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PubMed1996

Mycophenolate mofetil for the treatment of refractory, acute, cellular renal transplant rejection. The Mycophenolate Mofetil Renal Refractory Rejection Study Group.

In a 6-month open label, randomized, multicenter trial, we compared the efficacy and safety of mycophenolate mofetil (MMF) with high dose intravenous steroids (IVS) for the treatment of refractory, acute cellular rejection in recipients of first or second cadaveric or living-donor renal allografts. A total of 150 patients were enrolled and randomized in a 1-to-1 ratio to receive oral MMF 1.5 g twice daily (n=77) or i.v. methylprednisolone 5 mg/kg for 5 days (n= 73), tapered over the subsequent 5 days to 20 mg/day or the baseline dose of steroid given on the day before the diagnosis of rejection. Patients in both groups generally received cyclosporine and maintenance doses of corticosteroids throughout the study period. The IVS group (but not the MMF group) was generally maintained on azathioprine. The primary efficacy variable was graft and patient survival at 6 months. Graft loss and death were reduced by 45% in the MMF treatment group; 19 patients (26.0%) in the IVS group experienced graft loss or died, compared with 11 patients (14.3%) in the MMF group (P=0.081, sequential probability ratio test analysis). In the IVS group, 64.4% of patients experienced either subsequent biopsy proven rejection, presumptive rejection (presumed rejection clinically diagnosed but not biopsy proven and treated with a full course of immunosuppressive therapy), or treatment failure (premature termination for any reason, including death, graft loss, or an adverse event) compared with 39.0% in the MMF group (P=0.001, Cochran-Mantel-Haenszel [CMH] general association test). One or more full courses of immunosuppressive treatment for subsequent rejection episodes were administered to 35.6% of patients in the IVS group and 24.7% of patients in the MMF group. The number of patients who received full courses of corticosteroids for subsequent episodes of rejection was equal in the 2 groups, but the number of patients who received full courses of antilymphocyte therapy was more than twice as great in the IVS group (n = 18) compared with the MMF group (n=8). Adverse events were reported in 74.6% of patients who received IVS and in 93.5% of patients who received MMF. A cerebral lymphoma developed in 1 patient in each group, and a lymphoproliferative disorder developed in 2 patients in the MMF group; in 1 of these patients, the lymphoproliferative disorder was subsequently determined to be present before study entry. Opportunistic infections occurred in 35% of patients in each treatment group.

Adolescent↗

PubMed1998

Mycophenolate mofetil for the treatment of a first acute renal allograft rejection: The Mycophenolate Mofetil Acute Renal Rejection Study Group.

BACKGROUND: Mycophenolate mofetil (MMF) significantly reduces the incidence of acute allograft rejection in renal transplant patients. The effect of adding MMF to the immunosuppressive regimen of patients with established rejection is unknown. The purpose of the current study was to compare the safety and efficacy of the addition of MMF to the treatment regimen of an early first acute cellular rejection. METHODS: The study was a double-blind, double-dummy controlled clinical trial of 221 renal transplant recipients experiencing the first biopsy-proven rejection within 6 months of transplant performed at 15 U.S. and Canadian centers. A total of 113 patients received MMF (1.5 g twice daily) and intravenous corticosteroids, and 108 patients received azathioprine (AZA) (1-2 mg/kg/day) and intravenous corticosteroids. The intravenous corticosteroids in each group consisted of 5 mg/kg/day for 5 days followed by an oral steroid taper. End points for the study were the first use of antilymphocyte therapy, the number of courses of antirejection therapy given during the first 6 months, and graft and patient survival at 1 year. RESULTS: At 6 months, 16.8% of the MMF-treated patients and 41.7% of the AZA-treated patients required at least one course of antilymphocyte therapy (P < 0.0001). The number of patients requiring full courses of antirejection therapy for the treatment of rejection was less in the MMF-treated group (24.8%) versus the AZA-treated group (58.3%) (P < 0.0001). The proportion of patients with the use of antilymphocyte therapy or treatment failure during the first 6 months was 29.2% vs. 51.9% (P=0.0006) in the MMF versus the AZA groups, respectively. By 1 year after enrollment, 10 patients (8.9%) in the MMF-treated group lost their graft or died versus 16 patients (14.8%) in the AZA-treated group. More patients in the MMF group withdrew because of an adverse event: 20 patients (17.7%) compared with 11 AZA-treated patients (10.2%). CONCLUSIONS: MMF administered in combination with pulse corticosteroids significantly decreases the subsequent use of antilymphocyte therapy in the treatment of acute renal allograft rejection. In addition to being a safe and effective prophylactic agent, MMF added to steroids improves the rate of reversal of acute rejection episodes.

Adult↗

PubMed2006

Does the Banff rejection activity index predict outcome in patients with early acute cellular rejection following liver transplantation?

The Banff schema incorporates a semiquantitative scoring system for grading of acute cellular rejection (ACR) of the liver allograft. The Banff rejection activity index (RAI) comprises 3 components scored from 0 to 3: venous endothelial inflammation (E); bile duct damage (B); and portal inflammation (P); the scores are combined to an overall score (the RAI). The purpose of this research was to determine the prognostic value of the Banff RAI score in predicting the response to increased immunosuppression and the long-term outcome of the graft. A retrospective study was done of patients undergoing primary liver transplantation between January 2000 and October 2004 with tacrolimus-based immunosuppression; 495 patients were included, 231 had histologically-confirmed ACR, 193 responded to 1 cycle of high-dose steroids. There was no correlation between the total RAI score and response to steroids, resistant rejection, development of chronic rejection, or graft survival. The E score was related to patient survival, a lower score being associated with a worse outcome (P = 0.048). In multivariable analysis, serum bilirubin, serum aspartate aminotransferase, and E score were significant predictors of death (P = 0.012). In univariable analysis, B score and bilirubin were significantly related to "resistant rejection" (P = 0.018 and 0.002, respectively), but only bilirubin was significant in multivariable analysis (logistic regression). In conclusion, although the Banff RAI score is a useful marker of the severity of rejection, neither the total RAI score nor any of the individual components correlated with response to steroids or graft survival.

Adolescent↗

PubMed2005

Role of cold ischemia in acute rejection: characterization of a humoral-like acute rejection in experimental renal transplantation.

The aim of the study was to characterize the role of cold ischemia in the process of acute rejection using an experimental renal transplant model. Syngeneic renal transplants were performed between Wistar Agouti rats and allogeneic grafts using Wistar-Agouti rats as recipients of Brown-Norway kidneys. For cold ischemia (CI), kidneys were preserved in Euro-Collins (4 degrees C/ 2.5 hours). Rats were bilaterally nephrectomized at the moment of renal transplant and did not receive any immunosuppressant. The groups were NoAR (n = 6): immediate syngeneic transplant; CI-NoAR (n = 6): syngeneic transplant with CI; AR (n = 13): immediate allogeneic graft; CI-AR (n = 6): allogeneic graft with CI. Allogeneic rats were followed for the survival study. Syngeneic rats, with mean survival time beyond 6 months, were sacrificed on the day 7 to compare grafts with those in the allogeneic groups. H&E- and PAS-stained grafts were evaluated using the Banff criteria. Tissue INF-gamma and TNF-alpha were quantified by RT-real time-PCR on the kidney grafts. Renal insufficiency did not appear in the NoAR group, but it did from the posttransplant day 5 in both acute rejection groups. While NoAR kidneys showed well-conserved renal architecture, then AR group displayed variable degrees of tubular necrosis with scarce cellular infiltration, interstitial hemorrhage, vascular damage with fibrinoid necrosis, perivascular edema, and nuclear disruption. Cold ischemia in rejecting animals increased the mortality rate due to renal insufficiency and accelerated acute rejection. Independently of CI, the proinflammatory cytokines TNF-alpha and INF-gamma were increased in both rejection groups. In conclusion, addition of CI overactivates the acute rejection process via a humoral component.

Acute Disease↗

PubMed2002

Evaluation of peripheral blood CD4 and CD8 lymphocyte subsets, CD69 expression and histologic rejection grade as diagnostic markers for the presence of cardiac allograft rejection.

We investigated the dynamics of the CD4+ and CD8+ lymphocyte subsets, and the expression of activation markers in cardiac transplant recipients. We tested 132 peripheral blood samples from 62 cardiac transplant recipients using fluorescent staining and flow cytometry analysis. The results were correlated with histological rejection grade of concurrently taken biopsies, and 5-year survival of the recipients. A decrease in the total T lymphocyte subset, and in CD4+ lymphocytes was associated with higher rejection grade and lesser survival. An increase (5-11%) of double positive CD4+ CD8+ lymphocytes was observed; these were mostly CD4brightCD8dim. The CD4/CD8 ratio was significantly (P < 0.00) lower in the transplant recipients than in normal individuals. CD69 expression was higher than CD54 and CD154 expression on CD4 and CD8 lymphocytes of cardiac transplant recipients; correlation between these activation markers was excellent (P < 0.001). Fluorescent staining for CD69 was often of low intensity. Multiple regression for % CD8+ CD69+ cells and survival, and for % CD69+ T cells and rejection grade yielded a significant correlation (P < 0.050). Both % CD8+ CD69+ and % CD69+ T cells were significantly higher in samples with severe and moderate rejection grade (grades 3A, 3B and 4) than in samples which showed no, minimal or mild rejection (grades < or = 2); P-values were 0.052 and 0.003, respectively. Preliminary results indicated that false negative results could be contributed to increased immunosuppression. We conclude that CD69 expression on circulating CD4 and CD8 lymphocytes is a useful parameter for the diagnosis of moderate and severe rejection.

Antigens, CD↗

PubMed1998

The self-fulfilling prophecy in close relationships: rejection sensitivity and rejection by romantic partners.

The authors hypothesized a self-fulfilling prophecy wherein rejection expectancies lead people to behave in ways that elicit rejection from their dating partners. The hypothesis was tested in 2 studies of conflict in couples: (a) a longitudinal field study where couples provided daily-diary reports and (b) a lab study involving behavioral observations. Results from the field study showed that high rejection-sensitive (HRS) people's relationships were more likely to break up than those of low rejection-sensitive (LRS) people. Conflict processes that contribute to relationship erosion were revealed for HRS women but not for HRS men. Following naturally occurring relationship conflicts, HRS women's partners were more rejecting than were LRS women's partners. The lab study showed that HRS women's negative behavior during conflictual discussions helped explain their partners' more rejecting postconflict responses.

Adult↗

PubMed1998

Synergistic effects of mycophenolate mofetil and sirolimus in prevention of acute heart, pancreas, and kidney allograft rejection and in reversal of ongoing heart allograft rejection in the rat.

BACKGROUND: The effect of mycophenolate mofetil (MMF) and sirolimus (rapamycin, RAPA) mono- and combination-therapy was examined in prevention of acute heart, pancreas, and kidney allograft rejection and in reversal of ongoing heart allograft rejection in the rat. METHODS: Both drugs were administered orally for up to 30 days. Eleven groups (n=6) were involved in the first part of the heart allografting model. Brown Norway (RT1n) to Lewis (RT1(1)) combination was used in the heart and pancreas transplantation models, whereas Buffalo (RT1b) to Wistar Furth (RT1u) was used in the kidney transplantation model. RESULTS: The naive control group showed a mean survival time of 6.5+/-0.6 days. There were graded dose-responses to monotherapy of MMF 10 and 20 mg(kg/ day (12.5+/-2.6 days; 19.3+/-9.0 days) and RAPA 0.2, 0.4, 0.8, and 1.8 mg/kg/day (19.2+/-2.0 days; 30.0+/-7.3 days; 50.8+/-12.5 days; 51.2+/-2.6 days), respectively (P=0.001). Results with the combined use of drugs indicate that a synergistic or very strong synergistic interaction was produced when compared with monotherapy of MMF or RAPA: MMF 10 mg(kg/day+RAPA 0.2 mg/kg(day (52.7+/-5.7 days, combination index [CI] =0.189), MMF 20 mg(kg/day+RAPA 0.2 mg/kg/day (57.7+/-5.7 days, CI=0.084), MMF 10 mg/kg/day+RAPA 0.4 mg(kg/day (50.2+/-13.5 days, CI=0.453), and MMF 20 mg/kg(day+ RAPA 0.4 mg/kg(day (51.5+/-6.8 days, CI=0.439), respectively. These results were repeatable in the prevention of acute pancreas and kidney allograft rejection in the rat. In the second part of the study of reversal of ongoing acute heart allograft rejection model, the combined treatment of MMF 10 mg/kg(day+RAPA 0.2 mg/ kg(day (35.5+/-16.0 days, CI=0.794) and MMF 20 mg/kg day+RAPA 0.2 mg(kg/day (57.2+/-4.7 days, CI=0.310) represented synergistic interaction compared with monotherapy of MMF or RAPA. CONCLUSIONS: Concomitant therapy of MMF and RAPA produces a synergistic effect in prevention of heart, pancreas, and kidney allograft rejection and in reversal of ongoing heart allograft rejection in the rat.

Acute Disease↗

PubMed2000

Renal allograft rejection with normal renal function in simultaneous kidney/pancreas recipients: does dissynchronous rejection really exist?

BACKGROUND: Between July 1, 1994 and December 1, 1998, 147 simultaneous kidney/pancreas transplantations were performed at our center. Of 95 patients who experienced at least one acute renal allograft rejection episode after transplantation, 7 (7.4%) developed rejection in the presence of stable and normal or near-normal renal function. METHODS: The indication for renal allograft biopsy was a rising serum lipase, i.e., suspected pancreatic rejection. All seven patients were treated with steroids and augmentation of the tacrolimus dose, with a fall in the serum lipase and no change in the serum creatinine. RESULTS: The serum creatinine levels just before, at the time of, 1 week after the biopsy, and at most recent follow-up were 1.4+/-0.4, 1.3+/-0.3, 1.2+/-0.2, and 1.2+/-0.2 mg/dl. The serum lipase levels just before, at the time of, 1 week after the biopsy, and at most recent follow-up were 1022+/-1157 mg/dl, 874+/-996 mg/dl, 243+/-260 mg/dl, and 94+/-75 mg/dl. The tacrolimus dosages and levels at the time of the biopsy and 1 week later were 14.9+/-5.0 mg/day and 15.0+/-4.0 ng/ml, and 16.4+/-6.3 mg/day and 15.1+/-6.8 ng/ml. CONCLUSIONS: These findings suggest that, in patients undergoing simultaneous kidney/pancreas transplantation, the entity of dissynchronous pancreatic allograft rejection without renal allograft rejection may not really exist. These data also make an additional fundamental point that acute rejection may occur in patients with normal and stable renal function.

Graft Rejection↗

PubMed2004

Rejection sensitivity and the defensive motivational system: insights from the startle response to rejection cues.

Rejection sensitivity (RS) is the disposition to anxiously expect, readily perceive, and intensely react to rejection. This study used the startle probe paradigm to test whether the affect-based defensive motivational system is automatically activated by rejection cues in people who are high in RS. Stimuli were representational paintings depicting rejection (by Hopper) and acceptance (by Renoir), as well as nonrepresentational paintings of either negative or positive valence (by Rothko and Miro, respectively). Eyeblink startle magnitude was potentiated in people high in RS when they viewed rejection themes, compared with when they viewed nonrepresentational negative themes. Startle magnitude was not attenuated during viewing of acceptance themes in comparison with nonrepresentational positive themes. Overall, the results provide evidence that for people high in RS, rejection cues automatically activate the defensive motivational system, but acceptance cues do not automatically activate the appetitive motivational system.

Adolescent↗

PubMed2005

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

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

Adult↗

PubMed1992

Evidence for a role for T cell receptors (TCR) in the effector phase of acute bone marrow graft rejection. TCR V beta 5 transgenic mice lack effector cells able to cause graft rejection.

Lethally irradiated mice reject within 24 h certain marrow grafts, a phenomenon called either allogeneic or hybrid resistance. The cells responsible for this rejection (NK1+ CD3+ cells (TNK) express Ag of NK cells as well as the TCR-associated CD3 complex. This raises the question whether TCR participate in the function of these cells during graft rejection. By using flow cytometry it is shown that the majority of TNK cells expresses the TCR-alpha/beta chains and by using adoptive cell transfer assays evidence is presented that it is the TCR-alpha/beta expressing cells that cause rejection. To explore whether any particular TCR chains have to be expressed on these cells, C57L mice were assayed and found to be responders suggesting that the V beta chains deleted in these mice are not obligatory. However, introduction of a specific TCR V beta 5 chain into C57BL/6 mice as a transgene leads to inability to transfer resistance. TNK cells of V beta 5 transgenic mice express the introduced gene suggesting that it is the transgenic TCR that is responsible for the lack of function. In assessing T cell functions in V beta 5 transgenic mice it is shown that although these mice generate CTL specific for H-2d targets there is a deficiency to recognize H-2Dd, i.e., of determinants presumed to be recognized in the acute rejection mechanism. Thus TNK cells and CTL share the inability to recognize H-2Dd epitopes due to expression of the V beta 5 transgene. The notion that TCR on TNK cells play a role in the acute rejection process makes it necessary to postulate a receptor selection mechanism for these cells.

Acute Disease↗

PubMed1992

Chronic rejection of rat renal allograft. I. Histological differentiation between chronic rejection and cyclosporin nephrotoxicity.

Chronic allograft rejection is both a clinical and a histopathological diagnosis. Until recently, the histological definition of chronic renal allograft rejection was based on clinical diagnostic biopsies, where the evidence was partially obscured by recurrence of the original renal disease, and/or by administration of immunosuppressive drugs. In this communication, we present an experimental rat model for chronic renal allograft rejection, devoid of recurrence of the original disease. By comparing allografts to similarly immunosuppressed syngeneic transplants, we define which histological features should be attributed to chronic rejection and which to cyclosporin nephrotoxicity. Rat renal transplants were performed from DA (Ag-B4, RT1av1) to WF strain (Ag-B2, RT1u) or, for control, to DA strain, and immunosuppressed for 2 or 3 weeks with cyclosporin using a variety of different dosages. The animals were monitored weekly for serum creatinine levels and for blood cyclosporin concentrations, and core needle biopsies were performed on the grafts at regular intervals. At 3 months post-transplantation the animals were sacrificed and a complete histopathological evaluation was performed. Thirty-one histological variables were scored blindly by two investigators and separately for the graft interstitium, glomeruli, tubuli, and the graft vasculature. The following histological alterations were significantly more prominent in allografts than in similarly immunosuppressed syngeneic transplants: the intensity of interstitial inflammation, particularly the degree of pyroninophilia within the inflammatory cell population; the extent of glomerular mesangial matrix increase, basement membrane thickening, and glomerular sclerosis; the increase in the vascular intimal thickness affecting in particular the first and second order branches of the renal artery; and the obliteration of the graft vasculature. These alterations were considered as being primarily due to chronic rejection. In contrast, the extent of interstitial fibrosis and the extent of tubular changes, including tubular epithelial vacuolation, epithelial atrophy, and tubular basement membrane changes, were not significantly different in the allografts as compared to the syngeneic controls. These alterations were attributed primarily to cyclosporin nephrotoxicity. Serial monitoring of the grafts by needle biopsies clarified the sequence of events in the development of the chronic alterations in the transplant. The first event, as expected, was tubulointerstitial pyroninophilic inflammation, resembling that of acute episodes of rejection. This was significantly stronger and appeared earlier in allografts immunosuppressed for 2 rather than for 3 weeks. Vascular alterations developed next. The last to develop were the glomerular lesions.

Animals↗

PubMed1991

Noninvasive assessment of cardiac transplant rejection. A critical look at the approach to acute rejection.

The diagnosis of acute rejection remains a key issue in the management of the heart transplant recipient. Myocardial biopsy for tissue examination is the basic step for screening and diagnosis of acute rejection. Although endomyocardial biopsy is reliable, it is an inefficient approach to screening after transplantation and yielded only a 14% rate of positive results in the author's experience, from 1983 to 1990, of 568 biopsies. A reliable noninvasive method for screening acute rejection is therefore needed. Numerous noninvasive methods have been studied to monitor the systemic immune process against the allograft or to evaluate the effect of rejection on graft function and status. For 13 methods of evaluating immune process against the allograft the sensitivity and specificity ranged from 13% to 95% and 19% to 94% respectively. For nine methods of evaluating allograft function, sensitivity and specificity ranged from 60% to 93% and 65% to 97% respectively. Overall, methods monitoring allograft function and status have better results in predicting acute rejection. Nevertheless, the author estimated that 15 episodes of acute rejection would have been missed by these monitoring methods in his group of patients.

Acute Disease↗

PubMed1986

Induction of bone marrow allograft rejection and hybrid resistance in nonresponder recipients by antibody: is there evidence for a dual receptor interaction in acute marrow graft rejection?

Acute marrow graft rejection in allogeneic or semiallogeneic donor-recipient mouse combinations has been suggested to be caused by natural killer (NK) cells. The unique in vitro specificity of NK cells for tumor cells, however, does not explain the specific rejection of bone marrow grafts by NK cells. Recent experiments have implicated antibody in marrow graft recipients as the specificity-inducing component that guides NK cells in an antibody-dependent cytotoxic (ADCC) reaction to attack the marrow graft. On the basis of this hypothesis, one would postulate that nonresponder marrow graft recipients can be converted into responders by injection with antibody of appropriate specificity. Results presented in this report show that this is indeed possible. Specific monoclonal or polyclonal antibody of IgG isotype induces marrow graft rejection in nonresponder recipients. This can be demonstrated in allogeneic as well as in semi-allogeneic (hybrid resistance) donor-recipient strain combinations. Antibody-induced marrow graft rejection is independent of complement and dependent on the presence of NK cells. Surprisingly, graft rejection induced by antibody is quite efficient in allogeneic and semiallogeneic marrow donor-recipient combinations, whereas it is generally poor in syngeneic combinations. This result is not understood if NK cells lyse bone marrow cells solely in an ADCC-type reaction. Because NK cells can lyse targets in an antibody-dependent as well as independent reaction, it is proposed that the binding of NK cells to targets via their receptors plays an additional role in the rejection of bone marrow in vivo. Preliminary evidence for this possibility is that NK cells in the apparent absence of antibody may have a detectable suppressive effect on the growth of marrow grafts in F1 hybrid mice transplanted with parental marrow grafts.

Animals↗

PubMed1984

[111-Indium-labeled thrombocytes in the diagnosis of acute kidney transplant rejections and in monitoring the therapy of rejection reactions with prostacyclin].

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

Acute Disease↗

PubMed1994

Failure of anti-T cell monoclonal antibodies to prevent acute tumor allograft rejection is associated with their inability to deplete or inactivate T cells at the site of rejection.

The ability of anti-T cell mAb therapy to prevent acute rejection of a tumor allograft was studied. Injection of both anti-CD4 and anti-CD8 rat Ig2b mAbs 1 day before intraperitoneal implantation of P815 tumor cells into AB6F1 mice prevented tumor rejection in most of the mice. However, injection of the same mAbs on day 8 of tumor growth, i.e., 2 days before the onset of tumor rejection, failed to prevent rapid elimination of P815 cells from the peritoneal cavity. Flow cytometric analysis revealed that whereas splenic T cells remained depleted in these mice for up to 6 days after mAb injection, peritoneal T cells returned to control levels in 4-6 days. Moreover, a significant number of rat IgG+ cells were found in the peritoneal cavity 2 days after mAb administration, thus demonstrating that T cells were not depleted but coated with the mAbs at that time. The antitumor activity of the mAb-coated T cells was not impaired, in that CD8+ peritoneal cells from mice rejecting allogeneic P815 tumor on day 10, and rat IgG+ peritoneal cells taken from mice 2 days after giving them anti-CD8 mAb on day 8, were similarly highly cytotoxic against P815 cells in vitro. Taken together, the results demonstrate that the failure of anti-T cell mAb therapy to prevent the acute rejection of allogeneic P815 tumor was associated with resistance of T cells at the site of rejection to the action of anti-T cell mAbs in vivo.

Acute Disease↗

PubMed1993

Characteristics of aggressive-rejected, aggressive (nonrejected), and rejected (nonaggressive) boys.

95 boys at 3 developmental levels (ages 6-8, 8-10, 10-12) were selected on the basis of sociometric and aggression ratings to represent 4 groups: (1) aggressive and rejected, (2) aggressive (not rejected), (3) rejected (not aggressive), or (4) neither aggressive nor rejected. Behavioral observations, teacher ratings, peer ratings, and open-ended peer interviews were collected to characterize the behaviors of these boys in 3 social domains (conduct problems, sociability/withdrawal, and adaptability/responsivity to peer expectations). Distinct problem profiles emerged. Aggressive-rejected boys exhibited more diverse and severe conduct problems that did aggressive boys, along with greater deficiencies in the domain of adaptability. Nonaggressive rejected children were considered by teachers and peers to be shy and passive, deficient in prosocial behaviors, atypical, and socially insensitive. Grade-level decreases in physical aggression and increases in peer-reported atypical/insensitive behaviors corresponded to developmental differences in group characteristics.

Aggression↗

PubMed1995

[Corticoid-resistant rejection and humoral rejection. The diagnostic criteria and therapeutic management].

The standard treatment of rejection episodes post-heart transplantation is based on high dose of steroids followed by monoclonal or policlonal antibodies directed against T lymphocytes like ATG or OKT3. When this treatment is insufficient it can be used other drugs like metothrexate, ciclofosfamide and another procedures such as total lymphoid irradiation, plasmapheresis or photopheresis. Cardiac allograft rejection is defined by histologic features that include the presence of lymphocytic infiltration of the myocardium with or without necrosis and this histologic pattern is termed cellular rejection. However there is a second form of acute rejection, associated with capillary injury, usually mediated by humoral immune response and without interstitial infiltrates which has been named vascular or humoral rejection. Vascular allograft rejection is commonly resistant to standards forms of immunosuppressive therapy and may result in irreversible allograft dysfunction and reduced patient survival.

Acute Disease↗