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

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)
 ...
PMID:[Transplantation en masse of abdominal organs]. 155 35

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.
 ...
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.
 ...
PMID:The many faces of multivisceral transplantation. 202 70

Clinical pancreas transplantation (txp) using a pancreaticoduodenal allograft (pda) and the donor spleen has been applied as treatment for insulin-dependent diabetes mellitus. Inclusion of the spleen in the pda is purported to protect against thrombosis and may be of possible immunological benefit. In pancreatectomized pigs, we compared the results of pda txp with (n = 8) and without (n = 10) the donor spleen. Animals were maintained on cyclosporine (6 mg/kg/day i.v.) and prednisolone (1.5 mg/kg/day i.v. tapered over 7 days to a maintenance dose of 0.5 mg/kg/day i.v.). Pancreatic exocrine enzyme replacement was administered daily. In 10 recipients of the technically successful pda without the spleen, rejection (blood glucose greater than 150 mg/dl) was not seen in the 28 days after txp. Mean daily blood glucose was 95 +/- 8 mg/dl during this period. In contrast, 5 of 8 recipients of the technically successful pda with the donor spleen rejected their grafts an average of 13 days (range 7-16) after txp (P less than 0.01). Mean daily blood glucose was 88 +/- 21 mg/dl prior to the declaration of rejection and increased to 275 +/- 59 mg/dl after rejection (P less than 0.0001). Rejection was histologically confirmed in all cases. None of the recipients of the pda with the donor spleen developed signs of graft-versus-host disease. Glucose tolerance testing carried out 28 days after transplantation in normoglycemic pigs from both experimental groups demonstrated no difference between the groups. In the porcine pda model used in this study, the inclusion of the spleen in the pda was associated with rejection of the transplant.
 ...
PMID:Association of inclusion of the donor spleen in pancreaticoduodenal transplantation with rejection. 241 99

Gliotoxin (GT) is a fungal metabolite that reduces the ability of murine macrophages to react immunologically in vitro. It is also capable of modulating the immunogenicity of murine bone marrow cells, so that the onset of graft-versus-host disease in fully allogeneic bone marrow chimeras is delayed. The present study examines the effect of GT on human fetal cells, both in terms of reduction of immunogenicity and toxicity. GT (10 micrograms/ml) significantly decreased the responsiveness in mixed lymphocyte cultures of cells derived from human fetal pancreas, spleen, liver and bone marrow. This concentration of GT was, however, mildly toxic to explants of the pancreas, with a significant reduction in insulin secretion from this tissue during the first day of its organ culture, but not thereafter. GT-treated pancreatic explants were lighter and contained less insulin than the untreated controls 3 months after the tissue had been implanted beneath the renal capsule of nude mice. This difference was not apparent 3 weeks after transplantation into these animals. It is hypothesized that the immunomodulating effect of GT (at a concentration less than 10 micrograms/ml) may be of benefit in treating allografted human fetal pancreas before it is transplanted, as it has for murine adult bone marrow cells.
 ...
PMID:Immunomodulation of human fetal cells by the fungal metabolite gliotoxin. 248 85

Twenty-three patients with recent onset Type 1 (insulin-dependent) diabetes in whom residual insulin secreting B cells were present and 12 patients with disease of more prolonged duration (maximum 9 years), 8 of whom had residual B cells, were studied. Aberrant expression of Class II major histocompatibility complex molecules was demonstrated immunohistochemically on insulin secreting B cells in 21 out of 23 patients with recent onset disease and 6 of the patients with more prolonged disease. No such expression was seen on glucagon secreting A cells or somatostatin secreting D cells. Islets where there was marked hyperexpression of Class I major histocompatibility complex molecules on islet endocrine cells were seen in all cases in which residual B cells were present. Ninety-two per cent of insulin containing islets but only 1% of insulin deficient islets exhibited this phenomenon (p less than 0.001, Chi-squared test). There was evidence to suggest that both these abnormalities of major histocompatibility complex expression preceded insulitis within a given islet. They also appeared to be unique to Type 1 diabetes, being absent in pancreases of patients with Type 2 (non-insulin-dependent) diabetes, chronic pancreatitis, cystic fibrosis, graft-versus-host disease and Coxsackie B viral pancreatitis. The development of autoimmunity to B cells in Type 1 diabetes may be a "multistep" process in which abnormalities of major histocompatibility complex expression on islet endocrine cells are crucial events.
 ...
PMID:Aberrant expression of class II major histocompatibility complex molecules by B cells and hyperexpression of class I major histocompatibility complex molecules by insulin containing islets in type 1 (insulin-dependent) diabetes mellitus. 330 84

In a study of pancreases from 75 patients who died at presentation of Type I diabetes there was selective destruction of beta cells associated with islet inflammation (insulitis). According to a recent hypothesis, aberrant expression of Class II major histocompatibility complex (MHC) products on a target cell may allow presentation of organ specific surface antigen(s) to potentially autoreactive T helper lymphocytes and thus lead to autoimmunity. Aberrant expression of Class II MHC was demonstrated immunohistochemically on beta cells in 21 out of 23 patients with recent onset diabetes. No such expression was seen on the other pancreatic endocrine cells. Ninety-four per cent of insulin-containing islets in these patients had marked hyperexpressions of Class I MHC affecting all endocrine cells in these islets. Insulin deficient islets were not thus affected. Both these abnormalities of MHC expression appeared to precede insulitis within a given islet and appeared to be unique to Type I diabetes, being absent in pancreases of patients with Type II diabetes, chronic pancreatitis, cystic fibrosis, graft-versus-host disease and Coxsackie B viral pancreatitis. The development of autoimmunity to beta cells in Type I diabetes may be a 'multistep' process in which abnormalities of MHC expression are crucial events.
 ...
PMID:C. L. Oakley lecture (1987). The pathogenesis of beta cell destruction in type I (insulin-dependent) diabetes mellitus. 330 29

Twenty consecutive patients with diabetes who were dependent upon insulin underwent simultaneous pancreatic-duodenal and renal transplantation at our center between March 1984 and August 1985. Eighteen patients are alive, 17 have functioning renal allografts and 13 have normal fasting blood sugar levels and are free of insulin use. Pancreatic graft loss was secondary to venous thrombosis in four instances and inadequate perfusion in one. Graft versus host disease occurred in three patients with composite pancreatic and splenic grafts, which led to a policy of not including the spleen as part of the graft. Serum creatinine levels were a more sensitive indicator of rejection than blood sugar levels which represent a distinct advantage of the simultaneous pancreatic and renal procedure, as compared with pancreatic transplantation after renal transplantation. Duodenal intestinal anastomosis appeared to be a satisfactory way of establishing exocrine pancreatic drainage. As results of pancreatic transplantation continue to improve, this procedure should no longer be considered as experimental.
 ...
PMID:Surgical treatment of diabetic nephropathy with simultaneous pancreatic duodenal and renal transplantation. 352 Sep 3

After immunization with SRBC, the number of plaque-forming cells (PFC) in the spleen of alloxan-diabetic mice, in nondiabetic TIR mice and in alloxan-diabetic TIR mice was significantly decreased as compared with control non-diabetic donors. The ability of lymphocytes from alloxan-diabetic mice to adoptively restore the suppressed immune response of TIR mice, was reduced in comparison with the effect of lymphocytes from normal, nondiabetic donors. Local GVH reaction in nondiabetic rat recipients provoked by lymphocytes from control healthy mice was 5.6 +/- 0.7 mm. Significantly lower rate of local GVH reaction after injection of lymphocytes from diabetic donors was found in diabetic as in nondiabetic recipients as well. Treatment of alloxan-diabetic mice with thymus extract or with insulin, partly restored depressed function of the humoral and cellular system. Treatment of diabetic mice with both thymus extract and insulin, was even more effective in restoring of their immune reactivity. Diabetic condition strongly influenced the function of the immune system. This could be attributed to depletion of T-lymphocytes, changed relations between the lymphocyte subpopulations in diabetic donors, and disturbance of lymphocyte metabolism.
 ...
PMID:Influence of the thymus extract on the immunological function of animals with experimental diabetes. 354 1

The pathologic symptoms in F1 mice with chronic graft-vs-host disease (GVHD) (GVH F1) strongly resemble those of systemic lupus erythematosus (SLE). Mice with SLE-like GVHD do not produce antibodies to a number of non-self and self antigens. This finding is inconsistent with the widely accepted view that the (auto)-antibody formation in SLE is polyclonal in the sense that B cells are triggered at random, i.e., irrespective of their specificity. In the present study, therefore, we performed a systematic study of the kinetics of total IgM- and IgG-secreting splenic B cells and tested their specificities. The total IgM-secreting B cell population was increased only in the first week after the initiation of SLE-like GVHD; it seemed to reflect a random, but self-limited, polyclonal B cell stimulation. In contrast, the total number of IgG-secreting cells in the GVH F1 mice was increased to a much higher extent than that of the IgM-secreting cells and remained increased. At no time during GVHD was there an increase in the number of plaque-forming cells (PFC) spontaneously secreting IgG antibodies to non-self antigens. The GVH reaction (GVHR) did, however, lead to the appearance of PFC that secreted IgG antibodies to DNA. Similarly, the GVH F1 mice showed high serum titers of antibodies to self antigens characteristic of SLE and to endogenous viruses, but during the entire observation period they failed to develop serum antibodies to non-self antigens and insulin. Hence, the enhanced production of Ig, especially that of IgG, that occurs in SLE-like GVHD is not a random process, because it requires the presence of antigen, or signal 1. The data support our hypothesis that only certain kinds of self antigen, such as DNA and cell membrane epitopes, can cross-link the Ig receptors on the corresponding B cells and thus provide an adequate signal 1. Given the increase in help, or signal 2, in chronic GVHD, only the B cell clones that simultaneously receive an adequate signal 1 seem to be driven into clonal proliferation and IgG secretion.
 ...
PMID:Further evidence against random polyclonal antibody formation in mice with lupus-like graft-vs-host disease. 632 91


1 2 3 4 5 Next >>