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)

8 patients with severe and 4 with non-severe aplastic anaemia, aged 7 to 46 years, whose suppressor lymphocyte activity was in most cases elevated and who had no histocompatible sibling donor, underwent 1-2 courses of ALG/ATG treatment. 6 patients got CR and 1 PR and during 1-4 years they live with sustaining haemopoiesis, independent of blood transfusion (except one in PR). Among these seven responders increased suppressor lymphocyte activity normalized in 6. The adverse effects of the treatment were granulocyto- and thrombocytopenia, subfebrile states, hepatotoxicity, serum sickness and skin allergy. Five patients died because of early or late complications of the treatment or it's failure. Our results, similar to other authors', are like after BMT and supports the immunological mechanism of A.A. Immunosuppressive treatment with ALG/ATG has many advantages: no need to have identical bone marrow donor, no GVHD, possibility of treatment of patients over 30, even pretreated with blood transfusions, and finally much lower costs and efforts.
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PMID:ALG/ATG treatment--a useful alternative for BMT in selected aplastic anaemia patients. 248 Feb 77

The pathogenetic mechanisms underlying common, and less common but severe, adverse cutaneous drug reactions are reviewed. Pharmacogenetic variability may account for a susceptibility to serious drug reactions to sulphonamides and anticonvulsants, as well as to lupus erythematosus (LE)-like syndrome. Exanthematous drug reactions may have an immunological basis. Cell mediated cutaneous drug reactions, including lichenoid reactions, LE-like syndrome, fixed drug eruption, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis, will inevitably involve elements of the skin immune system. Graft-versus-host disease provides a useful model for aspects of these drug-induced disorders. Urticaria, angioedema, anaphylaxis and anaphylactoid reactions may involve Type I immunoglobulin (Ig)-mediated or Type III hypersensitivity, or may be caused by pharmacological, non-allergic means. Drug-induced vasculitis, serum sickness and the Arthus phenomenon are manifestations of the immune complex disease. Drug-induced pemphigus may involve immune dysregulation, but several thiol-containing drugs are able to cause antibody-independent acantholysis directly.
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PMID:Mechanisms of drug eruptions: Part I. 748 37

The prognosis of patients showing glomerulosclerosis as a complication of an immunologically mediated kidney disease is poor. To improve the diagnosis and treatment of these patients, it is important to understand the processes involved in the development of glomerulosclerosis. In this study, we investigated the molecular composition of experimental end-stage glomerular sclerotic lesions and their pathogenesis in chronic graft-versus-host disease (GvHD) in the mouse and chronic serum sickness in the rat. Accumulation studies were performed to determine the degree of specific trapping of constituents from the circulation. Two different models were investigated to determine whether differences in disease initiation resulted in different compositions of the glomerulosclerotic lesions. In both models, glomerulosclerosis was preceded by expansion of the mesangial matrix and thickening of the glomerular basement membrane (GBM). The end-stage sclerotic lesions consisted mainly of fibronectin, which appeared to displace the other extracellular matrix (ECM) components peripherally in the mesangial matrix and GBM. The abundance of fibronectin in the lesions was not reflected in the mRNA levels for this component. Indeed, antibodies directed against the cellular form of fibronectin did not stain positive in the end-stage lesions. These findings, together with accumulation studies, suggest that specific accumulation rather than de novo synthesis of fibronectin plays a major role in the development of experimental glomerulosclerosis, which appears to be independent of the pathway of induction.
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PMID:Specific accumulation of exogenous fibronectin in experimental glomerulosclerosis. 763 29

Increased mRNA and protein expression of extracellular matrix (ECM) components, including fibronectin, occurs during the development of glomerulonephritis and glomerulosclerosis in immunologically mediated kidney diseases. However, in addition to these quantitative changes in ECM expression, qualitative changes in these molecules may contribute to malformations in the composition of the glomerular matrix. These qualitative changes may include alterations in the splicing pattern of the V-region of fibronectin, since this region plays a role in its accumulation. The splicing patterns of this region have been studied in chronic graft-versus-host disease (GvHD) in mice, a model of lupus nephritis, and in chronic serum sickness (CSS) in rats, a model of immune complex nephritis. Cloning of the mouse fibronectin V-region from kidney tissue revealed 96.1 per cent homology with the corresponding domain in rat fibronectin. PCR (polymerase chain reaction) analysis of RNA from isolated glomeruli revealed three isoforms of this region in both mouse and rat fibronectin, namely inclusion or exclusion of the whole region, or exclusion of only the CS1 domain. In both models, increased exclusion of the V-region was observed early in the disease. However, in GvHD the splicing pattern returned to normal, whereas in CSS the shift persisted during the course of the experiment. Differentiated expression of fibronectin isoforms may exert an important effect on the structure and biological function of the glomerulus and may thus play a role in the development of glomerulonephritis and glomerulosclerosis.
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PMID:Cloning of the mouse fibronectin V-region and variation of its splicing pattern in experimental immune complex glomerulonephritis. 869 28

Expansion of the glomerular mesangial matrix (MM), thickening of the glomerular basement membrane (GBM), and eventually the development of glomerulosclerosis are often seen in immunologically mediated kidney diseases. In addition to quantitative changes in the extracellular matrix (ECM), qualitative changes in ECM molecules may contribute to alterations in the composition of the glomerular matrix. The expression of collagen IV, alpha 1-5(IV) mRNA, and polypeptides was therefore investigated during the development of chronic graft-versus-host disease (GvHD) in mice, a model for lupus nephritis, and in chronic serum sickness (CSS) in rats, a model for membranous nephropathy. Immunohistochemical studies showed increased mesangial expression of alpha 1 and alpha 2 early in the disease, but only late in the GBM. In contrast, alpha 3 and alpha 4 increased in the GBM during disease, but not in the MM. The mRNA levels for all collagen IV chains were increased in isolated glomeruli before morphological alterations were detectable. The mRNA increase was earlier and more profound for alpha 3, alpha 4 and alpha 5 than for alpha 1 and alpha 2. Expression of alpha 3(IV) was greatest in GvHD, whereas expression of alpha 4 was greatest in CSS. As determined by in situ hybridization (ISH), alpha 1 mRNA was observed dispersed in the glomerulus, but alpha 3, alpha 4, and alpha 5 mRNAs were mainly located in cells at the periphery of the glomerular tuft. The changes in the relative abundance of collagen IV mRNA in disease states may perturb the collagen IV network, altering glomerular structure and function, and may thereby play a central role in the development of glomerulonephritis and glomerulosclerosis.
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PMID:Differential expression of collagen IV isoforms in experimental glomerulosclerosis. 961 84

We report our experiences with HLA-matched unrelated bonemarrow transplantation combining a preconditioning regimen of cyclophosphamide, antithymocyte globulin (ATG), and total body irradiation for two patients with severe aplastic anemia (SAA) who had already undergone repeated blood transfusions. Short-term methotrexate and cyclosporine were administered for graft-versus-host disease (GVHD) prophylaxis. Both patients achieved rapid engraftment within 3 weeks, furthermore, neither acute nor chronic GVHD developed. Our conditioning regimen appeared to be well-suited for unrelated bone marrow transplantation in heavily transfused SAA patients. However, both patients experienced bouts of fever about 20-30 and 40-50 days after transplantation, and it was difficult to differentiate whether they were affected by acute GVHD, cytomegalovirus (CMV) infections, or serum sickness. Because weakly positive CMV antigenemia was detected, both patients were given ganciclovir. Although their fever did not respond initially, it gradually subsided following the combined administration of prednisolone. These outcomes suggest it is essential that attention be devoted to the potential for serum sickness and the high risk of herpes virus infections, particularly by CMV, following the use of intensive preconditioning regimens that include ATG.
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PMID:[Unrelated bone marrow transplantation in two severe aplastic anemia patients preconditioned with a regimen of cyclophosphamide, antithymocyte globulin, and total body irradiation]. 1022 28

We report our experience in successful unrelated-donor bone marrow transplantation in 2 cases of beta-thalassemia major, which are approved to be the first 2 cases in Asia. The 2 children receiving transplantation of the bone marrow from unrelated donors were diagnosed as having beta-thalassemia major, whose gene mutation type was homozygous and double heterozygote. High-resolution HLA typing found a mismatch with 1 sub-locus in both cases, and red blood cell type was mismatched in 1 case. Pretransplant conditioning protocol contained busulfan (BU, 16 mg/kg x b.w.), cyclosphamide (CY, 200 mg/kg x b.w.), anti-thymocyte globulin (ATG, 90 mg/kg x b.w.) and fludarabine (25 mg x d-1 x m-2). To prevent graft-versus-host disease (GVHD) episodes, cyclosporine-A (Cs-A) and methotrexate (MTX) were administered. The 2 cases experienced condition resembling serum sickness during pretransplant conditioning. After bone marrow transplantation, 1 case had grade acute GVHD in the skin, another developed grade acute GVHD in both the skin and intestinal tract, but the condition was brought under control in both cases after proper treatment. The time for peripheral neutrophil granulocyte recovery to above 0.5 x 10(9)/L was 19 and 16 days postoperatively, respectively, and the time of WBC recovery to normal was 54 and 80 days postoperatively. Platelet recovery to over 50 x 10(9)/L occurred on postoperative days 61 and 90, and Hb recovered to above 100 g/L in both case on days 110 and 83 respectively. The time of final blood transfusion was 53 and 62 days postoperatively for the 2 patients. Gene mutation type in the 2 cases was switched to normal of the donors. After retrieval of relative literature, the 2 cases were approved as the first 2 successful unrelated-donor bone marrow transplantation cases in Asia. This will provide a new possibility of donor supply for hematopoietic stem cells transplantation in thalassemia.
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PMID:Unrelated bone marrow transplantation for beta-thalassemia major: report of the first 2 successful cases in Asia. 1265 Dec 55

Based on the results achieved in single human hand transplantations, we decided to perform the first double hand transplantation with a conventional immunosuppressive protocol in a patient with a high potential for functional recovery. Two years after transplantation the efficacy and the safety of this immunosuppressive protocol are evaluated. The recipient was a 33-yr-old man suffering from a traumatic amputation of both hands in 1996. Five HLA-A, -B, and -DR mismatches were present with the donor; T and B cell cross-match was negative. Immunosuppressive protocol included tacrolimus, prednisone, mycophenolate mofetil and, for induction, antithymocyte globulins and then anti CD25 monoclonal antibody. Reconstitution of lymphocyte populations proceeded normally. Neither anti-HLA antibodies nor chimerism in peripheral blood were detected. Two episodes of acute rejection characterized by maculopapular lesions occurred on days 53 and 82 after transplantation. Skin biopsies revealed a dermal lymphocytic infiltrate. Both episodes were completely and rapidly reversed by topical clobetasol and increased systemic corticosteroid therapy. The only side-effects related to treatment were reversible serum sickness and hyperglycemia. No infectious complications and malignancies occurred. No signs of graft-versus-host disease have been detected. This case of double hand transplantation shows that conventional immunosuppression is effective and safe to ensure survival and functional recovery of the grafted limb.
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PMID:First human double hand transplantation: efficacy of a conventional immunosuppressive protocol. 1470 30

Fibronectin (FN) is the main extracellular matrix component in glomerulosclerotic lesions. There are different FN isoforms that result from alternative splicing at the EDA and EDB regions of FN mRNA. Increased inclusion of EDA and EDB, which can be elicited by TGFbeta, may be conducive to the development of glomerulosclerosis (GS). TGFbeta and IL-4 have previously been shown to play a role in the development of GS. In this study, the mRNA splicing patterns for EDA+ and EDB+ fibronectin were investigated in vivo in various experimental sclerotic glomerulopathies, in vitro in rat mesangial cells (MC) that were stimulated by TGFbeta or transfected with IL-4, and in human kidney biopsies with GS from patients with various kidney diseases. Analysis of glomerular FN mRNA demonstrated inclusion of both ED regions in rats with anti-Thy1 nephritis or chronic serum sickness and in mice with anti-GBM glomerulonephritis. Inclusion of both the EDA and EDB regions was associated with glomerular TGFbeta expression. In contrast, in mice with Th2-mediated graft-versus-host disease, a model for lupus nephritis, the FN transcripts included neither the EDA nor the EDB region, and renal TGFbeta expression was absent. Compared to normal MCs in culture, MCs transfected with IL-4 produced lower amounts of FN and demonstrated less EDA inclusion, while MC that had been treated with TGFbeta showed increased production of FN and more EDA inclusion. Renal biopsies from patients with renal diseases, except those taken from patients with lupus nephritis, showed higher TGFbeta levels, higher FN levels, and more EDA inclusion than controls. TGFbeta may be a key player in the development of GS by inducing local FN production and alternative splicing of FN mRNA. In lupus glomerulonephritis, in which the involvement of TGFbeta in GS is less prominent, Th2 cytokines such as IL-4 probably account for increased intrarenal collagen synthesis and subsequent FN accumulation from the circulation. In conclusion, neither alternative FN splicing, nor a high transcription level of TGFbeta, appears to be a general prerequisite for the development of GS.
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PMID:Alternatively spliced isoforms of fibronectin in immune-mediated glomerulosclerosis: the role of TGFbeta and IL-4. 1537 54