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)

Delayed erythroid recovery is common after bone marrow transplantation (BMT), with some patients continuing to require red blood cell (RBC) transfusion support for as long as 1 year. While the etiology is multifactorial, inadequate stimulation of erythroid progenitors by the erythroid growth factor, erythropoietin, may play a role. In this study, the erythropoietin response to anemia of 70 consecutive patients undergoing BMT at the Johns Hopkins Oncology Center was compared with the erythropoietin response in uncomplicated iron deficiency anemia. Erythropoietin levels were elevated for the degree of anemia early after BMT; however, at the time of marrow recovery, erythropoietin levels were significantly suppressed in both allogeneic and autologous BMT patients compared with the iron-deficient patients. Patients with acute graft-versus-host disease (GVHD) had a more marked suppression of the erythropoietin response to anemia. In the patients who remained anemic for extended periods of time (up to 12 months after BMT), an inadequate erythropoietin response to anemia persisted. Delayed erythroid recovery after BMT is associated with inadequate erythropoietin levels. Therefore, recombinant human erythropoietin may be useful in the treatment of the anemia associated with both autologous and allogeneic BMT.
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PMID:Impaired erythropoietin response to anemia after bone marrow transplantation. 142 81

Prophylactic irradiation of blood and blood components is accepted practice in order to prevent graft-versus-host disease from infused lymphocytes. Irradiation, however, results in increased red cell potassium (K+) loss, along with other possible effects that may affect red cell function and viability. Lipid peroxidation (LP), a process initiated by the production of oxygen free radicals, is increased in red cells in the presence of reactive iron species and various heme moieties. In this report, it is noted that not only is plasma K+ significantly increased following blood irradiation, but LP is also increased compared with paired non-irradiated blood samples. Furthermore, various metal chelators significantly reduce LP in the irradiated samples. These chelators also significantly reduced the rate of cellular K+ loss during the four day 37 degrees C incubation period. This study further suggests that the addition of selected metal chelators may be effective in both irradiated and non-irradiated stored blood by improving the function and viability of transfused erythrocytes.
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PMID:The effect of metal chelators on lipid peroxidation in irradiated erythrocytes. 145 32

The effect of human iron-saturated transferrin (siderophilin) on the engraftment of H-2-incompatible bone marrow and on the induction of durable allogeneic, hemopoietic chimerism was investigated in BALB/c mice grafted with bone marrow from C57BL/6 donors, and in C57BL/6 mice grafted with bone marrow from C3H/He donors. Administration of transferrin to mice after irradiation and marrow transplantation resulted in considerable protection, yielding permanent allogeneic chimerism in BALB/c mice. No effect was observed in the C57BL/6 mice in which transplantation of bone marrow from C3H/He donors provided a high survival rate even without any further treatment. Serum levels of transferrin were remarkably constant in these mice and no significant differences were seen in the circadian cycle, after lethal irradiation and at different times after marrow transfer. A modest rise of transferrin occurred only in the course of chronic graft-versus-host disease. It thus seems that the promoting effects of transferrin [Pierpaoli et al: Cell Immunol 1991; 134:225-234] depend on the murine, histoincompatible H-2 combination utilized and is not attributable to quantitative changes of transferrin levels after marrow transplantation. The utilization of more specific activity of the transferrin is thus feasible.
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PMID:Effect of human transferrin on the engraftment of allogeneic bone marrow in various strans of lethally irradiated mice. 147 97

Cell-free supernatants of rabbit bone marrow were fractionated, separated, and purified by Ultrogel and Superose chromatography. A single fraction promoted engraftment of allogeneic bone marrow and enduring hemopoietic chimerism across the H-2 barrier in lethally irradiated mice. This "bio-active" fraction, analyzed by reducing SDS-PAGE electrophoresis, and transblotted on PVDF membrane, and purified by reverse-phase HPLC and SDS-PAGE electrophoresis yielded a main prealbumin band that when examined for primary structure by Edman degradation, proved to be rabbit transferrin. This was also attested by highly specific precipitation of the prealbumin band with polyclonal antibodies to rabbit transferrin. Iron-saturated human transferrin, lactotransferrin, and egg transferrin (conalbumin) were assayed in irradiated C57BL/6 mice infused with bone marrow from histoincompatible BALB/c donors. Mice treated with iron-loaded transferrins survive and develop enduring allogeneic chimerism with no discernible signs of graft-versus-host disease. Iron carrier proteins thus provide an unique means of achieving successful engraftment of allogeneic bone marrow in immunologically hostile murine H-2 combinations.
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PMID:Iron carrier proteins facilitate engraftment of allogeneic bone marrow and enduring hemopoietic chimerism in the lethally irradiated host. 201 4

Rabbit bone marrow supernatants were fractionated and purified by Ultrogel and Superose chromatography. A unique fraction promoted engraftment of allogenic bone marrow and enduring hemopoietic chimerism across the histocompatibility (H-2) barrier in lethally irradiated mice. This fraction analysed by reducing SDS-PAGE electrophoresis and transblotted on PVDF membrane or purified by reverse-phase HPLC and SDS-PAGE electrophoresis yielded a main pre-albumin band that was examined for primary structure by Edman degradation. It appeared to be rabbit transferrin. Iron saturated human transferrin, lactotransferrin and egg transferrin (conalbumin) were then tested in irradiated C57B1/6 mice transplanted with bone marrow from histoincompatible BALB/CJ donors. Most mice treated with iron-loaded transferrins survived and developed enduring allogeneic chimerism with no discernible signs of graft-versus-host disease at 10 months posttransplant. Observation of these animals is still carried on. Iron carrier proteins seem to provide a novel unexpected means for achieving a successful engraftment of allogeneic bone marrow in immunologically hostile murine H-2 combinations and may open a new approach in the clinical area.
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PMID:[The effect of iron carrier proteins on the transplantation of H-2 locus-incompatible bone marrow in irradiated mice]. 225 17

The present studies dealt with the pathogenesis of renal involvement in murine chronic graft-versus-host disease, which is a model for human systemic lupus erythematosus. The disease was induced in (C57BL10xDBA/2)F1 hybrids by injection of DBA/2 lymphocytes. The animals developed systemic disease accompanied by deposition of autoantibodies in the glomeruli and a lupus type of nephritis. Antibodies were eluted from glomeruli isolated during various stages of the disease by magnetic extraction from iron-perfused kidneys. For assessment of the specificity of the antibodies, we used indirect immunofluorescence, an enzyme-linked immunosorbent assay, and immunoblotting. In glomeruli from week 4, autoantibodies were found to be directed against several antigens, among which were the glomerular basement membrane component laminin and the glomerular enzyme dipeptidyl peptidase IV, whereas week 8 glomeruli also showed antibodies directed against nuclear antigens. Both laminin and dipeptidyl peptidase IV are known nephritogenic antigens occurring in renal tubular epithelial brush border preparations. Antibodies eluted from isolated glomeruli of diseased animals bound in a granular pattern along the glomerular capillary wall after in vivo transfer. Anti-renal tubular epithelial antibodies in the sera of diseased animals were affinity purified and injected into naive mice, which induced immune complex glomerulonephritis and proteinuria, thus confirming the nephritogenic role of these autoantibodies in this model.
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PMID:Characterization and in vivo transfer of nephritogenic autoantibodies directed against dipeptidyl peptidase IV and laminin in experimental lupus nephritis. 239 30

Resting PEC and fractions of spleen cells adherent to nylon wool (NASC) or polystyrene (PASC) from A/Ph mice evoke a weak regional GVHR or no systemic GVHR in (B10 X A/Ph)F1 hybrids. Blockage of macrophages in vivo by silica or silica gels or removal in vitro of cells phagocytosing iron particles did not change GVH reactivity of A/Ph spleen cells. Addition of PEC or NASC from A/Ph mice to the A/Ph spleen cell suspension somewhat suppressed regional GVHR but enhanced systemic GVHR. Addition of PASC from A/Ph mice, conversely, enhanced regional GVHR and suppressed systemic GVHR. Repeated administration of silica and silica gel to the recipients suppressed regional GVHR; a single dose of silica was most effective at suppression when given one day before the cells. Systemic GVHR was not influenced by this treatment of the recipients. The results indicate that macrophages do not directly induce a GVHR, but they serve as important targets in regional GVHR. In regional and systemic GVHR macrophages perform regulatory functions. Macrophages of donor origin may modify both types of GVHR significantly, depending on the source and type of macrophages and the treatment of donors.
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PMID:A study of the role of macrophages in the graft-versus-host reaction. 298 74

Seven patients with acute leukemia were treated by allogenic bone marrow transplantation from HLA matched sibling. The conditioning regimen was classical using cyclophosphamide and Total Body Irradiation, followed by methotrexate. All patients were given ketoconazole (400 mg per day in a single dose) as antifungal prophylaxis for 6 months. Serum ketoconazole levels were measured using the inhibition assay of mycotic culture in gelose, and they were studied at 0, 1, 2, 4 and 6 h after ketoconazole ingestion, and repeated serially after bone marrow transplantation. In these transplanted patients, absorption of ketoconazole could be delayed, with the maximum levels at 4 h or 6 h after ingestion. Most measurements showed appropriate levels (maximum levels greater than 1 mg/l) even after the third week post transplantation. With the exception of severe acute GVH disease (1 patient), the ketoconazole absorption was adequate in minor or mild GVH disease (6 patients) and in chronic GVH disease (2 patients). In four patients ketoconazole absorption was compared with gut absorption tests (Schilling's test, Iron absorption test, xylose test): In all patients the maximum serum levels of ketoconazole were correct, even in three patients with abnormal gut absorption tests. In this series, no life-threatening mycotic infection occurred, and the three deaths observed showed no mycotic infection.
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PMID:Serum levels of ketoconazole in bone marrow transplanted patients. 631 9

Patients who require a bone marrow transplant (BMT) for leukaemia, lymphoma or other haematological disorders receive large quantities of blood products, including red cell concentrates, during the transplant period. Many receive red cell transfusions as part of treatment prior to BMT, adding to the potential iron load. However, organ dysfunction as a consequence of the transfused iron load would be surprising given the amounts of iron transfused. We studied 76 survivors of allogeneic and autologous BMT who were at least 1 year post-transplant and found that the majority (88%) had raised ferritins. Impaired liver function was common in these patients and in half was unexplained by viral hepatitis, veno-occlusive disease or graft-versus-host disease (GVHD), suggesting that iron overload may be an important contributing factor to liver disease in the stable post-transplant setting. This view is supported by the observation of improving liver function tests in 10 patients after a trial of venesection therapy.
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PMID:Iron overload and liver dysfunction after allogeneic or autologous bone marrow transplantation. 867 57

Severe aplastic anemia (SAA) is a disease associated with high mortality. For young patients with HLA identical siblings, allogeneic bone marrow transplantation (BMT) offers the best chance of cure. Favourable results have also been reported using immunosuppressive therapy (IST). Transplantation is usually favoured for patients below 45 years of age. We report our experience of 11 allogeneic and one syngeneic BMT for adult Chinese patients with SAA, over a 4-year period from 1991 to 1995. Ten of the 12 (83 per cent) patients had received and failed prior IST including anti-thymocyte globulin (ATG) before being referred for BMT. Neutrophil and platelet engraftment was successful in 11 of them (92 per cent) and nine were completely transfusion independent after transplantation. Their overall 3-year survival was 67 per cent. The compromised overall result was due to a number of cases transplanted after a long time delay. No patient transplanted beyond 3 years from the initial time of diagnosis of SAA achieved long-term marrow engraftment, and they all eventually succumbed. On univariate analysis, a longer time delay and hence a larger amount of blood products exposure, were highly significantly statistically associated with inferior marrow engraftment and patient survival. Other factors including age, iron status, infused cell dose and the conditioning protocol were not found to significantly affect engraftment and survival. Graft versus host disease was clinically mild or absent in most patients. This may be related to ethnicity or previous ATG exposure. In conclusion, early allogeneic BMT was a safe and effective treatment in our small series of patients with SAA failing IST.
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PMID:Allogeneic bone marrow transplantation for severe aplastic anemia: the Hong Kong scenario. 1006 11


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