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 survival of dogs exposed to fission neutron irradiation, a component in the radiation dose of reactor accidents, was improved by the administration of DLA-identical allogeneic bone marrow but not by the administration of DLA-mismatched allogeneic bone marrow. The level of survival observed at 2.55 Gy was similar to that observed after autologous bone marrow transplantation. The transplanted allogeneic bone marrow, however, survived for only 2-3 weeks, but provided enough mature peripheral blood cells during this time to endure the initial radiation insult. Subsequent recovery of autologous bone marrow led to the ultimate survival of the dogs. Additional radiation protocols were evaluated in order to obtain permanent engraftment of the donor marrow cells. A higher neutron dose or a second radiation of 6.0 Gy gamma rays led to severe damage of the gastrointestinal tract and an early death. A third regimen, a second radiation dose of 4.0 Gy of gamma rays, led to permanent engraftment in one dog but its survival was complicated by graft-versus-host disease.
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PMID:Improved survival of dogs exposed to fission neutron irradiation and transplanted with DLA identical bone marrow. 333 85

In vitro treatment of bone marrow grafts with absorbed rabbit-antidog thymocyte globulin (ATG) prevented graft-versus-host disease in a substantial number of the dogs differing by one DLA haplotype. Absorbed ATG has now been used for serological identification of canine lymphocyte populations. Specific labeling of canine T-lymphocytes by absorbed ATG could be demonstrated by (a) a distribution of ATG-positive cells in suspensions of canine lymphoid organs similar to that of T cells observed in other species and by specific staining of paracortical thymus-dependent lymph node areas in immunohistochemistry, (b) complementary labeling of nylon-wool-separated cells by ATG and antiimmunoglobulin sera, and (c) correlation of ATG surface labeling with responder activities in mixed lymphocyte cultures.
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PMID:Serological identification and separation of canine lymphocyte subpopulations. 621 Feb 5

We examined the effect of methotrexate (MTX) combined with cyclosporine (CSP) on the prevention of graft-versus-host disease (GVHD) in dogs. Ten recipients were prepared for grafting with 9 Gy of total-body irradiation and given marrow and buffy coat cells from littermate donors differing for one DLA haplotype (AA leads to AB or AB leads to AC). MTX (0.4 mg/kg) was given i.v. on days 1, 3, 6, and 11. CSP was given i.m. on days 0 to 7 and orally on days 8 to 100. The dose was 15 mg/kg/day on days 0 to 25, 10 mg/kg/day on days 26 to 50, 5 mg/kg/day on days 51 to 75, and 5 mg/kg every other day on days 75 to 100. All ten dogs had sustained engraftment. Three dogs died, one with pneumonia (day 57), one with pneumonia and GVHD (day 107), and one with convulsions (day 204). Seven dogs are surviving at 210 to 493 days, and all are complete chimeras; five are well and two have chronic GVHD that developed after immunosuppressive treatment had been stopped. These results with a combination of MTX and CSP as GVHD prophylaxis are superior to those obtained previously with MTX alone in dogs given marrow grafts from DLA-haploidentical littermates.
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PMID:Combined immunosuppression with cyclosporine and methotrexate in dogs given bone marrow grafts from DLA-haploidentical littermates. 636 90

We examined the effect of methotrexate (MTX) and cyclosporin A (Cy A) on engraftment, graft-versus-host disease (GVHD), and the induction of tolerance in dogs prepared for marrow transplantation by 9 Gy of total body irradiation and grafted with bone marrow and buffy coat cells. Nineteen dogs were given grafts from DLA-identical littermates followed by immunosuppression with Cy A for 25 or 100 days. All had sustained engraftment, and 12 became healthy long-term chimeras. Sixty dogs were given grafts from DLA-nonidentical unrelated donors. Among nine given MTX only postgrafting, one rejected the graft nd eight died with GVHD. Among 18 dogs given Cy A only postgrafting, eight failed to achieve engraftment, seven died of various causes, and three died with GVHD. Thirty-four dogs were given both MTX and Cy A in various regimens postgrafting. The only long-term survivors were 4 of 10 dogs given MTX on days 1, 3, 6, and 11 and Cy A from days 0 through 100. Two have chronic GVHD. We conclude that Cy A can induce graft-host tolerance across minor, but not major, histocompatibility differences. The combination of MTX early after transplantation with Cy A prevents failure of engraftment of histoincompatible marrow and some recipients become long-term survivors.
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PMID:Cyclosporin A and methotrexate in canine marrow transplantation: engraftment, graft-versus-host disease, and induction of intolerance. 675 Aug 77

Our studies have provided further data to support the concept of resistance to engraftment in the dog. Resistance seems to be mediated by antigens coded for by loci different from but linked to DLA. Resistance can be abrogated by the addition of viable lymphoid cells to the marrow inoculum, by high-dose (fractionated) TBI of the recipient and by MTX given postgrafting. CyA has an adverse effect on engraftment probably by interfering with the graft-facilitating effect of donor lymphocytes. GVHD following allogeneic marrow transplantation appears to be mediated by DLA and non-DLA antigens. GVHD can be prevented or ameliorated in recipients of DLA identical littermate marrow by postgrafting CyA or MTX. With DLA nonidentical or unrelated grafts MTX or even more so a combination of MTX and CyA appear to be able to induce tolerance in some recipients.
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PMID:Marrow graft studies in dogs: factors influencing resistance to engraftment and graft-versus-host disease. 676 39

We recognized two distinct clinical and histologic syndromes of acute and chronic graft-versus-host disease (GVHD) in irradiation chimeric dogs given hemopoietic grafts from DLA-nonidentical littermate donors. Clinically acute GVHD developed, with a median onset of 13 days after the transplant, and was characterized by skin erythema, jaundice, diarrhea, and gram-negative infections; the median survival of these dogs was 29.5 days. Chronic GVHD developed a median of 124 days after the transplant and was characterized by generalized skin ulcerations, massive ascites, and gram-positive infections; the median survival of these dogs was 150 days. Chronic GVHD could be distinguished histologically from acute GVHD by epidermal atrophy and dermal fibrosis and by bile duct proliferation, bridging, piecemeal necrosis, and portal fibrosis in the liver. Questions related to GVHD in man can be investigated in this model of acute and chronic GVHD in a large outbred species.
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PMID:Acute and chronic graft-versus-host disease in dogs given hemopoietic grafts from DLA-nonidentical littermates. Two distinct syndromes. 676 33

Bone marrow transplants with low marrow cell doses (less than or equal to 4 x 10(8) cells/kg) from unrelated donors were carried out in 16 dogs conditioned with 9 Gy (900 rad) of total body irradiation. No immunosuppression was given after grafting. Eleven donor-recipient pairs were phenotypically identical (group 1) for the known antigens of the canine major histocompatibility complex (DLA) and in five the donor was homozygous and the recipient heterozygous for DLA (group 2), as determined by serological histocompatibility typing and mixed leukocyte cultures including homozygous cell typing. In addition, lymphocytes from donors and recipients in group 1 were mutually nonreactive in cell-mediated lympholysis; lymphocytes from recipients in group 2 were not cytotoxic against donor cells. Eight dogs rejected their grafts and eight showed sustained engraftment; of these, four died from graft-versus-host disease. The incidence of rejection was higher than in DLA-identical littermates but lower than in DLA-nonidentical unrelated or littermate dogs. These results indicate that antigens different from the recognized alleles at DLA are involved in the control of engraftment. These antigens most likely represent the expression of unrecognized differences within DLA or are coded for by a locus different from but linked to DLA-A, B, C or D; they are not recognized in the cell-mediated lympholysis assay.
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PMID:Marrow grafts between phenotypically DLA-identical and haploidentical unrelated dogs: additional antigens controlling engraftment are not detected by cell-mediated lympholysis. 703 18

Procedures for total and selective gastrointestinal decontamination of dogs are described. The selective procedure removed only Gram negative aerobic bacteria, yeast and fungi. Dogs receiving total decontamination were less susceptible to the GI syndrome following total body irradiation (TBI) than dogs receiving conventional care. After TBI and allogeneic bone marrow transplantation, serum albumin levels decreased in conventional animals, but remained normal in totally or selectively decontaminated animals. Exogenous infections occurred frequently in both irradiated, and totally decontaminated animals, but were absent in selectively decontaminated animals. Endogenous infections after total body irradiation were prevented only by total decontamination. Endogenous infections occurred in selectively decontaminated animals, but with milder clinical symptoms than in conventional animals. Appearance of donor type leukocytes and serum gamma globulin was slower in decontaminated animals than in conventionally treated controls. Acute graft versus host disease caused by a limited number of lymphocytes of a DLA identical littermate donor were prevented by selective gastrointestinal decontamination. Complications due to late immune reconstitution obscured the effect of decontamination on delayed graft versus host disease.
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PMID:Gastrointestinal decontamination of dogs treated with total body irradiation and bone marrow transplantation. 704 95

Marrow transplants were carried out between unrelated DLA-nonidentical dogs. Recipients were conditioned for transplantation by total body irradiation (TBI) given eigher as a single dose of 9 Gy (900 rad) or fractionated in three increments of 6 Gy (600 rad) each at intervals of 48 hr. All recipients received marrow, less than or equal to 4 x 10(8) cells/kg, and no buffy coat cells. No immunosuppression was given after grafting. All 10 dogs given single dose total body irradiation failed to show engraftment and died with marrow aplasia and infectious complications (median survival 12 days). In contrast, all 10 dogs given fractionated TBI had sustained engraftment and died with graft-versus-host disease (GVHD) and infectious complications (median survival 12.5 days). None of the dogs died from radiation-induced gastroenteritis. In conclusion, resistance to DLA-nonidentical unrelated marrow grafts can be abrogated by high-dose TBI. This technique may allow hemopoietic engraftment even after i vitro manipulation of the marrow such as lymphocyte depletion by cell separation or treatment with anti-T cell antisera.
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PMID:Engraftment of DLA-nonidentical unrelated canine marrow after high-dose fractionated total body irradiation. 704 71

Previous studies found that marrow allografts from DLA-identical littermates resulted in survival of 60% of recipient dogs after an otherwise lethal dose of 450 cGy of total body irradiation (TBI), either because of successful allografts or autologous recovery after rejection of the allografts. Forty percent of dogs died with marrow aplasia after allograft rejection. The current study asked whether allogeneic engraftment could be enhanced and survival improved by treating allograft recipients with high doses of corticosteroids or with cyclosporine (CSP), administered either before or after transplantation. Five dogs in group 1 received corticosteroids beginning on day -5 and ending on day 32 after transplant. The starting dose was 12.5 mg of prednisone per kilogram orally twice daily. All five dogs rejected their allografts; three died early with marrow aplasia and two showed endogenous marrow recovery. Nine dogs received CSP from day -6 to day -1 before transplantation at a dose of 20 mg/kg/d intravenously administered in divided doses. All nine dogs rejected the marrow allograft; six died with marrow aplasia and three survived with endogenous marrow recovery. Seven dogs received CSP after transplantation at a dose of 30 mg/kg/d orally from day -1 to day 35. All seven had sustained allografts (two mixed chimeras and five complete donor-type chimeras) and became healthy long-term survivors without graft-versus-host disease. These results extend previous observations and confirm that grafts of marrow from DLA-identical littermates improved survival of dogs exposed to low but otherwise lethal doses of TBI. Additional therapy with high-dose corticosteroids administered peritransplantation and posttransplantation or CSP administered before transplantation neither enhanced the rate of allogeneic engraftment nor improved survival; however, CSP administered after transplantation resulted in successful allografts and event-free survival in all cases.
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PMID:DLA-identical bone marrow grafts after low-dose total body irradiation: effects of high-dose corticosteroids and cyclosporine on engraftment. 749 99


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