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)

Oral mucosal biopsies of 12 allogeneic marrow transplant recipients with chronic graft-versus-host disease (GVHD) involving the mouth were compared with biopsies taken before transplantation. They were also compared with biopsies from otherwise healthy patients with oral lichen planus, and with those from a control group of normal individuals. Biopsies from chronic GVHD exhibited a low number of infiltrating T lymphocytes (CD3 cells) compared with those from oral lichen planus, which showed intense cell infiltration (p less than 0.005). The ratio of CD4 to CD8 cells in biopsies taken after the manifestation of chronic GVHD exhibited no consistent variation compared with those taken before transplantation or with biopsies of oral lichen planus. The CD4/CD8 ratio in all groups investigated varied between 4:1 and 6:1. The number of natural killer cells (CD57), was increased in biopsy specimens taken before transplantation compared with the other groups. The frequency of homing receptor, Leu-8 bearing T cells was low in the biopsy specimens of all groups, compared with the corresponding frequency in peripheral blood (10-45 and 60-90%, respectively; p less than 0.001). In the biopsies from chronic GVHD and oral lichen planus the number of lymphocytes with transferrin receptors was increased compared with the pretransplant and control groups. Virtually no infiltrating cells were carrying interleukin-2 receptors (CD25) in any of the groups studied. Langerhans cells (CD1) were more frequently found in the specimens from chronic GVHD and oral lichen planus than in the pretransplant specimens and the control group (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A comparative immunological analysis of the oral mucosa in chronic graft-versus-host disease and oral lichen planus. 135 59

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 localization of transferrin and C3d receptors in various skin lesions and normal appearing skin have been studied on sections with the PAP technique. The transferrin receptor was recognized in the lower epidermis from psoriatic plaques. Here it was more evident than in other inflammatory or hyperproliferative disorders where it was mainly detected on the basal cells. In healthy skin or lesions of lichen planus, scleroderma and ichthyosis the transferrin receptor was not detected in the epidermis. The C3d receptor was in normal skin found on the basement membrane and on elastic fibres in the papillary dermis. The basement membrane was strongly marked in pemphigoid but was not seen in lichen planus and Ehlers-Danlos syndrome. In patients with urticaria factitia, contact dematitis, psoriasis and Darier's disease the suprabasal cells also expressed C3d whereas in other dermatoses the epidermis was negative. Colloid bodies in lichen planus and GVH reactions expressed both the transferrin receptor and C3d.
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PMID:Detection of transferrin and C3d receptors in the skin of patients with various dermatoses. 197 52

Two-colour fluorescence flow cytometry was utilized to define subsets within the Leu-3+ (T4+) helper-inducer and the Leu-2+ (T8+) cytotoxic-suppressor T cell subpopulations in recipients of unmanipulated HLA-identical sibling bone marrow transplants. The absolute number of activated cytotoxic-suppressor T cells expressing the HLA-DR and OKT10 activation antigens was increased. The proportion (or relative number) of cells bearing each of these activation antigens was also elevated in both the Leu-2+ and the Leu-3+ subpopulations, with up to 60% of Leu-2+ cells and up to 40% of Leu-3+ cells expressing them. Interestingly, absolute numbers of cells expressing two other activation-associated antigens, the interleukin-2 (IL-2) and transferrin receptors, were not increased in either major T cell subpopulation, although the relative number of Leu-3+ cells expressing both these surface structures was increased early post-transplant. Three putative functional subsets were also enumerated: the Leu-3+, Leu-8+ suppressor-inducer subset was depressed in absolute and relative numbers at most time points post-transplant. The Leu-4+, Leu-15+ suppressor-effector subset subpopulation was normal at all time points posttransplant, while the Leu-2+, 9.3+ cytotoxic precursor subset showed low relative and absolute numbers both early and late post-transplant. None of the abnormalities demonstrated in the present study was correlated with presence or absence of graft-versus-host disease. The study further demonstrates the heterogeneity of the abnormalities in the immune system after human marrow transplantation and lays the basis for functional studies involving these cell populations.
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PMID:T cell subpopulations defined by monoclonal antibodies after HLA-identical sibling marrow transplantation. II. Activated and functional subsets of helper-inducer and cytotoxic-suppressor subpopulations defined by two-colour fluorescence flow cytometry. 297 8

A lupus-like disease characterized by a severe immune complex glomerulonephritis and IgG autoantibody production was induced in (C57BL/6 X DBA/2)F1 mice by injection of parental DBA/2 lymphoid cells. The ensuing graft-vs-host (GVH) reaction resulted in a 10- and a 100-fold increase in serum IgG antibody levels to denatured DNA and total histones, respectively, compared with that in F1----F1 control mice. The level of anti-DNA antibodies peaked 2 wk after injection of DBA/2 cells and preceded peak anti-histone levels by approximately 2 wk. Anti-histone antibodies were generated predominantly to histones H1, H2A, and H2B, a profile different from that observed in NZB/NZW and MRL-lpr/lpr mice. The marked increase in IgG antinuclear antibodies did not correlate with increases in total IgG serum levels and was not associated with comparable increases in antibodies to transferrin, hemoglobin, fibrinogen, or thyroglobulin. Selective autoantibody production was also observed in vitro, wherein GVH spleen cells produced high levels of IgG antibodies to total histones and denatured DNA but not to these non-nuclear protein antigens. In contrast, spleen cells stimulated in vitro with lipopolysaccharide produced equivalent amounts of antibodies to all antigens tested. Our results are in agreement with those of other investigators and collectively suggest that IgG autoantibodies in GVH disease, and possibly in spontaneous lupus-like disease, are not secondary to a generalized B cell activation, but may be selectively generated in response to self antigens with unique configurational properties.
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PMID:Autoimmunization in murine graft-vs-host disease. I. Selective production of antibodies to histones and DNA. 387 58

Transferrin levels were measured immunochemically and the levels of several other plasma proteins were estimated by high resolution agarose gel electrophoresis in serial serum samples from nine patients undergoing bone marrow transplantation for aplastic anemia or leukemia. Three of five patients with low pretreatment transferrin levels died during initial hospitalization, and the other two suffered severe complications prior to recovery. All four patients with pretreatment transferrin levels within the normal range were discharged, three of them with minimal complications. Serial studies demonstrated that transferrin levels fell with the onset of infections or graft-versus-host disease and rose with recovery. Similar changes were not seen with any of the other plasma proteins measured. These results suggest that measurement of serum transferrin may reveal important prognostic information about patients undergoing bone marrow transplantation.
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PMID:Transferrin in disease. I: A potential prognostic indicator in patients undergoing bone marrow transplantation. 637 29

The validity of biochemical indices routinely used for nutritional assessment was evaluated in patients undergoing allogeneic bone marrow transplantation for hematologic malignancies. Sixteen patients received total parenteral nutrition (TPN) for 15 days (35 kcal kg.body wt-1.day-1; 1.4 g amino acid.kg body wt-1.day-1) starting 1 day after transplantation. Nutritional status was evaluated before and after the TPN period by determining anthropometric (body weight, triceps skinfold thickness, and midarm circumference) and biochemical (transferrin, prealbumin, ceruloplasmin, and C3c) indices. Anthropometric indices, which were within the normal range before TPN, were not changed on day 15; transferrin and prealbumin concentrations significantly (p = 0.03) decreased whereas ceruloplasmin and C3c significantly (p = 0.03) increased. The levels of acute-phase proteins (alpha-1-acid glycoprotein, alpha-1-antitrypsin, and C-reactive protein), determined in 8 of the 16 patients at the same time intervals, were increased after 15 days of TPN and were significantly inversely correlated with transferrin and prealbumin. On the basis of these data, it appears that biochemical indices are not sufficiently reliable in the nutritional assessment of bone marrow transplantation patients because the levels of these substances are markedly affected by the acute-phase response secondary to febrile episodes and graft-versus-host disease, which frequently complicate transplantation.
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PMID:Biochemical indices may not accurately reflect changes in nutritional status after allogeneic bone marrow transplantation. 874 94

Gallium is a group IIIa metal that has efficacy in the therapy of malignant disorders such as lymphoma and urothelial tract tumors. Preclinical studies also indicate a role for gallium in autoimmune disorders, suggesting that gallium is able to modulate T-cell immune reactivity. The purpose of this study was to examine the in vitro and in vivo immunomodulatory action of gallium on T-cell function. Since gallium binds to transferrin in vivo, in vitro studies evaluated the effect of transferrin-gallium (Tf-Ga) on human T cells. Tf-Ga inhibited the mitogen-induced proliferative response of peripheral blood mononuclear cells (PBMC) in a dose-dependent fashion. Alloantigen-induced proliferation was also potently suppressed when evaluated in a mixed lymphocyte culture assay. Tf-Ga affected a significant reduction in the density of IL-2 receptors on activated T cells and a slight reduction in the number of CD3+/CD25+ T cells in PHA-stimulated cultures. Neither secretion of interleukin-2 (IL-2) nor the induction of IL-2-stimulated lymphokine-activated killer activity, however, was inhibited by Tf-Ga. Tf-Ga produced significant upregulation of the transferrin receptor (CD71) in T cells as determined by flow cytometric analysis and northern blot assay, but did not affect the percentage of CD3+/ CD71+ T cells after mitogen stimulation. To assess the in vivo effects of gallium on alloreactive T cells, we evaluated the immunosuppressive effect of gallium in a murine model of graft-versus-host disease (GVHD). Administration of gallium significantly prolonged survival in mice undergoing severe GVHD, suggesting that gallium can ameliorate GVH reactivity. Collectively, these data demonstrate that, at clinically achievable concentrations, Tf-Ga potently inhibits T-cell activation and that this immunosuppressive property of gallium may be of adjunctive therapeutic value in the management of disorders characterized by the presence of autoreactive or alloreactive T-cell populations.
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PMID:Modulation of in vitro and in vivo T-cell responses by transferrin-gallium and gallium nitrate. 887 4


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