急、慢性排斥反应中的意义

    Institute of Scientific and Technical Information of China (English)

    丁小明; 焦凤梅; 王晓红; 薛武军; 田普训; 李杨; 田晓辉

    2013-01-01

    Objective To evaluate the association of major histocompatibility complex class I chain related gene A (MICA) antibodies with acute rejection (AR), chronic rejection (CR) and renal function after renal transplantation. Methods Serum MICA antibodies were detected with ELISA before and after transplantation with also examinations of panel reactive antibodies (PRA), serum creatinine, urine, graft ultrasound, lymphocyte subsets and the pathology of graft biopsy. The study was carried out in two parts to monitor MICA antibodies in acute and chronic rejections after renal transplantation. Results In the first part of the study 18 of the 41 recipients experienced episodes of acute rejection, and the incidence rate was markedly higher in MICA+group than in MICA-group (P<0.05). Compared with the recipients with stable renal functions, the patients with acute graft rejection showed a significantly higher positivity rate of MICA antibodies. Postoperative MICA antibody monitoring showed that MICA antibody level increased gradually 2-3 days after the occurrence of acute rejection; anti-rejection treatment lowered serum creatinine to a normal level but MICA antibodies remained positive. In the second part, 21 of 40 patients had chronic graft rejection and showed significantly higher positivity rate of MICA than the patients with stable renal functions (P<0.05). In patients with chronic rejections, the serum creatinine levels were significantly higher in MICA+than in MICA-cases (P<0.05). Graft biopsy of all MICA+cases showed C4d deposition. Conclusion The status of MICA antibodies can predict the occurrence and treatment outcomes of acute rejection, and also as one of the major causes of chronic graft rejection, they affect the long-term survival of the renal grafts.%目的探讨肾移植受者的抗MICA抗体水平与急性和慢性排斥反应的相关性及其对移植肾功能的影响。方法采用酶联免疫吸附方法检测接受同种异体肾移植手术的患者血

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

    Science.gov (United States)

    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

  5. Transplant rejection in terrestrial molluscs

    Directory of Open Access Journals (Sweden)

    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

  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

    Institute of Scientific and Technical Information of China (English)

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

    DEFF Research Database (Denmark)

    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...... routine monitoring of graft function by global longitudinal strain as supplement to routine left ventricular ejection fraction and diastolic Doppler measurements....

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

    Directory of Open Access Journals (Sweden)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. Pericytes, microvasular dysfunction, and chronic rejection.

    Science.gov (United States)

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

    2015-04-01

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

  11. Cellular metabolic, stress, and histological response on exposure to acute toxicity of endosulfan in tilapia (Oreochromis mossambicus).

    Science.gov (United States)

    Kumar, Neeraj; Sharma, Rupam; Tripathi, Gayatri; Kumar, Kundan; Dalvi, Rishikesh S; Krishna, Gopal

    2016-01-01

    Endosulfan is one of the most hazardous organochlorines pesticides responsible for environmental pollution, as it is very persistent and shows bio-magnification. This study evaluated the impact of acute endosulfan toxicity on metabolic enzymes, lysozyme activities, heat shock protein (Hsp) 70 expression, and histopathology in Tilapia (Oreochromis mossambicus). Among the indicators that were induced in dose dependent manner were the enzymes of amino acid metabolism (serum alanine aminotransferase and aspartate aminotransferase), carbohydrate metabolism (serum lactate dehydrogenase), pentose phosphate pathway (Glucose-6-phosphate dehydrogenase) as well as lysozyme and Hsp70 in liver and gill, while liver and gill Isocitrate dehydrogenase (TCA cycle enzyme) and marker of general energetics (Total adenosine triphosphatase) were inhibited. Histopathological alterations in gill were clubbing of secondary gill lamellae, marked hyperplasia, complete loss of secondary lamellae and atrophy of primary gill filaments. Whereas in liver, swollen hepatocyte, and degeneration with loss of cellular boundaries were distinctly noticed. Overall results clearly demonstrated the unbalanced metabolism and damage of the vital organs like liver and gill in Tilapia due to acute endosulfan exposure.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Associations between three specific a-cellular measures of the oxidative potential of particulate matter and markers of acute airway and nasal inflammation in healthy volunteers

    NARCIS (Netherlands)

    Janssen, Nicole A H; Strak, Maciej; Yang, Aileen; Hellack, Bryan; Kelly, Frank J; Kuhlbusch, Thomas A J; Harrison, Roy M; Brunekreef, Bert; Cassee, Flemming R; Steenhof, Maaike; Hoek, Gerard

    2015-01-01

    INTRODUCTION: We evaluated associations between three a-cellular measures of the oxidative potential (OP) of particulate matter (PM) and acute health effects. METHODS: We exposed 31 volunteers for 5 h to ambient air pollution at five locations: an underground train station, two traffic sites, a farm

  14. Serum inter-cellular adhesion molecule 1 is an early marker of diagnosis and prediction of severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Hai-Hang Zhu; Lin-Lin Jiang

    2012-01-01

    AIM:To determine if serum inter-cellular adhesion molecule 1 (ICAM-1) is an early marker of the diagnosis and prediction of severe acute pancreatitis (SAP)within 24 h of onset of pain,and to compare the sensitivity,specificity and prognostic value of this test with those of acute physiology and chronic health evaluation (APACHE) Ⅱ score and interleukin-6 (IL-6).METHODS:Patients with acute pancreatitis (AP) were divided into two groups according to the Ranson's criteria:mild acute pancreatitis (MAP) group and SAP group.Serum ICAM-1,APACHE Ⅱ and IL-6 levels were detected in all the patients.The sensitivity,specificity and prognostic value of the ICAM-1,APACHE Ⅱ score and IL-6 were evaluated.RESULTS:The ICAM-1 level in 36 patients with SAP within 24 h of onset of pain was increased and was significantly higher than that in the 50 patients with MAP and the 15 healthy volunteers (P < 0.01).The ICAM-1 level (25 ng/mL) was chosen as the optimum cutoff to distinguish SAP from MAP,and the sensitivity,specificity,positive predictive value,negative predictive value (NPV),positive likelihood ratio and negative likelihood ratio were 61.11%,71.42%,0.6111,0.7142,2.1382 and 0.5445,respectively.The area under the curve demonstrated that the prognostic accuracy of ICAM-1 (0.712) was similar to the APACHE-Ⅱ scoring system (0.770) and superior to IL-6 (0.508) in distinguishing SAP from MAP.CONCLUSION:ICAM-1 test is a simple,rapid and reliable method in clinical practice.It is an early marker of diagnosis and prediction of SAP within the first 24 h after onset of pain or on admission.As it has a relatively low NPV and does not allow it to be a stand-alone test for the diagnosis of AP,other conventional diagnostic tests are required.

  15. 尿CD54+淋巴细胞在肾移植急性排斥反应中的变化%Changes of urine CD54+ lymphocytes in acute rejection after renal transplantation

    Institute of Scientific and Technical Information of China (English)

    李沙丹; 王亮; 王庆堂; 陈卫国; 杨航; 周鹏; 梁平; 李晓伟

    2011-01-01

    背景:正常肾脏、肾小管上皮和血管内皮细胞仅有少量CD54表达,当发生急性排斥反应时,肾小管上皮细胞和血管内皮细胞CD54表达明显增加,同时大量白细胞浸润;间质浸润细胞和肾小管上皮细胞CD54表达增加.目的:探讨流式细胞仪检测尿CD54+淋巴细胞对移植肾急性排斥反应的诊断价值.方法:来自解放军成都军区总医院的肾移植后恢复正常者(n=18)、出现急性排斥反应者(n=8)、移植肾功不全者(n=9)以及健康志愿者(n=10).流式细胞仪比较各组移植前后尿液中CD54+淋巴细胞比率变化.结果与结论:尿CD54+淋巴细胞在肾移植患者出现排斥反应时明显增加(P < 0.01),抗排斥治疗后逐渐下降.移植肾功能正常者和移植肾功不全者CD54轻度升高.提示尿液中CD54+淋巴细胞水平能准确反映肾移植物移植后患者的免疫状态,可作为肾移植后急性排斥反应的特异标志.%BACKGROUND: The expression of CD 54 is low in normal kidney, renal tubular epithelium andvascularendothelialcelfe.CD54expression in renal tubular epithelial celt; and vascular endothelial cells increases obviously when acute rejection occurres. In themeantime, the C054 express ion level in renal tubular epithelial cells increases along with interstitial renal edema and massiveleukocyte infiltration.OBJECT rVE: To assess the value of flow cytometer detection for urine CD54* lymphocytes in the diagnosis of a cute rejectionafter renal transplantation.METHODS: Participants were renal transplant recipients from General Hospital of Chengdu Military Area Command of ChinesePLA, including patients obtained normal renal function 07=13), patients with acute rejection f/r=8) and patients with graftdysfunction(n=9). Hearthy volunteers were included as control (i?=1O). Urine CD54* lymphocyte rates of each group werecompared by flow cytometer before and after transplantation.RESULTS ANO CONCLUSION: The expression of urine CDS^ rymphocytes

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

    Science.gov (United States)

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

    2012-10-01

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

  17. Experience with the Wujciak-Opelz allocation system in a single center: an increase in HLA-DR mismatching and in early occurring acute rejection episodes.

    Science.gov (United States)

    Vereerstraeten, P; Abramowicz, D; De Pauw, L; Kinnaert, P

    1998-01-01

    The present single-center, retrospective study was undertaken to assess the impact of the Wujciak-Opelz allocation system (XCOMB), currently used within Eurotransplant for renal allografts, on the incidence of early occurring rejection episodes (RE). Implementation of the system resulted in an increase of HLA-DR mismatches (MM), while the incidence of HLA-A + B + DR MM remained unchanged. During the 1st post-transplant month, the total number of RE, expressed per patient-months, increased by 64% (0.326 vs 0.199, P = 0.007); when considering only severe and irreversible RE, the increase was 76% (0.158 vs 0.090, P = 0.011). In contrast, from the 2nd to the 12th post-transplant month, the incidence of RE, regardless of severity, was similar before and after implementation of XCOMB. As early occurring RE have detrimental effects on long-term graft outcome, these observations, if confirmed on a larger scale, would justify changes in the allocation algorithm. PMID:9787415

  18. IL-6 Promotes Cardiac Graft Rejection Mediated by CD4+ Cells1

    OpenAIRE

    Booth, Adam Jared; Grabauskiene, Svetlana; Wood, Sherri Chan; Lu, Guanyi; Burrell, Bryna E.; Bishop, D. Keith

    2011-01-01

    IL-6 mediates numerous immunologic effects relevant to transplant rejection; however its specific contributions to these processes are not fully understood. To this end, we neutralized IL-6 in settings of acute cardiac allograft rejection associated with either CD8+ or CD4+ cell dominant responses. In a setting of CD8+ cell dominant graft rejection, IL-6 neutralization delayed the onset of acute rejection while decreasing graft infiltrate and inverting anti-graft Th1/Th2 priming dominance in ...

  19. MDMA DECREASES THE EFFECTS OF SIMULATED SOCIAL REJECTION

    OpenAIRE

    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...

  20. 大鼠肝移植急性排斥反应的淋巴细胞蛋白质组学研究%Proteomics analysis of lymphocyte involving in acute rejection after liver transplantation within rats

    Institute of Scientific and Technical Information of China (English)

    张国伟; 周杰

    2008-01-01

    Objective To screen specific functional proteins from lymphocyte involved in acute rejection using differential proteomics research.Methods Two groups of rat liver transplantation models were established(isograft as control and allograft as acute rejection groups)by transplantation within Wistar rats,and between Wistar and SD.Morphology study were performed by histochemistry tech,followed by serum cytokine detection with ELISA.With 2-dimensional electrophoresis,proteomes of lymphocyte from the rats of different groups were separated and 2 proteome profiles were established.Comparing with the 2 profiles,25 spots were selected and picked for in gel digestion,followed for analysis by matrix assisted laser desorption ionization(MALDI)-time of fly(TOF)/TOF MS.Two of the proteins were detected with Western blot to verify the changing profiles.Results The results of morphology analysis and detection of cytokines(IL-2 and IFN-γ)indicate that the animal models were established successfully and acute rejection happened after transplantation for 3 days.Twenty-five differential proteins were found out to be associated with acute rejection,among which 13 proteins were upregulated and 12 downregulated.The expression alterations of 2 proteins(β-actin and carbonic anhydrase)are consistent with proteomics analysis results showing in Western blot.Conclusions Twenty-five specific proteins exploiting mechanism of acute rejection are screened out,including IL-2 and carbonic anhydrase,which maybe benefit for the further works.%目的 利用差异蛋白质学寻找肝移植急性免疫排斥反应相关功能蛋白.方法 选取SD大鼠与Wistar大鼠,建立大鼠同种异体肝移植的动物模型(急性排斥组)和大鼠同基因移植的动物模型(对照组);使用组织化学方法 对移植肝脏进行形态学观察;利用ELISA检测受体血清细胞因子;通过双向凝胶电泳分离急性排斥组和对照组肝移植后受体大鼠脾脏的淋巴细胞蛋白质,通过

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

    Directory of Open Access Journals (Sweden)

    Fernando Giron

    2010-01-01

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

  2. Discerning Rejection of Technology

    Directory of Open Access Journals (Sweden)

    Sudhir Rama Murthy

    2013-04-01

    Full Text Available Technology is innate to modern society and primarily embodies human intellect. It greatly influences development, societal functioning, and sociotechnical transitions. Rapid technological advancements, made possible with advancement in science, human ingenuity, and competitive markets, provide human society with affordable and unlimited choice. A society can be viewed, with an individual as the fundamental unit, or as a community, or state/nation. In one view, sustainability can be viewed through a matrix of societal, economic, and environmental configurations associated with the three societal levels. Technological advancement and complexity can either remain simple and amenable to the user or, as emerging in recent years, may daunt the user to keep away. While the phenomenon of technology adoption (acceptance in society has been well appreciated, the increasingly characteristic phenomenon of technology rejection is yet to be understood and studied. Technology rejection is not merely a negation of its acceptance, and hence requires to be discerned carefully. Rejection also does not imply in its totality, but varies in terms of its kind and/or intensiveness. While rejection is discernable at all these three levels of society, this study remains focused at the level of the user (individual. It attempts to discern rejection of technology and discusses its distinctness from technology acceptance through an exhaustive literature study. The article initially discusses the technology–society nexus and provides a preliminary technology–user interface model leading to a detailed discussion into the determinants of technology rejection.

  3. Role of spleen in acute rejection of mice undergoing allogeneic liver transplantation%脾脏在小鼠同种肝移植排斥反应中的作用

    Institute of Scientific and Technical Information of China (English)

    万赤丹; 黄韬; 勾善淼; 周静; 刘涛; 王春友

    2008-01-01

    目的 观察脾切除在小鼠同种肝移植急性排斥反应过程中的作用.方法 双袖套法建立小鼠原位肝移植模型,随机分为3组,即建模保留脾脏组、建模3 d后切除脾脏与建模同时切除脾脏组,各组于移植术后14 d处死,ELESA法测定血清IgM水平;肝功能检测采用速率法;流式细胞仪检测CD4与CD8T细胞亚群;并同时行肝脏及脾脏的病理形态观察.结果 建模保留脾脏组、建模3 d后切除脾脏与建模同时切除脾脏组血清IgM水平分别为3.0181±0.4627、3.0936±0.4559、3.1953±0.4449,各组间差异无统计学意义(P>0.05);ALT水平分别为108.6875±20.3657、83.0000±22.7799、76.8000±19.5784,差异有统计学意义(P<0.05);AST水平分别为:105.3750±29.0583、93.0000±22.7799、93.2000±33.4220,各组间差异无统计学意义(P>0.05);CD46+/CD8+T细胞分别为:1.9162±0.2778、1.5654±0.4750、1.4616±0.2762,差异有统计学意义(P>0.05);3组肝脏间质及汇管区淋巴细胞浸润程度依次减弱,供肝灶状坏死程度逐渐减轻,在保留脾脏组中建模后第14天脾脏边缘区及淋巴鞘较建模同时切除的脾脏增宽.结论 在小鼠同种异体肝移植排斥反应中细胞免疫起主要作用,脾切除可部分抑制同种异体肝移植急性排斥反应,保护供体肝脏.%Objective To study the role of spleen in acute rejection of mice undergoing aUogeneie liver transplantation.Methods Orthotopic liver transplantation was performed from C57BL mice to KM mice by using a two-cuff teehinique.C57BL mice as receptors were divided into 3 groups by simple random method:Group A ( n = 18 ),transplantion without splenectomy; Group B ( n = 18),transplantion and splenectomy were done simultaneously; Group C ( n = 18 ) ,spleneetomy was done 3 days after liver transplantation.All mice were killed 14 days after liver transplantation.ALT,AST,IgM,subgroups of T cells,pathological changes of lvier and kidney were analyzed.Results There was

  4. Mouse kidney transplantation: models of allograft rejection.

    Science.gov (United States)

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

    2014-01-01

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

  5. SOC REJECTION BY NANOFILTRATION

    Science.gov (United States)

    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...

  6. Effect of artesunate on acute rejection after small intestine transplantation in rats%青蒿琥酯对大鼠小肠移植急性排斥反应的作用

    Institute of Scientific and Technical Information of China (English)

    于小迪; 王为忠; 焦婕英; 郑建勇; 赵正维

    2014-01-01

    BACKGROUND:As the potent, specific immunosuppressants emerge, the survival rate after intestinal transplantation is improved to some extent. However, the adverse effects of immunosuppressants and expensive treatment costs are not tolerable for many patients. Therefore, it is clinical y meaningful to choose traditional Chinese medicine which presents immunosuppressive effects. Artesunate has immune suppression effect, reduces acute rejection fol owing smal intestine transplantation, and improves the success rate of smal intestine transplantation. OBJECTIVE:To observe the effect and action mechanism of artesunate in acute rejection after smal intestine transplantation in rats. METHODS:Al ogeneic smal intestine transplantation models were established in the closed group of Sprague-Dawley rats and Wistar rats, and then were randomly divided into three groups, syngenic transplantation group (SD→SD), al ogeneic transplantation group (Wistar→SD), and artesunate treatment group (Wistar→SD+artesunate 60 mg/kg per day, intraperitoneal injection). RESULTS AND CONCLUSION:Rats in syngenic transplantation group survived for more than 10 days and they were al kil ed on day 10. The average survival of rats in al ogeneic transplantation group and artesunate treatment group was respectively (6.73±0.58) days and (8.50±0.74) days, with significant differences between the two groups (P0.05), serum interferon-gamma expression level in treatment group was higher than syngenic transplantation group (P  目的:观察青蒿琥酯在大鼠小肠移植急性排斥反应中的作用及其机制。  方法:选用封闭群SD大鼠和Wistar大鼠建立同种异基因小肠移植模型,随机分为3组:①同基因移植组(SD→SD)。②异基因移植组(Wistar→SD)。③异基因移植+青蒿琥酯治疗组(Wistar→SD+青蒿琥酯60 mg/(kg•d),腹腔注射)。  结果与结论:同基因移植组大鼠存活均超过10 d,并于第10天全部处死。异基

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

    Institute of Scientific and Technical Information of China (English)

    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.

  8. Modeling rejection immunity

    Directory of Open Access Journals (Sweden)

    Gaetano Andrea De

    2012-05-01

    Full Text Available Abstract Background Transplantation is often the only way to treat a number of diseases leading to organ failure. To overcome rejection towards the transplanted organ (graft, immunosuppression therapies are used, which have considerable side-effects and expose patients to opportunistic infections. The development of a model to complement the physician’s experience in specifying therapeutic regimens is therefore desirable. The present work proposes an Ordinary Differential Equations model accounting for immune cell proliferation in response to the sudden entry of graft antigens, through different activation mechanisms. The model considers the effect of a single immunosuppressive medication (e.g. cyclosporine, subject to first-order linear kinetics and acting by modifying, in a saturable concentration-dependent fashion, the proliferation coefficient. The latter has been determined experimentally. All other model parameter values have been set so as to reproduce reported state variable time-courses, and to maintain consistency with one another and with the experimentally derived proliferation coefficient. Results The proposed model substantially simplifies the chain of events potentially leading to organ rejection. It is however able to simulate quantitatively the time course of graft-related antigen and competent immunoreactive cell populations, showing the long-term alternative outcomes of rejection, tolerance or tolerance at a reduced functional tissue mass. In particular, the model shows that it may be difficult to attain tolerance at full tissue mass with acceptably low doses of a single immunosuppressant, in accord with clinical experience. Conclusions The introduced model is mathematically consistent with known physiology and can reproduce variations in immune status and allograft survival after transplantation. The model can be adapted to represent different therapeutic schemes and may offer useful indications for the optimization of

  9. Heat rejection system

    Science.gov (United States)

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

    1980-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Shilpa eRavinder

    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.

  11. DIGE proteome analysis reveals suitability of ischemic cardiac in vitro model for studying cellular response to acute ischemia and regeneration.

    Directory of Open Access Journals (Sweden)

    Sina Haas

    Full Text Available Proteomic analysis of myocardial tissue from patient population is suited to yield insights into cellular and molecular mechanisms taking place in cardiovascular diseases. However, it has been limited by small sized biopsies and complicated by high variances between patients. Therefore, there is a high demand for suitable model systems with the capability to simulate ischemic and cardiotoxic effects in vitro, under defined conditions. In this context, we established an in vitro ischemia/reperfusion cardiac disease model based on the contractile HL-1 cell line. To identify pathways involved in the cellular alterations induced by ischemia and thereby defining disease-specific biomarkers and potential target structures for new drug candidates we used fluorescence 2D-difference gel electrophoresis. By comparing spot density changes in ischemic and reperfusion samples we detected several protein spots that were differentially abundant. Using MALDI-TOF/TOF-MS and ESI-MS the proteins were identified and subsequently grouped by functionality. Most prominent were changes in apoptosis signalling, cell structure and energy-metabolism. Alterations were confirmed by analysis of human biopsies from patients with ischemic cardiomyopathy.With the establishment of our in vitro disease model for ischemia injury target identification via proteomic research becomes independent from rare human material and will create new possibilities in cardiac research.

  12. Increased cellular hypoxia and reduced proliferation of both normal and leukaemic cells during progression of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Jensen, P O; Mortensen, B T; Hodgkiss, R J;

    2000-01-01

    The microenvironmental changes in the bone marrow, spleen and liver during progression of the transplantable promyelocytic leukaemia in the Brown Norwegian rat (BNML) have been studied. We used flow cytometry to estimate cellular hypoxia and proliferation based on in vivo pulse...... in the bone marrow and liver, reaching a level of 65-87% in these organs at day 32. At day 32, the NITP+ fraction of RM124+ cells had increased significantly in the bone marrow and spleen to 88% and 90%, respectively. The corresponding fractions of NITP+ normal cells reached 63% and 65%, respectively. From......-labelling with a mixture of 2-nitroimidazole linked to theophylline (NITP) and bromodeoxyuridine (BrdUrd). The leukaemic cells were identified with the RM124 antibody. In rats inoculated with leukaemic cells the fraction of RM124+ cells was significantly increased from day 20 onwards in the spleen and from day 27...

  13. Prostanoids modulate inflammation and alloimmune responses during graft rejection

    Directory of Open Access Journals (Sweden)

    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.

  14. Rejection sampling in demand systems

    OpenAIRE

    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.

  15. Radionuclide diagnosis of allograft rejection

    Energy Technology Data Exchange (ETDEWEB)

    George, E.A.

    1982-10-01

    Interaction with one or more anatomical and physiopathological characteristics of the rejecting renal allograft is suggested by those radioagents utilized specifically for the diagnosis of allograft rejection. Rejection, the most common cause of declining allograft function, is frequently mimicked clinically or masked by other immediate or long term post transplant complications. Understanding of the anatomical pathological features and kinetics of rejection and their modification by immunosuppressive maintenance and therapy are important for the proper clinical utilization of these radioagents. Furthermore, in selecting these radionuclides, one has to consider the comparative availability, preparatory and procedural simplicity, acquisition and display techniques and the possibility of timely report. The clinical utilities of radiofibrinogen, /sup 99m/Tc sulfur colloid and /sup 67/Ga in the diagnosis of allograft rejection have been evaluated to a variable extent in the past. The potential usefulness of the recently developed preparations of /sup 111/In labeled autologous leukocytes and platelets are presently under investigation.

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

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2015-12-01

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

  20. DYNAMICS OF IRIG IN TREATMENT OF HEART TRANSPLANT REJECTIONS

    Directory of Open Access Journals (Sweden)

    A. O. Shevchenko

    2015-01-01

    Full Text Available In cardiac recipients non-invasive monitoring will identify the risk of acute rejection, as well as reduce the number of routine biopsies. The relation between the development of the transplanted heart rejection and the change of elastic properties of common carotid artery has been proved. Aim: to analyze dynamics of iRIG in treatment of graft rejection in heart recipients.Materials and methods. 59 heart recipients were examined: 21 patients (ptswithout rejection, 20 pts – with rejection after 1st biopsy, 15 pts – with rejection after 1st and 2 biopsies, 3 pts – with persistent rejection after all biopsies. iRIG was estimated using empirical equation.Results. Dynamics of iRIG in pts. without rejection according to all biopsies over time was not signifi cantly changed 6280 ± 2143, 6083 ± 2388, 6362 ± 1984 and 6188 ± 3012 cm/sec2 (p = 0.11, p = 0.13, p = 0.17 between the 1st and 2nd, 2nd and 3rd, 3rd and 4th values, respectively. In pts. with rejection iRIG decreased during treatment, but was signifi cantly higher even after successful treatment. In patients with persistent rejection iRIG did not decrease and tended to increase (17 459 ± 9702 cm/sec2 on the results of the 1st biopsy to 21 305 ± 10 448 cm/sec2 on the results of the 4th biopsy.Conclusions. In patients with heart transplant iRIG does not change signifi cantly with the time after transplantation. iRIG increases in all types of rejection, followed by its decrease in the course of therapy; in patients with persistent rejection iRIG remains high. Evaluation of iRIG can be used for non-invasive monitoring of patients after heart transplantations (HTx and to identify patients at high risk of transplant rejection.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  3. The Expression Pattern of the Pre-B Cell Receptor Components Correlates with Cellular Stage and Clinical Outcome in Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Chen, Dongfeng; Zheng, Junxiong; Gerasimcik, Natalija; Lagerstedt, Kristina; Sjögren, Helene; Abrahamsson, Jonas; Fogelstrand, Linda; Mårtensson, Inga-Lill

    2016-01-01

    Precursor-B cell receptor (pre-BCR) signaling represents a crucial checkpoint at the pre-B cell stage. Aberrant pre-BCR signaling is considered as a key factor for B-cell precursor acute lymphoblastic leukemia (BCP-ALL) development. BCP-ALL are believed to be arrested at the pre-BCR checkpoint independent of pre-BCR expression. However, the cellular stage at which BCP-ALL are arrested and whether this relates to expression of the pre-BCR components (IGHM, IGLL1 and VPREB1) is still unclear. Here, we show differential protein expression and copy number variation (CNV) patterns of the pre-BCR components in pediatric BCP-ALL. Moreover, analyzing six BCP-ALL data sets (n = 733), we demonstrate that TCF3-PBX1 ALL express high levels of IGHM, IGLL1 and VPREB1, and are arrested at the pre-B stage. By contrast, ETV6-RUNX1 ALL express low levels of IGHM or VPREB1, and are arrested at the pro-B stage. Irrespective of subtype, ALL with high levels of IGHM, IGLL1 and VPREB1 are arrested at the pre-B stage and correlate with good prognosis in high-risk pediatric BCP-ALL (n = 207). Our findings suggest that BCP-ALL are arrested at different cellular stages, which relates to the expression pattern of the pre-BCR components that could serve as prognostic markers for high-risk pediatric BCP-ALL patients. PMID:27611867

  4. Tacrolimus alleviates acute liver graft rejection by inhibiting glucocorticoid-induced tumor necrosis factor-related protein ligand in rats%他克莫司通过抑制GITRL减轻大鼠肝移植排斥反应的研究

    Institute of Scientific and Technical Information of China (English)

    魏思东; 龚建平; 李金政; 黄中荣

    2011-01-01

    目的 探讨他克莫司(FK506)抑制大鼠肝移植排除反应中的作用机制。方法建立大鼠原位肝移植模型,分为3组。耐受组为Brown Norway (BN)到Lewis肝移植;排斥组为Lewis到BN肝移植;他克莫司(FK506)组在建立排斥模型基础上于术后注射FK506。术后7d检测肝组织病理改变及糖皮质激素诱导的肿瘤坏死因子相关蛋白配体(GITRL)的表达、Kupffer细胞GITRL的表达及细胞因子的改变。结果与耐受组比较,排斥组肝脏及kupffer细胞中GITRL表达升高,采用FK506后,降低了GITRL表达(P<0.05)。与耐受组比较,排斥组血清及kupffer细胞中IFN-γ表达升高,IL-10降低(P<0.05),而在FK506组,与排斥组比较,血清及kupffer细胞中IFN-γ表达降低,IL-10表达升高(P<0.05)。结论FK506能减轻大鼠肝移植后的急性排斥反应,其机制与降低GITRL的表达有关。%Objective To investigate the mechanism underlying the inhibitory effect of tacrolimus (FK506) against acute liver graft rejection. Methods Rat models of orthotopic liver transplantation were divided into 3 groups, namely the tolerance group with Brown Norway (BN) rats as the donors and Lewis rats as the recipients, rejection group with Lewis rats as donors and BN rats as recipients, and FK506 group with the same donor-recipient pair as in the rejection group and FK506 treatment. The recipients were sacrificed 7 days after the transplantation, and the hepatic histology, cytokine levels, and glucocorticoid-induced tumor necrosis factor-related protein ligand (GITRL) expression in the liver and Kupffer cells were observed and detected. Results Compared with the tolerance group, the rejection group showed increased GITRL expressions in the liver and Kupffer cells (PO.05), which was significantly lowered by FK506 treatment (PO.05). Acute liver graft rejection caused significantly elevated interferon-y (IFN-y) levels and decreased interieukin-10 (IL-10) levels in the plasma

  5. Roles of nitric oxide synthase in acute rejection of intestinal transplantation in rats%一氧化氮合成酶在大鼠小肠移植急性排斥反应中的作用

    Institute of Scientific and Technical Information of China (English)

    李晓林; 邹小明; 李云龙; 宋茂力; 李刚

    2012-01-01

    目的 观察神经型(nNOS)和诱导型一氧化氮合成酶(iNOS)在大鼠小肠移植急性排斥反应(AR)中作用.方法 行大鼠原位小肠移植.实验分为2组.1组:同系移植组(Lewis→Lewis,12例);2组:同种移植组(DA→Lewis,12例).观察术后生存时间.再灌注30 min、术后1、3、5、7d检测血清一氧化氮(NO)浓度;开腹行麦芽糖吸收实验;切取移植肠管,苏木素-伊红(HE)染色后光镜检查.免疫组织化学法观察移植肠nNOS和iNOS的活性.逆转录-聚合酶链反应(RT-PCR)法检测移植肠nNOS mRNA和iNOS mRNA的表达.结果 A组生存时间>30 d.B组生存时间为(6.83±0.75)d.再灌注后A组nNOS染色与mRNA表达明显减弱,此后nNOS染色和mRNA表达分别于术后3、7d恢复正常.再灌注后A组iNOS染色与mRNA表达增强,此后逐渐减弱.与A组比较,术后3~7 d,B组nNOS染色减弱,iNOS染色增强,血清NO水平明显升高(P<0.05),血糖吸收值显著降低(P<0.01);术后5、7d,B组nNOS mRNA表达显著下降(P<0.001),iNOS mRNA表达明显增强(P<0.01).结论 在AR过程中,nNOS可能调节了iNOS的表达;nNOS的活性和表达与移植肠管的结构和吸收功能密切相关;iNOS的激活是加重组织损伤的重要因素之一.%Objective To evaluate the role of neuronal (nNOS) and inducible nitric oxide synthase (iNOS) in acute rejection (AR) of intestinal transplantation in rats.Methods The rat orthotopic intestinal transplantation was performed.Animals were assigned to following 2 groups:isograft group ( A,Lewis→Lewis,n =12) ; allograft group (B,DA→Lewis,n =12).The survival time was observed.At 30 min,postoperative day (POD) 1,3,5 and 7,the serum nitric oxide (NO) levels were measured,the maltose absorption tests were performed,and intestinal specimens were resected for light microscopy after H&E staining.The activity of nNOS and iNOS was examined by immunohistochemistry.The expression levels of nNOS and iNOS mRNA were detected by using reverse

  6. Diagnosis and treatment of acute rejection following small bowel transplantation%小肠移植术后排斥反应的诊断与治疗四例报告

    Institute of Scientific and Technical Information of China (English)

    李元新; 李宁; 李幼生; 倪小冬; 李民; 汪志明; 吴波; 王剑; 黎介寿

    2009-01-01

    Objective To investigate the clinical experience in diagnosis and treatment of acute rejection (AR) following small bowel transplantation.Methods Patients received 1 g of Solu-Medrolfollowed by 30 mg Alemtuzumab infusion during SBTx and another gram of Solu-Medrol before reperfusion.Tacrolimus monotherapy without steroid was used for maintenance immunosuppression.The tacrolimus trough levels were 10~15μg/L during the first 3 months,declined to 5~10 μg/L at the 4th~6th month,and then taped to 5 μg/L after 7 months.AR was monitored by clinical observation,endoscopies of the intestinal graft and histological evaluation of the graft biopsies.The histologic criteria for grading intestinal AR were based on the results of the pathology workshop at the 8th International Small Bowel Transplant Symposium in 2003.IND and mild AR episodes were treated by steroid and increasing level of tacrolimus to 15 μg/L,and moderate AR treated by a bolus of Solu-Medrol,followed by a declining cycle of steroid plus an increase in tacrolimus.The systemic anti-infectious prophylaxis and suspending enteral nutrition were also introduced.Results Two recipients survived more than 1 year,one patient is currently at 8 months and another at 4 months post-SBTx, Four episodes of IND to mild AR verified by pathology through ileoscopical biopsy were found at 1-3 months,3 episodes of IND to mild AR at 4-6 months,and 2 episodes of moderate AR at 7-12 months.Patients totally recovered after low dose steroid or bolus steroid was given.The recovery time from IND or mild ACR was 2-8 days,and that from moderate ACR was 15 days.Grafts achieved excellent function as all 4 patients withdrew TPN 2-3 weeks postoperatively and lived on normal oral intake.Conclusion Pathology of the graft biopsies through ileoscopy is a"golden standard"of diagnosis of AR following small bowel transplantation.A bolus of Solu-Medrol,followed by a declining cycle of steroid plus an increase in tacrolimus can effectively

  7. Proteomic analysis of the serum from patients with acute rejection after liver transplantation%肝移植术后急性排斥患者血清的蛋白质组学分析

    Institute of Scientific and Technical Information of China (English)

    蒋琪; 茹雅维; 李克秋; 李光

    2015-01-01

    Objective To investigate the protein markers that specifically expressed in patients with acute rejection (ACR) after liver transplantation, and to explore preliminarily the mechanisms. Methods Serum samples from three patients with pathologically confirmed ACR after liver transplantation in Tianjin First Central Hospital were collected as ACR group. Three serum samples from patients with normal liver function indicators after liver transplantation were collected as No-ACR group. And six serum samples from healthy examination were mixed with equal amount as healthy control group. Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) was employed to separate, screen and identify the differentially expressed proteins between three groups. KEGG and STRING software were applied to deeply analyze the data of three groups. Results A total of 88 differentially expressed proteins were found between ACR group and healthy control group. There were 39 differentially expressed proteins between No-ACR group and healthy control group. Ten differentially expressed proteins were acquired between ACR group and No-ACR group. Comparing 88 and 10 differentially expressed proteins, 9 proteins were the same. Among 88 differentially expressed proteins, 30 of them showed a direct interaction, and can be positioned in 13 signaling pathways based on KEGG and STRING software. Fourteen (46.67%) of the 30 proteins were located in the complement and coagulation cascade pathway. Among 39 differentially expressed proteins, which were detected between No-ACR group and control group, 10 proteins showed a direct interaction including 9 proteins concentrated in the complement and coagulation cascade pathway. Conclusion By proteomic analysis, nine differentially expressed proteins are obtained, which may be regarded as the candidate bio-markers for ACR early diagnosis after liver transplantation. The complement and coagulation cascades system is significantly adjusted after liver

  8. 肾移植术后急性体液性排斥反应的监测及其临床意义%Significance of monitoring acute humoral rejection after renal transplantation

    Institute of Scientific and Technical Information of China (English)

    李留洋; 陈剑荣; 钱俊; 李民; 郭颖; 刘永光; 赵明

    2012-01-01

    目的 探讨肾移植后发生急性体液性排斥反应(AHR)的可能机制,及其在临床早期诊断和防治AHR中的重要意义.方法 回顾分析2006年1月至2010年12月间296例肾移植受者的临床资料.肾移植术后,采用酶联免疫吸附试验(ELISA)动态监测受者群体反应性抗体(PRA)和供者特异性抗体(DSA)水平,采用免疫组织化学法和HE染色检查移植肾组织的病理形态学改变及C4d的沉积、浸润淋巴细胞表面分子标记.AHR诊断标准参照Banff 2005标准,并结合受者的临床相关指标.结果 296例受者中,术后共有25例发生了AHR,发生率为8.4% (25/296).术前PRA阳性者和阴性者术后AHR的发生率分别为23.1%(6/26)和7.0%(19/270),两者比较,差异有统计学意义(P<0.01).术后发生AHR和未发生AHR受者的DSA阳性率分别为88.0%(22/25)和0.4%(1/271),出现C4d沉积阳性率分别为80.0%(20/25)和6.7% (4/60),两者间DSA阳性率和C4d沉积阳性率的比较,差异均有统计学意义(P<0.01).通过调整免疫抑制方案和(或)应用静脉注射免疫球蛋白、血浆置换、抗胸腺细胞球蛋白及利妥昔单抗等治疗后,19例AHR被逆转,其余6例因治疗无效,发生移植肾破裂,导致移植肾被切除.结论 PRA和DSA在肾移植术后AHR的发生中起重要作用,术后应立即开始监测PRA和DSA,以达到预防、早期诊断和合理治疗AHR的目的,进而改善移植肾的存活.%Objective To investigate the possible mechanisms of acute humoral rejection (AHR) after renal transplantation and the significance of early diagnosis and prevention.Methods The clinical data of 296 cases receiving renal transplantations from January 2006 to December 2010 were retrospectively analyzed. After renal transplantation,the dynamic changes of panel reactive antibodies (PRA) and donor specific antibodies (DSA) in peripheral blood were monitored by using ELISA,and C4d deposition and molecular markers of infiltrating

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

    OpenAIRE

    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...

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

    Institute of Scientific and Technical Information of China (English)

    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.

  11. Variable Heat Rejection (VHR) Project

    Data.gov (United States)

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

  12. 嗜酸性粒细胞升高在诊断肝移植术后迟发性急性排斥反应中的价值%Diagnostic value of increased eosinophil count for late acute rejection after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    汪国营; 李华; 张剑; 汪根树; 易慧敏; 易述红; 姜楠; 张琪; 杨扬

    2013-01-01

    Objective To evaluate the predictive value of increased eosinophil count in peripheral blood in the diagnosis of acute rejection (AR) occurred 6 months or later following liver transplantation (LT).Methods The peripheral blood eosinophil count the day before or on the day of biopsy in 185 biopsies from 161 liver transplant patients were retrospectively analyzed.Patients were divided into AR group and non-acute rejection (NAR) group according to histopathologic findings.Differential white cell counts were compared between two groups.The rates of increased eosinophil count were compared among early (the first month post-transplant),mid-term (from 1 to 6 months),and late acute rejection (after 6 months) post-transplant.Absolute eosinophil count greater than 0.4 × 109/L or relative eosinophil count greater than 4% was defined as elevated.The sensitivity and specificity of increased eosinophil count for diagnosing late AR was calculated.Results Of the 185 liver biopsies,110 were diagnosed as acute rejection,including 32 cases of early AR (29.1%),54 cases of mid-term AR (49.1%),and 24 cases of late AR (21.8%).The overall white cell count,absolute and relative neutrophil count were significantly lower in the AR group than in the NAR group,while relative lymphocyte count,absolute and relative eosinophil count were significantly higher in the AR group than in the NAR group.There were 28 biopsies with an elevated eosinophil count.Of the 25 biopsies with elevated eosinophil count in AR group,only 2 (6.3%) were in early AR,with 13 in mid-term AR (24.1%) and 10 in late AR (41.7%),respectively.The sensitivity and specificity of increased absolute and relative eosinophil count to predict late AR was 41.7% and 100%,respectively.Conclusions Eosinophil counts in peripheral blood in AR group after LT are significantly higher compared with those in non-acute rejection group.Increased eosinophil count has high diagnostic value for diagnosing late acute rejection

  13. The expression and level of vascular endothelial growth factor in the acute rejection reaction of orthotopic liver transplantation in rats%血管内皮生长因子在大鼠肝移植急性排斥反应时的表达

    Institute of Scientific and Technical Information of China (English)

    周天保; 杨广顺

    2008-01-01

    目的 研究血管内皮生长因子(vascular endothelial growth factor,VEGF)在大鼠肝移植急性排斥反应(acute rejection reaction,ARR)中的表达水平,探讨VEGF在细胞介导的肝移植ARR时免疫炎症反应和血管新生的关键中介分子.方法 采用ELISA法及免疫组化EnVision法对VEGF在大鼠肝移植ARR时的表达及血浆中的水平进行了检测.结果 ELISA血清及免疫组化检测显示VEGF在急性排斥组被检测到的水平和表达均比在对照组明显增高,差异有统计学意义(P<0.05),且以术后2天水平最高.结论 VEGF在移植排斥反应中起着重要作用,其表达水平和移植物存活时间有非常密切关系,并且它是一种早期就表达的作用因子.%Objective This study was to detect the expression and level of vascular endothelial growth factor(VEGF)in the acute rejection reaction of orthotopic liver transplantation in rats,which attempted to prove whether VEGF is the key molecule mediating the inter-permeate and inter-enhancement mediated by cells between Angiogenesis and inflammation reaction Methods Expressions of VEGF in plasm in liver and spleen were detected using immunohistochemical staining.The levels of VEGF were measured with enzyme linked immunosorbent assay(ELISA).Results The expression of VEGF in liver,spleen and the level of VEGF in plasma in experiment group were higher than that in the control group(P<0.05),which were the highest in two days after operation.Conclusion VEGF may play a significant role in the acute rejection reaction of orthotopic liver transplantation in rats.There was a close relation between the expression and level of VEGF in liver,spleen and survival time of graft.VEGF was a kind factor which is expressed in early stage.

  14. 超声造影诊断胰肾联合移植术后胰腺急性排异反应的价值%The value of contrast-enhanced ultrasound in diagnosis of acute rejection after pancreas transplantation

    Institute of Scientific and Technical Information of China (English)

    武红涛; 唐缨; 李菊香; 牛宁宁; 赵静雯; 王玉红

    2016-01-01

    Objective To investigate the clinical value of contrast-enhanced ultrasound (CEUS) in the diagnosis and grading of acute rejection of the transplanted pancreas after simultaneous pancreas-kidney transplantation.Methods Seventy cases pancreas grafts underwent gray scale ultrasound,color Doppler flow imaging(CDFI) and CEUS examination,the contrast agent perfusion processes were observed,and the parameters of time intensity curves(time-intensity curve,TIC) were calculated.The CEUS results were compared with the pathological findings.Results Twenty-one cases were acute rejection in 70 cases,of which 10 cases were mild,8 cases were moderate and 3 cases were severe;and 49 cases were non-rejection.①Gray scale and CDFI ultrasound:The pancreatic grafts of acute rejection were edema and enlarged,the parenchyma echo were decreased.The artery resistance index(RI) were significant different between acute rejection group and non-rejection group (0.77 ± 0.05 vs 0.74 ± 0.10,P <0.05),but there were no significant differences between mild,moderate and severe group (P >0.05).②CEUS:TIC curves showed a significantly longer time to reach peak [TTP,(21.7 ± 4.3)s vs (13.0 ± 2.9) s,P <0.01] and significantly reduced peakintensity(PI,18.8 ± 7.9 vs 29.6 ± 2.4,P <0.05).There was no significant difference between the mild and moderate groups (P >0.05) but statistically difference was found when the severe group compared with the other two groups (P <0.05).Conclusions CEUS can be used to observe the perfusion of the vascular and parenchyma of the pancreas,the results also can be quantitative analyzed.It is an effective method for the diagnosis of pancreas acute rejection of simultaneous pancreas-kidney transplantation.%目的 探讨超声造影诊断胰肾联合移植术后胰腺不同程度急性排异反应的临床价值.方法 对70例胰肾联合移植术后移植胰腺行灰阶、彩色多普勒血流成像(CDFI)及超声造影检查,观察造影剂灌注过程,绘

  15. Nucleic Acid Drugs for Prevention of Cardiac Rejection

    Directory of Open Access Journals (Sweden)

    Jun-ichi Suzuki

    2009-01-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  17. Leukocytic acetylcholine in chronic rejection of renal allografts

    OpenAIRE

    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...

  18. Perturbations in the Urinary Exosome in Transplant Rejection

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-01-05

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

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

    Science.gov (United States)

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

    2013-09-01

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

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

    Directory of Open Access Journals (Sweden)

    André Dong Won Lee

    2004-06-01

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

  1. 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

    Institute of Scientific and Technical Information of China (English)

    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

  2. Peer Group Rejection and Children's Outgroup Prejudice

    Science.gov (United States)

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

    2010-01-01

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

  3. 7 CFR 58.136 - Rejected milk.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Rejected milk. 58.136 Section 58.136 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Milk § 58.136 Rejected milk. A plant shall reject specific milk from a producer if the milk fails...

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

    Science.gov (United States)

    Rose, Marlene L

    2013-11-01

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

  5. Serum beta-2-Microglobulin level: A parameter for early diagnosis of renal allograft rejection

    Directory of Open Access Journals (Sweden)

    Rezai A

    1994-05-01

    Full Text Available For monitoring of renal transplant function, serum B2m was evaluated in 23 recipients. According to clinical diagnosis the patients were in four groups: 1 Successful renal transplant; the mean concentration of SB2m pretransplantation was 73.1±26.1 mg/L but decreased to nearly normal level (4.43±1.17 mg/L within 24-48h and then reached to 3.1 mg/L duting 20 days after transplantation. 2 Renal dysfunction (except rejection; the maximum changes of SB2m was 1.1 mg/L/day and no significant changes of SB2m were found between this group and group 1. 3 Accelerated and acute rejection; during immunological rejection crisis, SB2m level increased and after response to antirejection therapy decreased. The daily changes of SB2m allowed to diffrentiate renal dysfunction fom rejection in 84% of cases. Moreover according to SB2m fluctuation levels, SB2m had a prognostic pattern for acute rejection due to significant differences between the level of SB2m on the day of clinical diagnosis of rejection and 4 days previously (P<0.025, and also 2 days before rejection (P<0.025, while this pattern was not found for serum creatinin and BUN.

  6. 肾移植一年后急性排斥反应时移植肾组织中C4d表达阳性的临床研究%Effects of C4d deposition in peritubular capillary of patients with acute renal allograft rejection one year post-transplant on the prognosis of renal allograft

    Institute of Scientific and Technical Information of China (English)

    蔡明; 许亮; 许晓光; 王强; 李州利; 韩永; 石炳毅

    2010-01-01

    Objective To analyze C4d deposition in the patients with late acute renal allograft rejection,and explore the role of C4d in grafts survival and grafts loss. Methods Thirty-six patients clinical and pathologically diagnosed as having acute rejection more than one year post-transplant were selected. C4d was detected by immunohistochemistry in renal allograft biopsies. The effect of C4d deposition on long-term graft survival was studied. Results Among 36 recipients with late acute renal allograft rejection, 16 cases were positive for C4d (44.4 %) and 20 negative for C4d (55.6 %). Five cases experienced graft loss in C4d positive group (31.3 %), while 6 cases in C4d negative group (30.0%). There was no significant difference in the graft loss rate between C4d-positive group and C4d-negative group. Log-Rank test demonstrated there was no significant difference in graft survival between C4d-positive group and C4d-negative group. The count of the interstitial infiltrated eosinophils in renal allograft was (9.4 + 4.5) and (2.6 + 1.8) respectively in the C4d-positive group and C4dnegative group (P<0.05). Conclusion C4d deposition in peritubular capillary of the recipients with late acute renal allograft rejection might not be a prognostic marker for graft outcome.%目的 观察肾移植1年后发生急性排斥反应时移植肾组织中补体片段C4d的表达情况,分析其对移植肾功能及预后的影响.方法 选择肾移植时间超过1年,临床诊断为急性排斥反应并经病理穿刺活检证实的肾移植受者36例为研究对象.以第1例受者移植肾组织穿刺时间为观察起点(2006年3月),以此项研究结束时间为观察终点(2010年4月).应用C4d多克隆抗体对移植肾穿刺组织行免疫组织化学染色,检测C4d在移植肾组织中的表达情况;根据检测结果,分为C4d阳性组和阴性组,分析和比较两组在观察时间段内移植肾功能的变化及存活时间.结果 在36例受者

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

    Science.gov (United States)

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

    2010-12-01

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

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

    Science.gov (United States)

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

    2013-12-01

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

  9. Perturbations in the Urinary Exosome in Transplant Rejection

    Directory of Open Access Journals (Sweden)

    Tara eSigdel

    2015-01-01

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

  10. 致敏肾移植受者抗MICA抗体的表达对术后早期排斥反应和肾功能的影响%Expression of anti-MICA antibodies and its influence on acute rejection and allograft function of sensitized renal recipients in early post-transplant course

    Institute of Scientific and Technical Information of China (English)

    张小东; 杨晓勇; 李晓北; 张际青; 杨毅; 尹航; 胡小鹏; 任亮; 王玮; 刘航

    2010-01-01

    Objective To explore the expression of anti-MICA antibodies and evaluate its influence on acute rejection and renal function in early period after renal transplantation. Methods A total of 29 sensitized subjects (PRA>20 %) were enrolled in this study. All the patients underwent protein A immunoabsorption treatment and the expression of anti-MICA antibodies was detected before and after treatment. Triple immunosuppressive regimen consisting of tacrolimus, mycophenolate mofetil (MMF) and steroid was given to prevent graft rejection. The correlation between the expression of anti-MICA antibodies and acute rejection or serum creatinine (SCr) level was analyzed.Results The expression of anti-MICA antibodies was detected in 8 candidates (27. 6 % ,8/29) ,and 6 kinds of anti-MICA antibodies simultaneously expressed were found in one individual, 3 kinds in one case,and sole kind in 6 patients. There was no significant difference in acute rejection rate between positive anti-MICA antibodies group and negative group [37.5 % (3/8) vs 38. 1% (8/21), P>0.05). The positive expression rate of anti-MICA antibodies in the recipients with PRA ≥40% was higher than that in those with PRA <40% [43. 8 % (7/16) vs 7. 7 % (1/13),P<0.05]. The SCr level in patients positive for anti-MICA antibodies was markedly higher than that in those negative anti-MICA antibodies at the 1st week postoperatively ( 135.4 ± 21.4 vs 108. 6 -+ 31.6 μmol/L, P<0.05). The SCr level in the patients with positive anti-MICA antibodies, however, was reduced to the normal range at the 2nd week after surgery (P>0.05). The levels of anti-MICA antibodies were continuously decreased in the candidates undergoing protein A irnmunoadsorption treatment. Conclusion Higher expression of anti-MICA antibodies exists in sensitized recipients and possesses an influence on the recovery of renal function in early postoperative period. Protein A immunoadsorption can eliminate anti-MICA antibodies effectively in

  11. Cellular automata

    CERN Document Server

    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

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

    NARCIS (Netherlands)

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

    2001-01-01

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

  13. Early peri-operative hyperglycaemia and renal allograft rejection in patients without diabetes

    Directory of Open Access Journals (Sweden)

    Russ Graeme R

    2000-10-01

    Full Text Available Abstract Background Patients with diabetes have an increased risk for allograft rejection, possibly related to peri-operative hyperglycaemia. Hyperglycaemia is also common following transplantation in patients without diabetes. We hypothesise that exposure of allograft tissue to hyperglycaemia could influence the risk for rejection in any patient with high sugars. To investigate the relationship of peri-operative glucose control to acute rejection in renal transplant patients without diabetes, all patients receiving their first cadaveric graft in a single center were surveyed and patients without diabetes receiving cyclosporin-based immunosuppression were reviewed (n = 230. Records of the plasma blood glucose concentration following surgery and transplant variables pertaining to allograft rejection were obtained. All variables suggestive of association were entered into multivariate logistic regression analysis, their significance analysed and modeled. Results Hyperglycaemia (>8.0 mmol/L occurs in over 73% of non-diabetic patients following surgery. Glycaemic control immediately following renal transplantation independently predicted acute rejection (Odds ratio=1.08. 42% of patients with a glucose Conclusion Hyperglycaemia is associated with an increased risk for allograft rejection. This is consistent with similar findings in patients with diabetes. We hypothesise a causal link concordant with epidemiological and in vitro evidence and propose further clinical research.

  14. Bone marrow transplantation in the rat. I. Histologic correlations and quantitation of cellular infiltrates in acute graft-versus-host disease.

    OpenAIRE

    Renkonen, R; Häyry, P.

    1984-01-01

    In an attempt to define which cytologic manifestations of inflammation are characteristic of acute graft-versus-host disease (aGVHD), the authors have analyzed hematologic reconstitution in the bone marrow, spleen, and blood of bone marrow transplant recipients and correlated these events to concomitant cytologic changes in the parenchymal target organs. After bone marrow transplantation from Lewis to BN strain, the strongest inflammatory changes were observed in the liver, a "model" parenchy...

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  17. EXPRESSION OF ICAM-1 AND LFA-1 MOLECULES IN RELATION TO RENAL ALLOGRAFT REJECTION IN RATSA

    Institute of Scientific and Technical Information of China (English)

    黄孝伦; 沈文律; 李幼平; 周泽清; 谭建三

    1999-01-01

    Objective. The purpose of this study was to assess the renal graft expression of ICAM-I (intercellular adhesion moleculeq) and LFA l(lymphocyte function-aa.soziated antigen-1)molecule with relation to graft rejection. Methods. Rat kidney traansplantation was performed according to the procedure of Kamada with some modification. Experimental rats were dividod into 5 groups. The survival time of recipient rats and function of grafts after renal transplantation were observed. The sections of renal graft were mined forantibody ICAM-1 and LFA-1, and then quantification of ICAM-1 and LFA-1 expression was accomplished by computer image analysis. Results. ICAM-1 and LFA-1 increased significantly in the renal allograft rejection group as compared with the non-rejection groups(P<0. 05). Conclustion. Both biopsy of renal graft and monitoring of ICAM-1 and LFA-1 are useful tools in diagnosing and treating acute rejection.

  18. A proteomic analysis of allograft rejection in rats after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    ZHANG ChunChao; ZHU Feng; WEI JianFeng; ZHENG ShuSen; LI LanJuan

    2007-01-01

    In order to understand the allograft rejection in orthotopic liver transplantation (OLT), an allograft rejection rat model was established and studied by proteomic approach. The protein expression profiles of liver tissues were acquired by fluorescence two-dimensional difference gel electrophoresis (2D DIGE)that incorporated a pooled internal standard and reverse fluorescent labeling method. The expression levels of 27 protein spots showed significant changes in acute rejection rats. Among these spots, 19were identified with peptide mass fingerprinting using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) after tryptic in-gel digestion. The results of the present paper could be helpful for our better understanding of allograft rejection in organ transplantation.

  19. EXPRESSION OF ICAM-1 AND LFA-1 MOLECULES IN RELATION TO RENAL ALLOGRAFT REJECTION IN RATS

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Objective.The purpose of this study was to assess the renal graft expression of ICAM-1(intercellular adhesion molecule-1) nd LFA-1(lymphocyte function-associated antigen-1)molecule with relation to graft rejection.Methods.Rat kiney transplantation was performed according to the procedure of Kamada with some modification.Experimental rats were divided into 5 groups.The survival time of recipient rats and function of grafts after renal transplantation were observed.The sections of renal graft were stained for monoclonal antibody ICAM-1 and LFA-1, and then quantification of ICAM-1 and LFA-1 expression was accomplished by computer image analysis.Results.ICAM-1 and LFA-1 increased significantly in the renal allograft rejection group as compared with the non-rejection groups(P<0.05).Conluson.Both biopsy of renal graft and monitoring of ICAM-1 and LFA-1 are useful tools in diagnosing and treating acute rejection.

  20. Modulation of early stress-related biomarkers in cytoplasm by the antioxidants silymarin and quercetin using a cellular model of acute arsenic poisoning.

    Science.gov (United States)

    Soria, Elio A; Eynard, Aldo R; Bongiovanni, Guillermina A

    2010-12-01

    Several pathologies (e.g. cancer and diabetes) are increased in arsenic-exposed populations, with oxidative stress being a major toxicological mechanism. Since the flavonoids silymarin (S) and quercetin (Q) are antioxidants and may protect cells, it would be valuable to develop a model which allows assessing the potential of xenobiotic against arsenic cytotoxicity in an efficient and rapid way. Thus, the oxidant production [e.g. reactive oxygen species and reactive nitrogen species (RNS)], the molecular parameters of biological response [e.g. plasma membrane composition, actin microfilaments and activated diphosphorilated c-Jun N-terminal kinase (JNK)] and cellular viability were determined in CHO-K1 cells treated with arsenite (As), S and Q. Arsenic caused loss of the cellular viability in a time-dependent manner. This effect was accompanied by a lipid hydroperoxide (LHP) formation, with no RNS induction or ganglioside content changes being found. Both flavonoids counteracted oxidative damage. Despite all treatments had unspecific responses on nitrite cellular release along the time, there was no relation between them and the cellular viability. Arsenic induced cytoplasmic microfilament rearrangement (tight perinuclear distribution with projections, stress fibres and pseudopodia) which was reversed by S. Also, activated JNK showed a similar distribution to actin. Contrarily, Q caused a dysmorphic granular pattern, thus behaving as a toxic agent. Summing up, toxic levels of arsenic disturb the redox homeostasis with LHP induction and early triggering of stress responses in cytoskeleton and cell signalling. Using the proposed model, only S showed to protect cells from arsenical cytotoxicity without own toxic properties. Thus, S might be considered for modulation of the human arsenic susceptibility.

  1. Correlation of human leucocyte antigen matching to acute rejection and allograft survival after renal allograft%肾移植患者抗人类白细胞抗体配型与术后急性排斥反应及移植肾存活的关系

    Institute of Scientific and Technical Information of China (English)

    李留洋; 赵明; 陈剑荣; 钱俊; 李民; 孙尔维; 郭颖; 岳良升; 范礼佩; 陈桦

    2008-01-01

    BACKGROUND: Panel reactive antibody (PRA) can mediate hyperacute rejection, and lead to decrease in success rate of transplantation and survival rate of renal graft in highly sensitized recipients compared to non-sensitized recipients.OBJECTIVE: According to human leucocyte antigen (HLA) cross-matching standards to select suitable donors for sensitized recipients and to evaluate the incidence of acute rejection and survival rate of renal allografts.DESIGN: Case observation.SETTING: Zhujiang Hospital of Southern Medical University.PARTICIPANTS: 136 sensitized recipients with positive PRA underwent renal transplantation in Department of Organ Transplantation, Zhujiang Hospital of Southern Medical University between January 1997 and December 2003 were selected, including 41 males and 95 females, aged (45±9) years. Recipients of first, second, third, and fourth transplant were 115, 18, 2 and 1 case, respectively. The informed consent was obtained from all patients. The protocol was approved by Hospital Ethics Committee. Lambda antigen tray (LAT) and LAT-Mix were purchased from One Lambda, Inc, USA. Special monoclonal tray -Asian HLA class Ⅰ (SMT72R) and Micro SSP Generic HLA Class Ⅱ (DRB/DQB) were also purchased from One Lambda, Inc, USA.METHODS: Pre-operative PRA levels and specificity of recipients were detected by ELISA test with Lambda antigen tray (LAT). Donor and recipient HLA class Ⅰ typing was performed with special tray - Asian HLA class Ⅰ (SMT72R), and HLA class Ⅱ gene typing with Micro SSP Generic HLA Class Ⅱ (DRB/DQB) (Micro-SSP). HLA-matching between donor and recipient was performed according to HLA cross-reactive group (CREG) standards by UNOS and class Ⅱ antigen permissible mismatch. The incidence of acute rejection and survival rate of renal allografts were evaluated within 1, 3 and 5 years.MAIN OUTCOME MEASURES: ①PRA levels and specificity of sensitized recipients before and after transplantation; ②HLA-matching between donor and

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

    OpenAIRE

    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...

  3. THE ROLE OF SPECKLE-TRACKING ECHOCARDIOGRAPHY TECHNIQUE AT THE STAGE OF SUBCLINICAL HEART TRANSPLANT REJECTION

    Directory of Open Access Journals (Sweden)

    T. V. Stavenchuk

    2015-01-01

    Full Text Available Aim. To identify new predictors of heart transplant rejection by using speckle-tracking echocardiography technique. Materials and methods. 117 recipients were included into research. The follow-up period in S.V. Ochapovsky Region Clinical Hospital No 1 was from March 2010 to April 2015. The groups were allocated based on results of the retrospective analysis of biopsies: group 1 (n = 68, recipients without signs of cellular and humoral rejection (AMR0 ACR0; group 2 (n = 28, recipients with ACR1; group 3 (n = 16, patients with ACR2; group 4 (n = 5, patients with chronic rejection. The analysis of the results was carried out with endomyocardial biopsy, coronary angiography, transthoracic echocardiography (TTE, tissue Doppler imaging, speckle-tracking echocardiography. Results. Early complications include infections and rejection of heart transplant. Cellular rejection is diagnosed in 70% of cases, humoral rejection in 30% of cases. The disease of coronary arteries is a kind of late complications. It was diagnosed in 13.7%. Fraction rejection sensitivity was 63%, specificity was 97% in recipients with ACR1 while carrying out TTE for the purpose of identification of early diagnostic criterion of rejection; recipients with ACR2 had 75% and 96%, respectively. While carrying out PW sensitivity and specificity Е/А in recipients with ACR1 were 83% and 53%, respectively; recipients with ACR2 had 85% and 52%, respectively. While carrying out PW-TDI sensitivity and specificity Е in recipients with ACR1 were 83% and 58%, respectively; recipients with ACR2 had 88% and 60%, respectively. The assessment of myocardial deformation of the left ventricle is as follows: global peak systolic strain in recipients without rejection (GLPS LV – (–17.54 ± 3.71%, р = 0.0012; recipients with (ACR1, AMR1 had GLPS LV (–10.52 ± 1.8%, p = 0.0012; recipients with ACR2 had (–6.44 ± 1.8%, p = 0.002; recipients with chronic rejection had (–9.43 ± 1.8%, p = 0

  4. Not all rejections are alike; competence and warmth as a fundamental distinction in social rejection

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    OpenAIRE

    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.

  6. An adaptive algorithm for noise rejection.

    Science.gov (United States)

    Lovelace, D E; Knoebel, S B

    1978-01-01

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

  7. 21 CFR 1230.47 - Rejected containers.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rejected containers. 1230.47 Section 1230.47 Food... FEDERAL CAUSTIC POISON ACT Imports § 1230.47 Rejected containers. (a) In all cases where the containers... notification to the importer that the containers must be exported under customs supervision within 3...

  8. Renal allograft rejection. Unusual scintigraphic findings

    Energy Technology Data Exchange (ETDEWEB)

    Desai, A.G.; Park, C.H.

    1986-11-01

    During sequential renal imagining for evaluation of clinically suspected rejection, focal areas of functioning renal tissue were seen in two cases of renal transplant in the midst of severe and irreversible renal allograft rejection. A probable explanation for this histopathologically confirmed and previously unreported finding is discussed.

  9. 大鼠口腔黏膜急性排斥反应外周血CD68水平与巨噬细胞浸润的相关性研究%Correlation between the CD68 proportion of peripheral blood mononuclear cell and macrophage infiltration during acute rejection of rat oral mucosal xenotransplantation

    Institute of Scientific and Technical Information of China (English)

    左雯鑫; 王红; 李晓宇; 陶小安; 程斌

    2011-01-01

    Objective To investigate the role of the dynamic process of peripheral blood CD68 mononuclear cells proportion and macrophages inflitration and possible correlation between them during acute rejection of rat oral mucosal xenotransplantation. Methods Thirty-six female wistar rats were divided into three groups randomly, including xenotransplantation group( n = 15 ), trauma control group( n = 12) and normal control group ( n = 9). The rat oral mucosa xenotransplantation model was established. The flow cytometry was used to evaluate the peripheral blood CD68 mononuclear cell and immunohistochemical assay performed to detect the macrophages infiltration one week (W1), two weeks (W2)and four weeks (W4) after xenotransplantation. Results The peripheral blood CD68 mononuclear cells percentage of each xenotransplantation group presented a rise and fall tendency at the three time points, and the peak value appeared at W4(43. 1% ), and the nadir at W2( 10.4% ). The macrophage counts achieved peak value in xenotransplantation group at W1 [ 580.0 (195.5) cell/high power field ], and then reduced with time. Conclusions The mononuclear cells and macrophage were capable of recognizing the xenograft and directly participated the acute rejection of rat oral mucosal xenotransplantation. The peripheral blood mononuclear cells percentage could reflect macrophage infiltrating condition at the early stage of the acute rejection.%目的 探讨大鼠外周血CD68单核细胞比例和颊黏膜巨噬细胞浸润变化及二者相关性在口腔黏膜急性排斥反应中的作用和意义.方法 36只雌性Wistar大鼠按随机数字表随机分为移植组(15只)、创伤对照组(12只)及正常对照组(9只),建立口腔黏膜异种移植模型,分别于术后1、2、4周采用流式细胞术检测各组大鼠外周血CD68单核细胞百分数,免疫组化SP法检测颊黏膜巨噬细胞CD68的表达.结果 移植组3个时点外周血CD68单核细胞百分数呈高低起伏的变

  10. Image rejects/retakes-radiographic challenges

    International Nuclear Information System (INIS)

    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

  11. Image rejects/retakes--radiographic challenges.

    Science.gov (United States)

    Waaler, D; Hofmann, B

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ali H Dalloul

    2013-12-01

    Full Text Available Solid organs have been transplanted for decades. Since the improvement in graft selection and in medical and surgical procedures, the likelihood of graft function after one year is now close to 90%. Nonetheless even well-matched recipients continue to need medications for the rest of their lives hence adverse side effects and enhanced morbidity. Understanding Immune rejection mechanisms, is of increasing importance since the greater use of living-unrelated donors and genetically unmatched individuals. Chronic rejection is devoted to T-cells, however the role of B-cells in rejection has been appreciated recently by the observation that B-cell depletion improve graft survival. By contrast however, B-cells can be beneficial to the grafted tissue. This protective effect is secondary to either the secretion of protective antibodies or the induction of B-cells that restrain excessive inflammatory responses, chiefly by local provision of IL-10, or inhibit effector T-cells by direct cellular interactions. As a proof of concept B-cell-mediated infectious transplantation tolerance could be achieved in animal models, and evidence emerged that the presence of such B-cells in transplanted patients correlate with a favorable outcome. Among these populations, regulatory B-cells constitute a recently described population. These cells may develop as a feedback mechanism to prevent uncontrolled reactivity to antigens and inflammatory stimuli. The difficult task for the clinician, is to quantify the respective ratios and functions of tolerant vs effector B-cells within a transplanted organ, at a given time point in order to modulate B-cell-directed therapy. Several receptors at the B-cell membrane as well as signaling molecules, can now be targeted for this purpose. Understanding the temporal expansion of regulatory B-cells in grafted patients and the stimuli that activate them will help in the future to implement specific strategies aimed at fighting chronic

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2000-12-01

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

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

    International Nuclear Information System (INIS)

    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

  15. Rejection of pharmaceuticals by forward osmosis membranes.

    Science.gov (United States)

    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

  16. Variation of tumor necrosis factor-alpha during acute rejection after liver transplantation in a rhesus monkey%恒河猴肝移植模型移植后急性排斥反应时肿瘤坏死因子α的变化

    Institute of Scientific and Technical Information of China (English)

    张熙冰; 冉江华; 刘静; 张升宁; 李来邦; 陈奕明; 高杨; 李望; 李立

    2014-01-01

    BACKGROUND:Tumor necrosis factor-αis an inflammatory cytokine involved in the immune response and increasing graft antigen expression. OBJECTIVE:To investigate the relationship between tumor necrosis factor-αin the liver tissue and acute rejection after liver transplantation in a rhesus monkey. METHODS:Liver transplant models in rhesus monkey were constructed by the improved vascular dual cuff, supporting tube of biliary tract and artery anastomosis method. The successful models were randomly divided into experimental group (no immunosuppressant treatment in perioperative period) and control group (treated by immunosuppressant in perioperative period). Then the blood samples and liver tissue were col ected at 6, 12, 24, and 72 hours after surgery. Al ograft rejections of liver transplantation were monitored by liver function tests, hematoxylin-eosin staining and Banff score. Final y, the expression level of tumor necrosis factor-αwas detected by western blot analysis and immunohistochemistry technique. RESULTS AND CONCLUSION:The expression of tumor necrosis factor-αin the experimental group and control group began to increase at 6 hours, reached the peak at 12 hours, and then decreased at 24-72 hours. The changes of expression level were the most obvious in the experimental group. At 6, 12, 24 and 72 hours, the expression of tumor necrosis factor-αin the experimental group was significantly higher than that in the control group (P<0.05). This change appeared earlier than pathological changes in the liver and liver function. Variations in the expression of tumor necrosis factor-αafter liver transplantation have important implications for early diagnosis of acute rejection after liver transplantation.%背景:肿瘤坏死因子α是一种炎性细胞因子,参与移植免疫反应并增加移植物抗原表达,并在其中发挥着重要作用。目的:分析恒河猴肝移植后肝组织中肿瘤坏死因子α的变化与急性排斥反应的关系。

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2015-02-01

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

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Directory of Open Access Journals (Sweden)

    Lucy C Sullivan

    Full Text Available 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.

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

    Science.gov (United States)

    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

  2. Rhoh deficiency reduces peripheral T-cell function and attenuates allogenic transplant rejection

    DEFF Research Database (Denmark)

    Porubsky, Stefan; Wang, Shijun; Kiss, Eva;

    2011-01-01

    better graft function. This effect was independent of the lower T-cell numbers in Rhoh-deficient recipients, because injection of equal numbers of Rhoh-deficient or control T cells into kidney transplanted mice with SCID led again to a significant 60% reduction of rejection. Mixed lymphocyte reaction...... deficiency in a clinically relevant situation, in which T-cell inhibition is desirable. In murine allogenic kidney transplantation, Rhoh deficiency caused a significant 75% reduction of acute and chronic transplant rejection accompanied by 75% lower alloantigen-specific antibody levels and significantly...

  3. Cellular Telephone

    Institute of Scientific and Technical Information of China (English)

    杨周

    1996-01-01

    Cellular phones, used in automobiles, airliners, and passenger trains, are basically low-power radiotelephones. Calls go through radio transmitters that are located within small geographical units called cells. Because each cell’s signals are too weak to interfere with those of other cells operating on the same fre-

  4. Structural Decoupling and Disturbance Rejection in a Distillation Column

    DEFF Research Database (Denmark)

    Bahar, Mehrdad; Jantzen, Jan; Commault, C.;

    1996-01-01

    Introduction, distillation column model, input-output decoupling, disturbance rejection, concluding remarks, references.......Introduction, distillation column model, input-output decoupling, disturbance rejection, concluding remarks, references....

  5. Anti-rejection effect of ethanol extract of Poria cocos wolf in rats after cardiac allograft implantation

    Institute of Scientific and Technical Information of China (English)

    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.

  6. Corneal Graft Rejection: Incidence and Risk Factors

    Directory of Open Access Journals (Sweden)

    Alireza Baradaran-Rafii

    2008-12-01

    Full Text Available

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

  7. Image rejects in general direct digital radiography

    International Nuclear Information System (INIS)

    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

  8. THE VALUE OF EXTRACORPOREAL PHOTOCHEMOTHERAPY IN RENAL TRANSPLANT REJECTION INHIBITION

    Directory of Open Access Journals (Sweden)

    V. A. Fedulkina

    2016-01-01

    Full Text Available The aim of the study was to determine the value of extracorporeal photochemotherapy (EPCT in the induction of tissue tolerance in renal transplantation. EPCT was applied to 24 renal transplant recipients in early postoperative period, the control group consisted of paired transplant recipients. In the group using EPCT over a three-year period of observation no clinical or histological signs of rejection were observed. In the control group, histologically confirmed rejection was observed in 4 cases, in 2 cases transplantectomy due to acute rejection. The reducing incidence of infectious complications in the study group compared with the control one (4 and 19 cases, respectively and decreasing number of hospitalizations on various reasons (8 and 47 cases in the study and control groups, respectively were also noted. Three-year graft survival was 100% and 83.3% in the study and the control groups, respectively. Using immunological tests in 30 days after transplantation the stable number of cells expressing coactivation molecules (57.7 ± 18.2 and 52.7 ± 23.2%, respectively, p > 0.05 and the density of their co-expression (22.7 ± 6.0 and 19.6 ± 7.0 units, respectively, p > 0.05 were demonstrated, while in the study group, the pronounced and statistically significant reduction both in the amount of cells expressing co-activation receptors (from 57.7 ± 18.2 to 34.5 ± 11.4%, p < 0.05 and in the density of these receptors on naive helper T-lymphocytes (from 22.7 ± 6.0 to 16.8 ± 5.1 units, p < 0.05 was revealed. Thus, it is noted that EPCT provides induction of tolerance to MHC antigens in kidney transplantation due to reducing expression of coactivation molecules which promote the second signaling pathway to T-cell receptor activation. 

  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

    Institute of Scientific and Technical Information of China (English)

    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. 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

    Institute of Scientific and Technical Information of China (English)

    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.

  11. Effect of prolonged ischemic time in normal temperature on acute rejection in a rat allotransplantation model%常温下不同时长的缺血对大鼠皮瓣异体移植后排斥反应的影响

    Institute of Scientific and Technical Information of China (English)

    肖博; 黎鸿章; 殷悦; 郭树忠

    2011-01-01

    Objective To examine how ischemic time under common temperature affects acute rejection by using a rat vascularized skin transplantation model.Methods Vascularized groin flaps were transplanted from BN to Lewis rats with 1,2,3 and 4 h of ischemic time (Isc-1 h,2 h,3 h,4 h groups) under common temperature,and the allografts in each group were evaluated daily.Groin flaps were transplanted from Lewis to Lewis rats as control group.Biopsy samples taken from the each group on the postoperative day 2-8 were graded for signs of acute rejection.Biopsy samples taken from each group on the postoperative day 6 were stained for chemokine receptor CXCR3.Results When the ischemia time was 1,2,3 and 4 h,the survival time of the grafts was (9.0 ± 1.2),(8.6 ±1.1),(8.8 ± 1.3),and (7.0 ± 0.8) days respectively.The survival time in Isc-4 h group was significantly shorter than in other groups (P<0.05).Histological evaluation showed acceleration of activated lymphocyte infiitration in the Isc-4 h group as compared with other g.roups.Furthermore,the proportion of CXCR3 positive cells in the Isc-4 h group was (50.1 ± 8.4) %,significantly higher than that in the other groups on the day 6 after transplantation.Conclusion When ischemic time was over 3 h,the immune response is accelerated.The acceleration is associated with the higher expression of CXCR3 in the infiltrated cells.%目的 探讨常温下不同时长的缺血对大鼠皮瓣异体移植后排斥反应的影响.方法 Brown Norway(BN)大鼠下腹部皮瓣原位移植至Lewis大鼠,根据移植皮瓣在常温下总缺血时间的不同分为lh、2h、3h和4h组.另以供、受鼠均为Lewis大鼠5对作为对照组,该组移植皮瓣常温下总缺血时间为4h.观察移植后皮瓣的存活情况;术后取皮瓣组织,行HE染色以观察排斥反应的发生情况;行CXC趋化因子受体3(CXCR3)免疫组化染色,观察CXCR3阳性细胞的浸润情况.结果 lh、2h、3h和4h组移植皮瓣的存活时间分别为(9

  12. A proteomic analysis of allograft rejection in rats after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In order to understand the allograft rejection in orthotopic liver transplantation (OLT), an allograft re- jection rat model was established and studied by proteomic approach. The protein expression profiles of liver tissues were acquired by fluorescence two-dimensional difference gel electrophoresis (2D DIGE) that incorporated a pooled internal standard and reverse fluorescent labeling method. The expression levels of 27 protein spots showed significant changes in acute rejection rats. Among these spots, 19 were identified with peptide mass fingerprinting using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) after tryptic in-gel digestion. The results of the present paper could be helpful for our better understanding of allograft rejection in organ transplantation.

  13. Treatment of Antibody-Mediated Rejection in Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  15. Large Solar-Rejection Filter

    Science.gov (United States)

    Roberts, William; Sheikh, David; Patrick, Brian

    2007-01-01

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

  16. Clinical observation of the effect of tacrolimus (Prograf) against renal allograft rejection in 294 cases

    Institute of Scientific and Technical Information of China (English)

    YU Li-xin; YE Gui-rong; DENG Wen-feng; FU Shao-jie; DU Chuan-fu; MIAO Yun; YAO Bing

    2002-01-01

    Objective: To study the effect of tacrolimus (Prograf, FK506) in preventing renal allograft rejection. Methods: The curative effect, therapy index, toxicity and side effects of FK506 were observed in 294renal transplant recipients among whom 268 received FK506 24 h after the operation and the other 26 with cyclosporine (CsA) developed acute rejection after transplantation and were given FK506 to replace methylprednisolone (MP) when the latter did not result. All the patients were given oral mycophenolate mofetil (MMF, 1.0 g/d) and meticorten (Pred, 30 mg/d) 24 h later after operation. Results: In the 268 recipients previously mentioned, the incidence of acute rejection was 10. 45%, glycometabolism disorder 9.33%, nervous system disturbance 1.59%, liver function abnormality 2.99%, nephrotoxicity 1.87%, gastrointestinal disorder 17. 5%, cytomegalovirus (CMV) viremia 2.99%, and non-CMV pulmonary infection 1. 59%(4/268), with 1 fatal case for cerebral hemorrhage with normal allograft function and another 2 non-fatal cases in which function loss resulted in removal of the allografts. The blood trough concentrations of FK506were between 5 and 20μg/L. In the 26 cases of steroid-resistant rejection, 23 (88. 46%, 23/26) were reversed and the rest 3 required plasma exchange and application of OKT3 before recovery. Conclusion: As a safe and effective immunosuppressant, FK506 can reduce the incidence of allograft rejection in kidney transplant recipients with little side effects or toxicity, which is particularly applicable in patients with steroid-resistant rejection or CsA nephrotoxicity. Attention should to be paid to glycometabolism disorder due to FK506, however, the long-term effects of FK506 need further investigation.

  17. Preventing Allograft Rejection by Targeting Immune Metabolism

    Directory of Open Access Journals (Sweden)

    Chen-Fang Lee

    2015-10-01

    Full Text Available Upon antigen recognition and co-stimulation, T lymphocytes upregulate the metabolic machinery necessary to proliferate and sustain effector function. This metabolic reprogramming in T cells regulates T cell activation and differentiation but is not just a consequence of antigen recognition. Although such metabolic reprogramming promotes the differentiation and function of T effector cells, the differentiation of regulatory T cells employs different metabolic reprogramming. Therefore, we hypothesized that inhibition of glycolysis and glutamine metabolism might prevent graft rejection by inhibiting effector generation and function and promoting regulatory T cell generation. We devised an anti-rejection regimen involving the glycolytic inhibitor 2-deoxyglucose (2-DG, the anti-type II diabetes drug metformin, and the inhibitor of glutamine metabolism 6-diazo-5-oxo-L-norleucine (DON. Using this triple-drug regimen, we were able to prevent or delay graft rejection in fully mismatched skin and heart allograft transplantation models.

  18. CARDIAC TRANSPLANT REJECTION AND NON-INVASIVE COMON CAROTID ARTERY WALL FUNCTIONAL INDICES

    Directory of Open Access Journals (Sweden)

    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

  19. Video auditing techniques for breaker reject

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Solar dynamic space power system heat rejection

    Science.gov (United States)

    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.

  1. PREVENTION AND TREATMENT OF REJECTION AFTER SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    Lei Yang; Yong-feng Liu; Shu-rong Liu; Gang Wu; Jia-lin Zhang; Yi-man Meng; Shao-wei Shong; Gui-chen Li

    2005-01-01

    Objective To explore methods of preventing and reversing rejection after simultaneous pancreas-kidney (SPK) tran splantation. Methods Seventeen patients underwent SPK transplantation from September 1999 to September 2003 were reviewed retrospectively. Immunosuppression was achieved by a triple drug regimen consisting of cyclosporine, mycophenolate mofteil (MMF), and steroids. Three patients were treated with anti-CD3 monoclone antibody (OKT3, 5 mg· d-1) for induction therapy for a mean period of 5-7 days. One patients received IL-2 receptor antibodies (daclizumab) in a dose of 1 mg· kg-1 on the day of transplant and the 5th day posttransplant. One patient was treated with both OKT3 and daclizumab for induction. Results No primary non-functionality of either kidney or pancreas occurred in this series of transplantations. Function of all the kidney grafts recovered within 2 to 4 days after transplantation. The level of serum creatinine was 94 ± 11 μmol/L on the 7th day posttransplant. One patient experienced the accelerated rejection, resulting in the resection of the pancreas and kidney grafts because of the failure of conservative therapy. The incidence of the first rejection episodes at 3 months was 47.1% (8/17). Only the kidney was involved in 35.3% (6/17); and both the pancreas and kidney were involved in 11.8% (2/17). All these patients received a high-dose pulse of methylprednisone (0.5 g·d-1) for 3 days. OKT3 (0.5 mg·d-1) was administered for 7-10 days in two patients with both renal and pancreas rejection. All the grafts were successfully rescued. Conclusion Rejection, particularly acute rejection, is the major cause influencing graft function in SPK transplantation. Monitoring renal function and pancreas exocrine secretion, and reasonable application of immunosuppressants play important roles in the diagnosis and treatment of rejection.

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

    Directory of Open Access Journals (Sweden)

    Marcos V. Silva

    2012-01-01

    Full Text Available Kidneys are one of the most frequently transplanted human organs. Immunosuppressive agents may prevent or reverse most acute rejection episodes; however, the graft may still succumb to chronic rejection. The immunological response involved in the chronic rejection process depends on both innate and adaptive immune response. T lymphocytes have a pivotal role in chronic rejection in adaptive immune response. Meanwhile, we aim to present a general overview on the state-of-the-art knowledge of the strategies used for manipulating the lymphocyte activation mechanisms involved in allografts, with emphasis on T-lymphocyte costimulatory and coinhibitory molecules of the B7-CD28 superfamily. A deeper understanding of the structure and function of these molecules improves both the knowledge of the immune system itself and their potential action as rejection inducers or tolerance promoters. In this context, the central role played by CD28 family, especially the relationship between CD28 and CTLA-4, becomes an interesting target for the development of immune-based therapies aiming to increase the survival rate of allografts and to decrease autoimmune phenomena. Good results obtained by the recent development of abatacept and belatacept with potential clinical use aroused better expectations concerning the outcome of transplanted patients.

  3. Mycophenolate Mofetil with Low Dose CsA for Chronic Rejection in Primary Cadaveric Renal Recipients

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To investigate the clinical efficacy of mycophenolate mofetil(MMF) with low dose CsA for chronic rejection in primary cadaveric renal recipients. Methods A total of 8 renal recipients who were clinically diagnosed as chronic rejection were given triimmunosuppressive agents: MMF 1.5~2.0 g/d+ CsA 2 to 3 mg/kg*d-1 and pred 10 mg/d.Results Blood creatinine reduced to normal level and urine protein disappeared in five cases, blood creatinine and urine protein decreased obviously in two cases, and kidney function deteriorated in another patient 4 to 9 weeks after this strategy. No acute rejection episodes or liver damage occurred among these patients during treatment. White blood cells reduced in one case, but it improved after therapy. Conclusion  MMF combined with low dose CsA can bring a considerable efficacy in reversing chronic rejection of renal recipients. This immunosuppressive strategy may be a useful routine in the treatment of chronic rejection.

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

    Science.gov (United States)

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

    1996-10-01

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

  5. Rejection Pathways in Heart Transplant Recipients

    NARCIS (Netherlands)

    N.M. van Besouw (Nicole)

    1999-01-01

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

  6. Waste heat rejection from geothermal power stations

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, R.C.

    1978-12-01

    This study of waste heat rejection from geothermal power stations is concerned only with the heat rejected from the power cycle. The heat contained in reinjected or otherwise discharged geothermal fluids is not included with the waste heat considered here. The heat contained in the underflow from the flashtanks in such systems is not considered as part of the heat rejected from the power cycle. By following this definition of the waste heat to be rejected, various methods of waste heat dissipation are discussed without regard for the particular arrangement to obtain heat from the geothermal source. Recent conceptual design studies made for 50-MW(e) geothermal power stations at Heber and Niland, California, are of particular interst. The former uses a flashed-steam system and the latter a binary cycle that uses isopentane. In last-quarter 1976 dollars, the total estimated capital costs were about $750/kW and production costs about 50 mills/kWhr. If wet/dry towers were used to conserve 50% of the water evaporation at Heber, production costs would be about 65 mills/kWhr.

  7. Development of enhanced sulfur rejection processes

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-03-01

    Research at Virginia Tech led to the development of two complementary concepts for improving the removal of inorganic sulfur from many eastern U.S. coals. These concepts are referred to as Electrochemically Enhanced Sulfur Rejection (EESR) and Polymer Enhanced Sulfur Rejection (PESR) processes. The EESR process uses electrochemical techniques to suppress the formation of hydrophobic oxidation products believed to be responsible for the floatability of coal pyrite. The PESR process uses polymeric reagents that react with pyrite and convert floatable middlings, i.e., composite particles composed of pyrite with coal inclusions, into hydrophilic particles. These new pyritic-sulfur rejection processes do not require significant modifications to existing coal preparation facilities, thereby enhancing their adoptability by the coal industry. It is believed that these processes can be used simultaneously to maximize the rejection of both well-liberated pyrite and composite coal-pyrite particles. The project was initiated on October 1, 1992 and all technical work has been completed. This report is based on the research carried out under Tasks 2-7 described in the project proposal. These tasks include Characterization, Electrochemical Studies, In Situ Monitoring of Reagent Adsorption on Pyrite, Bench Scale Testing of the EESR Process, Bench Scale Testing of the PESR Process, and Modeling and Simulation.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

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

    2016-11-01

    This study investigates abuse and rejection sensitivity as important correlates of risky sexual behavior in the context of substance use. Victims of abuse may experience heightened sensitivity to acute social rejection and consequently engage in risky sexual behavior in an attempt to restore belonging. Data were collected from 258 patients at a substance use treatment facility in Washington, D.C. Participants' history of abuse and risky sexual behavior were assessed via self-report. To test the mediating role of rejection sensitivity, participants completed a social rejection task (Cyberball) and responded to a questionnaire assessing their reaction to the rejection experience. General risk-taking propensity was assessed using a computerized lab measure. Abuse was associated with increased rejection sensitivity (B=0.124, SE=0.040, p=0.002), which was in turn associated with increased risky sex (B=0.06, SE=0.028, p=0.03) (indirect effect=0.0075, SE=0.0043; 95% CI [0.0006, 0.0178]), but not with other indices of risk-taking. These findings suggest that rejection sensitivity may be an important mechanism underlying the relationship between abuse and risky sexual behavior among substance users. These effects do not extend to other risk behaviors, supporting the notion that risky sex associated with abuse represents a means to interpersonal connection rather than a general tendency toward self-defeating behavior. PMID:27344009

  10. Intrathymic inoculation of donor liver specific antigen alleviates rejection of liver allotransplantation

    Institute of Scientific and Technical Information of China (English)

    贾长库; 郑树森; 章爱斌

    2003-01-01

    Use and effects of liver specific antigen in orthotopic liver transplantations were researched 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 common situation and survival time, rejection grades, NF-κB activity of splenocytes and IL-2mRNA expression of grafted liver were used to analyze acute rejection severity and immune state of animals in different groups. The common situation of group I was very well after transplantation and no signs of rejection were found. Recipients of group II lost body weight progressively. All dead within day 9 to day 13 posttransplantation; median survival time was 10.7±0.51 days. It was an optimal acute rejection control. As for group III, 5 out of 6 recipients survived for a long time and common situation was remarkably better than that of group II. Its rejection grades were significantly lower than that of group II(P<0.05). NF-κB activity was only detected in group I at day 5 and day 7 after transplantation, whereas high activity of NF-κB was detected at all time points in groupII and the low NF-κB activity detected in group III was significantly lower than that of group II (P<0.05). No IL-2mRNA expression was detected at any time point in group I,whereas high level expression was detected at all time points in group II and the low level expression only detected at day 3 in group III was significantly lower than that of group II (P<0.05). Conclusion: LSA is an important transplantation antigen which is involved directly in the immunorejection of liver transplantation. We report here for the first time that intrathymic inoculation of LSA can alleviate the rejection of liver allotransplantation; and that grafts can survive for a long time thereby, thus leading to a novel way to achieve liver transplantation immunotolerance.

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

    NARCIS (Netherlands)

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

    2003-01-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

  13. Chronic Kidney Isograft and Allograft Rejection

    Institute of Scientific and Technical Information of China (English)

    严群; 张鹏; 杨传永

    2002-01-01

    Summary: In this study antigen-independent factor in the pathogenesis of chronic rejection of organ transplants was examined. Kidney isografts and allografts were transplanted orthotopically into bilaterally nephroectomized rat recipients and studied functionally, morphologically and immunohistologically, at serial intervals up to 52 weeks after transplantation. Allograft recipients developed progressive proteinuria after 12 weeks, with gradual renal failure ultimately leading to death. At the same time, morphological changes, including progressive arteriosclerosis and glomerulosclerosis, tubular atrophy and interstitial fibrosis, developed. Immunohistologically, macrophages infiltrated glomeruli during this period and cytokines became unregulated. Our resuits showed that antigen-independent functional and morphological changes occurred in long-term kidney isografts and mimicked those appearing much earlier in allografts that reject chronically.Initial injury and extent of functioning renal mass is suggested to be important factor for such late changes.

  14. Interference Rejection Techniques in DSSS Communication System

    Institute of Scientific and Technical Information of China (English)

    GONGXiangyang; HUGuangrui

    2003-01-01

    It is known that the narrowband interfer-ence rejection capability of a direct sequence (DS) spread spectrum (SS) system can be enhanced considerably by an interference rejection algorithm prior to correlating it with the pseudo noise (PN) sequence. For narrowband gaussian noise (NGN), the techniques in common use are transver-sal filter. It models SS signal and NGN as stationary, then utilizes temporal correlation difference between SS signal and NBL however, SS signal and NGN are cyclostation-ary (CS). CS signal has correlation in frequency domain called spectrum correlation, which can not be employed by transversal filter. In this article, SS signal and NBIare modeled as CS and FRESH filter is adopted to exploit the correlation both in time domain and frequency domain.Computer simulation shows that FRESH filter can improve the system performance considerably compared with con-ventional transversal filter.

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

    Directory of Open Access Journals (Sweden)

    V. N. Poptsov

    2015-01-01

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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2015-01-01

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

  18. Acute Renal Failure - A Serious Complication in Patients After Kidney Transplantation.

    Science.gov (United States)

    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

  19. Mechanisms involved in antibody- and complement-mediated allograft rejection

    OpenAIRE

    Wasowska, Barbara A.

    2010-01-01

    Antibody-mediated rejection has become critical clinically because this form of rejection is usually unresponsive to conventional anti-rejection therapy, and therefore, it has been recognized as a major cause of allograft loss. Our group developed experimental animal models of vascularized organ transplantation to study pathogenesis of antibody- and complement-mediated endothelial cell injury leading to graft rejection. In this review, we discuss mechanisms of antibody-mediated graft rejectio...

  20. 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

    Institute of Scientific and Technical Information of China (English)

    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

  1. Two cases of hepatobiliary scintigraphy of liver transplantation in rejection

    Energy Technology Data Exchange (ETDEWEB)

    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).

  2. Two cases of hepatobiliary scintigraphy of liver transplantation in rejection

    International Nuclear Information System (INIS)

    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)

  3. USA: California rejects mandatory GMO labelling

    OpenAIRE

    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 ...

  4. Uremic escape of renal allograft rejection

    Energy Technology Data Exchange (ETDEWEB)

    van Schilfgaarde, R. (Rijksuniversiteit Leiden (Netherlands). Academisch Ziekenhuis); van Breda Vriesman, P.J.C. (Rijksuniversiteit Limburg Maastricht (Netherlands). Dept. of Immunopathology)

    1981-10-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Bueno V.

    2002-01-01

    Full Text Available Organ transplantation can be considered as replacement therapy for patients with end-stage organ failure. The percent of one-year allograft survival has increased due, among other factors, to a better understanding of the rejection process and new immunosuppressive drugs. Immunosuppressive therapy used in transplantation prevents activation and proliferation of alloreactive T lymphocytes, although not fully preventing chronic rejection. Recognition by recipient T cells of alloantigens expressed by donor tissues initiates immune destruction of allogeneic transplants. However, there is controversy concerning the relative contribution of CD4+ and CD8+ T cells to allograft rejection. Some animal models indicate that there is an absolute requirement for CD4+ T cells in allogeneic rejection, whereas in others CD4-depleted mice reject certain types of allografts. Moreover, there is evidence that CD8+ T cells are more resistant to immunotherapy and tolerance induction protocols. An intense focal infiltration of mainly CD8+CTLA4+ T lymphocytes during kidney rejection has been described in patients. This suggests that CD8+ T cells could escape from immunosuppression and participate in the rejection process. Our group is primarily interested in the immune mechanisms involved in allograft rejection. Thus, we believe that a better understanding of the role of CD8+ T cells in allograft rejection could indicate new targets for immunotherapy in transplantation. Therefore, the objective of the present review was to focus on the role of the CD8+ T cell population in the rejection of allogeneic tissue.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    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

  8. The Rejection-Rage Contingency in Borderline Personality Disorder

    Science.gov (United States)

    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. Multivisceral transplantation in pigs: a clinicopathological analysis of tissue rejection.

    Directory of Open Access Journals (Sweden)

    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.

  10. Cellular: Toward personal communications

    Science.gov (United States)

    Heffernan, Stuart

    1991-09-01

    The cellular industry is one of the fastest growing segment of the telecommunications industry. With an estimated penetration rate of 20 percent in the near future, cellular is becoming an ubiquitous telecommunications service in the U.S. In this paper we will examine the major advancements in the cellular industry: customer equipment, cellular networks, engineering tools, customer support, and nationwide seamless service.

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

    Directory of Open Access Journals (Sweden)

    Kathryn J. Lindley

    2012-01-01

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

  12. Nanoparticle Enhanced MRI Scanning to Detect Cellular Inflammation in Experimental Chronic Renal Allograft Rejection

    Directory of Open Access Journals (Sweden)

    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.

  13. Regulatory Allospecific T Cell Clones Abrogate Chronic Allograft Rejection

    OpenAIRE

    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...

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

    OpenAIRE

    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...

  15. The private rejection of unfair offers and emotional commitment

    OpenAIRE

    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...

  16. Community rejection following sexual assault as ‘forced migration’

    OpenAIRE

    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.

  17. Cytomegalovirus and chronic allograft rejection in liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Liang-Hui Gao; Shu-Sen Zheng

    2004-01-01

    Cytomegalovirus (CMV) remains one of the most frequent viral infections and the most common cause of death after liver transplantation (LT). Chronic allograft liver rejection remains the major obstacle to long-term allograft survival and CMV infection is one of the suggested risk factors for chronic allograft rejection. The precise relationship between cytomegalovirus and chronic rejection remains uncertain.This review addresses the morbidity of cytomegalovirus infection and the risk factors associated with it, the relationship between cytomegalovirus and chronic allograft liver rejection and the potential mechanisms of it.

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

    Directory of Open Access Journals (Sweden)

    Dua Harminder

    1999-01-01

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

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

    Science.gov (United States)

    Sánchez-Fueyo, Alberto; Strom, Terry B

    2011-01-01

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

  20. Chronic Rejection in Human Vascularized Composite Allotransplantation (Hand and Face Recipients): An Update.

    Science.gov (United States)

    Kanitakis, Jean; Petruzzo, Palmina; Badet, Lionel; Gazarian, Aram; Thaunat, Olivier; Testelin, Sylvie; Devauchelle, Bernard; Dubernard, Jean-Michel; Morelon, Emmanuel

    2016-10-01

    Vascularized composite tissue allografts (VCA) have become a viable option to restore severely damaged parts of the body that cannot be repaired with conventional surgical techniques. Acute rejection develops frequently in the early postgraft period both in human and experimental VCA, but the possibility of human VCA to undergo chronic rejection (CR) remained initially unknown. The experience gained over the years shows that, similar to solid organ transplants (SOT), human VCA can also develop CR. Chronic rejection is clinically mostly apparent on the skin and targets preferentially skin and deep vessels, leading, as in SOT, to graft vasculopathy and often to graft loss. Dermal sclerosis and adnexal atrophy are additional features of CR. The pathogenetic immune mechanisms involved (cell-mediated versus humoral) remain incompletely known. The changes of CR can be detected with skin and deep tissue biopsies. Modern in vivo imaging tools can detect vascular narrowing and have the advantage of being noninvasive. However, the diagnosis and treatment of CR remain challenging, as several important questions remain to be answered: a more accurate definition of CR in VCA is needed to establish criteria allowing an accurate and early diagnosis. The pathogenetic mechanisms of CR need to be better understood to allow more efficacious treatment. Favoring/triggering factors of CR need to be better known so that they can be avoided. As in SOT, there is a need for efficient tolerance-inducing protocols that will favor graft acceptance and (ideally) circumvent the necessity of lifelong immunosuppression. PMID:27163543

  1. EFFECT OF DIETARY FISH-OIL ON RENAL-FUNCTION AND REJECTION IN CYCLOSPORINE-TREATED RECIPIENTS OF RENAL-TRANSPLANTS

    NARCIS (Netherlands)

    VANDERHEIDE, JJH; BILO, HJG; DONKER, JM; WILMINK, JM; TEGZESS, AM

    1993-01-01

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

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

    Science.gov (United States)

    2010-04-01

    ... bids; or (2) Acceptance of the offer of another bidder who, at bid opening, makes written request that... 25 Indians 1 2010-04-01 2010-04-01 false Acceptance and rejection of bids. 163.18 Section 163.18... Forest Management and Operations § 163.18 Acceptance and rejection of bids. (a) The high bid received...

  3. Graft rejection after hematopoietic cell transplantation with nonmyeloablative conditioning

    DEFF Research Database (Denmark)

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

    2008-01-01

    -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...

  4. Heterosexual Rejection and Mate Choice: A Sociometer Perspective

    Directory of Open Access Journals (Sweden)

    Lin eZHANG

    2015-12-01

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

  5. 48 CFR 1419.505 - Rejecting Small Business Administration recommendations.

    Science.gov (United States)

    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...

  6. 48 CFR 19.505 - Rejecting Small Business Administration recommendations.

    Science.gov (United States)

    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...

  7. 48 CFR 219.505 - Rejecting Small Business Administration recommendations.

    Science.gov (United States)

    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...

  8. 48 CFR 2919.505 - Rejecting Small Business Administration recommendations.

    Science.gov (United States)

    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...

  9. 48 CFR 14.404-2 - Rejection of individual bids.

    Science.gov (United States)

    2010-10-01

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

  10. 48 CFR 814.404-2 - Rejection of individual bids.

    Science.gov (United States)

    2010-10-01

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

  11. Family Rejection Triples Risk for Suicide Attempts by Transgender People

    Science.gov (United States)

    ... 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 ...

  12. Subclinical Rejection in Renal Transplantation: Reappraised.

    Science.gov (United States)

    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

  13. Ferrite grade iron oxides from ore rejects

    Indian Academy of Sciences (India)

    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.

  14. Alpha Background Rejection in Bolometer Detectors

    Science.gov (United States)

    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.

  15. Solar gains and thermal rejects by ventilation

    International Nuclear Information System (INIS)

    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)

  16. Background Assay and Rejection in DRIFT

    CERN Document Server

    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...

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

    Science.gov (United States)

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

    2005-10-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    KAUST Repository

    Valladares Linares, Rodrigo

    2011-12-01

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

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

    Science.gov (United States)

    Plaisier, Xanthe S.; Konijn, Elly A.

    2013-01-01

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

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

    Science.gov (United States)

    Plaisier, Xanthe S; Konijn, Elly A

    2013-06-01

    Adolescence is an important developmental stage during which both peers and the media have a strong influence. Both peer rejection and the use of morally adverse media are associated with negative developmental outcomes. This study examines processes by which peer rejection might drive adolescents to select antisocial media content by tying together developmental research on peer rejection and research on media effects. Assumed underlying mechanisms are rejection-based anger and frustration and the adolescent's moral judgment. A between-participants experimental design manipulated peer rejection versus acceptance in adolescents (Mage = 13.88 years; N = 74) and young adults (Mage = 21.37 years; N = 75), applying the Cyberball paradigm. Measures included the State Anger Inventory (STAXI) to assess feelings of rejection and the newly devised Media, Morals, and Youth Questionnaire (MMaYQue) to assess media preferences and moral judgment of media content. Using bootstrapping analyses, a double mediation was established: Higher levels of state anger in peer-rejected adolescents induced more tolerable moral judgments of antisocial media content, subsequently instigating a preference for antisocial media content. In contrast, the young adult sample showed no relations between peer rejection and antisocial media preference. Results are discussed within a downward spiral framework of combined peer and media influences. PMID:22799588

  3. The innate immune response in ischemic acute kidney injury

    OpenAIRE

    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...

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

    Directory of Open Access Journals (Sweden)

    Jiachuan Xiong

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

  5. Acute Bronchitis

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    1998-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Lifang Zhu

    2015-01-01

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

  10. SCHEDULING WITH REJECTION AND NON-IDENTICAL JOB ARRIVALS

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Science.gov (United States)

    Guinn, David; Burgermeister, Diane M

    2016-01-01

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

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

    Science.gov (United States)

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

    2013-06-01

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

  13. Non-clairvoyant weighted flow time scheduling with rejection penalty

    DEFF Research Database (Denmark)

    Chan, Ho-Leung; Chan, Sze-Hang; Lam, Tak-Wah;

    2012-01-01

    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...

  14. Community rejection following sexual assault as ‘forced migration’

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

  16. Hyperacute Rejection of a Living Unrelated Kidney Graft

    Directory of Open Access Journals (Sweden)

    Dietlind Tittelbach-Helmrich

    2014-01-01

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

  17. Main feed water pump NPSH control during load rejection transient

    International Nuclear Information System (INIS)

    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)

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

    Science.gov (United States)

    Chew, F S

    1991-03-01

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

  19. Multivisceral transplantation in pigs: a clinicopathological analysis of tissue rejection.

    OpenAIRE

    Mitsuoka,Shintaro; Tanaka,Noriaki; Orita, Kunzo

    1995-01-01

    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 tran...

  20. On Properties of Update Sequences Based on Causal Rejection

    OpenAIRE

    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...

  1. THE EXPERIENCE OF IMMUNOHISTOCHEMICAL INVESTIGATION OF ENDOMIOCARDIAL BIOPSIES FOR THE DIAGNOSIS OF THE HUMORAL REJECTION IN THE PATIENTS WITH HEART ALLOGRAFT

    Directory of Open Access Journals (Sweden)

    A. G. Kupriyanova

    2009-01-01

    Full Text Available The aim of present study was to characterize immunohistological features of humoral (antibody-mediated rejection, AMR by evaluating their manifestation, localization and distribution in endomiocardial biopsies (EMBs from patients after heart transplantation. The role of AMR in the development of allograft vasculopathy is investigated widely. The examine of more than 1000 EMBs maid it possible to elaborate the diagnostic criteria of acute humoral rejection, to characterize immunomorfological peculiarities of long-term heart allograft and demonstrated the relation AMR with the early development of coronary artery diseases. 

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

    KAUST Repository

    Valladares Linares, Rodrigo

    2014-07-17

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

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

    Science.gov (United States)

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

    2014-03-01

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

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

    Science.gov (United States)

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

    2012-11-15

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

  5. A novel noninvasive method to detect rejection after heart transplantation

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2014-03-01

    Chronic rejection is the primary cause of long-term failure of transplanted organs and is often viewed as an antibody-dependent process. Chronic rejection, however, is also observed in mice and humans with no detectable circulating alloantibodies, suggesting that antibody-independent pathways may also contribute to pathogenesis of transplant rejection. Here, we have provided direct evidence that chronic rejection of vascularized heart allografts occurs in the complete absence of antibodies, but requires the presence of B cells. Mice that were deficient for antibodies but not B cells experienced the same chronic allograft vasculopathy (CAV), which is a pathognomonic feature of chronic rejection, as WT mice; however, mice that were deficient for both B cells and antibodies were protected from CAV. B cells contributed to CAV by supporting splenic lymphoid architecture, T cell cytokine production, and infiltration of T cells into graft vessels. In chimeric mice, in which B cells were present but could not present antigen, both T cell responses and CAV were markedly reduced. These findings establish that chronic rejection can occur in the complete absence of antibodies and that B cells contribute to this process by supporting T cell responses through antigen presentation and maintenance of lymphoid architecture. PMID:24509079

  7. The private rejection of unfair offers and emotional commitment.

    Science.gov (United States)

    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

  8. Mice aorta loop grafting: A new model which separate vascular rejection and neointimal formation in chronic rejection

    Institute of Scientific and Technical Information of China (English)

    陈勇; 窦科峰; 何勇; 孙凯

    2003-01-01

    Objective: To study the cause and mechanism of transplantation vasculopathy which characterized by accelerated graft arteriosclerosis (AGA), we established a mouse aorta graft model. Methods: A segment of thoracic aortas of B10.A (2R) mice were transplanted to C57BL/10 mice abdominal aorta by end to side anastomoses. The different time point collected grafts were analyzed by morphological, histochemical and electro microscopic methods. Results: Rejection was manifested as a concentric progressive destruction of the smooth muscle cells. In contrast, the endothelial inflammation and subsequent neointimal proliferation characteristic of AGA was localized to the regions of turbulent flow, i.e. the junction of the graft with the recipient aorta. Conclusion: This model separates the processes of rejection and neointimal formation which usually manifested together in the lesion of AGA, elucidate that different mechanisms control vascular rejection and neointimal formation in chronic rejection.

  9. Modelling cellular behaviour

    Science.gov (United States)

    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.

  10. Reversible quantum cellular automata

    CERN Document Server

    Schumacher, B

    2004-01-01

    We define quantum cellular automata as infinite quantum lattice systems with discrete time dynamics, such that the time step commutes with lattice translations and has strictly finite propagation speed. In contrast to earlier definitions this allows us to give an explicit characterization of all local rules generating such automata. The same local rules also generate the global time step for automata with periodic boundary conditions. Our main structure theorem asserts that any quantum cellular automaton is structurally reversible, i.e., that it can be obtained by applying two blockwise unitary operations in a generalized Margolus partitioning scheme. This implies that, in contrast to the classical case, the inverse of a nearest neighbor quantum cellular automaton is again a nearest neighbor automaton. We present several construction methods for quantum cellular automata, based on unitaries commuting with their translates, on the quantization of (arbitrary) reversible classical cellular automata, on quantum c...

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

    Science.gov (United States)

    Sarwal, Minnie; Sigdel, Tara

    2013-01-01

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

  12. Consecutive Low Doses of Cyclosporine A Induce Pro-Inflammatory Cytokines and Accelerate Allograft Skin Rejection

    Directory of Open Access Journals (Sweden)

    Luis I. Terrazas

    2011-05-01

    Full Text Available Cyclosporine A (CsA is a fungus-derived molecule with potent immunosuppressive activity that has been largely used to downregulate cell-mediated immune responses during transplantation. However, previous data have indicated that CsA shows immunomodulatory activity that relays on the antigen concentration and the dose of CsA used. To test the hypothesis that minimal doses of CsA may show different outcomes on grafts, we used an experimental model for skin transplants in mice. ICR outbred mice received skin allografts and were either treated daily with different doses of CsA or left untreated. Untreated mice showed allograft rejection within 14 days, with graft necrosis, infiltration of neutrophils and macrophages and displayed high percentages of CD8+ T cells in the spleens, which were associated with high serum levels of IL-12, IFN-g and TNF-α. As expected, mice treated with therapeutic doses of CsA (15 mg/kg did not show allograft rejection within the follow-up period of 30 days and displayed the lowest levels of IL-12, IFN-g and TNF-α as well as a reduction in CD8+ lymphocytes. In contrast, mice treated with consecutive minimal doses of CsA (5 × 10−55 mg/kg displayed an acute graft rejection as early as one to five days after skin allograft; they also displayed necrosis and strong inflammatory infiltration that was associated with high levels of IL-12, IFN-g and TNF-α. Moreover, the CD4+ CD25hiFoxP3+ subpopulation of cells in the spleens of these mice was significantly inhibited compared with animals that received the therapeutic treatment of CsA and those treated with placebo. Our data suggest that consecutive, minimal doses of CsA may affect Treg cells and may stimulate innate immunity.

  13. Crossmatch testing in kidney transplantation: Patterns of practice and associations with rejection and graft survival

    International Nuclear Information System (INIS)

    Methods of crossmatch testing prior to kidney transplantation are not standardized and there are limited large-scale data on the use and outcomes implications of crossmatch modality. Data describing the most sensitive crossmatch modality for crossmatch-negative kidney transplants were drawn from the Organ Procurement and Transplant Network Registry. Within the cohort transplanted in 1999-2005, we identified patient and transplant characteristics predictive of each testing modality by multivariate logistic regression. We assessed associations of crossmatch modality with rejection risk by logistic regression and with graft survival by Cox's hazards analysis. Among 230,995 transplants, use of flow cytometry with T-and B-lymphocytes (T and B FC) increased progressively in 1987-2005. Among the recent transplants performed in 1999-2005 (n=64,320), negative T and B FC crossmatch was associated with 15% lower relative risk of first-year acute rejection (adjusted HR 0.85, 95% CI 0.80-0.89) compared to negative T-antihuman-globulin and B-National Institutes of Health/Wash (T AHG and B) crossmatch. Five-year graft survival after transplant with negative T and B FC (82.6%) was modestly better than after negative T AHG and B (81.4%, P0.008) or T AHG crossmatch (81.1%, P 60 years. Many subgroups for whom negative T and B FC crossmatch predicted lower rejection risk (Caucasians, deceased donor recipients, re-transplants) were not more likely to be crossmatched by this method. We conclude that current practice patterns have not aligned utilization of T and B FC crossmatch with associated benefits. Prospective evaluation of the relationship of crossmatch modality with outcomes is warranted. (author)

  14. Computational chemical imaging for cardiovascular pathology: chemical microscopic imaging accurately determines cardiac transplant rejection.

    Directory of Open Access Journals (Sweden)

    Saumya Tiwari

    Full Text Available Rejection is a common problem after cardiac transplants leading to significant number of adverse events and deaths, particularly in the first year of transplantation. The gold standard to identify rejection is endomyocardial biopsy. This technique is complex, cumbersome and requires a lot of expertise in the correct interpretation of stained biopsy sections. Traditional histopathology cannot be used actively or quickly during cardiac interventions or surgery. Our objective was to develop a stain-less approach using an emerging technology, Fourier transform infrared (FT-IR spectroscopic imaging to identify different components of cardiac tissue by their chemical and molecular basis aided by computer recognition, rather than by visual examination using optical microscopy. We studied this technique in assessment of cardiac transplant rejection to evaluate efficacy in an example of complex cardiovascular pathology. We recorded data from human cardiac transplant patients' biopsies, used a Bayesian classification protocol and developed a visualization scheme to observe chemical differences without the need of stains or human supervision. Using receiver operating characteristic curves, we observed probabilities of detection greater than 95% for four out of five histological classes at 10% probability of false alarm at the cellular level while correctly identifying samples with the hallmarks of the immune response in all cases. The efficacy of manual examination can be significantly increased by observing the inherent biochemical changes in tissues, which enables us to achieve greater diagnostic confidence in an automated, label-free manner. We developed a computational pathology system that gives high contrast images and seems superior to traditional staining procedures. This study is a prelude to the development of real time in situ imaging systems, which can assist interventionists and surgeons actively during procedures.

  15. Acute Pancreatitis and Pregnancy

    Science.gov (United States)

    ... 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 ...

  16. The cell cycle and acute kidney injury

    OpenAIRE

    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...

  17. The composition of the microbiota modulates allograft rejection.

    Science.gov (United States)

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

    2016-07-01

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

  18. The composition of the microbiota modulates allograft rejection.

    Science.gov (United States)

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

    2016-07-01

    Transplantation is the only cure for end-stage organ failure, but without immunosuppression, T cells rapidly reject allografts. While genetic disparities between donor and recipient are major determinants of the kinetics of transplant rejection, little is known about the contribution of environmental factors. Because colonized organs have worse transplant outcome than sterile organs, we tested the influence of host and donor microbiota on skin transplant rejection. Compared with untreated conventional mice, pretreatment of donors and recipients with broad-spectrum antibiotics (Abx) or use of germ-free (GF) donors and recipients resulted in prolonged survival of minor antigen-mismatched skin grafts. Increased graft survival correlated with reduced type I IFN signaling in antigen-presenting cells (APCs) and decreased priming of alloreactive T cells. Colonization of GF mice with fecal material from untreated conventional mice, but not from Abx-pretreated mice, enhanced the ability of APCs to prime alloreactive T cells and accelerated graft rejection, suggesting that alloimmunity is modulated by the composition of microbiota rather than the quantity of bacteria. Abx pretreatment of conventional mice also delayed rejection of major antigen-mismatched skin and MHC class II-mismatched cardiac allografts. This study demonstrates that Abx pretreatment prolongs graft survival, suggesting that targeting microbial constituents is a potential therapeutic strategy for enhancing graft acceptance. PMID:27322054

  19. Rejection mechanisms for contaminants in polymeric reverse osmosis membranes

    CERN Document Server

    Shen, Meng; Lueptow, Richard M

    2016-01-01

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

  20. Ipsilateral Lymphadenectomy to Inhibit Corneal Allograft Rejection in Rats

    Institute of Scientific and Technical Information of China (English)

    LING Shiqi; HU Yanhua

    2005-01-01

    In order to investigate the ipsilateral lymphadenectomy for inhibiting rejection in rat corneal transplantation, corneal allogenic transplantation models were established in rats. Eighteen female Wister rats were used as donors, and 36 Sprague Dawley rats as recipients. After penetrating corneal transplantation, recipients were randomly divided into 3 groups: group A (control group);group B, the ipsilateral lymphadenectomy group; group C, the bilateral lymphadenectomy group.Among 12 rats in each group, the corneas of 2 rats in each group were used for pathological study at day 14 after the transplantation, and the remaining 10 rats were used for studying corneal rejection by a slit lamp. The time points when allograft rejection occurred were recorded and mean survival time (MST) was compared. The results showed that MST in groups B and C was 46.30±9.464 days and 44.43 ± 7. 604 days, respectively, which was significantly prolonged as compared with that in group A (10.71±1. 567 days, P<0.01). There was no significant difference in MST between groups B and C (P>0.05). Itwas concluded that both bilateral and ipsilateral lymphadenectomy therapies could effectively inhibit the corneal allograft rejection. Ipsilateral lymphadenectomy is a less complex surgical procedure and is just as effective in preventing rejection.

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

    Science.gov (United States)

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

    1989-01-01

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

  2. Analysis of NAD(P)H fluorescence components in cardiac myocytes from human biopsies: a new tool to improve diagnostics of rejection of transplanted patients

    Science.gov (United States)

    Cheng, Y.; Mateasik, A.; Poirier, N.; Miró, J.; Dahdah, N.; Chorvat, D., Jr.; Chorvatova, A.

    2009-02-01

    Tissue autofluorescence is one of the most versatile non-invasive tools for mapping the metabolic state in living tissues. Increasing interest in the imaging and diagnosis of living cells and tissues, based on their intrinsic fluorescence rather than fluorescence labeling, is closely connected to the latest developments in high-performance spectroscopic and microscopic techniques. We investigate metabolic state of cardiac cells isolated from one additional human biopsy from transplanted pediatric patients presenting either no rejection (R0) or mild rejection (R1). Two different approaches for isolation of human cardiac myocytes are also compared. Spectrally-resolved fluorescence lifetime detection of NAD(P)H fluorescence (excitation by pulsed 375 nm picosecond laser) is tested as a promising new tool for quantitative analysis of intrinsic cellular autofluorescence signals in living cardiomyocytes. This work opens new horizons in the evaluation of cardiac transplant rejection using latest fluorescence imaging approaches.

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

    Science.gov (United States)

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

    2014-10-01

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

  4. Heterogeneous cellular networks

    CERN Document Server

    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

  5. Bronchitis - acute

    Science.gov (United States)

    ... 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. Acute pancreatitis

    OpenAIRE

    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...

  7. Acute pancreatitis

    OpenAIRE

    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....

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-01-01

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

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

    Science.gov (United States)

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

    2009-09-01

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

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

    Science.gov (United States)

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

    2015-08-01

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

  11. Nanostructured cellular networks.

    Science.gov (United States)

    Moriarty, P; Taylor, M D R; Brust, M

    2002-12-01

    Au nanocrystals spin-coated onto silicon from toluene form cellular networks. A quantitative statistical crystallography analysis shows that intercellular correlations drive the networks far from statistical equilibrium. Spin-coating from hexane does not produce cellular structure, yet a strong correlation is retained in the positions of nanocrystal aggregates. Mechanisms based on Marangoni convection alone cannot account for the variety of patterns observed, and we argue that spinodal decomposition plays an important role in foam formation.

  12. Cellular Cardiomyoplasty: Clinical Application

    OpenAIRE

    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...

  13. An image rejection circuit with sign detection only

    OpenAIRE

    Lerstaveesin, Supisa

    2006-01-01

    In direct-conversion receivers, radio frequency (RF) signals are down-converted to zero or low intermediate frequency (IF) using complex in-phase and quadrature (I/Q) mixers with no prior image filtering. Due to I/Q path gain and phase errors, image leaks into the signal band during the down-conversion process. A generic image rejection algorithm is proposed to reject image in the baseband using a zero-forcing sign-sign adaptive feedback concept. The orthonormal property of complex I/Q channe...

  14. Solar dynamic organic Rankine cycle heat rejection system simulation

    Science.gov (United States)

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

    1987-01-01

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

  15. Belief decision support and reject for textured images characterization

    CERN Document Server

    Martin, Arnaud

    2008-01-01

    The textured images' classification assumes to consider the images in terms of area with the same texture. In uncertain environment, it could be better to take an imprecise decision or to reject the area corresponding to an unlearning class. Moreover, on the areas that are the classification units, we can have more than one texture. These considerations allows us to develop a belief decision model permitting to reject an area as unlearning and to decide on unions and intersections of learning classes. The proposed approach finds all its justification in an application of seabed characterization from sonar images, which contributes to an illustration.

  16. Causes of rejection of beef bulls in breeding soundness evaluation

    Directory of Open Access Journals (Sweden)

    Silvio Renato Oliveira Menegassi

    2012-07-01

    Full Text Available The objective of this study was to analyze the rates of rejection in the different steps of the breeding soundness evaluation of beef bulls in the state of Rio Grande do Sul, Brazil. The breeding soundness of 22,113 young and mature bulls of 14 beef breeds, participating in the Program of Reproductive Evaluation (PARTO was evaluated in the experiment. Data concerning to the causes of rejection in the four steps of the breeding soundness evaluation (general physical examination, genital tract examination, semen evaluation and sexual behavior assessment were analyzed by the Chi-square test and univariate regression analysis. According to year, general physical examination, genital tract examination and semen evaluation determined the rejection of 0.9% to 2.5%, 5.1% to 7.7%, 1.8% to 5.3%; and 4.2% to 6.7%, 7.3 to 9.3%, and 2.5% to 5.5% of young and mature bulls, respectively. Mature bulls presented higher chances of rejection than young bulls in the general physical examination in every year evaluated; as to the genital tract examination, their chances of rejection were higher in years I and II, but not in year III. In the semen evaluation, there was no difference between the ages assessed in any of the three years evaluated. Sexual behavior assessment accounted for the rejection of 1.9 to 6.0% of the young bulls and 2.9% to 3.9% of mature bulls, in accordance with the years evaluated; in years I and II, mature bulls presented higher rejection rates than young bulls. These results confirm the importance of performing all steps of the breeding soundness evaluation, including the sexual behavior assessment as a work routine, rather than an additional, optional stage of the evaluation, which should be carried out before the breeding season. The results indicate the relationship between bull age and rejection rate in the breeding soundness evaluation.

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

    Science.gov (United States)

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

    2016-09-01

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

  18. Transgenic mice designed to express human α-1,2-fucosyltransferase in combination of human DAF and CD59 to avoid xenograft rejection

    Institute of Scientific and Technical Information of China (English)

    LIU BingQian; CHENG ChuanYu; WU YuDong; WEI JinXing; LI GuangSan; MA TengXiang

    2008-01-01

    The expression of human α-1,2-fucosyltransferase (HT) or complement regulatory proteins has been proved as an strategy to overcome hypercute rejection in discordant xenogeneic organ transplantation.In this study, we examined whether peripheral blood mononuclear cells (PBMCs) from polytransgenic mice expressing the human HT, and complement regulatory proteins (DAF and CD59), can provide more effective protection against xenograft rejection. Transgenic mice were produced by co-injection of gene constructs for human HT, DAF and/or CD59. Flow Cytometry (FCM) was used to screen the positive transgenic mice. PBMCs from transgenic mice were incubated with 15% human serum to evaluate natural antibody binding, complement activation and expression of adhesion molecules.Three transgenes were strongly expressed in PBMCs of transgenic mice, and HT expression significantly reduced expression of the major xenoepitope galactose-α-1,3-galactose (α-Gal). Functional studies with PBMCs showed that co-expression of HT and DAF or CD59 markedly increased their resistance to human serum-mediated cytolysis when compared with single transgenic PBMCs. Moreover,the combined expression of triple transgenes in PBMCs led to the greatest protection against human serum-mediated cytolyais, avoided hyperacute rejection and reduced expression of adhesion molecules. Strong co-expression of triple transgenes was completely protected from xenograft hyperacute rejection and partially inhibited acute vascular rejection. The studies suggest that engineering mice to express triple molecules represents an critical step toward prolonging xenograft survival and might be more suitable for xenotransplantation.

  19. Transgenic mice designed to express human α-1,2-fucosyltransferase in combination of human DAF and CD59 to avoid xenograft rejection

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The expression of human α-1,2-fucosyltransferase (HT) or complement regulatory proteins has been proved as an strategy to overcome hypercute rejection in discordant xenogeneic organ transplantation. In this study, we examined whether peripheral blood mononuclear cells (PBMCs) from polytransgenic mice expressing the human HT, and complement regulatory proteins (DAF and CD59), can provide more effective protection against xenograft rejection. Transgenic mice were produced by co-injection of gene constructs for human HT, DAF and/or CD59. Flow Cytometry (FCM) was used to screen the positive transgenic mice. PBMCs from transgenic mice were incubated with 15% human serum to evaluate natural antibody binding, complement activation and expression of adhesion molecules. Three transgenes were strongly expressed in PBMCs of transgenic mice, and HT expression signifi- cantly reduced expression of the major xenoepitope galactose-α-1,3-galactose (α-Gal). Functional studies with PBMCs showed that co-expression of HT and DAF or CD59 markedly increased their re- sistance to human serum-mediated cytolysis when compared with single transgenic PBMCs. Moreover, the combined expression of triple transgenes in PBMCs led to the greatest protection against human serum-mediated cytolysis, avoided hyperacute rejection and reduced expression of adhesion mole- cules. Strong co-expression of triple transgenes was completely protected from xenograft hyperacute rejection and partially inhibited acute vascular rejection. The studies suggest that engineering mice to express triple molecules represents an critical step toward prolonging xenograft survival and might be more suitable for xenotransplantation.

  20. Acute pancreatitis

    Directory of Open Access Journals (Sweden)

    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.

  1. Acute pancreatitis

    Directory of Open Access Journals (Sweden)

    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.

  2. Information about radiographic films rejects of dental x-rays

    International Nuclear Information System (INIS)

    The purpose of this research was to qualify and quantify the number of dental x-ray films rejected in a Porto Alegre clinic. As we analyzed the captured data, it was concluded that, our of 1066 peri-apical films, we had a total percentage of 4.5% in relation to the total of the exams made. This 4.5% consists of the following rejects: placement, patient movement, technical errors, diaphragm, too much clarity in the result, double exposure, prolongation, shortness, darkened for not have been shot, superposed film. Because of that, the rejection, due to the bad placement of the film, is the one with the larger percentage value, i.e., 1.22% of the 4.5%. With the knowledge of the types of rejects and their causes, it was possible to correct some sources of systematic errors minimizing the repetition of the exams, saving costs, time and diminishing the ionizing radiation exposure for the patient, odontologist and his technical staff, which will be proved. (authors). 4 refs., 1 tab

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

    Science.gov (United States)

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

    2014-01-01

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

  4. Examining Appearance-Based Rejection Sensitivity during Early Adolescence

    Science.gov (United States)

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

    2013-01-01

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

  5. Duke power cities training, electrodes for low weld reject rate

    International Nuclear Information System (INIS)

    An intensive training program has allowed Duke Power Co. to achieve a reject rate of less than 1% in pipe and plate welds at its giant Catawba Nuclear Power Station, 30 miles southwest of Charlotte, NC. Constructed on a 418 acre site, the Catawba Station is scheduled to furnish 2240 megawatts of electricity from two reactors. Completion is set for 1983, and Duke will use around 208,000 lb (94,000 kg) of welding electrodes a year to complete the job. The reject rate on welding Schedule 40 pipe from 1 to 34 in. (2.5-86.4 cm) in diameter is 0.6%, and on carbon steel plate up to 3 in. (7.6 cm) thick the reject rate is 0.7%. In both instances the electrodes used are 0.045 in. (1.14 mm) Dual Shield 7000 (AWS E70T-1) and iron powder low hydrogen Atom Arc (AWS E7018). ''Intensive welder training no doubt has achieved such a high degree of success in low reject rates on our nuclear specification welds, but the welder must also have an electrode that has a certain amount of built-in ''forgiveness'' in the event of human oversight.''

  6. 48 CFR 619.505 - Rejecting Small Business Administration recommendations.

    Science.gov (United States)

    2010-10-01

    ... Small Business Administration recommendations. The Procurement Executive is the agency head for the... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Rejecting Small Business Administration recommendations. 619.505 Section 619.505 Federal Acquisition Regulations System DEPARTMENT...

  7. 48 CFR 1319.505 - Rejecting Small Business Administration recommendations.

    Science.gov (United States)

    2010-10-01

    ... Small Business Administration recommendations. (a) The designee authorized to render a decision on the Small Business Administration's appeal of the contracting officer's decision is set forth in CAM 1301.70... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Rejecting Small...

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

    Science.gov (United States)

    Kim, Sun-Woong; Choi, Dong-You

    2016-01-01

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

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

    Science.gov (United States)

    Kim, Sun-Woong; Choi, Dong-You

    2016-01-01

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

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

    Science.gov (United States)

    Hamburger, Susan

    2011-01-01

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

  11. Diffusion-based outlier rejection for underwater navigation

    DEFF Research Database (Denmark)

    Vike, Steinar; Jouffroy, Jerome

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

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

    Science.gov (United States)

    Scalise, Lorenzo; Marchionni, Paolo; Carnielli, Virgilio

    2010-04-01

    Pulse oximetry (PO) is a non-invasive medical device used for monitoring of the arterial oxygen saturation (SaO2) and in particular of haemoglobin oxygenation in blood. Oxygen saturation is commonly used in any setting where the patient blood oxygen saturation is unstable, including Neonatal Intensive Care Unit (NICU). The main factor affecting PO's output data is the presence of voluntary or involuntary motion artifacts or imperfect skin-sensor contact. Various methods have been employed to reject motion artifact but have met with little success. The aim of the present work is to propose a novel measurement procedure for real-time monitoring and validation of the oxygen saturation data as measured in standard pulse oxymeter. The procedure should be able to individuate and reject erroneous saturation data due to incorrect transducer-skin contact or motion artifact. In the case of short sequences of rejected SpO2 data (time durationoximeter (HRSAT) and the SpO2 value. In order to remove the erroneous SpO2 values reported in the rough data in coincidence of motion artifact (top, right), we have implemented a specific algorithm which provides at the output a new sequence of SpO2 data (validated SpO2 data). With the aim to "rescue" SpO2 value rejected by the previously presented algorithm, we have implemented an algorithm able to provide the "most-probable" SpO2 values in the case of single rejected values or in the case of short sequences of invalidated data (oximeter are not validated by the use of our method (corresponding to a total time of 16 hr, 8min and 40s). The use of the proposed algorithm aiming to "rescue" data from short sequences of rejected data (< 8s) allows to increase the validated data of the 2.5%t(equivalent to 8hr, 40 min and 16s), allowing a percent of usable data of the 95.7%. Once implemented in clinic, it could be used to identify the period of the day in which the percent of rejected data increase or correlate this data to clinical procedure

  13. Fate of Manuscripts Rejected From the Red Journal

    International Nuclear Information System (INIS)

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

  14. Fate of Manuscripts Rejected From the Red Journal

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Alice Tung Wan Song

    2015-02-01

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

  17. Perceived childhood paternal acceptance-rejection among adults

    International Nuclear Information System (INIS)

    Objective: To determine the childhood perceptual difference of paternal acceptance-rejection between those having psychological disorders and non-clinical population during adulthood. Study Design: Comparative study. Place and Duration of Study: Karwan-e-Hayat, Psychiatric Care and Rehabilitation Centre, Keamari, Karachi, Pakistan, from January to August 2011. Methodology: To test our hypotheses, 69 participants were selected from Karwan-e-Hayat Psychiatric Care and Rehabilitation Centre, Karachi on the basis of purposive sampling technique and 79 from Karachi city on the basis of convenient sampling technique. To measure their perceived paternal acceptance-rejection during childhood, Adult Parental acceptance-rejection questionnaire (PARQ)/control: father-short form (Urdu translation) was administered. The statistical analysis of data was done with the predictive analytics software (PASW). Results: One hundred and forty eight (78 males and 70 females) participants with mean age of 31.28 +- 9.54 years were included. Out of them 69 (40 males and 29 females) were clinical cases of depression, mania and psychosis with mean age of 33.26 +- 9.51 years. Seventy nine (38 males and 41 females) were normal individuals with mean age of 29.54 +- 9.29 years of the demographics corresponding to the clinical population. Independent t-test revealed a significant difference in perceived childhood father acceptance-rejection between clinical and non-clinical population (p < 0.05) and significant gender difference (p < 0.05). Conclusion: The studied clinical population and male participants perceived to be more rejected by their father during their childhood than non-clinical population and female participants. (author)

  18. Epigenetics and Cellular Metabolism

    Science.gov (United States)

    Xu, Wenyi; Wang, Fengzhong; Yu, Zhongsheng; Xin, Fengjiao

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well. PMID:27695375

  19. Architected Cellular Materials

    Science.gov (United States)

    Schaedler, Tobias A.; Carter, William B.

    2016-07-01

    Additive manufacturing enables fabrication of materials with intricate cellular architecture, whereby progress in 3D printing techniques is increasing the possible configurations of voids and solids ad infinitum. Examples are microlattices with graded porosity and truss structures optimized for specific loading conditions. The cellular architecture determines the mechanical properties and density of these materials and can influence a wide range of other properties, e.g., acoustic, thermal, and biological properties. By combining optimized cellular architectures with high-performance metals and ceramics, several lightweight materials that exhibit strength and stiffness previously unachievable at low densities were recently demonstrated. This review introduces the field of architected materials; summarizes the most common fabrication methods, with an emphasis on additive manufacturing; and discusses recent progress in the development of architected materials. The review also discusses important applications, including lightweight structures, energy absorption, metamaterials, thermal management, and bioscaffolds.

  20. Epigenetics and Cellular Metabolism

    Science.gov (United States)

    Xu, Wenyi; Wang, Fengzhong; Yu, Zhongsheng; Xin, Fengjiao

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well.

  1. Vicarious group-based rejection: creating a potentially dangerous mix of humiliation, powerlessness, and anger.

    Directory of Open Access Journals (Sweden)

    Tinka M Veldhuis

    Full Text Available Rejection can convey that one is seen as inferior and not worth bothering with. Is it possible for people to feel vicariously rejected in this sense and have reactions that are similar to those following personal rejection, such as feeling humiliated, powerless, and angry? A study on personal rejection was followed by two main studies on vicarious group-based rejection. It was found that merely observing rejection of ingroup members can trigger feelings of humiliation that are equally intense as those experienced in response to personal rejection. Moreover, given that the rejection is explicit, vicariously experienced feelings of humiliation can be accompanied by powerlessness and anger. Potentially, this combination of emotions could be an important source of offensive action against rejecters.

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

    Science.gov (United States)

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

    2016-09-01

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

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

    Science.gov (United States)

    Bowman, Caitlin R; Dennis, Nancy A

    2016-08-01

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

  4. Cellular Response to Irradiation

    Institute of Scientific and Technical Information of China (English)

    LIU Bo; YAN Shi-Wei

    2011-01-01

    To explore the nonlinear activities of the cellular signaling system composed of one transcriptional arm and one protein-interaction arm, we use an irradiation-response module to study the dynamics of stochastic interactions.It is shown that the oscillatory behavior could be described in a unified way when the radiation-derived signal and noise are incorporated.

  5. The New Cellular Immunology

    Science.gov (United States)

    Claman, Henry N.

    1973-01-01

    Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

  6. Emergency surgical treatment of complicated acute pancreatitis after kidney transplantation with acute rejection: Case report and literature review

    Directory of Open Access Journals (Sweden)

    Dušan Klos

    2016-06-01

    Conclusions: With regard to the patient's comorbidities, early surgical therapy was indicated – drainage and closed lavage and immunosuppressive medication as a suspected tobe ethiological factor was discontinued. This course of treatment led to a complete recovery with preservation of good function of the cadaverous kidney.

  7. ST2 IN REJECTION OF THE TRANSPLANTED HEART

    Directory of Open Access Journals (Sweden)

    O. P. Shevchenko

    2015-01-01

    Full Text Available This review summarizes the current literature devoted to the analysis of prognostic role of ST2 biomarker in rejection of the transplanted heart. ST2 is one of the most promising diagnostic markers of the development and severity of heart failure as well as the mortality risk in patients with cardiovascular diseases. ST2 is expressed in cardiomyocytes in response to a variety of pathological processes and mechanical damage to the heart, which allows diagnosing cardiovascular diseases before clinical manifestations. Presumably, measuring the level of ST2 in heart transplant may have diagnostic and prognostic value in the assessment of graft and risk of rejection. Currently, accumulated clinical data on the role of given biomarker in heart transplantation are not enough, and further research on the relation of ST2 levels with different clinical and laboratory parameters in heart recipients is necessary. 

  8. Background rejection in NEXT using deep neural networks

    CERN Document Server

    Renner, J; Vidal, J Muñoz; Benlloch-Rodríguez, J M; Botas, A; Ferrario, P; Gómez-Cadenas, J J; Álvarez, V; Azevedo, C D R; Borges, F I G; Cárcel, S; Carrión, J V; Cebrián, S; Cervera, A; Conde, C A N; Díaz, J; Diesburg, M; Esteve, R; Fernandes, L M P; Ferreira, A L; Freitas, E D C; Goldschmidt, A; González-Díaz, D; Gutiérrez, R M; Hauptman, J; Henriques, C A O; Morata, J A Hernando; Herrero, V; Jones, B; Labarga, L; Laing, A; Lebrun, P; Liubarsky, I; López-March, N; Lorca, D; Losada, M; Martín-Albo, J; Martínez-Lema, G; Martínez, A; Monrabal, F; Monteiro, C M B; Mora, F J; Moutinho, L M; Nebot-Guinot, M; Novella, P; Nygren, D; Para, A; Pérez, J; Querol, M; Ripoll, L; Rodríguez, J; Santos, F P; Santos, J M F dos; Serra, L; Shuman, D; Simón, A; Sofka, C; Sorel, M; Toledo, J F; Torrent, J; Tsamalaidze, Z; Veloso, J F C A; White, J; Webb, R; Yahlali, N; Yepes-Ramírez, H

    2016-01-01

    We investigate the potential of using deep learning techniques to reject background events in searches for neutrinoless double beta decay with high pressure xenon time projection chambers capable of detailed track reconstruction. The differences in the topological signatures of background and signal events can be learned by deep neural networks via training over many thousands of events. These networks can then be used to classify further events as signal or background, providing an additional background rejection factor at an acceptable loss of efficiency. The networks trained in this study performed 15-60% better than previous methods developed based on the use of the same topological signatures, and there is potential for further improvement.

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

    Science.gov (United States)

    Zhao, Shen; Gao, Zhiqiang

    2014-07-01

    Industrial processes are typically nonlinear, time-varying and uncertain, to which active disturbance rejection control (ADRC) has been shown to be an effective solution. The control design becomes even more challenging in the presence of time delay. In this paper, a novel modification of ADRC is proposed so that good disturbance rejection is achieved while maintaining system stability. The proposed design is shown to be more effective than the standard ADRC design for time-delay systems and is also a unified solution for stable, critical stable and unstable systems with time delay. Simulation and test results show the effectiveness and practicality of the proposed design. Linear matrix inequality (LMI) based stability analysis is provided as well.

  10. HF radar sea clutter rejection by nonlinear projections

    Institute of Scientific and Technical Information of China (English)

    Zhou Gongjian; Jin Yonggao; Dong Huachun; Quan Taifan

    2005-01-01

    In the background of signal detection for high frequency (HF) radar, the sea clutter is quite significant and can mask some weak target signals. A new clutter rejection method named "nonlinear projection" is given to improve the SNR of the target. This approach is based on the recent observation that HF sea clutter may be modeled as a nonlinear deterministic dynamical system. After approximating the multidimensional reconstruction of the clutter by a low-dimensional attractor, projections onto this attractor can separate the clutter from other components. Real sea clutter, simulated target data and real target data are used to show that a nonlinear clutter rejection method is a promising technique to suppress sea clutter and enhances target detection.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    Johnson, C. C.; Wydeven, T. J. (Inventor)

    1980-01-01

    Polymeric membranes suitable for use in reverse osmosis water purification because of their high urea and salt rejection properties are prepared by generating a plasma of an unsaturated hydrocarbon monomer and nitrogen gas from an electrical source. A polymeric membrane is formed by depositing a polymer of the unsaturated monomer from the plasma onto a substrate, so that nitrogen from the nitrogen gas is incorporated within the polymer in a chemically combined form.

  13. The Health and Earnings of Rejected Disability Insurance Applicants

    OpenAIRE

    John Bound

    1989-01-01

    Applicants for Social Security Disability Benefits who fail to pass the medical screening form a natural 'control' group for beneficiaries. Data drawn from the 1972 and 1978 surveys of the disabled done for the Social Security Administration show that fewer than 50% of rejected male applicants work. Typical earnings of those that do are less than 50% of median earnings for other men their age. These data cast doubt on recent econometric work which suggests that the disincentive effects of DI ...

  14. Aggression and Peer Rejection among Children with Conduct Disorder

    OpenAIRE

    Somaieh Salehi; Sidek Mohd Noah; Maznah Baba; Wan Marzuki Wan Jaafar

    2013-01-01

    Children with Conduct Disorder suffer from aggression and peer difficulties. This study provides an overview of aggression and peer rejection among children with Conduct Disorder worldwide and in Iran. This study is based on researches from library archives specially focused on studies have been done in Iran. First Conduct Disorder, its’ prevalence, subtypes, and other comorbid disorders are explained. Next, studies regarding aggression among aggressive children and children with conduct prob...

  15. Dynamic positioning system based on active disturbance rejection technology

    Science.gov (United States)

    Lei, Zhengling; Guo, Chen; Fan, Yunsheng

    2015-08-01

    A dynamically positioned vessel, by the International Maritime Organization (IMO) and the certifying class societies (DNV, ABS, LR, etc.), is defined as a vessel that maintains its position and heading (fixed location or pre-determined track) exclusively by means of active thrusters. The development of control technology promotes the upgrading of dynamic positioning (DP) systems. Today there are two different DP systems solutions available on the market: DP system based on PID regulator and that based on model-based control. Both systems have limited disturbance rejection capability due to their design principle. In this paper, a new DP system solution is proposed based on Active Disturbance Rejection Control (ADRC) technology. This technology is composed of Tracking-Differentiator (TD), Extended State Observer (ESO) and Nonlinear Feedback Combination. On one hand, both TD and ESO can act as filters and can be used in place of conventional filters; on the other hand, the total disturbance of the system can be estimated and compensated by ESO, which therefore enhances the system's disturbance rejection capability. This technology's advantages over other methods lie in two aspects: 1) This method itself can not only achieve control objectives but also filter noisy measurements without other specialized filters; 2) This method offers a new useful approach to suppress the ocean disturbance. The simulation results demonstrate the effectiveness of the proposed method.

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

    Science.gov (United States)

    Luo, Qi; Luo, Xi; Li, Xinyang

    2016-04-01

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

  17. Differential role of CD4+ cells in the sensitization and effector phases of accelerated graft rejection.

    Science.gov (United States)

    Sablinski, T; Sayegh, M H; Hancock, W W; Kut, J P; Kwok, C A; Milford, E L; Tilney, N L; Kupiec-Weglinski, J W

    1991-01-01

    Although CD4-targeted therapy markedly prolongs survival of organ allografts in naive rodents, its effects in primed hosts have not been studied. In our model of accelerated rejection (ACCR) of cardiac Tx in rats, treatment with BWH-4, a CD4 mAb (IgG2a), in the sensitization (between skin and heart Tx) but not in the effector (after cardiac Tx) phase, abrogated fulminant less than 36 hr rejection response and prolonged Tx survival to ca. 11 days. This effect correlated with decreased frequency of circulating CD4+ cells, but it did not depend upon their total depletion. It was also related to BWH-4 mAb-mediated elimination/depression of strong anti-donor humoral responses and cellular responses as determined by lymphocyte-mediated cytotoxicity and mixed lymphocyte reaction and mounted otherwise at the time of engraftment by untreated sensitized hosts. Immunoperoxidase studies of cardiac Tx from BWH-4-conditioned recipients revealed reduced T and B cell activities, reflected in abolition/reduction in deposition of humoral mediators, infiltrating cells, intra-Tx elaboration of interleukin-2 and interferon-gamma, and cell activation. This first report of the successful use of CD4 mAb in sensitized recipients of vascularized organ Tx, stresses the role of CD4+ cells as potential targets for immunosuppression in the sensitization phase of accelerated Tx injury. The beneficial therapeutic effect, probably due to both depletion and functional inhibition of CD4+ T cells, has been achieved by using relatively low doses of BWH-4 mAb. PMID:1824805

  18. Inferring Acceptance and Rejection in Dialogue by Default Rules of Inference

    CERN Document Server

    Walker, M A

    1996-01-01

    This paper discusses the processes by which conversants in a dialogue can infer whether their assertions and proposals have been accepted or rejected by their conversational partners. It expands on previous work by showing that logical consistency is a necessary indicator of acceptance, but that it is not sufficient, and that logical inconsistency is sufficient as an indicator of rejection, but it is not necessary. I show how conversants can use information structure and prosody as well as logical reasoning in distinguishing between acceptances and logically consistent rejections, and relate this work to previous work on implicature and default reasoning by introducing three new classes of rejection: {\\sc implicature rejections}, {\\sc epistemic rejections} and {\\sc deliberation rejections}. I show how these rejections are inferred as a result of default inferences, which, by other analyses, would have been blocked by the context. In order to account for these facts, I propose a model of the common ground that...

  19. Molecular and Cellular Signaling

    CERN Document Server

    Beckerman, Martin

    2005-01-01

    A small number of signaling pathways, no more than a dozen or so, form a control layer that is responsible for all signaling in and between cells of the human body. The signaling proteins belonging to the control layer determine what kinds of cells are made during development and how they function during adult life. Malfunctions in the proteins belonging to the control layer are responsible for a host of human diseases ranging from neurological disorders to cancers. Most drugs target components in the control layer, and difficulties in drug design are intimately related to the architecture of the control layer. Molecular and Cellular Signaling provides an introduction to molecular and cellular signaling in biological systems with an emphasis on the underlying physical principles. The text is aimed at upper-level undergraduates, graduate students and individuals in medicine and pharmacology interested in broadening their understanding of how cells regulate and coordinate their core activities and how diseases ...

  20. Magnetic Cellular Switches

    OpenAIRE

    Overby, Darryl R.; Alenghat, Francis J.; Montoya-Zavala, Martín; Bei, HuCheng; Oh, Philmo; Karavitis, John; Ingber, Donald E.

    2004-01-01

    This paper focuses on the development of magnetic cellular switches to enable magnetic control of intracellular functions in living mammalian cells, including receptor signal transduction and gene transcription. Our approach takes advantage of the mechanosensitivity of adenosine 3′,5′-monophosphate (cAMP) induction and downstream transcription controlled by the cAMP regulatory element (CRE) to engineer gene constructs that optically report gene expression in living cells. We activate transcri...

  1. Comparison of the Image Rejection between the Passive and the Gilbert Mixer

    DEFF Research Database (Denmark)

    Wang, Xiaoyan; Andreani, Pietro

    2004-01-01

    This paper presents a comparison of the image rejection between Gilbert mixer and the passive mixer. A simple model for mixers is set up, and the image rejection performance of passive and Gilbert mixer is analyzed based on it. Simulations and calculations were done to compare the image rejection...... of the two mixers. The results show that the Gilbert mixer, comparing with the passive one, shows a stronger rejection to the amplitude error of the quadrature signals at its input....

  2. Critical Role for IL-6 in Hypertrophy and Fibrosis in Chronic Cardiac Allograft Rejection

    OpenAIRE

    Diaz, J. A.; Booth, A. J.; Lu, G.; Wood, S.C.; Pinsky, D.J.; Bishop, D. K.

    2009-01-01

    Chronic cardiac allograft rejection is the major barrier to long term graft survival. There is currently no effective treatment for chronic rejection except re-transplantation. Though neointimal development, fibrosis, and progressive deterioration of graft function are hallmarks of chronic rejection, the immunologic mechanisms driving this process are poorly understood. These experiments tested a functional role for IL-6 in chronic rejection by utilizing serial echocardiography to assess the ...

  3. Cellular therapy in Tuberculosis

    Directory of Open Access Journals (Sweden)

    Shreemanta K. Parida

    2015-03-01

    Full Text Available Cellular therapy now offer promise of potential adjunct therapeutic options for treatment of drug-resistant tuberculosis (TB. We review here the role of Mesenchymal stromal cells, (MSCs, as well as other immune effector cells in the therapy of infectious diseases with a focus on TB. MSCs represent a population of tissue-resident non-hematopoietic adult progenitor cells which home into injured tissues increase the proliferative potential of broncho-alveolar stem cells and restore lung epithelium. MSCs have been shown to be immune-modulatory and anti-inflammatory mediated via cell-cell contacts as well as soluble factors. We discuss the functional profile of MSCs and their potential use for adjunct cellular therapy of multi-drug resistant TB, with the aim of limiting tissue damage, and to convert unproductive inflammatory responses into effective anti-pathogen directed immune responses. Adjunct cellular therapy could potentially offer salvage therapy options for patients with drug-resistant TB, increase clinically relevant anti-M.tuberculosis directed immune responses and possibly shorten the duration of anti-TB therapy.

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

    Science.gov (United States)

    Bowman, Caitlin R; Dennis, Nancy A

    2015-06-01

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

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

    Science.gov (United States)

    Pachankis, John E.; Goldfried, Marvin R.; Ramrattan, Melissa E.

    2008-01-01

    On the basis of recent evidence suggesting that gay men are particularly likely to fear interpersonal rejection, the authors set out to extend the "rejection sensitivity" construct to the mental health concerns of gay men. After establishing a reliable and valid measure of the gay-related rejection sensitivity construct, the authors use this to…

  6. Immunologic Corneal Graft Rejection after Administration of Topical Latanoprost: a Report of Two Patients

    OpenAIRE

    Kouros Nouri-Mahdavi; Mohammad-Ali Javadi; Mohammad-Reza Jafarinasab

    2011-01-01

    Purpose: To report endothelial corneal graft rejection after administration of topical latanoprost eye drops. Case Report: Two eyes of two patients with a history of multiple intraocular procedures prior to penetrating keratoplasty developed endothelial graft rejection one month after administration of topical latanoprost. Cystoid macular edema developed simultaneously in one patient. Conclusion: Latanoprost may trigger endothelial graft rejection in susceptible eyes.

  7. Effect of mining rejects on the nutrient chemistry of Mandovi Estuary, Goa

    Digital Repository Service at National Institute of Oceanography (India)

    DeSousa, S.N.

    of mining rejects, suggest that the suspended sediments derived from the mining rejects adsorb phosphate and silicate, and remove them from the water column while the mining rejects act as a source of nitrate to the estuary. Large quantities (10 tonnes...

  8. Rejection Sensitivity and College Student Depression: Findings and Implications for Counseling

    Science.gov (United States)

    Mellin, Elizabeth A.

    2008-01-01

    This study examined whether rejection sensitivity, or the fear of interpersonal rejection, was related to depression among college students. The regression model that resulted from the study indicated that level of rejection sensitivity accounted for approximately 11% of variance in depression among students in the research. Implications for…

  9. 41 CFR 102-38.210 - What happens when bids have been rejected?

    Science.gov (United States)

    2010-07-01

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

  10. Environment Aware Cellular Networks

    KAUST Repository

    Ghazzai, Hakim

    2015-02-01

    The unprecedented rise of mobile user demand over the years have led to an enormous growth of the energy consumption of wireless networks as well as the greenhouse gas emissions which are estimated currently to be around 70 million tons per year. This significant growth of energy consumption impels network companies to pay huge bills which represent around half of their operating expenditures. Therefore, many service providers, including mobile operators, are looking for new and modern green solutions to help reduce their expenses as well as the level of their CO2 emissions. Base stations are the most power greedy element in cellular networks: they drain around 80% of the total network energy consumption even during low traffic periods. Thus, there is a growing need to develop more energy-efficient techniques to enhance the green performance of future 4G/5G cellular networks. Due to the problem of traffic load fluctuations in cellular networks during different periods of the day and between different areas (shopping or business districts and residential areas), the base station sleeping strategy has been one of the main popular research topics in green communications. In this presentation, we present several practical green techniques that provide significant gains for mobile operators. Indeed, combined with the base station sleeping strategy, these techniques achieve not only a minimization of the fossil fuel consumption but also an enhancement of mobile operator profits. We start with an optimized cell planning method that considers varying spatial and temporal user densities. We then use the optimal transport theory in order to define the cell boundaries such that the network total transmit power is reduced. Afterwards, we exploit the features of the modern electrical grid, the smart grid, as a new tool of power management for cellular networks and we optimize the energy procurement from multiple energy retailers characterized by different prices and pollutant

  11. Cellular phones: are they detrimental?

    Science.gov (United States)

    Salama, Osama E; Abou El Naga, Randa M

    2004-01-01

    The issue of possible health effects of cellular phones is very much alive in the public's mind where the rapid increase in the number of the users of cell phones in the last decade has increased the exposure of people to the electromagnetic fields (EMFs). Health consequences of long term use of mobile phones are not known in detail but available data indicates the development of non specific annoying symptoms on acute exposure to mobile phone radiations. In an attempt to determine the prevalence of such cell phones associated health manifestations and the factors affecting their occurrence, a cross sectional study was conducted in five randomly selected faculties of Alexandria University. Where, 300 individuals including teaching staff, students and literate employee were equally allocated and randomly selected among the five faculties. Data about mobile phone's users and their medical history, their pattern of mobile usage and the possible deleterious health manifestations associated with cellular phone use was collected. The results revealed 68% prevalence of mobile phone usage, nearly three quarters of them (72.5%) were complainers of the health manifestations. They suffered from headache (43%), earache (38.3%), sense of fatigue (31.6%), sleep disturbance (29.5%), concentration difficulty (28.5%) and face burning sensation (19.2%). Both univariate and multivariate analysis were consistent in their findings. Symptomatic users were found to have significantly higher frequency of calls/day, longer call duration and longer total duration of mobile phone usage/day than non symptomatic users. For headache both call duration and frequency of calls/day were the significant predicting factors for its occurrence (chi2 = 18.208, p = 0.0001). For earache, in addition to call duration, the longer period of owning the mobile phone were significant predictors (chi2 = 16.996, p = 0.0002). Sense of fatigue was significantly affected by both call duration and age of the user

  12. The identification of novel potential injury mechanisms and candidate biomarkers in renal allograft rejection by quantitative proteomics.

    Science.gov (United States)

    Sigdel, Tara K; Salomonis, Nathan; Nicora, Carrie D; Ryu, Soyoung; He, Jintang; Dinh, Van; Orton, Daniel J; Moore, Ronald J; Hsieh, Szu-Chuan; Dai, Hong; Thien-Vu, Minh; Xiao, Wenzhong; Smith, Richard D; Qian, Wei-Jun; Camp, David G; Sarwal, Minnie M

    2014-02-01

    Early transplant dysfunction and failure because of immunological and nonimmunological factors still presents a significant clinical problem for transplant recipients. A critical unmet need is the noninvasive detection and prediction of immune injury such that acute injury can be reversed by proactive immunosuppression titration. In this study, we used iTRAQ -based proteomic discovery and targeted ELISA validation to discover and validate candidate urine protein biomarkers from 262 renal allograft recipients with biopsy-confirmed allograft injury. Urine samples were randomly split into a training set of 108 patients and an independent validation set of 154 patients, which comprised the clinical biopsy-confirmed phenotypes of acute rejection (AR) (n = 74), stable graft (STA) (n = 74), chronic allograft injury (CAI) (n = 58), BK virus nephritis (BKVN) (n = 38), nephrotic syndrome (NS) (n = 8), and healthy, normal control (HC) (n = 10). A total of 389 proteins were measured that displayed differential abundances across urine specimens of the injury types (p 1.5) from all other transplant categories (HLA class II protein HLA-DRB1, KRT14, HIST1H4B, FGG, ACTB, FGB, FGA, KRT7, DPP4). Increased levels of three of these proteins, fibrinogen beta (FGB; p = 0.04), fibrinogen gamma (FGG; p = 0.03), and HLA DRB1 (p = 0.003) were validated by ELISA in AR using an independent sample set. The fibrinogen proteins further segregated AR from BK virus nephritis (FGB p = 0.03, FGG p = 0.02), a finding that supports the utility of monitoring these urinary proteins for the specific and sensitive noninvasive diagnosis of acute renal allograft rejection.

  13. The experimental treatment of corneal graft rejection with the interleukin-1 receptor antagonist (IL-1ra gene.

    Directory of Open Access Journals (Sweden)

    Jin Yuan

    Full Text Available PURPOSE: To investigate the protective effects of interleukin-1 receptor antagonist (IL-1ra gene transfer in a rat model of corneal graft rejection. METHODS: We constructed a recombinant plasmid (pcDNA3.1-hIL-1ra with high IL-1ra expression in eukaryotic cells. Using a Wistar-SD rat model of corneal graft rejection, we examined the effects of IL-1ra in vivo after cationic polymer jetPEI-mediated nonviral gene delivery. Four groups were included: negative controls (group I, n = 20, pcDNA3.1-hIL-1ra corneal stromal injection (group II, n = 34, pcDNA3.1-hIL-1ra anterior chamber injection (group III, n = 34, and 500 µg/ml IL-1ra protein subconjunctiva injection (group IV, n = 20. IL-1ra expression after transfection was evaluated by real-time polymerase chain reaction (RT-PCR and western blotting. The rejection indices of corneal grafts were analysed in the different groups. The expression levels of transforming growth factor β1 (TGF-β1, inflammatory chemokines including RANTES, interleukin-1 (IL-1 and the numbers of CD4+ and CD8+ T cells in the grafts were determined by biochemical assays at different time points after corneal transplantation. RESULTS: Various degrees of inflammatory cell infiltration and graft neovascularisation were observed by histopathology. After injecting the pcDNA3.1-hIL-1ra plasmid into the cornea, IL-1ra mRNA and protein expression was detected in the corneal stroma and reached a peak on day 3. The graft survival curves indicated that the corneal transparency rates of grafts in the IL-1ra gene-treated group and the IL-1ra protein-treated group were higher compared with the untreated group (P<0.05. During the period of acute rejection, TGF-β1, RANTES, IL-1α and IL-1β levels in the grafts in the IL-1ra treatment groups were lower than the control group (P<0.05. CD4+ and CD8+ T cell counts were reduced significantly in the corneal grafts of groups II, III and IV compared with group I (P<0.05. CONCLUSION

  14. Acute dyspnea

    International Nuclear Information System (INIS)

    Radiodiagnosis is applied to determine the causes of acute dyspnea. Acute dyspnea is shown to aggravate the course of pulmonary diseases (bronchial asthma, obstructive bronchitis, pulmonary edema, throboembolism of pulmonary arteries etc) and cardiovascular diseases (desiseas of myocardium). The main tasks of radiodiagnosis are to determine volume and state of the lungs, localization and type of pulmonary injuries, to verify heart disease and to reveal concomitant complications

  15. Engineering Cellular Metabolism

    DEFF Research Database (Denmark)

    Nielsen, Jens; Keasling, Jay

    2016-01-01

    of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation.......Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds...

  16. Rays Sting: The Acute Cellular Effects of Ionizing Radiation Exposure.

    Science.gov (United States)

    Franco, A; Ciccarelli, M; Sorriento, D; Napolitano, L; Fiordelisi, A; Trimarco, B; Durante, M; Iaccarino, G

    2016-05-01

    High-precision radiation therapy is a clinical approach that uses the targeted delivery of ionizing radiation, and the subsequent formation of reactive oxygen species (ROS) in high proliferative, radiation sensitive cancers. In particular, in thoracic cancer ratdiation treatments, can not avoid a certain amount of cardiac toxicity. Given the low proliferative rate of cardiac myocytes, research has looked at the effect of radiation on endothelial cells and consequent coronary heart disease as the mechanism of ratdiation induced cardiotoxicity. In fact, little is known concerning the direct effect of radiation on mitochondria dynamis in cardiomyocyte. The main effect of ionizing radiation is the production of ROS and recent works have uncovered that they directly participates to pivotal cell function like mitochondrial quality control. In particular ROS seems to act as check point within the cell to promote either mitochondrial biogenesis and survival or mitochondrial damage and apoptosis. Thus, it appears evident that the functional state of the cell, as well as the expression patterns of molecules involved in mitochondrial metabolism may differently modulate mitochondrial fate in response to radiation induced ROS responses. Different molecules have been described to localize to mitochondria and regulate ROS production in response to stress, in particular GRK2. In this review we will discuss the evidences on the cardiac toxicity induced by X ray radiation on cardiomyocytes with emphasis on the role played by mitochondria dynamism.

  17. Rays Sting: The Acute Cellular Effects of Ionizing Radiation Exposure.

    Science.gov (United States)

    Franco, A; Ciccarelli, M; Sorriento, D; Napolitano, L; Fiordelisi, A; Trimarco, B; Durante, M; Iaccarino, G

    2016-05-01

    High-precision radiation therapy is a clinical approach that uses the targeted delivery of ionizing radiation, and the subsequent formation of reactive oxygen species (ROS) in high proliferative, radiation sensitive cancers. In particular, in thoracic cancer ratdiation treatments, can not avoid a certain amount of cardiac toxicity. Given the low proliferative rate of cardiac myocytes, research has looked at the effect of radiation on endothelial cells and consequent coronary heart disease as the mechanism of ratdiation induced cardiotoxicity. In fact, little is known concerning the direct effect of radiation on mitochondria dynamis in cardiomyocyte. The main effect of ionizing radiation is the production of ROS and recent works have uncovered that they directly participates to pivotal cell function like mitochondrial quality control. In particular ROS seems to act as check point within the cell to promote either mitochondrial biogenesis and survival or mitochondrial damage and apoptosis. Thus, it appears evident that the functional state of the cell, as well as the expression patterns of molecules involved in mitochondrial metabolism may differently modulate mitochondrial fate in response to radiation induced ROS responses. Different molecules have been described to localize to mitochondria and regulate ROS production in response to stress, in particular GRK2. In this review we will discuss the evidences on the cardiac toxicity induced by X ray radiation on cardiomyocytes with emphasis on the role played by mitochondria dynamism. PMID:27326395

  18. Beneficiation of limestone plant rejects for value addition.

    Science.gov (United States)

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

    2013-11-15

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

  19. Thermal storage for industrial process and reject heat

    Science.gov (United States)

    Duscha, R. A.; Masica, W. J.

    1978-01-01

    Industrial production uses about 40% of the total energy consumed in the United States. The major share of this is derived from fossil fuel. Potential savings of scarce fuel is possible through the use of thermal energy storage (TES) of reject or process heat for subsequent use. Results of study contracts awarded by the Department of Energy (DOE) and managed by the NASA Lewis Research Center have identified three especially significant industries where high temperature TES appears attractive - paper and pulp, iron and steel, and cement. Potential annual fuel savings with large scale implementation of near-term TES systems for these three industries is nearly 9 million bbl of oil.

  20. Rejection Mechanism in 2D Bounded Confidence Provides more Conformity

    CERN Document Server

    Huet, Sylvie; Jager, Wander

    2014-01-01

    We add a rejection mechanism (negative influence) into a two-dimensions bounded confidence model. The principle is that one shifts aways from a close attitude of one's interlocutor, when there is a strong disagreement on the other attitude. The model shows metastable clusters, which maintain themselves through opposite influences of competitor clusters. Our analysis and first experiments support the hypothesis that the number of clusters grows linearly with the inverse of the uncertainty, whereas this growth is quadratic in the bounded confidence model.

  1. Muon identification and pion rejection in the 4th concept

    Indian Academy of Sciences (India)

    John Haupton

    2007-12-01

    We describe a completely new way to reconstruct and identify muons with high efficiency and very high pion rejection in the 4th concept detector. The dual-solenoid magnetic field allows the reconstruction and precision momentum measurement of muons down to a few GeV (just the energy loss in the 10-int calorimeter and the coil) and the dual-readout calorimeter provides a new, unique and powerful separation of muons from pions. We use test beam data for the calorimeter and calculations for the magnetic fields

  2. Windows for accepting or rejecting solar-heat gain

    Science.gov (United States)

    Peck, J. F.; Thompson, T. L.; Kessler, H. J.

    1982-09-01

    Ordinary fenestration may be modified at low cost using various combinations of windows, duotone venetian blinds, and drapes to control the solar heat gain. In the winter, solar radiation may be absorbed by dark blinds and transferred to the air, minimizing fading of furnishings while collecting useful energy. In the summer, more than 90% of the total potential window heat gain may be rejected by exhausting evaporatively cooled air over the blinds. The performance of several window configurations was analyzed, modeled on a computer, and verified experimentally.

  3. Automatic Carrier Landing System with Gust-rejection Capability

    Institute of Scientific and Technical Information of China (English)

    曹东; 杨一栋; 余勇; 范彦铭

    2004-01-01

    A new direct-lift control carrier landing mode is advanced, and it is proved to be very effective to keep the attitude angle and path angle constant when the aircraft is in the blind area of tracking radar and the guidance system is shut off. The direct-lift control mode is achieved with the symmetric deflection of the flaps and dynamic decoupling for minor disturbance of the angle of attack. This mode changes an aircraft' s model from a short-period oscillation model to a non-oscillation one, which could evidently increase the gust-rejection capability of the aircraft.

  4. Motivated Rejection of (Climate) Science: Causes, Tools, and Effects

    Science.gov (United States)

    Lewandowsky, S.

    2015-12-01

    Although the relevant scientific community long ago settled on the conclusion that human economic activities are causing climate change through the emission of greenhouse gases, a small but vocal number of dissenters remains unconvinced by the evidence. I examine the cognitive and motivational factors that underlie the rejection of scientific evidence, and I illustrate the techniques by which contrarians seek to shape public debate and mislead the public. I also suggest that contrarian activities have seeped into the scientific community and have arguably altered the interpretation of the risks posed by climate change.

  5. Full load rejection procedure for Point Lepreau GS

    International Nuclear Information System (INIS)

    In 1999 WANO issued Significant Operating Event Report 99-01 recommending that the industry verify whether or not currently approved procedures were adequate for a loss or degradation of the electrical grid. A detailed review identified that the procedures available at the time were not adequate to respond effectively to such a disturbance. Operations personnel reviewed operating expectations and the expected plant response to a Loss of Grid and updated the Operating Manual to cover 'Full Load Rejection'. Operations used the simulators to validate the procedure and train crews and Licensed staff. The revised documentation was approved and implemented. (author)

  6. PD1-Expressing T Cell Subsets Modify the Rejection Risk in Renal Transplant Patients

    Science.gov (United States)

    Pike, Rebecca; Thomas, Niclas; Workman, Sarita; Ambrose, Lyn; Guzman, David; Sivakumaran, Shivajanani; Johnson, Margaret; Thorburn, Douglas; Harber, Mark; Chain, Benny; Stauss, Hans J.

    2016-01-01

    We tested whether multi-parameter immune phenotyping before or after renal ­transplantation can predict the risk of rejection episodes. Blood samples collected before and weekly for 3 months after transplantation were analyzed by multi-parameter flow cytometry to define 52 T cell and 13 innate lymphocyte subsets in each sample, producing more than 11,000 data points that defined the immune status of the 28 patients included in this study. Principle component analysis suggested that the patients with histologically confirmed rejection episodes segregated from those without rejection. Protein death 1 (PD-1)-expressing subpopulations of regulatory and conventional T cells had the greatest influence on the principal component segregation. We constructed a statistical tool to predict rejection using a support vector machine algorithm. The algorithm correctly identified 7 out of 9 patients with rejection, and 14 out of 17 patients without rejection. The immune profile before transplantation was most accurate in determining the risk of rejection, while changes of immune parameters after transplantation were less accurate in discriminating rejection from non-rejection. The data indicate that pretransplant immune subset analysis has the potential to identify patients at risk of developing rejection episodes, and suggests that the proportion of PD1-expressing T cell subsets may be a key indicator of rejection risk. PMID:27148254

  7. CELLULAR INTERACTIONS MEDIATED BY GLYCONECTIDS

    Directory of Open Access Journals (Sweden)

    O.Popescu

    1999-01-01

    Full Text Available Cellular interactions involve many types of cell surface molecules and operate via homophilic and/or heterophilic protein-protein and protein-carbohydrate binding. Our investigations in different model-systems (marine invertebrates and mammals have provided direct evidence that a novel class of primordial proteoglycans, named by us gliconectins, can mediate cell adhesion via a new alternative molecular mechanism of polyvalent carbohydrate-carbohydrate binding. Biochemical characterization of isolated and purified glyconectins revealed the presence of specific carbohydrate structures, acidic glycans, different from classical glycosaminoglycans. Such acidic glycans of high molecular weight containing fucose, glucuronic or galacturonic acids, and sulfate groups, originally found in sponges and sea urchin embryos, may represent a new class of carbohydrate carcino-embryonal antigens in mice and humans. Such interactions between biological macromolecules are usually investigated by kinetic binding studies, calorimetric methods, X-ray diffraction, nuclear magnetic resonance, and other spectroscopic analyses. However, these methods do not supply a direct estimation of the intermolecular binding forces that are fundamental for the function of the ligand-receptor association. Recently, we have introduced atomic force microscopy to quantify the binding strength between cell adhesion proteoglycans. Measurement of binding forces intrinsic to cell adhesion proteoglycans is necessary to assess their contribution to the maintenance of the anatomical integrity of multicellular organisms. As a model, we selected the glyconectin 1, a cell adhesion proteoglycan isolated from the marine sponge Microciona prolifera. This glyconectin mediates in vivo cell recognition and aggregation via homophilic, species-specific, polyvalent, and calcium ion-dependent carbohydrate-carbohydrate interactions. Under physiological conditions, an adhesive force of up to 400 piconewtons

  8. Acute myelogenous leukemia (AML) - children

    Science.gov (United States)

    Acute myelogenous leukemia - children; AML; Acute myeloid leukemia - children; Acute granulocytic leukemia - children; Acute myeloblastic leukemia - children; Acute non-lymphocytic leukemia (ANLL) - children

  9. Antibody-dependent cellular cytotoxicity and skin disease

    Energy Technology Data Exchange (ETDEWEB)

    Norris, D.A.; Lee, L.A.

    1985-07-01

    Antibody dependent cellular cytotoxicity (ADCC) is a recently described mechanism of immunologic lysis in which cellular targets sensitized by specific antibodies are efficiently and selectively lysed by Fc receptor (FcR) bearing nonspecific effectors. Immunoglobulins of various classes (IgG, IgM, IgA, IgE) and various cellular effectors (large granular lymphocytes, monocyte/macrophages, T lymphocytes, neutrophils, and eosinophils) can induce ADCC in vitro, and the importance of ADCC in vivo is being tested experimentally in resistance to viral, bacterial, and parasitic infection, in tumor surveillance, in allograft rejection, and in inflammatory diseases. There is much indirect evidence that ADCC may be the mechanism of damage of different cellular targets in skin diseases, but the best direct evidence concerns immunologic keratinocyte damage, especially in cutaneous lupus erythematosus (LE). The authors have shown that keratinocytes of several species are highly susceptible to lymphocyte and monocyte-mediated ADCC, but not to neutrophil or eosinophil ADCC in vitro using two different cytotoxicity assays. In contrast, complement was a relatively ineffective mediator of lysis of metabolically intact keratinocyte targets. Patients with certain cutaneous lupus syndromes have serum antibodies capable of inducing monocyte and lymphocyte ADCC of targets coated with extractable nuclear antigens. The authors have shown that these antigens apparently move to the cell membrane of keratinocytes in vitro following ultraviolet irradiation. In an animal model, they have shown that antibodies to SSA/Ro bind to human keratinocytes in vivo, especially after ultraviolet irradiation.

  10. Implementation and Rejection of Industrial Steam System Energy Efficiency Measures

    Energy Technology Data Exchange (ETDEWEB)

    Therkelesen, Peter; McKane, Aimee

    2013-05-01

    Steam systems consume approximately one third of energy applied at U.S. industrial facilities. To reduce energy consumption, steam system energy assessments have been conducted on a wide range of industry types over the course of five years through the Energy Savings Assessment (ESA) program administered by the U.S. Department of Energy (U.S. DOE). ESA energy assessments result in energy efficiency measure recommendations that are given potential energy and energy cost savings and potential implementation cost values. Saving and cost metrics that measure the impact recommended measures will have at facilities, described as percentages of facility baseline energy and energy cost, are developed from ESA data and used in analyses. Developed savings and cost metrics are examined along with implementation and rejection rates of recommended steam system energy efficiency measures. Based on analyses, implementation of steam system energy efficiency measures is driven primarily by cost metrics: payback period and measure implementation cost as a percentage of facility baseline energy cost (implementation cost percentage). Stated reasons for rejecting recommended measures are primarily based upon economic concerns. Additionally, implementation rates of measures are not only functions of savings and cost metrics, but time as well.

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

    Directory of Open Access Journals (Sweden)

    Olivia R. Blume

    2012-01-01

    Full Text Available Antibody-mediated rejection (AMR is a major cause of late kidney transplant failure. It is important to have an understanding of human-leukocyte antigen (HLA typing including well-designed studies to determine anti-MHC-class-I-related chain A (MICA and antibody rejection pathogenesis. This can allow for more specific diagnosis and treatment which may improve long-term graft function. HLA-specific antibody detection prior to transplantation allows one to help determine the risk for AMR while detection of DSA along with a biopsy confirms it. It is now appreciated that biopsy for AMR does not have to include diffuse C4d, but does require a closer look at peritubular capillary microvasculature. Although plasmapheresis (PP is effective in removing alloantibodies (DSAs from the circulation, rebound synthesis of alloantibodies can occur. Splenectomy is used in desensitization protocols for ABO incompatible transplants as well as being found to treat AMR refractory to conventional treatment. Also used are agents targeted for plasma cells, B cells, and the complement cascade which are bortezomib rituximab and eculizumab, respectively.

  12. Parametric Adaptive Radar Detector with Enhanced Mismatched Signals Rejection Capabilities

    Directory of Open Access Journals (Sweden)

    Liu Bin

    2010-01-01

    Full Text Available We consider the problem of adaptive signal detection in the presence of Gaussian noise with unknown covariance matrix. We propose a parametric radar detector by introducing a design parameter to trade off the target sensitivity with sidelobes energy rejection. The resulting detector merges the statistics of Kelly's GLRT and of the Rao test and so covers Kelly's GLRT and the Rao test as special cases. Both invariance properties and constant false alarm rate (CFAR behavior for this detector are studied. At the analysis stage, the performance of the new receiver is assessed and compared with several traditional adaptive detectors. The results highlight better rejection capabilities of this proposed detector for mismatched signals. Further, we develop two two-stage detectors, one of which consists of an adaptive matched filter (AMF followed by the aforementioned detector, and the other is obtained by cascading a GLRT-based Subspace Detector (SD and the proposed adaptive detector. We show that the former two-stage detector outperforms traditional two-stage detectors in terms of selectivity, and the latter yields more robustness.

  13. Potential use of power plant reject heat in commercial aquaculture

    Energy Technology Data Exchange (ETDEWEB)

    Olszewski, M.

    1977-01-01

    Current research and commercial activities in aquaculture operations have been reviewed. An aquaculture system using mostly herbivorous species in pond culture is proposed as a means of using waste heat to produce reasonably priced protein. The system uses waste water streams, such as secondary sewage effluent, animal wastes, or some industrial waste streams as a primary nutrient source to grow algae, which is fed to fish and clams. Crayfish feed on the clam wastes thereby providing a clean effluent from the aquaculture system. Alternate fish associations are presented and it appears that a carp or tilapia association is desirable. An aquaculture system capable of rejecting all the waste heat from a 1000-MW(e) power station in winter can accommodate about half the summer heat rejection load. The aquaculture facility would require approximately 133 ha and would produce 4.1 x 10/sup 5/ kg/year of fish, 1.5 x 10/sup 6/ kg/year of clam meat, and 1.5 x 10/sup 4/ kg/year of live crayfish. The estimated annual pretax profit from this operation is one million dollars. Several possible problem areas have been identified. However, technical solutions appear to be readily available to solve these problems. The proposed system shows considerable economic promise. Small scale experiments have demonstrated the technical feasibility of various components of the system. It therefore appears that a pilot scale experimental facility should be operated.

  14. Automatic misclassification rejection for LDA classifier using ROC curves.

    Science.gov (United States)

    Menon, Radhika; Di Caterina, Gaetano; Lakany, Heba; Petropoulakis, Lykourgos; Conway, Bernard A; Soraghan, John J

    2015-08-01

    This paper presents a technique to improve the performance of an LDA classifier by determining if the predicted classification output is a misclassification and thereby rejecting it. This is achieved by automatically computing a class specific threshold with the help of ROC curves. If the posterior probability of a prediction is below the threshold, the classification result is discarded. This method of minimizing false positives is beneficial in the control of electromyography (EMG) based upper-limb prosthetic devices. It is hypothesized that a unique EMG pattern is associated with a specific hand gesture. In reality, however, EMG signals are difficult to distinguish, particularly in the case of multiple finger motions, and hence classifiers are trained to recognize a set of individual gestures. However, it is imperative that misclassifications be avoided because they result in unwanted prosthetic arm motions which are detrimental to device controllability. This warrants the need for the proposed technique wherein a misclassified gesture prediction is rejected resulting in no motion of the prosthetic arm. The technique was tested using surface EMG data recorded from thirteen amputees performing seven hand gestures. Results show the number of misclassifications was effectively reduced, particularly in cases with low original classification accuracy. PMID:26736304

  15. Salt rejection and water transport through boron nitride nanotubes.

    Science.gov (United States)

    Hilder, Tamsyn A; Gordon, Daniel; Chung, Shin-Ho

    2009-10-01

    Nanotube-based water-purification devices have the potential to transform the field of desalination and demineralization through their ability to remove salts and heavy metals without significantly affecting the fast flow of water molecules. Boron nitride nanotubes have shown superior water flow properties compared to carbon nanotubes, and are thus expected to provide a more efficient water purification device. Using molecular dynamics simulations it is shown that a (5, 5) boron nitride nanotube embedded in a silicon nitride membrane can, in principle, obtain 100% salt rejection at concentrations as high as 1 M owing to a high energy barrier while still allowing water molecules to flow at a rate as high as 10.7 water molecules per nanosecond (or 0.9268 L m(-2) h(-1)). Furthermore, ions continue to be rejected under the influence of high hydrostatic pressures up to 612 MPa. When the nanotube radius is increased to 4.14 A the tube becomes cation-selective, and at 5.52 A the tube becomes anion-selective. PMID:19582727

  16. Nationalism and patriotism: national identification and out-group rejection.

    Science.gov (United States)

    Mummendey, A; Klink, A; Brown, R

    2001-06-01

    It is argued that the differentiation between nationalism and patriotism proposed in the literature can be seen as analogous to judgments based on different types of comparisons: intergroup comparisons with other nations are associated with intergroup behaviour that corresponds to nationalism, whereas temporal or standard comparisons are linked with behaviour that corresponds to patriotism. Four studies (N = 103, 107, 96 and 105) conducted in Germany and Britain examined the hypothesis that national identification and in-group evaluation only show a reliable relationship with out-group rejection under an intergroup comparison orientation. Participants were primed with either an intergroup comparison, a temporal comparison or no explicit comparison orientation. A subsequent questionnaire assessed in-group (own country) identification, in-group evaluation (i.e. national pride) and rejection of national out-groups. Across all four studies, both in-group identification and in-group evaluation show a stronger correlation with out-group derogation if participants were primed with an intergroup comparison orientation compared to temporal and control conditions. Results are discussed with regard to nationalism and patriotism as well as Hinkle and Brown's (1990) model on relational vs. autonomous orientations.

  17. Integrated cellular systems

    Science.gov (United States)

    Harper, Jason C.

    The generation of new three-dimensional (3D) matrices that enable integration of biomolecular components and whole cells into device architectures, without adversely altering their morphology or activity, continues to be an expanding and challenging field of research. This research is driven by the promise that encapsulated biomolecules and cells can significantly impact areas as diverse as biocatalysis, controlled delivery of therapeutics, environmental and industrial process monitoring, early warning of warfare agents, bioelectronics, photonics, smart prosthetics, advanced physiological sensors, portable medical diagnostic devices, and tissue/organ replacement. This work focuses on the development of a fundamental understanding of the biochemical and nanomaterial mechanisms that govern the cell directed assembly and integration process. It was shown that this integration process relies on the ability of cells to actively develop a pH gradient in response to evaporation induced osmotic stress, which catalyzes silica condensation within a thin 3D volume surrounding the cells, creating a functional bio/nano interface. The mechanism responsible for introducing functional foreign membrane-bound proteins via proteoliposome addition to the silica-lipid-cell matrix was also determined. Utilizing this new understanding, 3D cellular immobilization capabilities were extended using sol-gel matrices endowed with glycerol, trehalose, and media components. The effects of these additives, and the metabolic phase of encapsulated S. cerivisiase cells, on long-term viability and the rate of inducible gene expression was studied. This enabled the entrapment of cells within a novel microfluidic platform capable of simultaneous colorimetric, fluorescent, and electrochemical detection of a single analyte, significantly improving confidence in the biosensor output. As a complementary approach, multiphoton protein lithography was utilized to engineer 3D protein matrices in which to

  18. A fresh look at the fossil evidence for early Archaean cellular life

    OpenAIRE

    Brasier, Martin; McLoughlin, Nicola; Green, Owen; Wacey, David.

    2006-01-01

    The rock record provides us with unique evidence for testing models as to when and where cellular life first appeared on Earth. Its study, however, requires caution. The biogenicity of stromatolites and ‘microfossils’ older than 3.0 Gyr should not be accepted without critical analysis of morphospace and context, using multiple modern techniques, plus rejection of alternative non-biological (null) hypotheses. The previous view that the co-occurrence of biology-like morphology and carbonaceous ...

  19. Multiuser Cellular Network

    CERN Document Server

    Bao, Yi; Chen, Ming

    2011-01-01

    Modern radio communication is faced with a problem about how to distribute restricted frequency to users in a certain space. Since our task is to minimize the number of repeaters, a natural idea is enlarging coverage area. However, coverage has restrictions. First, service area has to be divided economically as repeater's coverage is limited. In this paper, our fundamental method is to adopt seamless cellular network division. Second, underlying physics content in frequency distribution problem is interference between two close frequencies. Consequently, we choose a proper frequency width of 0.1MHz and a relevantly reliable setting to apply one frequency several times. We make a few general assumptions to simplify real situation. For instance, immobile users yield to homogenous distribution; repeaters can receive and transmit information in any given frequency in duplex operation; coverage is mainly decided by antenna height. Two models are built up to solve 1000 users and 10000 users situations respectively....

  20. Extension of the rejection sensitivity construct to the interpersonal functioning of gay men.

    Science.gov (United States)

    Pachankis, John E; Goldfried, Marvin R; Ramrattan, Melissa E

    2008-04-01

    On the basis of recent evidence suggesting that gay men are particularly likely to fear interpersonal rejection, the authors set out to extend the rejection sensitivity construct to the mental health concerns of gay men. After establishing a reliable and valid measure of the gay-related rejection sensitivity construct, the authors use this to test the mediating effect of internalized homophobia on the relationship between parental rejection of one's sexual orientation and sensitivity to future gay-related rejection. The present data support this mediational model and also establish rejection sensitivity's unique contribution to unassertive interpersonal behavior in the context of internalized homophobia and parental rejection. The authors conclude that gay-related rejection sensitivity is a useful construct for clinicians working with gay men given the impact that past gay-related rejection can have on their gay clients' present cognitive-affective-behavioral functioning. The authors discuss the possibility of revising rejection-prone schemas in clinical work with gay men. Future research is necessary to further examine the internal processing and interpersonal functioning of gay men by using existing constructs (or modifications of them) that are likely to be particularly relevant to the unique concerns of this population. PMID:18377126