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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)

This study tests the hypothesis that small bowel transplantation alters the function of the intestine. The function of the small intestine was investigated after syngeneic (BN----BN or Lew----Lew) and fully allogeneic (BN----Lew) orthotopic total small intestinal transplantation (SIT) using a two-stage model. All animals were treated with cyclosporine A throughout the 60-day study period. Syngeneic transplantation reduced weight gain in the (BN----BN) rats, but not in the (Lew----Lew) animals. Allogeneic transplantation caused a reduction in weight gain for the first 30 days posttransplantation, which may have been associated with graft-versus-host disease. Thereafter, the rate of growth of allogeneic SIT animals was normal. Dietary fat absorption was reduced in all groups of transplanted animals. Intestinal permeability to mannitol and polyethylene glycol 400 (PEG-400) was increased by syngeneic transplantation in all groups, with further permeability increases to mannitol, lactulose, PEG-400, and 51Cr-EDTA after allogeneic SIT. The glucose-stimulated intestinal short circuit current was reduced by both syngeneic and allogeneic SIT, but the maximal active transport rate for glucose uptake was increased, as was the passive uptake of fatty acids. These functional alterations were not associated with changes in intestinal morphology or evidence of rejection. These findings demonstrate that: (1) SIT results in significant changes in the transport characteristics of the bowel, but these have a minimal impact on the well-being of the animal overall; (2) SIT induces an increase in intestinal permeability to mannitol and PEG-400, with a further increase in permeability to all markers following allogeneic SIT; (3) following SIT, and the immune events associated with allogeneic SIT, significant adaptation of the transplanted intestine occurs. We suggest that denervation of the small intestine after SIT is the underlying cause of the changes observed.
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PMID:Intestinal function following allogeneic small intestinal transplantation in the rat. 173 18

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.
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PMID:Association of inclusion of the donor spleen in pancreaticoduodenal transplantation with rejection. 241 99

Small bowel transplantation is a logical treatment in patients with the short bowel syndrome. The intestinal function can be permanently reestablished in animals with small bowel autografts. However, small bowel allotransplantation involves a considerable risk of immunological problems because of the large quantity of lymphoid tissue present in the graft. In non-immunosupprimized experimental animals, it triggers a vigorous rejection response and/or graft versus host disease (GVHD). The use of azathioprine and prednisone as immunosuppression has improved the graft survival minimally. The advent of cyclosporine has increased the survival of small bowel allografts in animal experiments considerably. Preoperative graft irradiation reduces the risk of GVHD. Monitoring of graft function is difficult. Histological evaluation of intestinal biopsy specimens is very useful and it can be combined with the determination of the absorptive function by 14C labelled carbohydrates (glucose, maltose). Twelve patients have undergone small bowel transplantation during the period 1964-1987. Eleven patients died a few weeks after the small bowel transplantation, the longest survivor died after 76 days (information is not available about the last small bowel transplanted patient). Four patients were treated with cyclosporine. Although the results so far have been depressing, a fundament has been created for further investigation in the field. Today, small bowel transplantation is an experimental treatment. It should only be considered for patients with serious and immediately life-threatening complications of the short bowel syndrome.
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PMID:[Small bowel transplantation. Animal experimental and clinical status]. 266 Mar 77

Patients who have lost such a large portion of their small bowel that they permanently require total parenteral nutrition for survival would greatly benefit by receiving a small-intestinal transplant. Over the past two decades, many experimental studies have delineated the specific problems surrounding small-bowel transplantation and provided strategies for their control. Control of rejection, the most difficult problem, may be achieved with a combination of cyclosporine, azathioprine, prednisone, antithymocyte globulin, and monoclonal antibodies. The threat of graft-versus-host disease originating from the allogeneic lymphatic tissues in the allograft is abolished by in vitro x-irradiation of the cold, nonperfused graft with 1000 rads. Monitoring of the intestinal allograft is possible with the combination of a function test (maltose absorption, glucose absorption, or any other function test) and repeated graft biopsy. Effective short-term preservation of small-bowel segments for up to 18 h is possible by intravascular flushing with a balanced electrolyte solution containing 3% fructose and by subsequent hypothermic storage. Clinical small-bowel transplantation is certainly not an imminent therapeutic tool. However, clinical trials in highly selected patients could be envisioned on the basis of our present understanding of small-bowel transplantation and of transplantation biology in general, and in view of the clinical successes achieved with duodenal grafts transplanted in conjunction with pancreatic grafts.
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PMID:Current status of small-bowel transplantation. 327 69

A model of combined pancreas-spleen transplantation (PST) was studied in LBN F1 recipients of Lewis grafts in order to evaluate the efficacy of pretransplant graft irradiation in preventing lethal graft-versus-host disease (GVHD). Recipients of unmodified PST uniformly developed severe GVHD and died (MST = 16.7 +/- 3.8 days). Whole body donor irradiation with either 500 or 250 rad prevented lethal GVHD. Similarly, ex vivo graft irradiation with either 1000 or 500 rad also resulted in normal weight gain, graft function, and host survival for the 6-week study period. Conversely, delay of graft irradiation until 3 days after transplantation failed to prevent this complication (MST = 15.8 +/- 3.7 days). Recipients of irradiated grafts displayed glucose tolerance tests that were identical to those in the control group indicating that the doses of radiation employed in these experiments were not deleterious to islet function. Irradiated spleen grafts appeared histologically normal at 6 weeks after transplantation. Cells derived from these grafts failed to stimulate lymph node enlargement in a popliteal lymph node assay for GVHD, suggesting that these spleens may have become repopulated with host cells. These experiments confirm that PST has the potential to cause lethal GVHD and suggest that pretransplant graft irradiation may be used to prevent its occurrence.
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PMID:Graft irradiation abrogates graft-versus-host disease in combined pancreas-spleen transplantation. 351 91

A minor (non-H-2) graft-vs.-host reaction (GVHR) was induced in adult irradiated (DBA/2 X B10.D2)F1 mice by hematopoietic parental B10.D2 cell grafts. Syngeneic (F1) cell transplantation was performed as control. In one set of experiments T4 plasma level (enzyme linked immunosorbent assay) was systematically followed up in individual GVHR and control mice. Compared to the control, GVHR triggered off a significant and sustained decrease of T4 plasma level. In another set of experiments, TSH plasma levels (RIA) were measured in killed animals. GVHR induced an early elevation of plasma TSH. In a third set of experiments, mice undergoing GVHR received daily injections of L-T4 (0.03, 0.15, or 0.3 microgram/mouse). Compared to the control (saline injected) GVHR mice, T4 supply did not improve GVHR state. No positive effect of the high dose and rather a negative effect of both lower doses especially on glucose plasma concentration, were observed. All these data suggest that thyroid gland is primarily and very early involved in the onset of the GVH disease.
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PMID:Endocrine involvement in minor (non-H-2) graft-versus-host reaction in mice. Early and primary thyroid failure. 356 37

Inbred strains of rats were used to analyze unidirectional host-versus-graft disease (transplant rejection) without graft-versus-host disease in small intestinal transplants and the immunosuppressive properties of cyclosporine (CsA). Forty-six Lewis rats received heterotopic transplants of the entire small bowel in four groups: Lewis-to-Lewis isografts, without CsA; Lewis-to-Lewis isografts, with CsA (15 mg/kg/day); (Lewis X ACI)F1-to-Lewis allografts, without CsA; (Lewis X ACI)F1-to-Lewis allografts, with CsA. Small bowel rejection was associated with gross morphological changes that preceded all other findings. A histologic scoring system assessed the degree of transplant rejection. A characteristic transient weight loss was seen in animals rejecting their bowels. Glucose absorption was impaired and polyethylene glycol absorption increased during rejection. Cyclosporine inhibited all of these changes in allografted rats. It is concluded that daily administration of cyclosporine is effective in preventing the morphologic and functional changes of acute transplant rejection in intestinal allografts and does not change these parameters in transplants that are not rejecting.
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PMID:Transplantation of the entire small bowel in inbred rats using cyclosporine. 357 68

Granulocyte transfusions have been complicated by graft-versus-host disease (GVHD) in the recipients. This risk can be eliminated by irradiation of the cell product. The effect of in vitro irradiation on elements of lymphocyte and granulocyte function was therefore studied in order to determine the dose of irradiation which blocked lymphocyte function without affecting the function of granulocytes. Lymphocyte blast transformation after stimulation with mitogens was reduced by 90% after irradiation with 1500 rad and by 97% after 5 000 rad. The response to microbial agents and allogeneic cells was far more radio-sensitive, being completely abolished after irradiation with 1 000 and 500 rad, respectively. Mobility was the function of polymorphonuclear leucocytes (PMN) most affected by irradiation, being slightly but significantly reduced after irradiation with 10 000-20 000 rad. The bactericidal activity was reduced only after irradiation with 40 000 rad or more, while the hexose monophosphate shunt activity and the myeloperoxidase activity were largely unaffected by irradiation with doses of up to 120 000 rad. Hence the results indicate that the irradiation of leucocytes intended for transfusion with a dose of 2 000 rad is likely to prevent GVHD without causing any apparent damage to the PMN.
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PMID:Effect of in vitro X-irradiation on lymphocyte and granulocyte function. 646 Oct 60

Irradiation of blood components eliminates the risk of transfusion-associated graft-versus-host disease. Freezing directed or rare red cell units that are irradiated but not transfused would facilitate inventory management and would increase the transfusion options for the involved patients. However, no studies have been performed to evaluate whether prestorage irradiation damages subsequently frozen red cells. Ten normal volunteers donated a unit of whole blood on two separate occasions. One unit was irradiated with 15 Gy (1500 rad), stored at 4 degrees C for 6 days, and then frozen and stored at -75 degrees C for 56 days. The other unit (control) was similarly stored but was not irradiated. Aliquots of the units were tested on Day 0 and Day 6 and, after deglycerolization, on Day 62. Comparison of means and changes in means showed no significant differences in red cell ATP, 2,3 DPG, or supernatant hemoglobin and glucose in control and irradiated units. The difference in the change in supernatant potassium from Day 0 to Day 6 in control and irradiated units was significant (1.5 to 28.6 mmol/L vs. 1.5 to 48.5 mmol/L: p < 0.0001). Irradiation did not cause significant differences in postdeglycerolization red cell recovery (control, 84.5% vs. irradiated, 81.2%) or in 24-hour posttransfusion autologous red cell survival (control, 91.1% vs. irradiated, 90.9%). Red cells can be irradiated, stored at 4 degrees C for 6 days, and subsequently frozen with no increase in detectable damage as compared to controls that were not irradiated.
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PMID:Characteristics of red cells irradiated and subsequently frozen for long-term storage. 848 41

Type I diabetes is a systemic autoimmune disease. Although transplantation of pancreatic tissues restores glucose homeostasis, grafts are affected by acute and chronic rejection as well as re-occurrence of autoimmune destruction. One newly recognized promising strategy to interrupt these detrimental processes is hematopoietic chimerism induced by bone marrow transplantation (BMT). The application of hematopoietic chimerism has three domains in the treatment of Type I diabetes mellitus: (1) tolerance induction to pancreas or pancreatic islet grafts; (2) prevention of the re-occurrence of autoimmune processes in the graft; (3) prevention of the onset of overt diabetes once the pre-diabetic state is clearly identified. Unfortunately, conventional BMT is associated with significant morbidity and mortality due to graft-versus-host disease (GVHD), failure of engraftment and lethal conditioning. The risk of these complications cannot be justified in the treatment of non-malignant diseases including Type I diabetes. This chapter will outline potential strategies to achieve hematopoietic chimerism without the risk of deadly complications. With these strategies, it may be possible to apply hematopoietic chimerism in the treatment of Type I diabetes, both to induce tolerance to islet allografts as well as to intervene and interrupt the autoimmune process in its early stages.
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PMID:Tolerance induction for islet transplantation. 986 69


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