TY - JOUR. T1 - Urine proteomic profiling for biomarkers of acute renal transplant rejection.. AU - Liang, Shu Ling. AU - Clarke, William. PY - 2010. Y1 - 2010. N2 - Acute allograft rejection is a serious impediment to long-term success in renal transplantation. Early detection of rejection is crucial for treatment of rejection, and can help avoid long-term effects such as chronic rejection or loss of the transplanted organ. The current diagnostic paradigm is a combination of clinical presentation, biochemical measurements (serum creatinine), and needle biopsy. There are significant efforts underway to find alternate biomarkers for early detection of acute rejection, including protein profiling of urine by mass spectrometry. One approach for protein profiling is to use affinity mass spectrometry - we describe a method for this using ProteinChips and SELDI-TOF mass spectrometry.. AB - Acute allograft rejection is a serious impediment to long-term success in renal transplantation. Early detection ...

TY - JOUR. T1 - Acute cellular rejection following human heart transplantation is associated with increased expression of vitronectin receptor (integrin αvβ3). AU - Yamani, Mohamad H.. AU - Yang, Jiacheng. AU - Masri, Carolyna S.. AU - Ratliff, Norman B.. AU - Bond, Meredith. AU - Starling, Randall C.. AU - McCarthy, Patrick. AU - Plow, Edward. AU - Young, James B.. PY - 2002/2. Y1 - 2002/2. N2 - The vitronectin receptor (integrin αvβ3), a cell-surface adhesion receptor, has been shown to play a significant role in endothelial cell migration, apoptosis, atherosclerosis, and T-lymphocyte activation. This study was undertaken to test the hypothesis that cardiac allograft rejection is associated with increased expression of αvβ3. We also determined whether fibronectin receptor (α5β1) and tissue factor are up-regulated in the presence of acute cellular rejection. We evaluated endomyocardial biopsy specimens with histologic evidence of different degrees of acute cellular rejection (grade 0, n ...

were present in biopsies from patients with subclinical rejection and largely absent in normal protocol biopsies. Transcripts for perforin, Fas ligand, and granzyme B were also present in patients with subclinical rejection, although in reduced amounts when compared to biopsies from patients with clinical rejection episodes. There were no differences in IL-10 and IL-15 transcripts in clinical and subclinical rejection biopsies. Additional, albeit indirect, data in favor of a pathogenic role for subclinical rejection comes from the early observation of Isoniemi et al, who reported that in patients who had not experienced clinical acute rejection episodes, the development of chronic histological changes occurred in inverse relation to the amount of immunosuppression they had received.15 Similarly, Legendre et al reported a patient cohort that never experienced clinical rejection episodes, in whom the development of chronic rejection at 2 years was preceded by subclinical rejection at three ...

TY - JOUR. T1 - Sero-molecular evaluation of human cytomegalovirus disease in renal transplant rejection.. AU - Kishore, Janak. AU - Mukhopadhyay, Chiranjoy. AU - Savitri, AU - Ayyagari, Archana. AU - Sharma, Rakesh Kumar. PY - 2004/1/1. Y1 - 2004/1/1. N2 - Cytomegalovirus (CMV) is the most common viral pathogen in renal transplant recipients resulting in graft rejection. The prevalence of CMV disease and renal graft rejection is not well studied in India. Sequential specimens from 32 renal allograft recipients were examined by using CMV IgM specific mu capture ELISA and DNA by PCR. Twelve of the 32 patients were CMV IgM positive and out of 12 patients, 9 had rejection and 4 experienced CMV disease. CMV IgM specific mu capture ELISA helped in diagnosis of CMV disease, though it is less sensitive in detection of rejection. PCR itself was proved not sensitive enough in detecting either CMV disease or rejection. At present, optimal laboratory detection of CMV infection in these patients can be ...

TY - JOUR. T1 - Nitric oxide production and nitric oxide synthase expression in acute human renal allograft rejection. AU - Albrecht, EWJA. AU - van Goor, H. AU - Tiebosch, ATMG. AU - Moshage, H. AU - Tegzess, Adam. AU - Stegeman, CA. PY - 2000/12/15. Y1 - 2000/12/15. N2 - Background Nitric oxide (NO) is produced by nitric oxide synthases (NOS), which are either constitutively expressed in the kidney or inducible, in resident and infiltrating cells during inflammation and allograft rejection. NO is rapidly degraded to the stable end products nitrite and nitrate, which can be measured in serum and urine, and may serve as noninvasive markers of kidney allograft rejection.Methods. Total nitrite and nitrate levels (NOx) were measured in serum and urine thrice meekly after an overnight fast in 18 consecutive patients following renal cadaveric transplantation. Inducible NOS (iNOS) and endothelial NOS (eNOS) expression was immunochemically determined in renal biopsy specimens with or without acute ...

Critical evaluation of radiolabeled lymphocytes to detect acute renal transplant rejection in a large animal model. - Get your full text copy in PDF #4818

Chronic renal transplant rejection is a form of renal transplant rejection. It usually later following transplantation. Pathology Chronic rejection is defined as a gradual deterioration in graft function beginning at least 3 months after transp...

A graft vessel preparation device and a method for using the graft vessel preparation device is provided. The graft vessel preparation device establishes and maintains a critical dimension on a graft vessel which corresponds to a dimension of an anastomosis site on a target vessel. One example of a graft vessel preparation device which prepares a graft vessel for a vascular anastomosis procedure includes a parallelogram linkage, a first spreader arm and a second spreader arm. The first spreader arm and the second spreader arm mount on opposing members of the parallelogram linkage in a parallel configuration. The spreader arms are configured in order to allow the placement of an end of a graft vessel over the spreader arms. The spreader arms are also configured to separate within an interior of the graft vessel once the graft vessel is placed over the spreader arms in order to establish a critical dimension. The critical dimension is established using a critical dimension locator. The critical dimension

Purpose: Belatacept as a high-affinity variant of CTLA-4Ig, has been applied into kidney transplantation to against acute rejection. However, adoption of Belatacept has been limited in part due to concerns regarding higher rates and grades of acute rejection in clinical trials specially in TCMR. Our previous research found that BTLA pathway was involved in pathogenesis of acute rejection in biopsy-proven patients and attenuated T cell mediated rejection in rat transplantation model.. *Methods: In this study we supposed a combined therapy, Belatacept combined with BTLA, could more effectively attenuated acute rejection after kidney transplantation. In vitro, we extracted the mature DCs and splenocyte from rats to do mixed lymphocyte reaction treated with or without Belatacept and BTLA-overexpression adenovirus. The cell proliferation was measured by BrdU analysis. Then the rat kidney transplantation model was used to research the graft rejection in single and combined therapy. The rats (n=5 each ...

Renal graft failure due to chronic rejection, also known as chronic allograft nephropathy, is one of the leading causes for repeat renal transplantation. Chronic rejection is characterized by progressive fibrosis and scarring. Renal biopsies of patients undergoing chronic rejection show greater expression of profibrotic cytokines, including TGF-beta and PDGF, than normal kidney tissue. Moreover, the cytokine activity of chronic rejection resembles that of other fibrosing renal diseases. Angiotensin converting enzyme inhibitors (ACEinh) and HMG-CoA reductase inhibitors have been shown to protect effectively against other types of fibrotic disease. These drugs may protect against fibrosis and preserve renal function in renal transplant patients with chronic rejection, in part by blocking activation of TGF-beta and PDGF. This study evaluates the impact of irbesartan (an AII-RB which acts similar to an ACEinh) and pravastatin on the clinical progression of chronic rejection and on the expression of ...

BACKGROUND: The potential therapeutic benefits of CD3 monoclonal antibodies, such as OKT3, have been limited by their immunogenicity and their propensity to activate a severe cytokine release syndrome. This has constrained the clinical use of OKT3 to the treatment of acute rejection episodes of organ allografts. METHODS: We have humanized a rat CD3 antibody and created a single amino acid substitution in position 297 of the IgG1 heavy chain to prevent glycosylation and, consequently, binding of the therapeutic antibody to Fc receptors and to complement. This antibody has been given as first line antirejection therapy in nine kidney transplant recipients with biopsy-proven acute rejection episodes. RESULTS: None of the patients demonstrated any antiglobulin response nor any significant cytokine release syndrome. Seven of the nine showed evidence of resolution of their rejection, although some patients experienced re-rejection. CONCLUSIONS: These findings suggest that CD3 antibodies can be engineered to

Introduction: Due to the parallel liver transplant, SLK recipients are thought to be protected from kidney rejection and receive similar immunosuppression (IS) as liver transplant alone (LTA). However, data to support this assumption and practice are not available.. Aim: To characterize the incidence and outcomes of rejection after SLK and compare outcomes and IS requirements to LTA.. Methods: All SLK recipients from 1996-2010 were included. A more recent SLK and LTA cohort (2007-10) given identical IS regimens were matched by age, transplant year, and liver disease.. Results: 181 received SLK: age 54.0 ± 10.8 years, 60.9 % male, 32.0 % HCV+. One year patient, liver, and kidney graft survival were 82.9%, 80.7% and 79.6 %, respectively. Kidney rejection occurred in 14.3%: 20 (11.0%) acute cellular (ACR), 4 (2.2%) antibody-mediated, and 2 (1.1%) chronic rejection (CR). Liver rejection occurred in 16.1%: 22 (12.2%) ACR and 7 (3.9%) CR. Graft failure (5 kidney, 4 liver) contributed to 9 (25.8%) ...

Looking for Antibody-Mediated Rejection? Find out information about Antibody-Mediated Rejection. Destruction of a graft by the immune system of the recipient. Rejection in a dream may suggest that there are feelings or situations the dreamer wants to be... Explanation of Antibody-Mediated Rejection

BACKGROUND Although many risk factors are reported about graft rejection after heart transplantation (HTx), the effect of HLA mismatch (MM) still remains unknown, especially in the Japanese population. The aim of the present study was to investigate the influence of HLA MM on graft rejection among HTx recipients in Japan. METHODS We retrospectively investigated the association of the number of HLA MM including class I (A, B) and class II (DR) (for each locus MM: 0 to 2, total MM: 0 to 6) and the incidence of moderate to severe acute cellular rejection (ACR) confirmed by endomyocardial biopsy (International Society for Heart and Lung Transplantation grade ≥ 3A/2R) within 1 year after HTx. RESULTS Between 2007 and 2014, we had 49 HTx cases in our institute. After excluding those with insufficient data and positive donor-specific antigen, finally 35 patients were enrolled. Moderate to severe ACR was observed in 16 (45.7%) patients. The number of HLA-DR MM was significantly associated with the

Cytokines present in the renal graft may have originated from either the donor or the recipient. Mutations in cytokine polymorphism sequences may alter transcription factor sites, which could alter transcription itself and subsequent cytokine production. However, the exact role of cytokine gene polymorphisms in transplant outcome remains controversial, with some groups showing a correlation,1-3 but others not.4,5. Tumour necrosis factor (TNF) is a proinflammatory cytokine. TNFα release has been correlated with the subsequent development of early graft failure. A G to A base change at position −308 of the TNFα promoter region has been described, resulting in two alleles TNF1 and TNF2.6 The TNF2 allele is in linkage disequilibrium with the major histocompatibility complex (MHC) haplotype A1-B8-DR3. Wilson et al have provided evidence that the TNF2 allele is a much stronger transcriptional activator than the TNF1 allele.7 The molecular mechanism to explain this has not been elucidated; there ...

Background: Regulatory T cells have been suggested to have a protective role against acute rejection in allograft recipients. However, there is little information available about their contribution to chronic rejection process. The role of transforming growth factor-beta 1 (TGF- β1) as a profibrogenic and/or immunoregulatory cytokine in renal allografts is also controversial. Objectives: To evaluate the frequency of CD4+CD25+CD127- and CD3+CD8+CD28- regulatory T cells in chronic allograft dysfunction (CAD) and to investigate the expression of TGF- β1 in renal allografts. Methods: Thirty biopsy-proven CAD patients were pair-matched with 30 stable graft function patients and a third group of healthy volunteers. Flowcytometry was performed on PBMCs to determine the frequency of CD3+CD8+CD28- and CD4+CD25+CD127- regulatory T cells in lymphocyt population. TGF- β1 gene expression was assessed by Real Time PCR. Results: The percentage of CD3+CD8+CD28- Tregs among renal allograft recipients was higher than

Background: Predisposing factors, long-term occurrence, and histopathological changes associated with recovery or progression to allograft failure from chronic rejection (CR) were studied in adult patients treated primarily with tacrolimus. Methods: CR cases were identified using stringent criteria applied to a retrospective review of computerized clinicopathological data and slides. Results: After 1973 days median follow- up, 35 (3.3%) of 1049 primary liver allograft recipients first developed CR between 16 and 2532 (median 242) days. The most significant risk factors for CR were the number (P,0.001) and histological severity (P,0.005) of acute rejection episodes and donor age ,40 years (P,0.03). Other demographic and matching parameters were not associated with CR in this cohort. Ten patients died with, but not of, CR. Eight required retransplantation because of CR at a median of 268 days. Ten resolved either histologically or by normalization of liver injury tests over a median of 548 days. ...

TY - JOUR. T1 - The Value of Protocol Biopsies to Identify Patients With De Novo Donor-Specific Antibody at High Risk for Allograft Loss. AU - Schinstock, Carrie. AU - Cosio, Fernando G. AU - Cheungpasitporn, W.. AU - Dadhania, D. M.. AU - Everly, M. J.. AU - Samaniego-Picota, M. D.. AU - Cornell, L.. AU - Stegall, Mark D. PY - 2017/6/1. Y1 - 2017/6/1. N2 - De novo donor-specific antibody (dnDSA) is associated with antibody-mediated rejection (AMR) and allograft loss, yet the allograft histology associated with dnDSA remains unclear. The aim of this study was to examine the allograft histology associated with dnDSA in patients with serial surveillance biopsies. We retrospectively studied adult conventional solitary kidney transplant recipients from October 2007 to May 2014. The definition of dnDSA was new donor-specific antibody (DSA) with mean fluorescence intensity (MFI) ,1000. The incidence of dnDSA was 7.0% (54 of 771) over mean follow-up of 4.2 ± 1.9 years. Patients with dnDSA had reduced ...

The aim of our study was to investigate the expression of kidney injury molecule-1 (KIM-1) in renal allograft biopsy samples and assess the clinical significance of its use as a biomarker for tissue damage. A total of 69 renal allograft biopsy samples from 17 patients with normal serum creatinine and 52 cases of increased serum creatinine were collected. They were divided into different groups according to the Banff 2007 diagnostic criteria. KIM-1 expression was detected by immunohistochemical methods and the association of KIM-1 and blood biochemical indexes was analyzed. KIM-1 expression increased as Banff 2007 classification grade increased and was positively correlated with tubular inflammation severity in the acute T-cell rejection group. Moreover, KIM-1 expression was strongly positive in the chronic active antibody-mediated rejection group. Interestingly, KIM-1 was weakly positive in the normal group without obvious acute rejection and injury of immunosuppressant toxicity. In this group, ...

Synonyms for Chronic rejection in Free Thesaurus. Antonyms for Chronic rejection. 41 synonyms for rejection: refusal, turning down, declining, dismissal, spurning, rebuff, knock-back, non-acceptance, denial, veto, dismissal, exclusion.... What are synonyms for Chronic rejection?

Sigma-Aldrich offers abstracts and full-text articles by [Thomas Bachelet, Celine Nodimar, Jean-Luc Taupin, Sebastien Lepreux, Karine Moreau, Delphine Morel, Gwendaline Guidicelli, Lionel Couzi, Pierre Merville].

In their paper published in this issue of Heart, Goland et al provide novel insights into changes in function of the transplanted heart within the first year (see page 1681).1 This paper, together with a recent article also published in this journal,2 contribute greatly in illuminating a field in which physiological investigation has been largely uncharted.. After the first heart transplant was performed by Christiaan Barnard in 1967, success was variable until immunosuppressive regimens were perfected.3 With these measures, and improved understanding of the immunology of rejection, the incidence of hyperacute allograft failure, largely due to hyperacute rejection, has become rare.4 However, acute rejection is still a concern, although its incidence decreases with time after transplantation5 most probably owing to the development of immune tolerance. Chronic rejection is a more difficult problem as it follows an insidious course. The histological hallmarks of chronic rejection in the ...

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Although the precise link between the increased incidence of allograft rejection in female heart transplant recipients remains uncertain, various gender-specific characteristics may predispose women to earlier rejection episodes. Critical care practitioners must be cognizant of the underlying immunologic factors that indicate higher risk in these recipients. Until the ideal treatment for cardiac rejection is discovered, identifying pertinent immunologic factors, attending to subtle symptoms, obtaining serial endomyocardial biopsies and initiating prompt, additional aggressive immunosuppressive protocols remain paramount in rendering quality patient care. Research must continue to elicit more specific tissue-typing antigens and more selective immunosuppressive agents that will ultimately result in prolonged survival of all heart transplant recipients. ...

Utku N, Heinemann T, Tullius SG, Bulwin GC, Beinke S, Blumberg RS, Beato F, Randall J, Kojima R, Busconi L, Robertson ES, Schülein R, Volk HD, Milford EL, Gullans SR. Prevention of acute allograft rejection by antibody targeting of TIRC7, a novel T cell membrane protein. Immunity. 1998 Oct; 9(4):509-18 ...

Kidney transplantation is the best treatment for many patients with kidney failure. Sometimes a transplanted kidney is rejected by the patients immune system. Many types of immune system cells, including B cells, are active in rejection. B cells produce antibodies against anything the body sees as non-self, like germs or a transplanted kidney. Most medicines that help prevent transplant rejection affect cells other than B cells. Belimumab is a medication used to treat a disease called lupus. Belimumab slows development of antibody-producing B cells. This study will test whether belimumab works on parts of the immune system that cause rejection. Twenty to thirty adults getting a kidney transplant will be in this study. Like flipping a coin, a computer will randomly assign half to be given belimumab and half to be given placebo (a fake medicine). Patients and doctors will not know which medicine was assigned until the study is over. A total of 7 doses of study medicine will be given through a ...

A method of diagnosing cardiac transplant rejection within a patient comprising, obtaining a sample of a biological fluid from the patient, and determining the level of a brain natriuretic peptide (BNP) or a fragment thereof, within the sample of body fluid. The step of determining the concentration of BNP involves an assay comprising at least one antibody exhibiting affinity for the BNP or a fragment thereof, and the biological fluid comprises plasma, urine or cerebrospinal fluid. Furthermore, the antibody used within the method may comprises a polyclonal antibody, a monoclonal antibody, or a combination thereof. Preferably, the method involves obtaining at least two of the samples of body fluid from the patient over a period of time and comparing the BNP levels, with an increase in BNP being indicative of an upcoming rejection episode.

A simple, inexpensive blood test could soon help doctors halt organ rejection before it impairs transplanted hearts and kidneys.. In the past, we couldnt spot rejection episodes until they harmed the organ, said Atul Butte, MD, PhD, who is co-senior author of the new research and an associate professor of medical informatics and of pediatrics at the Stanford University School of Medicine, in addition to director of the Center for Pediatric Bioinformatics at Lucile Packard Childrens Hospital. Our goal is to develop blood tests that will keep transplanted organs functioning so that patients can avoid a second transplant.. Butte and his collaborators have made a big step toward that goal. The Stanford team found three easily measured proteins that rise in the blood during acute rejection, in which a patients immune system attacks his or her transplanted organ. The research, which will be published online Sept. 23 in PLoS-Computational Biology, is the first-ever report of an immune-rejection ...

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immune Adenosine A2B Receptors Rabbit polyclonal to ZNF248, Ticlopidine hydrochloride manufacture The CD28/CTLA-4 blocker belatacept selectively inhibits alloreactive T cell responses but is associated with a high incidence of acute rejection following renal transplantation, which led us to investigate the etiology of belatacept resistant graft rejection. to Th1 cells, Th17 memory space cells indicated significantly higher levels of the coinhibitory molecule CTLA-4. Excitement in the presence of belatacept inhibited Th1 reactions but augmented Th17 cells due to higher level of sensitivity to coinhibition by CTLA-4. Th17 cells from renal transplant recipients were resistant to ex vivo CD28/CTLA-4 blockade with belatacept, and an elevated rate of recurrence of Th17 memory space cells was connected with acute rejection during belatacept therapy. These data focus on important variations in costimulatory and coinhibitory requirements of CD4+ memory space subsets, and demonstrate that the ...

For decades, immunologists have been trying to train the transplant recipients immune system to accept transplanted cells and organs without the long-term use of anti-rejection drugs. New University of Minnesota preclinical research shows that this is now possible.. In a study published in Nature Communications, researchers at the University of Minnesota Medical Schools Department of Surgery and Schulze Diabetes Institute, collaborating with colleagues at Northwestern University, have maintained long-term survival and function of pancreatic islet transplants despite complete discontinuation of all anti-rejection drugs on day 21 after the transplant. This study was performed in a stringent preclinical transplant setting in nonhuman primates, one step away from humans.. For many patients with end-stage organ failure, transplantation is the only effective and remaining treatment option. To prevent transplant rejection, recipients must take medications long-term that suppress the bodys immune ...

Addressing the etiological heterogeneity of interstitial fibrosis in kidney allografts represents an important challenge to improve long-term transplant outcomes. We investigated the determinants, clinical and histological phenotype, and outcome of i-IF/TA in a prospective cohort of kidney recipient

Check DSSSB Rejection List 2021 for the Post of Junior Engineerby Delhi Subordinate Services Selection Board (DSSSB) on its dsssb.delhi.gov.in Rejection List link and download the DSSSB Rejection List 2021 date sheet. Aspirants can check the complete details about DSSSB Rejection List 2021 and other important Latest updates on the DSSSB 2021 Rejection List on Fresherslive.

In a study published in Nature Communications, researchers at the University of Minnesota Medical Schools Department of Surgery and Schulze Diabetes Institute, collaborating with colleagues at Northwestern University, have maintained long-term survival and function of pancreatic islet transplants despite complete discontinuation of all anti-rejection drugs on day 21 after the transplant. This study was performed in a stringent preclinical transplant setting in nonhuman primates, one step away from humans.. For many patients with end-stage organ failure, transplantation is the only effective and remaining treatment option. To prevent transplant rejection, recipients must take medications long-term that suppress the bodys immune system. These immunosuppressive drugs are effective at preventing rejection over the short term; however, because anti-rejection drugs suppress all of the immune system nonspecifically, people taking these drugs face the risk of serious infections and even cancer. ...

Chronic rejection is the most common cause of late graft failure after solid organ transplantation. A model of chronic rejection, the rat aortic allograft, has histologic features that parallel those in the vessels of human transplanted organs. However, the molecular tools required to dissect the im …

Predicting liver transplant rejection The survival rate of liver transplant patients one year after treatment has improved from about 30 in the 1970s to more than 80, with acute cellular rejection ACR the most common complication. It occurs in about 30 of cases and is generally arrested by drug treatment. However, if ACR occurs more than one year...

Solid organ transplantation is a marvel of modern medicine; tens of thousands of patients await organs. Although the survival rate for transplant recipients has substantially improved over the past several decades, organ rejection remains a challenge. Transplant rejection mediated by alloreactive T cells, which react against tissue from a genetically distinct donor, and reperfusion injury, which is tissue damage that occurs when blood returns after oxygen deprivation, are two major mechanisms of long-term graft failure. A class of immunoglobulin M (IgM) autoantibodies of unknown function, which bind to leukocyte antigens and increase during inflammatory conditions, might help prevent such failure.. Because patients with high blood levels of such IgM antibodies show better transplant outcomes than those without, Lobo et al. examined whether these antibodies might protect against transplant rejection in mice. The authors transplanted genetically mismatched hearts into either wild-type or IgM ...

Oxford University scientists in the UK have shown that a powerful drug given at the time of a kidney transplant operation not only halves the early risk of rejection, but that it also allows a less toxic regimen of anti-rejection drugs to be used after the operation.

Lipocalin 2 (Lcn2) is rapidly produced by damaged nephron epithelia and is one of the most promising new markers of renal injury, delayed graft function and acute allograft rejection (AR);however, the functional importance of Lcn2 in renal transplantation is largely unknown. To understand the role of Lcn2 in renal AR, kidneys from Balb/c mice were transplanted into C57Bl/6 mice and vice versa and analyzed for morphological and physiological outcomes of AR at posttransplantation days 3, 5, and 7. The allografts showed a steady increase in intensity of interstitial infiltration, tubulitis and periarterial aggregation of lymphocytes associated with a substantial elevation in serum levels of creatinine, urea and Lcn2. Perioperative administration of recombinant Lcn2:siderophore:Fe complex (rLcn2) to recipients resulted in functional and morphological amelioration of the allograft at day 7 almost as efficiently as daily immunosuppression with cyclosporine A (CsA). No significant differences were ...

Rejection is a risk of transplantation. The phenomenon is usually caused by a reaction of the recipients immune system vis-à-vis the transplant, which it considers an invader. HLAs (human leucocyte antigens), which are present on the surface of all cells, are a sort of unique identifier for each person. In transplants, doctors try to avoid rejection by ensuring that the donor and recipient are compatible with regard to blood group and HLA antigens. Despite these precautions, one in ten transplants results in rejection. To solve this mystery, the researchers focused on blood vessels, an important component in transplantation. When blood vessels are damaged, rejection is more difficult to treat. We discovered that the damaged blood vessels release specific bits of cells: small membrane vesicles that put the immune system on alert. If we then perform a transplant, the immune system immediately attacks the donor organ, said Melanie Dieudé, a researcher at the CRCHUM and first author of the ...

What have we come to when grown people cannot take rejection? Did we never learn that as good as we might be, sometimes the other guy (or gal) is better?. Recently the organizers of a writing contest asked for prayer before they delivered the winning entries. Apparently, they feared the reactions of the losers. They even sent a letter of apology and encouragement for them.. Did this begin when we were passed through every grade simply because the new premise is that no one ever fails? Or was it because Mother didnt teach us to share? Or maybe the hockey coach made too much of us when we finally got our one goal of the season.. Rejection has a purpose and we miss out on that when we will not take rejection in stride.. But the rejection will force honesty, as God reveals who they really are. (Luke 2:35b, MSG). The thoughts of many hearts will be revealed. (Luke 2:35b, NIV). The secret thoughts and purposes of many hearts may be brought out and disclosed. (Luke 2:35b, AMP). So what does rejection ...

Rejection and criticism are part of being alive. We all experience it. The more we try to achieve something, impress someone, or get something, the more we will experience it. How well we accept it reflects our maturity. To accept rejection properly requires strength. For that reason, many psychologists advise us not to take it personally, even though we have invested so much. They suggest some form of emotional detachment, knowing that rejection does not necessarily imply that we are not good enough. Rejection does not also suggest that we are not worthy of someones love. We should avoid overthinking it and conclude that something is wrong with us. Rejection needs a strong personality, who will not take the sense of self from someones choice. According to experts, we should understand that our sense of self is completely independent of someones decision to accept or reject us. When we become aware that a person who rejected us has her own reasons. These reasons have usually been created by ...

Definition of rejections in the Financial Dictionary - by Free online English dictionary and encyclopedia. What is rejections? Meaning of rejections as a finance term. What does rejections mean in finance?

Failed Allografts. The reasons for liver allograft failure vary with the time since transplantation(1-6). Primary dysfunction because of ischemic/preservation injury and hepatic artery thrombosis and subsequent bile duct necrosis are the most common causes of liver within the first several weeks. Humoral and severe acute cellular rejection also occur during this time, but they are uncommon causes of early allograft failure. Frequently, a combination of the above factors ultimately contribute to deterioration of graft function(1-6). Between 2-3 weeks and 6 months after transplantation, delayed complications of early technical problems, such as the biliary sludge syndrome from ischemic cholangitis(7, 8), acute rejection and rapidly developing cases of chronic rejection(9, 10) are the major causes of graft failure. There are still graft failures that occur more than 6 months after transplantation, as a result of delayed technical complications. These usually involve the hepatic artery and ...

Basiliximab is a monoclonal interleukin-2 receptor antagonist commonly used for induction immunosuppression in lung transplantation. This single centre retrospective review of 119 patients transplanted between 1994 and 2009 examined the impact of the timing of basiliximab dosing on the frequency and severity of acute rejection, the development of BOS, and overall survival. Pre-implantation administration of […]. ...

While immunosuppressive drugs now permit good control of acute allograft rejection, chronic rejection remains an important medical problem, and the induction of stable transplantation tolerance has not yet been achieved in patients. 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), a secosteroid hormone that …

TY - JOUR. T1 - Multiparametric Cardiac Magnetic Resonance Imaging Can Detect Acute Cardiac Allograft Rejection After Heart Transplantation. AU - Dolan, Ryan S.. AU - Rahsepar, Amir A.. AU - Blaisdell, J.. AU - Suwa, Kenichiro. AU - Ghafourian, Kambiz. AU - Wilcox, Jane E. AU - Khan, Sadiya Sana. AU - Vorovich, Esther Elizabeth. AU - Rich, Jonathan D. AU - Anderson, Allen Sawyer. AU - Yancy, Clyde W. AU - Collins, Jeremy D.. AU - Carr, James. AU - Markl, Michael. PY - 2019/8/1. Y1 - 2019/8/1. N2 - Objectives: The purpose of this study was to evaluate the sensitivity of multiparametric cardiac magnetic resonance imaging (CMR) for the detection of acute cardiac allograft rejection (ACAR). Background: ACAR is currently diagnosed by endomyocardial biopsy, but CMR may be a noninvasive alternative because of its capacity for regional myocardial structure and function characterization. Methods: Fifty-eight transplant recipients (mean age 47.0 ± 14.7 years) and 14 control subjects (mean age 47.7 ± ...

TY - JOUR. T1 - The yield of surveillance endomyocardial biopsies as a screen for cellular rejection in pediatric heart transplant patients. AU - Levi, Daniel S.. AU - DeConde, Adam S.. AU - Fishbein, Michael C.. AU - Burch, Caron. AU - Alejos, Juan C.. AU - Wetzel, Glenn T.. PY - 2004/2. Y1 - 2004/2. N2 - Endomyocardial biopsy is commonly used to screen for cellular rejection in pediatric heart transplant patients. The yield of EMBs when combined with newly developed immunohistochemical techniques and modern immunosuppression in pediatric heart transplant patients is unknown. After OHT, surveillance biopsies were performed on a routine basis on all pediatric patients. EMBs were also performed on symptomatic OHT patients suspected to have rejection. All positive results (greater than ISHLT grade 1B) were confirmed with immunohistochemical staining. A retrospective review of consecutive EMBs performed in this institution from January 1995 to January 2003 was performed. The echocardiographic ...

TY - JOUR. T1 - Pancreas allograft rejection. T2 - Analysis of concurrent renal allograft biopsies and posttherapy follow-up biopsies. AU - Troxell, Megan L.. AU - Koslin, David Bradley. AU - Norman, Douglas. AU - Rayhill, Stephen. AU - Mittalhenkle, Anuja. PY - 2010/7/15. Y1 - 2010/7/15. N2 - Background: Pancreas and kidney allograft function is routinely monitored with serum studies (amylase, lipase, and creatinine). Increased levels commonly prompt tissue biopsy, to diagnose cause of graft dysfunction. Historically, pancreas allografts were infrequently biopsied, although serum enzymes and renal rejection may be poor surrogates for pancreas status. Methods: Pancreas allograft biopsies at our center were reviewed and reclassified according to University of Maryland (UMD) and Banff criteria; C4d immunostaining was performed. Findings were correlated with clinical data and renal allograft biopsies. Results: Fifty-six pancreas allograft biopsies from 27 patients were evaluated. UMD and Banff ...

Lung transplantation has become a therapeutic option for a number of end-stage pulmonary disorders. Lung transplant recipients experience more complications due to acute and chronic allograft rejection as compared to recipients of other solid organs. We postulated that the generation of TNF-alpha plays a significant role in the pathogenesis of acute lung allograft rejection. To test our hypothesis, we used a RT1-incompatible rat lung allograft model and demonstrated the time course, cellular source(s), and major compartment(s) of TNF production during the course of lung allograft rejection. This model allowed for immunogenetic standardization and reproducibility of lung allograft rejection across disparate major histocompatibility barriers. TNF production was characterized at the whole animal, organ, cellular, and molecular levels, and was found to be compartmentalized and expressed in a bimodal fashion from the lung allograft during lung allograft reimplantation and maximal rejection. Lung ...

Primary cilia are sensory organelles which co-ordinate several developmental/repair pathways including hedgehog signalling. Studies of human renal allografts suffering acute tubular necrosis have shown that length of primary cilia borne by epithelial cells doubles throughout the nephron and collecting duct, and then normalises as renal function returns. Conversely the loss of primary cilia has been reported in chronic allograft rejection and linked to defective hedgehog signalling. We investigated the fate of primary cilia in renal allografts suffering acute rejection. Here we observed that in renal allografts undergoing acute rejection, primary cilia were retained, with their length increasing 1 week after transplantation and remaining elevated. We used a mouse model of acute renal injury to demonstrate that elongated renal primary cilia in the injured renal tubule show evidence of smoothened accumulation, a biomarker for activation of hedgehog signalling. We conclude that primary cilium-mediated

OBJECTIVES: Primary cilia are sensory organelles which co-ordinate several developmental/repair pathways including hedgehog signalling. Studies of human renal allografts suffering acute tubular necrosis have shown that length of primary cilia borne by epithelial cells doubles throughout the nephron and collecting duct, and then normalises as renal function returns. Conversely the loss of primary cilia has been reported in chronic allograft rejection and linked to defective hedgehog signalling. We investigated the fate of primary cilia in renal allografts suffering acute rejection. RESULTS: Here we observed that in renal allografts undergoing acute rejection, primary cilia were retained, with their length increasing 1 week after transplantation and remaining elevated. We used a mouse model of acute renal injury to demonstrate that elongated renal primary cilia in the injured renal tubule show evidence of smoothened accumulation, a biomarker for activation of hedgehog signalling. We conclude that primary

Chronic rejection significantly limits long-term success of solid organ transplantation. De novo donor-specific antibodies (DSAs) to mismatched donor human leukocyte antigen after human lung transplantation predispose lung grafts to chronic rejection. We sought to delineate mediators and mechanisms of DSA pathogenesis and to define early inflammatory events that trigger chronic rejection in lung transplant recipients and obliterative airway disease, a correlate of human chronic rejection, in mouse. Induction of transcription factor zinc finger and BTB domain containing protein 7a (Zbtb7a) was an early response critical in the DSA-induced chronic rejection. A cohort of human lung transplant recipients who developed DSA and chronic rejection demonstrated greater Zbtb7a expression long before clinical diagnosis of chronic rejection compared to nonrejecting lung transplant recipients with stable pulmonary function. Expression of DSA-induced Zbtb7a was restricted to alveolar macrophages (AMs), and ...

TY - JOUR. T1 - A predictive model for acute allograft rejection of liver transplantation. AU - Liu, Chien-Liang. AU - Soong, Ruey Shyang. AU - Lee, Wei Chen. AU - Chen, De Hsuan. AU - Hsu, Shang Hwa. PY - 2018/3/15. Y1 - 2018/3/15. N2 - Orthotopic liver transplantation (OLT) has become an increasingly used treatment for end-stage liver disease. However, acute allograft rejection is still a problem in postoperative care of liver transplantation with immunosuppressive therapy and it can lead to allograft damage and harm the survival of liver transplantation patient. This work proposes to use data-driven approach to build a predictive model for acute rejection. We consider not only prediction accuracy, but also interpretability of the prediction outcome in building the predictive model, so that the medical staffs can identify how the prediction is induced from data. The experiments use the real data provided by liver transplantation intensive care unit (ICU) of Chang Gung Memorial Hospital, ...

Lerner DL, Chapman Q, Green KG, Saffitz JE. Reversible down-regulation of connexin43 expression in acute cardiac allograft rejection. J Heart Lung Transplant. 2001 Jan; 20(1):93-7 ...

TY - JOUR. T1 - Current Australian practice in the prevention and management of corneal allograft rejection. AU - Barker, Nigel H.. AU - Henderson, Timothy R.M.. AU - Ross, Carolyn A.. AU - Coster, Douglas J.. AU - Williams, Keryn A.. PY - 2000/10. Y1 - 2000/10. N2 - Purpose: To determine current practice in the prevention and management of corneal allograft rejection in Australia. Methods: A questionnaire was circulated to attendees at the 1998 Eye Bank Meeting in Adelaide. Twenty-four responses were received and analysed. Results: All respondents used topical corticosteroids for routine prophylaxis and to treat established rejection episodes. Prednisolone acetate was the most frequently prescribed topical corticosteroid. Systemic non-steroidal immunosuppression was prescribed almost exclusively for high-risk grafts. Seventy-five per cent of surgeons used systemic antiviral agents for the treatment of graft rejection in patients with Herpes simplex keratitis. Conclusion: There was a wide ...

AIMS: Exosome-mediated microRNA transfer is a recently discovered mode of cell-to-cell communication, in which microRNAs act as paracrine molecules, exerting their regulatory effects in recipient cells. T cells and endothelial cells are two main players in the mechanism of acute cellular cardiac rejection. The aim of this study was to investigate the role of exosomal microRNAs in the crosstalk between T cells and endothelial cells and its implications for the molecular mechanisms that drive acute cellular rejection in heart transplantation.. METHODS AND RESULTS: Exosomes isolated from serum samples of heart transplant patients with and without acute cardiac allograft rejection were profiled and showed enrichment of miR-142-3p, miR-92a-3p, miR-339-3p and miR-21-5p. Treatment of endothelial cells with the respected serum exosomes resulted the increased of miR-142-3p level in endothelial cells. Using T cells isolated from healthy donors and activated with either anti-CD3/CD28 antibody or IL-2/PHA, ...

The Banff Classification is a schema for nomenclature and classification of renal allograft pathology, established in 1991 by Kim Solez and Lorraine C. Racusen in Banff, Canada. The initiative was inspired by the then recent development of a consensus grading system for diagnosis of rejection in cardiac allografts led by Dr Margaret Billingham, a key participant at the first Banff meeting. Prior the Banff Classification there was no standardized, international classification for renal allograft biopsies, which resulted in considerable heterogeneity among pathologists in characterization of renal allograft biopsies. The first Banff schema was published in 1993, and has since undergone updates at regular intervals. The classification is expanded and updated every two years in meetings organized by the Banff Foundation for Allograft Pathology. An evaluation of the Banff Classification in March 2000 confirmed significant association between the revised Banff 97 classification and graft outcome. ...

Background. In renal transplantation, cold ischaemia (CI) determines acute rejection through innate immunity among others. Acute rejection episodes are a risk factor for late allograft dysfunction and proteinuria. This implies some alteration of the glomerular filtration barrier (GFB). Besides its effects on acute rejection, we hypothesized that CI might somehow damage the GFB being directly responsible for late proteinuria.. Methods. On rat kidney allografts suffering from antibody-mediated acute rejection with or without CI and compared with syngeneic grafts, we quantified the gene expression of innate and adaptive immune mediators and assessed the capillary glomerular basement membranes (CapBM) by immunostaining collagen-IV (ColIV). ColIV was also assessed in equivalent groups from a previous chronic study followed up for 24 weeks.. Results. CI up-regulated enzymes critical in the stabilization of collagen chains, increasing ColIV deposition and thickening the CapBM. CI increased the C4d and ...

TY - JOUR. T1 - Non-immunological risk factors associated with chronic allograft nephropathy following kidney transplantation. AU - Shiroki, Ryoichi. AU - Hoshinaga, Kiyotaka. PY - 2002/11/1. Y1 - 2002/11/1. N2 - Although the precise mechanisms are unclear, not only alloantigen-dependent but also antigen-independent factors are generally thought to influence the development of chronic allograft nephropathy (CAN). Among the non-immunological determinants, there are various factors related with donor, recipient and graft procurement. As donor factors, age and cause of death were demonstrated to be significantly independent in long-term graft survival of cadaveric kidney transplantation. Grafts from aged donors and from donors with athelosclerosis showed poor prognosis on graft survival. Regarding recipient factors, cardiovascular complications, as hypertension and hyperlipidemia, were responsible for graft as well as patient survival. In addition, CMV infection and drug nephrotoxicity were also ...

TY - JOUR. T1 - Combining theoretical and experimental techniques to study murine heart transplant rejection. AU - Arciero, Julia C.. AU - Maturo, Andrew. AU - Arun, Anirudh. AU - Oh, Byoung Chol. AU - Brandacher, Gerald. AU - Raimondi, Giorgio. PY - 2016/11/7. Y1 - 2016/11/7. N2 - The quality of life of organ transplant recipients is compromised by complications associated with life-long immunosuppression, such as hypertension, diabetes, opportunistic infections, and cancer. Moreover, the absence of established tolerance to the transplanted tissues causes limited long-term graft survival rates. Thus, there is a great medical need to understand the complex immune system interactions that lead to transplant rejection so that novel and effective strategies of intervention that redirect the system toward transplant acceptance (while preserving overall immune competence) can be identified. This study implements a systems biology approach in which an experimentally based mathematical model is used to ...

Allograft rejection and infection are the major sources of morbidity and mortality after heart transplant. Early differential diagnosis is clinically crucial but difficult. The aim of the study was to examine serum cytokine profiles associated with each entity and whether such profiles could help to differentiate between them. Heart allografts from Wistar rats were transplanted to Lewis rats as described by Yokoyama. Cardiac rejection and pulmonary bacterial infection were induced by Cyclosporine cessation and bacteria bronchus injection, and pathologically confirmed. Ninety serological cytokines profiles of the study objects were then simultaneously measured using a biotin label-based cytokine array. The fold change (FC) was used for relative cytokine concentration comparison analysis. Four cytokines in cardiac rejection group were significantly dysregulated as compared to health controls (β -Catenin, 0.51 FC; E-Selectin, 0.62 FC; IFN-gamma, 1.87 FC; and IL-13, 0.60 FC, respectively). In pulmonary

Purpose: : Previous studies have demonstrated that allergic conjunctivitis increases the incidence and tempo of corneal allograft rejection in mice. We wished to determine if Th2-based allergic inflammation in the lungs or Th1-based inflammation of the skin would exacerbate corneal graft rejection. Methods: : Airway hyperreactivity (AHR) was induced in BALB/c mice using either ovalbumin (OVA) or short ragweed extract (SRW). AHR was confirmed by plethysmography and by ELISA and histological analysis of bronchoalveolar lavage fluid (BALF). Contact hypersensitivity was induced by skin painting with oxazalone prior to corneal transplantation. Delayed-type hypersensitivity (DTH) responses to donor alloantigens and to skin sensitization were determined using conventional ear-swelling assays. C57BL/6 corneal allografts were transplanted orthotopically to naïve mice, mice sensitized and challenged with oxazalone, or mice with ongoing AHR. Results: : Mice with ongoing AHR that was induced with SRW ...

Introduction: The development of de novo donor-specific antibodies (dnDSA) has been associated with rejection and graft loss in kidney transplantation, and DSA screening is now recommended in all kidney transplant recipients. However, the clinical significance of dnDSA in patients with a stable creatinine remains unclear. Methods: We performed a retrospective cohort study of 103 patients receiving a first, kidney alone transplant between 12/1/2007 and 12/31/2013. Inclusion criteria were age ,18 years old at the time of transplant and at least two years of DSA monitoring. All patients underwent DSA screening every 3 months post-transplant with additional testing as clinically indicated. No treatment was given for DSAs in the absence of biopsy-proven rejection. Results: 20 patients (19%) developed dnDSA in the setting of a stable creatinine and 13 patients (13%) developed dnDSA in the setting of an elevated creatinine. Median follow-up time post-transplant was 4.1 (IQR 2.9-5.7) years. In a Cox ...

Global Markets Directs, Heart Transplant Rejection - Pipeline Review, H1 2020, provides an overview of the Heart Transplant Rejection

Avoiding HLA-DR mismatching appears to be beneficial in pediatric kidney transplant patients, however the likelihood of finding a matching donor must be considered against the wait time for a possible donation, according to a report in the July issue of Archives of Surgery, one of the JAMA/Archives journals.. Although avoiding HLA [human leukocyte antigen; cell surface antigens that regulate host cell responses to transplanted cells] antigen mismatching has been shown to benefit long-term graft survival, it has raised concerns about disadvantaging minority groups, particularly black patients, and pediatric patients, who have severe growth retardation and other problems when dialysis is prolonged before transplantation, the authors write as background information in the article. Currently, only HLA-DR matching is considered in the United Network for Organ Sharing (UNOS) organ allocation system.. To examine the relationship between HLA-DR mismatching and rejection, graft survival and ...

TY - JOUR. T1 - Heart transplant rejection with hemodynamic compromise. T2 - A multiinstitutional study of the role of endomyocardial cellular infiltrate. AU - Mills, R. M.. AU - Naftel, D. C.. AU - Kirklin, J. K.. AU - Van Bakel, A. B.. AU - Jaski, B. E.. AU - Massin, E. K.. AU - Eisen, H. J.. AU - Lee, F. A.. AU - Fishbein, D. P.. AU - Bourge, R. C.. AU - McGiffin, D. C.. AU - Weiss, T.. AU - Crosswyt, A.. AU - Austin, B.. AU - Early, L.. AU - Holmes, P.. AU - Veazey, M.. AU - Sims, P.. AU - Hubbard, K.. AU - Brush, J.. AU - Pritzker, M. R.. AU - Lake, K. D.. AU - OKane, M.. AU - Chapman, S.. AU - Hoffman, F.. AU - Seimers, N.. AU - Jorgensen, C.. AU - Pedersen, W.. AU - Joyce, L.. AU - Eales, F.. AU - Emery, R. W.. AU - Von Reuden, T.. AU - Bruhn, P.. AU - King, M.. AU - Arom, K.. AU - Hellman, K. J.. AU - Pacheco, D.. AU - Moore, C.. AU - Levin, S.. AU - Blair, P.. AU - Mudge, G. H.. AU - Jarcho, J.. AU - Johnson, P.. AU - Loh, E.. AU - Hobbs, R. E.. AU - Rincon, G.. AU - Bott-Silverman, ...

Adult mice can be rendered immunologically tolerant of allogeneic tissues if transplanted under cover of mAbs to CD4 and CD8. Tolerance generated in this manner is characterized by the presence of regulatory CD4+ T cells that can recruit naive T cells to become tolerant also through infectious tolerance. Regulatory CD4+ T cells can also suppress rejection of third party transplant Ags provided they are expressed on the same graft as the tolerated Ags. This process of linked suppression can act across whole MHC barriers and represents a powerful mechanism with therapeutic potential. Tolerance can also be induced to reprocessed minor transplantation Ags presented through host APCs (indirect recognition). We here demonstrate that linked suppression can also be induced through the indirect pathway. This finding may be important in the development of transplantation tolerance in the clinic.

TY - JOUR. T1 - Preoperative psychological factors predicting graft rejection in patients undergoing kidney transplant: a pilot study. AU - Citterio, Franco. AU - Calia, Rosaria. AU - Lai, C. AU - Aceto, P. AU - Luciani, M. AU - Saraceni, C. AU - Lai, S. AU - Gargiulo, A. PY - 2011. Y1 - 2011. N2 - The aim of this study was to investigate whether pretransplant psychological variables included in the CBA 2.0 Primary Scale-fear, personality, obsessive-compulsive symptoms, state and trait anxiety, psychological reactions, and depression-could predict graft rejection among patients undergoing kidney transplantation.. AB - The aim of this study was to investigate whether pretransplant psychological variables included in the CBA 2.0 Primary Scale-fear, personality, obsessive-compulsive symptoms, state and trait anxiety, psychological reactions, and depression-could predict graft rejection among patients undergoing kidney transplantation.. KW - Adult. KW - Analysis of Variance. KW - Female. KW - Graft ...

... SAN FRANCISCO July 30 2014 /-...The study shows that post-transplant treatment with C1-INH results in ... Antibody-mediated rejection is a severe form of rejection that can oc...The placebo-controlled single-center study evaluated 20 highly sensit...,Study,Suggests,C1-INH,May,Aid,in,Prevention,of,Antibody-Mediated,Rejection,Following,Kidney,Transplant,biological,advanced biology technology,biology laboratory technology,biology device technology,latest biology technology

BACKGROUND: The traditional method for assessing HLA antibodies in recipient serum samples is the complement-dependent cytotoxicity testing (CDC). Recently, the highly sensitive microbead-based Luminex assay was introduced and can detect low levels of anti-HLA Abs.. OBJECTIVE: To determine the impact of pretransplant donor-specific HLA antibodies (DSA) detectable by Luminex, despite a negative CDC crossmatch, on the outcomes of kidney transplantation. The correlation and cut-off value of panel reactive antibody (PRA) and DSA was also evaluated.. METHODS: Pre-transplant sera from 116 kidney transplant recipients with a negative CDC crossmatch were assessed for donor-specific HLA antibodies by using Luminex single antigen beads. The patients received kidney transplants at Ramathibodi Hospital between January 2003 and December 2007. The results were correlated with kidney graft outcomes.. RESULTS: DSA were found in 24.1% (28/116) of all recipients. Of the twenty-eight DSA positive patients, four ...

Backgrounds: Acute rejection and graft arterial disease (GAD) in cardiac transplantation are enhanced by inflammation and thrombus formation. However, little is known about the effect of plasminogen activator inhibitor-1 (PAI-1) in heart transplantation. Thus, the objective was to clarify the role of PAI-1 in the progression of rejection.. Methods and Results: Murine hearts were heterotopically transplanted using major mismatch combinations for evaluation of acute rejection and class II mismatch combinations for the GAD. We performed administration of the specific PAI-1 inhibitor (IMD-1622) into murine recipients of cardiac allografts. Nontreated allografts of the major mismatch group were acutely rejected (n=6; 7.3±0.2 days), while the PAI-1 inhibitor prolonged their survival (n=6; 13.7±2.4 days, P , 0.05). Pathologically, severe myocardial cell infiltration (40.8±3.3 %) and fibrosis (44.5±2.8 %) were observed in untreated allografts, the PAI-1 inhibitor attenuated infiltration (25.8±1.9 ...

We describe a caucasian 17-year old male, transplanted at three years of age because of ESRD due to congenital nephrotic syndrome (Finnish type), who lost his first graft due to chronic allograft nephropathy. While on the waiting list, he presented a progressive rise in Panel Reactive Antibodies levels (PRA 99.61%). The patient received a desensitization protocol based on plasmapheresis (PP), immunoglobulins and Rituximab, with minor response (post desensitization PRA 75%). He was enrolled in a National Protocol for organs allocation to immunized patients and received his second non-living HLA-compatible kidney transplant at the age of 16. He had prompt function of his allograft. On postoperative day 30 he developed a biopsy-proven antibody-mediated rejection (AMR) [Figure 1].. Post-transplant immunological monitoring showed donor-specific anti-DQ5 antibodies (DSA) that were already present at the time of transplantation. The patient received three methylprednisolone pulses and 45 PP sessions, ...

With the improved survival achieved in the 1980s it has become apparent that graft rejection is a major problem following liver transplantation [1]. Hyperacute rejection is uncommon, although syndromes of fulminant graft failure due to immunological mechanisms have been described. Acute cellular rejection occurs in approximately 70% of patients and usually responds to high-dose steroids. Between 10 and 15% develop chronic rejection, characterised by a progressive destruction of intrahepatic bile ducts which is irreversible [2]. The principal targets of both acute and chronic liver allograft rejection are intrahepatic bile ducts and endothelium [2]. The increased ability of these cell types to express MHC antigens and adhesion molecules may be responsible for their involvement [2, 3] and may be enhanced by the release of proinflammatory cytokines associated with viral infection, particularly CMV [3]. Although the importance of HLA matching remains unknown patients transplanted with ABO incompatible

Australian Medicines Handbook section 14.5.3 Anti-thymocyte globulin is indicated for the prophylaxis of renal graft rejection as well as the treatment of steroid-resistant renal transplant rejection. Kidney transplantation is the treatment of choice for most patients with end-stage renal disease. However, 15-35% of transplant recipients will experience one episode of acute rejection in the first year. Giving antibody to deplete thymocytes (T cells) is one way to suppress the immune system to prevent or reverse graft rejection. Anti-thymocyte globulin is a polyclonal antibody against human T cells. It is a gamma immunoglobulin produced by immunising rabbits. As well as depleting T cells in the circulation, anti-thymocyte globulin is also thought to reduce T cell proliferation, homing and cytotoxic effects within the body. Depletion of T cells occurs within a day of starting intravenous treatment. This immunoglobulin has been compared to other treatments in renal transplant patients who are also ...

Allograft rejection is the consequence of the recipients alloimmune response to nonself antigens expressed by donor tissues. After transplantation of organ allografts, there are two pathways of antigen presentation. In the direct pathway, recipient T cells react to intact allogeneic MHC molecules expressed on the surface of donor cells. This pathway would activate host CD4 or CD8 T cells. In contrast, donor MHC molecules (and all other proteins) shed from the graft can be taken up by host APCs and presented to recipient T cells in the context of self-MHC molecules - the indirect pathway. Such presentation activates predominantly CD4 T cells. A direct cytotoxic T-cell attack on graft cells can be made only by T cells that recognize the graft MHC molecules directly. Nontheless, T cells with indirect allospecificity can contribute to graft rejection by activating macrophages, which cause tissue injury and fibrosis, and are also likely to be important in the development of an alloantibody response ...

References. 1. Gjertson DW: Survival trends in long-term first cadaveric donor kidney transplants; in: Terasaki PI (ed): Clinical Tranplantation 1991. Los Angeles, UCLA Tissue Typing Laboratory p 225. 2. Paul LC, Benediktsson H: Chronic transplant rejection. Transplant Reviews 1993;7:96-113. 3. Tullius SG, Tilney NL: Both alloantigen-dependent and independent factors influence chronic allograft rejection. Transplantation 1995;59:313-318. 4. Kahan BD: Toward a rational design of clinical trials of immunosuppressive agents in transplantation. Immunol Review 1993;136:29-49. 5. Ludwig J, Wiesner RH, Batts KP, Perkins JD, Krom RA: The acute vanishing bile duct syndrome (acute irreversible rejection) after orthotopic liver transplantation. Hepatology 1987;7:476-483. 6. Kobashigawa JA, Katznelson SA, Laks H, Johnson JA, Yeatman L, Wang XM, Chia D, Terasaki PI, Sabad A, Cogert GA, Trosian K, Hamilton MA, Moriguchi JD, Kawata N, Hage A, Drinkwater DC, Stevenson LW: Effect of pravastatin on outcomes after ...

Purpose.: We investigated the phenotype of macrophages infiltrating rejected corneal allografts. Methods.: We performed allogeneic or syngeneic corneal transplantation in mice, and humanely killed animals at day 28 during allograft rejection when 60% of corneal allografts were rejected. We divided allografts into two groups: grafts with rejection as rejectors and grafts without rejection as nonrejectors, and analyzed for macrophage infiltration and their phenotype using immunohistochemistry. In addition, we investigated the time course of proinflammatory cytokines and chemokines by analyzing corneal grafts at days 7, 28, and 42 using real-time RT-PCR. Also, we assayed human corneal allografts with chronic graft failure. Results.: We found that a large number of CD11b+, F4/80+, or inducible nitrous oxide synthase cells (iNOS+) infiltrated corneal allografts during rejection in mice, while the cells were found rarely in syngeneic or allogeneic grafts that were not rejected. There were rare CD11c+ ...

Partial table of contents: A Short History of Renal Transplantation (R. Calne). Considerations in Organ Transplantation (R. Kerman). Pretransplantation and Posttransplantation Psychosocial Evaluation. (G. Wolff). Impact of Recipient Age on Renal Allograft Outcome (G. Arbus & D. Hebert). Steroid Withdrawal After Renal Transplantation (E. Ingulli & A. Tejani). Treatment of Acute Rejection (G. Offner). Urologic Complications in Renal Transplantation (O. Salvatierra). Noncompliance to Medical Regimens (B. Cole). Malignancy in Children (I. Penn). Long-Term Outcome of Kidney Transplantation in Children (D. Potter). Index.Pediatric Renal Transplantation, 1 was published 1994 under ISBN 9780471591207 and ISBN 0471591203. [read more] ...

Role of T cell recruitment and chemokine-regulated intra-graft T cell motility patterns in corneal allograft rejection.s profile, publications, research topics, and co-authors

This chapter will cover four conditions related to kidney (cadaver renal transplant [CRT], living-related renal transplant [LRRT]), simultaneous kidney-pancreas (SPKT), pancreas after kidney (PAKT), and pancreas (PTA) transplants: rejection, allograft dysfunction, anatomic complications and infection. The basic principles hold for all of the different transplants. Clinical features may overlap and therefore a high index of suspicion is required. Monitoring of laboratory tests (blood urea nitrogen/creatinine [BUN/Cr], amylase, lipase, glucose), ultrasound, biopsy, and a close relationship with the transplant surgeon and/or transplant nephrologist is paramount.. Rejection. Kidney and pancreas rejection can be either acute or chronic, with acute rejection being more common. Acute rejection generally can occur in the first few weeks to several months after transplant. Chronic rejection is usually a result of several episodes of acute rejection and presents as progressive deterioration of the ...

TY - JOUR. T1 - Quadruple immunosuppression in a pig model of small bowel transplantation. AU - Gruessner, Rainer W G. AU - Fasola, Carlos. AU - Fryer, Jon. AU - Nakhleh, Raouf E.. AU - Kim, Sung. AU - Gruessner, Angelika C.. AU - Beebe, David. AU - Moon, Chul. AU - Troppmann, Christoph. AU - Najarian, John S.. PY - 1996/2/15. Y1 - 1996/2/15. N2 - Rejection remains a major obstacle to successful small bowel transplantation in humans, irrespective of the immunosuppressants. Previous large animal studies have not used quadruple immunosuppression (with high- dose intravenous cyclosporine A [CSA]) for induction, followed by triple immunosuppression for maintenance therapy. Nor have immunosuppressive doses been comparable to clinical solid organ transplants. We studied, in 78 nonrelated outbred pigs, the effect of quadruple immunosuppression (including horse anti-pig thymocyte globulin [ATG] and high-dose intravenous CSA) on the incidence and severity of rejection in the early, critical ...

In addition to an improvement in survival post-transplantation, the studies of Kobashigawa et al. (77) and Wenke et al. (78) provide evidence for an immunomodulatory effect of statins. Pravastatin significantly decreased the rate of haemodynamically important rejection episodes (P, 0·01), associated with improved survival (77). This finding was reproduced in a small pilot study in renal transplant recipients, in whom pravastatin therapy also significantly reduced the incidence of acute rejection episodes (80).. The mechanism by which statins may interfere with the aggressive immunologically mediated process underlying allograft rejection remains unclear. One possible mechanism involves an indirect effect on the pharmacokinetics of cyclosporin. As this agent is lipophilic it is transported in the blood in LDL and HDL cores. Cyclosporin binding to lipoproteins accounts for approximately 35% of whole blood levels, thus any change in LDL-cholesterol may interfere with the removal of cyclosporin ...

Bierer, Barbara E., et al. Regulation of Cytotoxic T Lymphocyte-Mediated Graft Rejection Following Bone Marrow. Transplantation 46.6 (1988): 835-839.. ...

Outcomes of cardiac transplantation have been improved with immunosuppressive therapies that effectively reduce the risk of rejection and with prophylaxis against opportunistic infections. With the current management leading to decreased likelihood of hyperacute and acute rejections, efforts have been focused on improving long-term survival by targeting post-transplant complications associated with chronic rejection. Cardiac allograft vasculopathy (CAV) has been 1 of the main causes of mortality for heart transplant recipients (1). The CAV progression has been traditionally managed with mechanistic target of rapamycin inhibitors, such as sirolimus and everolimus. Though mechanistic target of rapamycin inhibitors have been successful in ameliorating or preventing CAV, they frequently cause many significant side effects, like pancytopenia, wound healing issues, renal dysfunction and hyperlipidemia (2). This has limited their widespread use. Statins have been demonstrated to reduce the incidence of ...

In organ transplantation, infection and rejection are major causes of graft loss. They are linked by the net state of immunosuppression. To diagnose and treat these conditions earlier, and to improve long-term patient outcomes, refined strategies for the monitoring of patients after graft transplantation are needed. Here, we show that a fast and inexpensive assay based on CRISPR-Cas13 accurately detects BK polyomavirus DNA and cytomegalovirus DNA from patient-derived blood and urine samples, as well as CXCL9 messenger RNA (a marker of graft rejection) at elevated levels in urine samples from patients experiencing acute kidney transplant rejection. The assay, which we adapted for lateral-flow readout, enables-via simple visualization-the post-transplantation monitoring of common opportunistic viral infections and of graft rejection, and should facilitate point-of-care post-transplantation monitoring. A fast and inexpensive point-of-care assay based on CRISPR-Cas13 accurately detects the DNA of

The improvement in graft function observed in the 1990s occurred during a discrete period of time between 1994 and 1997. Before and after these years, the mean GFR remained stable. This period of improvement coincides with the rapid adoption of mycophenolate mofetil for azathioprine in calcineurin-based immunosuppression protocols. The multivariate linear regression analysis revealed that not only mycophenolate mofetil but also use of tacrolimus was associated with improved GFR. Although the reduction in the rejection rate had a positive impact on graft function during the 1990s, it cannot explain the majority of the improvement noted in GFR between the two eras, because both patients with and without rejection improved almost equally in the two eras. To what extent immunologic versus nonimmunologic factors resulted in this improvement is unclear.. Subclinical rejection, which may be an important determinant of graft function, is a possible immunologic cause for the improvement in graft ...

In the present study, the predictors and outcomes associated with the trajectories of peer rejection were examined in a longitudinal sample of Italian children (338 boys, 269 girls) ages 10 to 14 years. Follow-up assessments included 60% of the original sample at age 16-17. Low, medium, and high rejection trajectory groups were identified using growth mixture models. Consistent with previous studies, we found that (a) being less prosocial and more physically aggressive at age 10 was characteristic of those children with the high rejection trajectory; (b) being less attractive was related to higher peer rejection from age 10 to 14; and (c) boys with a high rejection trajectory showed high levels of delinquency and anxiety-depression and low levels of academic aspiration at age 16-17, whereas girls with a high rejection trajectory showed low levels of academic aspiration and social competence at age 16-17 ...