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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methods that avoid chronic immunosuppression of transplant recipients must be developed to eliminate the various risk factors associated with such treatment (e.g., increased infections and malignancies). Pretransplant treatment of the graft with anti-Ia serum plus complement to eliminate "passenger cells" is one such method. An alternative approach is short-term treatment of the recipients with cyclosporine (CsA). In this study, parathyroid glands from Lewis X Brown Norway rats were cultured for one week at 37 degrees C and treated with anti-Ia and complement. Treated glands were transplanted into parathyroidectomized, hypocalcemic Wistar-Furth recipients that had received 30 mg/kg of CsA once a day for the three days prior to transplant. At 1 year posttransplant, 67% of the recipients had functional parathyroid allografts. Control rats (no CsA; fresh, untreated glands) rejected their grafts within 28 days. Controls given three days of CsA and transplanted with fresh, untreated glands all had functional grafts for greater than 56 days (median survival: 80.5 days). Prolongation of allograft survival with short-term, preoperative CsA demonstrates the efficacy of immunosuppression given only at the time of antigen presentation. This course of CsA allowed for indefinite graft survival when the recipient received a graft previously cultured and treated with Ia antiserum. These results are encouraging and should be evaluated further to determine whether similar approaches will be useful in human transplants.
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PMID:Extension of survival of rat parathyroid allografts by depletion of Ia donor cells plus preoperative cyclosporine. 330 39

Methods that avoid long-term immunosuppression must be developed for human parathyroid allotransplantation to be feasible. Pretransplant treatment of the graft to eliminate passenger cells is one such method. An alternative approach is short-term treatment of the recipients with cyclosporine (CsA). In this study, parathyroid glands from Lewis X Brown Norway rats were cultured for 1 week and treated with antiserum directed against class II major histocompatibility complex antigens. Treated glands were transplanted into hypocalcemic Wistar-Furth recipients that previously received 30 mg/kg of CsA once a day for 3 days before transplantation. At 280 days after transplantation, 67% of the recipients had functional parathyroid allografts. Control rats (no CsA; fresh, untreated glands) rejected these grafts within 28 days. Control rats given 3 days of CsA and transplanted with fresh, untreated glands had functional grafts for greater than 56 days (median survival, 80.5 days). Prolongation of allograft survival with short-term, preoperative CsA demonstrates the efficacy of immunosuppression given at the time of antigen presentation. This course of CsA is even more effective when the recipient receives a graft whose passenger cells are eliminated.
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PMID:Indefinite survival of rat parathyroid allografts without postoperative immunosuppression. 349 36

An inbred rat model of small bowel transplantation was used to study the metabolic consequences of systemic venous drainage of the graft. Lewis rats received either Lewis (isograft) or Lewis X Brown Norway F1 (allograft) small bowel grafts. Venous drainage of the isografts was to either the portal vein or the inferior vena cava. Allograft recipients underwent systemic venous drainage and were treated with a 4-week course of tapering cyclosporine. Ammonia levels in systemically drained isografts (108 +/- 5 microM/100 ml) were more than twice those in portally drained isografts (38 +/- 3, P less than 0.001), while amino acid analysis showed significant elevations in glycine, serine, asparagine, histidine, phenylalanine, and tyrosine. Ammonia levels decreased and amino acid alterations were generally corrected when animals were fed a modified protein diet low in aromatic and high in branched chain amino acids. Recipients of both systemically and portally drained isografts grew normally, while weight gain in allograft recipients was impaired. We conclude that systemic venous drainage of small bowel grafts results in altered ammonia and amino acid levels that resemble those found in models of hepatic encephalopathy; these changes can be significantly ameliorated by dietary modification; and the compromised growth seen in systemically drained allografted animals results from chronic rejection and/or cyclosporine rather than the partial porto-systemic shunt.
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PMID:Metabolic aspects of small bowel transplantation in inbred rats. 349 83

This study was initiated to evaluate the effects of varying the length and site of origin of small-intestine transplants on rejection and on graft-versus-host disease (GVHD). Eighty rats had heterotopic transplants performed with systemic venous drainage of the grafts. The host native bowel was left in situ and no immunosuppressive agents were used. Twenty male Lewis inbred (LEW) rats who received isogenic grafts survived without any evidence of rejection or GVHD. When intestine from Lewis X Brown Norway hybrid rats (LBN) was transplanted into LEW rats, rejection occurred between day 6 and 9 and the time of onset of rejection was not influenced either by the length of transplanted bowel (10 to 80 cm, n = 6 each) or by whether the graft was from the jejunum or the ileum. However, rates of survival for 100 days from rejection were significantly better if 10 cm (100%) or 20 cm (84%) was transplanted than if the grafts were 40 cm or more in length (56%). The LBN recipients of LEW allografts developed GVHD on days 7 through 9, and this response was similarly unrelated to the length or segment of bowel transplanted. However, host survival was quite dependent on graft segment length and site of origin. All animals who received 20 cm or less of proximal bowel survived (with GVHD but no evidence of rejection). While 50% of the animals that received proximal intestinal grafts 40 cm in length survived GVHD, none who received identical-sized grafts from the distal ileum survived (all were dead by day 20). Our data document that the results of small-intestine transplantation is dependent on the length and site of origin of the grafts.
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PMID:The effects of size and site of origin of intestinal grafts on small-bowel transplantation in the rat. 349 43

To determine the changes in myocardial water during acute cardiac rejection and the effects of Ciclosporin (CYA) on the myocardial water, 90 heterotopic cardiac transplants were performed in rats which were divided into 3 groups, namely those receiving 1) Lewis X Lewis isografts, 2) Lewis X Brown Norway allografts and 3) CYA treated allografts (15 mg/kg/day). The water content was measured in both recipient and donor hearts at 2, 4, 6 and 8 days after transplant. Pathological specimens were examined by light and electron microscopy, and scored on a 0 to 4+ scale of increasing evidence of rejection. The water content of the isografts showed no significant change throughout the post operative period. In contrast, the allografts had significant increase of water content as early as 2 days after transplant, compared to the isografts and recipients hearts. A significant difference in cellular infiltration was noted between isograft and allograft 4 days after transplant. CYA suppressed significantly the increase of myocardial water and cellular infiltration in the allografts. These data suggest that myocardial edema may precede cellular infiltration during the rejection process and it may be suppressed with CYA treatment. The measurement of myocardial water may be useful in early detection of acute cardiac allograft rejection and for examining the therapeutic effects of CYA.
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PMID:Early change of myocardial water during acute cardiac allograft rejection. 354 64

In small-bowel transplantation, the transfer of large numbers of donor lymphocytes with the intestinal allograft may provoke a lethal graft-versus-host reaction. The effectiveness of allograft irradiation in vitro as a method of preventing graft-versus-host disease (GVHD) was studied in a rat model of small-bowel transplantation, with the Lewis----Lewis X Brown Norway F1 hybrid strain combination. Cold harvested small-bowel allografts were irradiated immediately prior to heterotopic or orthotopic transplantation. Animals that had received heterotopic allografts irradiated with 0, 250, or 500 rad all died of GVHD after 14.4 +/- 3.0, 15.0 +/- 1.3, and 14.2 +/- 1.9 days, respectively. None of the animals that had received allografts treated with 1000 rad developed clinical or pathologic evidence of GVHD, however, and all survived for more than 6 months (P less than 0.001). Allograft function was studied in animals that underwent orthotopic transplantation. Recipients of nonirradiated orthotopic allografts all died of GVHD after 14.0 +/- 0.7 days, whereas recipients of allografts irradiated with 1000 rad all survived for more than 5 months (P less than 0.001). After 120 days, weight gain (51.8 +/- 11.7%), serum albumin (3.9 +/- 0.7 g/dl), serum triglycerides (67.0 +/- 24.3 mg/dl), CBC, and differential in these animals were not statistically different from those in either age-matched isograft recipients or normal animals, and when the rats were sacrificed, irradiated allografts showed no changes suggestive of radiation injury. These results indicate that irradiation of small-bowel allografts in vitro prevents development of GVHD, and that this can be achieved at a dose which does not cause injury to or malfunction of the allograft.
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PMID:In vitro allograft irradiation prevents graft-versus-host disease in small-bowel transplantation. 387 77

In this study the sequence of histologic changes in rejecting pancreatic allografts was correlated with the recurrence of hyperglycemia to evaluate the usefulness of serum glucose monitoring in pancreas transplantation. In addition, various immunosuppressive agents were evaluated for their efficacy in reversing rejection. Diabetic (streptozocin) Lewis rats were recipients of histoincompatible Lewis X Brown Norway F1 pancreatic grafts, which uniformly resulted in a fall in serum glucose levels from greater than 400 mg/dl to less than 150 mg/dl. Specimens were examined daily from the time of transplantation to determine the time of earliest histologic rejection. Functional rejection was defined as a rise in serum glucose levels to greater than 200 mg/dl and occurred at 8.5 +/- 0.8 days in the control group. Histologic evidence for rejection was present by day 3 as a perivascular lymphoid infiltrate while islets remained normal. Extensive cellular rejection of the exocrine tissue occurred by day 6 when most recipients were still normoglycemic. Complete pancreatic destruction was present by day 9. Antirejection therapy with methylprednisolone (MP), antithymocyte serum (ATS), or cyclosporine (CS) started at the time of recurrent hyperglycemia (days 8 or 9) and was uniformly unsuccessful in prolonging graft survival, with mean survival times of 8.3 +/- 0.8 (MP), 9.0 +/- 0.7 (ATS), and 9.3 +/- 0.4 (CS). In contrast, either ATS or CS but not MP begun on day 3, when histologic rejection was first observed, significantly prolonged graft survival to greater than 11 days in most recipients. We conclude that islet destruction is irreversible by the time that marked elevation in serum glucose levels occurs and therefore a more sensitive measure of pancreas rejection is needed. Furthermore, ATS and CS are more effective than are corticosteroids in reversing early rejection.
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PMID:Experimental pancreas allograft rejection: correlation between histologic and functional rejection and the efficacy of antirejection therapy. 389 43

The ability of proton NMR relaxation times to detect cardiac allograft rejection was studied in an inbred rat heterotopic cardiac transplantation model. Hearts from 25 Lewis X Brown Norway F1 hybrid rats were anastomosed to the abdominal aorta and vena cava of Lewis recipients; 25 Lewis donor hearts served as isograft controls. Groups of five allografts and five isografts were harvested daily between two and six days post-transplant. The relaxation times T1 and T2 of the transplanted hearts were determined in vitro with a 10 MHz spectrometer. T1 and T2 values in allografts did not differ significantly from those in isografts at days 2 and 3 post-transplant. However, at days 4, 5, and 6 T1 and T2 of the allografts were significantly prolonged. This finding correlated with an elevation in tissue water content and the onset of rejection as determined histologically. An additional 21 allografts, treated with cyclosporine, were studied in the same way from four to more than 100 days post-transplant. T1 and T2 values of these treated allografts did not change significantly during the observation period and were similar to the relaxation values obtained in the isografts at days 2 to 6. These data suggest that serial measurements of myocardial T1 and T2 may be useful in detecting acute cardiac allograft rejection and monitoring the effect of antirejection treatment.
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PMID:The detection of cardiac allograft rejection by alterations in proton NMR relaxation times. 390 83

We assessed the structural and functional evolution of small intestinal transplant rejection in a rat model by use of 1-micron section, electron microscopic, and in vitro electrophysiologic techniques to study jejunal mucosa 3, 6, and 9 d posttransplantation. The earliest structural abnormalities detected in jejunal loops transplanted from Lewis X Brown Norway F1 hybrids into Lewis rats occurred within 3 d posttransplantation and consisted of focal endothelial cell injury of the microvasculature and focal injury of crypt epithelial cells. Both alterations were associated with adjacent infiltration of large lymphoid cells, and both markedly progressed and became rather diffuse over the following 6 d. In contrast, villus absorptive cells were not markedly altered in structure until the 9th postoperative day. As compared with host jejuna, allograft jejunal epithelium demonstrated multiple functional abnormalities. Transepithelial resistance declined progressively by days 6 and 9 (both P less than 0.05), although baseline transepithelial spontaneous potential difference was only affected at day 9 (P less than 0.01). Stimulated absorption by allograft jejuna, as assessed by measuring electrical response to mucosal glucose, was not significantly diminished until day 9 (P less than 0.05). In contrast, stimulated secretion assessed by measurement of electrical response to serosal theophylline was diminished by day 6 (P less than .01). These data suggest that the earliest epithelial injury during rejection, as judged both structurally and functionally, occurs in the crypt and is paralleled by endothelial injury at the level of the microvasculature. Thus, the primary targets for rejection are most likely endothelial cells and crypt epithelial cells. In contrast, structural and functional impairment of villus epithelium is detectable only at substantially later times during rejection and are most likely secondary processes related to either ischemia produced by microvascular injury or decreased epithelial regenerative ability secondary to crypt injury. Last, we show that the detrimental structural and functional sequellae of jejunal transplantation across the major histocompatibility complex in this model is strikingly ameliorated with cyclosporine therapy.
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PMID:Structural and functional evolution of jejunal allograft rejection in rats and the ameliorating effects of cyclosporine therapy. 397 15

Lewis (LEW) rats immunized 3 weeks before by injection of DNP-KLH together with Bordetella pertussis showed high levels of DNP antibody as judged by serum binding of 10(-7) M 3H-DNP-lysine 10 days after secondary immunization with DNP-KLH. Sera obtained from LEW rats following secondary immunization with DNP-BGG showed reduced DNP hapten binding. However, injection of 10(8) F1 hybrid Lewis X Brown Norway spleen cells into DNP-primed LEW rats 2 days before secondary immunization with DNP-BGG significantly increased the level of serum binding of 3H-DNP-lysine. These results provide evidence that the allogeneic cellular reaction associated with a host-versus-graft response induced by injection of F1 hybrid lymphoid cells into DNP-primed parental strain recipients partially obviates the requirement for carrier-specific T cells in the secondary anti-DNP response thereby providing a stimulus for triggering primed host B cells to produce antibody.
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PMID:Hapten antibody production and the relevance of allogeneic reactions to elimination of the carrier effect. 615 32


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