Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was designed to determine whether .N = O produced in vivo during the rejection of histoincompatible tissues might permit serum NO2-/NO3- levels to serve as markers of a rejection reaction. Rat syngeneic and allogeneic liver, heart, bone marrow/spleen cell, small bowel, skin, and sponge matrix grafts were performed and the stable end-products of .N = O, NO2-/NO3-, were serially assayed in the serum of the grafted animals. A significant rise of serum NO2-/NO3- levels in the allografted animals preceded the onset of clinical signs of rejection or graft-versus-host disease, with the exception of the skin and sponge matrix graft models, where elevated serum NO2-/NO3- levels were never observed. In all transplant models, normal serum NO2-/NO3- levels were observed at all times in animals that received syngeneic grafts. Furthermore, treatment of allograft recipients with the immunosuppressive agents FK 506 or cyclosporine A inhibited .N = O production. Determination of serum creatinine levels demonstrated that the elevated serum NO2-/NO3- levels were not caused by kidney dysfunction. Serum NO2-/NO3- levels might be useful early serum markers of the initiation of a rejection reaction or graft-versus-host disease when functional markers of graft dysfunction are not apparent.
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PMID:Nitric oxide production in host-versus-graft and graft-versus-host reactions in the rat. 137 17

Under FK 506-based immunosuppression, the entire cadaver small bowel except for a few proximal and distal centimeters was translated to 17 randomly matched patients, of whom two had antigraft cytotoxic antibodies (positive cross-match). Eight patients received the intestine only, eight had intestine in continuity with the liver, and one received a full multivisceral graft that included the liver, stomach, and pancreas. One liver-intestine recipient died after an intestinal anastomotic leak, sepsis, and graft-versus-host disease. The other 16 patients are alive after 1 to 23 months, in one case after chronic rejection, graft removal, and retransplantation. Twelve of the patients have been liberated from total parenteral nutrition, including all whose transplantation was 2 months or longer ago. The grafts have supported good nutrition, and in children, have allowed growth and weight gain. Management of these patients has been difficult and often complicated, but the end result has been satisfactory in most cases, justifying further clinical trials. The convalescence of the eight patients receiving intestine only has been faster and more trouble free than after liver-intestine or multivisceral transplantation, with no greater difficulty in the control of rejection.
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PMID:Intestinal transplantation in composite visceral grafts or alone. 138 43

The transplantation of multiple abdominal viscera including liver-duodenum-pancreas, liver-stomach-duodenum-pancreas, and liver-intestine is being performed with increasing frequency and success. These procedures and other variations are derived from a seldom used multiple visceral operation in which all of the foregoing organs are transplanted in bloc. It is described here how the full multiple visceral transplantation and its less extensive derivatives are based on the same principles of procurement, preservation, and postoperative management. With all of these multiple organ permutations and with intestinal transplantation alone, management is complicated by inclusion in the grafts of a large lymphoreticular component which is capable of causing graft versus host disease (GVHD). Because of a systematic error in therapeutic philosophy, past efforts have been directed at altering or damaging the lymphoreticular cells by pretreatment or of the donor of the organs with drugs, irradiation or other means. From recent observations, the alternative approach is suggested of keeping these lymphoid depots intact which then become the site of 2 way cell traffic after transplantation. Under powerful immunosuppression such as that provided with FK 506, the donor lymphoreticular cells can circulate in the recipient without causing clinical GVHD, and the lymphoreticular cells in the graft become those of the recipient (local chimerism) without causing rejection. Even with avoidance of rejection and GVHD, metabolic interrelations between the grafted organs, and also between the graft organs and retained recipient viscera can affect the fate of the individual transplanted organs or retained recipient organs. The best delineated of these metabolic influences are mediated by the endogenous splanchnic hepatotrophic factors of which insulin has been the most completely studied.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Transplantation en masse of abdominal organs]. 155 35

The presence of recipient lymphocytes in grafts is thought to equate with rejection. Thus, we wished to follow the fate of lymphocytes after transplant of the small bowel. Three complete small-bowel transplants, two with the liver from the same donor also transplanted, were done successfully. Patients were immunosuppressed with FK 506. 5 to 11% of lymphocytes in the recipients' peripheral blood were of donor origin during the early postoperative period when there were no clinical signs of graft-versus-host disease. However, donor cells were no longer detectable after 12 to 54 days. Serial biopsy specimens of the grafted small bowel showed progressive replacement of lymphocytes in the lamina propria by those of the recipient's HLA phenotype. Lymphoid repopulation was complete after 10 to 12 weeks but the epithelial cells of the intestine remained those of the donor. The patients are on enteral alimentation after 5, 6, and 8 months with histopathologically normal or nearly normal intestines. Re-examination of assumptions about the rejection of intestinal grafts and strategies for its prevention are required following these observations.
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PMID:Replacement of donor lymphoid tissue in small-bowel transplants. 170 70

Severe graft-versus-host disease was induced by transplantation of ACI rat bone marrow and spleen cells into irradiated Lewis rat recipients. Treatment with FK 506 or cyclosporine A (CsA) was started after clinical and histologic evidence of acute GVHD was present. A 14-day course of FK 506 at 1.0 mg/kg/day could rescue 100% of the animals suffering from GVHD. In contrast only one half of the animals treated with CsA at a high dose of 25 mg/kg/day recovered. After cessation of immunosuppressive therapy, FK 506-treated animals displayed a marked prolonged disease-free interval as compared to CsA-treated bone marrow recipients. Recurrence of the disease in these animals could be prevented when FK 506 treatment was continued after the induction period with a low maintenance dose of 0.1 mg/kg/day every other day.
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PMID:FK 506 reverses acute graft-versus-host disease after allogeneic bone marrow transplantation in rats. 171 58

FK506 and cyclosporine were used for the prevention of acute graft-versus-host disease. Acute GVHD was induced in Lewis rats by total-body irradiation and subsequent reconstitution with allogeneic (ACI) bone marrow and spleen cells (BMTx). GVHD was assessed by both clinical and histologic parameters during the experiment duration of 60 days, and longer for selected animals. All untreated BM recipients died within 26 days from severe acute GVHD. GVHD was prevented with CsA during the period of immunosuppressive therapy, but it appeared within a few days afterward. FK506-treated BM recipients were also protected, but they had a markedly prolonged GVHD-free period after therapy was discontinued. Most such animals eventually developed GVHD but with notable exceptions. Maintenance therapy with doses of FK506 as low as 0.1 mg/kg every other day (1/20 of daily induction dose) was infallible insurance against delayed GVHD. The relevance of these findings to GVHD caused by lymphoid-containing solid organs such as the intestine was discussed.
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PMID:Prevention of graft-versus-host disease following allogeneic bone marrow transplantation in rats using FK506. 171 63

The transplantation of multiple abdominal viscera including liver-duodenum-pancreas, liver-stomach-duodenum-pancreas, and liver-intestine is being performed with increasing frequency and success. These procedures and other variations are derived from a seldom used multivisceral operation in which all of the foregoing organs are transplanted in bloc. It is described here how the full multivisceral transplantation and its less extensive derivatives are based on the same principles of procurement, preservation, and postoperative management. With all of these multiple organ permutations and with intestinal transplantation alone, management is complicated by inclusion in the grafts of a large lymphoreticular component which is capable of causing graft versus host disease (GVHD). Because of a systematic error in therapeutic philosophy, past efforts have been directed at altering or damaging the lymphoreticular cells by pretreatment of the donor or of the organs with drugs, irradiation or other means. From recent observations, the alternative approach is suggested of keeping these lymphoid depots intact which then become the site of 2 way cell traffic after transplantation. Under powerful immunosuppression such as that provided with FK 506, the donor lymphoreticular cells can circulate in the recipient without causing clinical GVHD, and the lymphoreticular cells in the graft become those of the recipient (local chimerism) without causing rejection. Even with avoidance of rejection and GVHD, metabolic interrelations between the grafted organs, and also between the graft organs and retained recipient viscera can affect the fate of the individual transplanted organs or retained recipient organs. The best delineated of these metabolic influences are mediated by the endogenous splanchnic hepatotrophic factors of which insulin has been the most completely studied. An understanding of these various immunologic and non-immunologic factors combined with the more potent immunosuppression which is now available is sure to stimulate efforts at transplantation of abdominal organs and particularly of the hollow viscera which heretofore have resisted such clinical efforts.
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PMID:[Multiple transplantation of abdominal organs]. 174 22

The transplantation of multiple abdominal viscera, including liver-duodenum-pancreas, liver-stomach-duodenum-pancreas and liver-intestine, is being performed with increasing frequency and success. These procedures and other variations are derived from a seldom used multivisceral operation in which all of the foregoing organs are transplanted en bloc. It is described herein how the full multivisceral transplantation and its less extensive derivatives are based on the same principles of procurement, preservation and postoperative management. With all of these multiple organ permutations and with intestinal transplantation alone, management is complicated by inclusion in the grafts of a large lymphoreticular component that is capable of causing graft versus host disease (GVHD). Because of a systematic error in therapeutic philosophy, past efforts have been directed at altering or damaging the lymphoreticular cells by pretreatment of the donor or of the organs with drugs, irradiation or other means. From recent observations, the alternative approach is suggested of keeping these lymphoid depots intact, which then become the site of two way cell traffic after transplantation. With the use of powerful immunosuppression, such as that provided with FK 506, the donor lymphoreticular cells can circulate in the recipient without causing clinical GVHD, and the lymphoreticular cells in the graft become those of the recipient (local chimerism) without causing rejection. Even with avoidance of rejection and GVHD, metabolic interrelations between the grafted organs, and also between the graft organs and retained recipient viscera can affect the fate of the individual transplanted organs or retained recipient organs. The best delineated of these metabolic influences are mediated by the endogenous splanchnic hepatotrophic factors, of which insulin has been the most completely studied. An understanding of these various immunologic and nonimmunologic factors combined with more potent immunosuppression that is now available is sure to stimulate efforts at transplantation of abdominal organs and particularly of the hollow viscera that have resisted such clinical efforts.
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PMID:The many faces of multivisceral transplantation. 202 70

The intestine was one of the first organs to be successfully transplanted experimentally. Results in humans were disappointing until recently, partly due to the large quantity of lymphoid tissue present in the intestine, resulting in a vigorous rejection process which is difficult to control. Recent advances in experimental studies have improved our knowledge about mechanisms of rejection and graft-versus-host disease, and have allowed the development of new immunosuppressive therapies. At the present time, major obstacles remain in clinical intestinal transplantation (i.e. difficulty of preventing rejection despite massive immunosuppression, high rate of postoperative sepsis). However, the protective effect of a concomitant transplanted liver and the use of FK 506 have allowed a dramatic improvement in clinical results, justifying continuation of experimentation of intestinal transplantation in humans.
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PMID:[Small intestine transplantation. Experimental and clinical results]. 750 99

Colon transplantation has been proposed as a method to improve the function of an intestinal allograft. The present study examined the risk of colon rejection and the effect of FK506 on colon rejection in BN-->LEW rats with orthotopic bowel transplants. The first 4 groups included rats with untreated allografts (group 1), rats with isografts treated with 0.6 mg/kg FK506 (group 2), rats with allografts treated with 0.6 mg/kg FK506 (group 3), and rats with allografts treated with 0.4 mg/kg FK506 (group 4). In each of these groups (10-12 rats), half of the animals received a small bowel graft only (SB), while the other half received a small bowel, ascending colon, and cecum graft (SBC). The animals were followed daily until they died or were killed at 4 weeks. In group 5, an additional 18 untreated rats with SBC allografts were randomly killed on the third, fifth, seventh, and tenth postoperative days to study the sequential histopathologic and immunopathologic changes of colon rejection. There was no difference in survival, body weight, nutritional parameters, or bacterial contamination after SB and SBC transplantation. Intestinal transit was slower after SBC than SB transplantation (P < 0.05). Sequential histopathologic studies revealed that (1) the severity and time course of colon rejection was similar to small intestine rejection, and (2) the features of colon rejection were similar to ulcerative colitis. There was no evidence of graft-versus-host disease after SBC transplantation. In summary, adding a segment of large bowel to a small bowel allograft does not increase the risk of rejection or surgical complications. The transplanted colon slows intestinal transit. Treatment with FK506 effectively prevents colon rejection. These data suggest that adding a colon graft may improve the outcome of clinical small bowel transplantation.
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PMID:Treatment with FK506 prevents rejection of rat colon allografts. 751 86


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