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)

Bacterial infection is a common complication after allogeneic bone marrow transplantation. It is related to the toxic effects of the conditioning regimen on mucosal surfaces, to bone marrow aplasia and to the prolonged lymphopenia with immune deficiency that lasts for several weeks after bone marrow transplantation. We have performed a prospective randomized study comparing two methods of prophylaxis. Group I (OA) received a combination of ofloxacin 400 mg/day and amoxicillin 20 g/day; group II (VTC) received the oral nonabsorbable antibiotics vancomycin 450 mg/day, tobramycin 450 mg/day and colistin 4.5.10(6) units daily, from day -15 to 15 days after discharge from laminar air flow (LAF) rooms. All patients were nursed in LAF rooms with a strict isolation procedure and sterile water and food. They were evaluated daily for clinical symptoms, and bacterial culture samples were taken from the throat, stools and blood twice weekly. Forty-four patients were randomized, 22 entered in group I (OA) and 22 in group II (VTC). There were no differences between the two groups in age (mean 33 years, range 11-54), sex, diagnosis and mean duration of agranulocytosis (21.8 days, range 10-49). Seven patients were excluded because of the selection of a resistant bacteria, 5 were in group I (OA), and 2 were in group II (VTC). The mean duration of fever was 9.2 +/- 7.1 days in group I (OA) and 13.7 +/- 6.8 days in group II (VTC; p = 0.05). There were no significant differences between the two groups in graft-versus-host disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prophylaxis of bacterial infections after bone marrow transplantation. A randomized prospective study comparing oral broad-spectrum nonabsorbable antibiotics (vancomycin-tobramycin-colistin) to absorbable antibiotics (ofloxacin-amoxicillin). 204 63

The immune deficiency induced by HIV has its origin in the interaction of the outer envelope glycoprotein gp120/gp41 with receptors present on human immunocytes. Virus binding to cells, virus entry and subsequent compartmentalization resulting in productive infection depends on the interaction of gp120/gp41 with CD4 and other accessory molecules. Gp120 and HIV are markedly immunosuppressive of T-cell responses and, in addition, HIV can functionally delete antigen responsiveness of T cells. Abolition of CD4 binding, by denaturation of gp120, allows study of T-cell epitopes in gp120 and shows the denatured molecule is highly immunogenic even in naive subjects (F. Manca, unpublished). The gp120-binding site of CD4 is shared with MHC class II molecules and the reaction of antibodies within this region of CD4 induces conformational changes that may be significant for virus entry into cells or for syncytial formation. The HIV envelope contains sites of sequence homology with monomorphic human MHC class II sites that do not appear to be naturally immunogenic in humans. In addition to the properties of gp120, it is hypothesized that HIV envelope may also represent an 'alloepitope' of class II to the human T-cell repertoire, and is therefore able to induce a chronic allogeneic response not dissimilar to experimentally induced GVHD. These features are of potential importance both for primary vaccination against HIV, and for the long-term treatment of HIV seropositive patients. Induction of effective T-cell responses to gp120 require use of a denatured or otherwise modified product lacking CD4-binding capacity. The potential distortion of the TCR repertoire by the class-II-homologous and CD4-interactive sequences must be assessed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:AIDS pathogenesis: HIV envelope and its interaction with cell proteins. 187 30

Injection of parental C57BL/10 spleen cells into unirradiated immune-competent (B10 x B10.BR)F1 hosts has been demonstrated to produce a graft-vs.-host-induced immune deficiency in T cell-mediated functions, including mitogen or alloantigen stimulated proliferation or cytotoxic T cell generation. The production of T cell-derived lymphokines affecting hematopoiesis was also altered during GVH. During the first two weeks of GVH, IL-3 and particularly GM-CSF were produced spontaneously; in subsequent weeks, the spontaneous production dropped to normal or subnormal levels. CSF content in concanavalin A-stimulated splenic supernatants was reduced at weeks 1-2, and declined to less than 5% of normal levels by 3-4 weeks of GVH. This decline in CSF content was correlated with a decrease in immune function as assessed by concanavalin A-stimulated IL-2 production and by generation of cytotoxic T lymphocytes. Concurrent with the recovery of immune function during GVH weeks 8-15, mitogen-stimulated production of CSF returned to normal levels. In addition to the decrease in CSF production identified in acute suppressive GVH, CSF content in concanavalin A-stimulated splenic supernatants was also decreased in chronic stimulatory GVH, generated in the strain combination (B6 x B6bm1)F1----(B6bm1 x B6bm12)F1. This decrease in CSF production correlated with a decrease in self-restricted T helper cell function. Finally, a decrease in both immune function and CSF production capacity was observed in the acute GVH following allogeneic (minor histocompatibility loci) bone marrow transplantation into irradiated hosts.
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PMID:Alterations in T cell-derived colony-stimulating factors associated with GVH-induced immune deficiency. 218 11

We review the first 100 patients receiving a bone marrow transplant as definitive therapy for their underlying disease. These patients were treated between May 1975 and June 1988. Median age was 8 years (range, 1 month to 43 years). Initially, patients were given transplants late in their disease but, as the programme progressed, patients were given transplants earlier and while in remission from their disease. The types of disease considered for treatment by bone marrow transplantation (BMT) expanded from leukaemia, and aplastic anaemia to include neuroblastoma, thalassaemia and immune deficiency. Initially matched donors were used but the source of marrow broadened to include mismatched family members, matched unrelated donors and autologous marrow. Problems after BMT were rejection (11%), acute graft-versus-host disease (GVHD) (45%), interstitial pneumonitis (22%) and relapse (36%). Recurrence of disease was the cause of half the deaths. GVHD was less frequent with the use of methotrexate and cyclosporin, T-cell depleted marrow or matched donors. Interstitial pneumonitis was more commonly associated with the use of mismatched donors and the development of GHVD. Relapse was less likely when BMT was undertaken in the first remission. At least one long-term side effect was seen in all patients treated with total body irradiation whereas no patient treated without irradiation had long-term side effects. The rate of disease free survival of patients at 24 months was 56% for matched, 48% for closely matched, 46% for autologous and 29% for mismatched transplants. For matched transplants mortality within the first 6 months after transplantation decreased from 28% before 1984 to 5% since 1984. Fifty-one patients have survived to June 1989, 49 of them disease free, for periods ranging from 12 to 123 months (median 29 months).
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PMID:Bone marrow transplantation: a review of a programme and its first 100 patients. 223 31

Utilization of bone marrow transplantation as a therapeutic modality continues to increase. More and more institutions are initiating bone marrow transplant programs. During the 33-year period between 1955 and 1987, more than 20,000 patients received allogeneic bone marrow transplants; more than 50% of these were performed in the 3 years, 1985-1987. Transplantation is an effective therapy for acute leukemia; in some instances it is the preferred treatment. In chronic myelogenous leukemia, severe aplastic anemia, and some genetic and immune deficiency diseases, bone marrow transplantation provides the only possibility for cure. Bone marrow transplantation is associated with serious problems such as graft-versus-host disease (GvHD), graft failure, interstitial pneumonitis and, until recently, the requirement for an HLA-identical sibling donor. In the past few years, an increasing number of transplants have been performed using HLA-partially matched related or unrelated donors with some success, the level of which is yet to be determined. The development of acute GvHD (8) and interstitial pneumonitis (9, 10) can often be predicted by risk factor assessment. Special precautions can then be taken for patients at high risk of these complications. In this report, current data from the International Bone Marrow Transplant Registry were summarized and several risk factors affecting outcome were identified.
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PMID:Current status of bone marrow transplantation. 248 30

Injection of B10.D2 cells into irradiated H-2d compatible (DBA/2xB10.D2)F1 recipients provokes a lethal GVH that can be abrogated by donor preimmunization against host-specific DBA/2 non-H-2 antigens. To study the possible relationship between the observed protection and restoration of immune responsiveness, we compared spleen cellularity, selected T and B cell functions, and NK activity in GVH and protected mice during the 1st month after grafting. Normal and isografted mice served as controls. GVH was found to be characterized by an early stimulation phase associated with splenomegaly and increased percentages (but not numbers) of Lyt-2+ and L3T4+ cells, followed by profound aplasia and abrogation of IL-2 production. Response to a B cell mitogen (LPS) is depressed, and cells from GVH mice exert a strong suppressive effect on the LPS and PHA responsiveness of normal cells. Suppression appears to be mediated by a radioresistant, nylon nonadherent, asialo GM1 negative cell expressing a low level of Thy-1 antigen. In contrast, protection correlates with progressive restoration of spleen cellularity and LPS responsiveness, with decreased but clearly detectable IL-2 production, and transient nonspecific suppressor activity. The immune status of protected mice resembles that of isografted controls. No correlation was found between mortality (or protection) and either PHA responsiveness, which remained depressed in all grafted mice throughout the observation period, or NK activity, which was strongly depressed in both GVH and protected mice. In conclusion, protection correlates with the disappearance of nonspecific suppressor cells and the restoration of cellularity and certain nonspecific immune functions. Donor immunization against host-specific non-H-2 antigens, which protects against mortality, also protects against GVH-associated immune deficiency.
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PMID:Lethal graft-versus-host reaction against non-H-2 antigens. I. Prevention of GVH-associated immunodeficiency by preimmunizing the donor against host-specific non-H-2 antigens. 252 8

In the present study, we tested the possibility that a vascularized allograft might induce immunological tolerance in a myeloablated host, similar to the tolerance induced by allogeneic bone marrow grafts. To this end, we developed a rhesus monkey model consisting of myeloablative total-body irradiation and T cell-depleted autologous marrow transplantation followed by MHC-mismatched heterotopic cardiac allograft implantation. Limiting dilution analysis was used to quantify residual marrow T cells following depletion. We found that (1) allograft survival was substantially prolonged in the absence of immunosuppressive drugs (median survival = 160 days) over that seen in controls treated identically but receiving non-T cell-depleted marrow (median survival = 14 days); (2) there was a correlation between allograft survival prolongation and the extent of marrow T cell depletion, with a maximum survival of 329 days associated with a residual marrow T cell content of 0.00014%; (3) nonspecific immune deficiency--and, possibly, specific unresponsiveness of limited duration (determined by cryopreserved donor and third-party skin grafting)--contributed to the rejection-free period seen in recipients of extensively depleted marrow; (4) late allograft rejection occurred in 3 of 3 long-term survivors, thereby demonstrating that permanent tolerance was not induced by the allograft across MHC barriers; and (5) as few as 1.4 x 10(4) infused marrow T cells/kg were sufficient to mediate acute allograft rejection, a threshold approximately 10-fold lower than that reported for the induction of acute graft-versus-host disease following allogeneic bone marrow transplantation.
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PMID:Cardiac allograft survival across major histocompatibility complex barriers in the rhesus monkey following T lymphocyte-depleted autologous marrow transplantation. II. Prolonged allograft survival with extensive marrow T cell depletion. 264 75

The clinical achievements in bone marrow transplantation are the culmination of more than 20 years of study of the principles of transplant biology, tissue typing, supportive care, and pregrafting and postgrafting regimens. Bone marrow transplantation, which involves replacing defective or abnormal marrow with normal donor marrow, is explored. The marrow transplant preparative regimen must suppress the recipient's response and destroy any malignant cells. Indications for bone marrow transplantation are outlined, and studies of the use of transplantation in the treatment of various disorders are discussed. Research continues to focus on the problems associated with marrow transplantation, which include immune deficiency, opportunistic infections, graft failure, the recurrence of the original disease, and acute and chronic graft-versus-host disease (GVHD).
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PMID:Bone marrow transplantation as treatment of hematologic disease. 294 22

The inoculation of B6D2F1 mice with T lymphocytes from the C57BL/6 parental strain induces an "immunosuppressive" graft-vs-host reaction (B6 GVH), whereas inoculation of T cells from the other, DBA/2 parental strain induces an "immunostimulatory" GVH reaction and a lupus-like disease (DBA GVH). The present study compares cytotoxic T lymphocyte (CTL) function in the spleens of these GVH mice as well as differences in the donor inoculum that could account for these different types of GVH. We observed that the B6 GVH induces an immunodeficiency that encompasses CTL precursors (and possibly T helper cells) and results in suppressor cells that abrogate responses to both trinitrophenyl (TNP)-modified self and third party alloantigens. In contrast, the DBA GVH induces only a T helper cell immunodeficiency and results in suppressor cells selective for class II restricted L3T4+ T helper cells. Chimeric T cells were detected in both types of GVH. In the B6 GVH both L3T4+ and Lyt-2+ donor cells were observed, although Lyt-2+ cells predominated. In the DBA GVH, donor T cells were almost exclusively of the L3T4+ phenotype. The lack of appreciable donor Lyt-2+ cells in the DBA GVH can be explained by a defect in the DBA donor inoculum manifested by a naturally occurring two-fold reduction in Lyt-2+ cell numbers as well as a nine-fold reduction in CTL precursors with anti-F1 specificity. T cells in the DBA inoculum, therefore, are predominantly L3T4+. A similar defect induced in B6 donor cells by anti-Lyt2 antibody and complement not only converted the suppressive GVH to a stimulatory GVH, as measured by anti-DNA antibodies, but also resulted in a T cell immune deficiency characteristic of the DBA GVH, i.e., a selective loss of the TNP-self CTL response. Thus the presence or absence of adequate numbers of functioning Lyt-2+ cells in the donor inoculum is correlated with the development of either a suppressive or stimulatory GVH, respectively. That donor Lyt-2+ cells mediate a suppressive GVH through cytolytic mechanisms is evidenced by greater than 70% reduction in B6 GVH spleen cell numbers and readily demonstrable anti-F1 CTL activity by these spleen cells despite an inability to generate anti-allogeneic or anti-TNP self CTL activity even in the presence of added T helper factors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of cytotoxic T lymphocytes in the prevention of lupus-like disease occurring in a murine model of graft-vs-host disease. 295 40

Adenosine deaminase (ADA) deficiency, an autosomal recessive inborn error of metabolism, leads to severe combined immune deficiency in man. This enzyme, although constitutively expressed in most tissues, is expressed at high level in immature T cells, and study of the pathophysiology of the disorder indicates that increased deoxyadenosine or altered methylation capacity have toxic effects on T-cell maturation. Although bone marrow transplantation can correct the immune deficiency, this therapy is associated with graft-versus-host disease and incomplete immune restoration, and so our laboratory and others have sought to develop a method of gene replacement as a possible treatment for the disease. Moreover, characterization of the complementary DNA of the human ADA gene and some of its mutants makes it possible to design gene transfer strategies. We have now subcloned a human adenosine deaminase cDNA into the retrovirus shuttle vector pZIP-SV(B), and in this way have isolated a cell line, 4.2T, which produces high titres of replication-defective retrovirus which have been used to transfer the gene for human ADA to mouse bone marrow cells. Transfer and expression of the neomycin-resistance gene (neo) and the ADA gene in murine bone marrow colony-forming units (CFU) was demonstrated by in vitro colony formation in the presence of the antibiotic G418 or 9-xylofuranosyladenine plus deoxycoformycin, respectively. Isoenzyme analysis also showed human ADA expression in the cultured mouse bone marrow.
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PMID:Expression of human adenosine deaminase in murine haematopoietic progenitor cells following retroviral transfer. 301 51


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