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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)

Experimental animal models of the two forms of toxic epidermal necrolysis have been reviewed: a murine model of staphylococcal-induced epidermolysis and a hamster model of graft-versus-host disease. In the former, a protein exotoxin, epidermolysin, has been purified and characterized. The exotoxin has a molecular weight of approximately 30,000 and causes a split beneath the granular layer. It is effective at 3 times 10(-12) moles. Epidermolysin does not require an intact complement system for its action since B10D2 mice deficient in C5 or mice injected with the decomplementing agent in cobra venom factor were susceptible to its epidermolytic effects. Neither are immunocompetent thymocytes required for the action of the toxin since hairless, athymic adult (nu/nu) mice are susceptible. A few reports of epidermolysis due to an exotoxin of group I Staphylococcus aureus have appeared. This toxin is antigenically different from the exotoxin of group II organisms. A model of drug-induced toxic epidermal necrolysis has been described in hamsters, but the toxic principle released from sensitized lymphoid cells has not yet been characterized.
J Invest Dermatol 1975 Jul
PMID:Studies of the mechanism of epidermal injury by a Staphylococcal epidermolytic toxin. 23 71

Graft-versus-host disease (GvHD) is the major cause of morbidity and mortality following bone marrow transplantation (BMT). The goal of this study of 69 cyclosporin-treated, allogeneic BMT patients was to identify early clinical, laboratory, or histopathologic indicators of the development of progressive, fatal GvHD. Peak values within 100 d of allogeneic BMT for total bilirubin, stool volume in a day, clinical stage of cutaneous GvHD (based on extent of rash), and overall clinical stage of GvHD (based on a combination of graft-versus-host reactions in the skin, liver, and gastrointestinal tract) were most useful (p less than 0.05, by logistic regression) in identifying those patients with clinically progressive and fatal GvHD. Peak values for each of these parameters were reached an average of 40 d or less after BMT. Each unit increase in peak clinical stage of rash (e.g., stage 2 versus stage 3) was associated with an odds ratio incremental risk of 5.8 for clinical progression of GvHD, and each tenfold increase in peak total bilirubin (e.g., 2 mg/dl versus 20 mg/dl) or stool output in a day (e.g., 100 cm3/d versus 1000 cm3/d) was associated with an incremental risk of 8.4 and 10.6, respectively, for a fatal outcome from GvHD. Number of exocytosed lymphocytes and dyskeratotic epidermal keratinocytes (DEK) per linear millimeter of epidermis, the presence of follicular involvement, and the degree of dermal perivascular lymphocytic infiltration in 121 skin biopsy specimens were not associated with the development of progressive or fatal GvHD. Pretransplant total body irradiation was associated (p = 0.03, by Mann-Whitney U testing) with an increased number of DEK in skin biopsy specimens taken less than 20 d after BMT. This study demonstrates that monitoring of total bilirubin, stool output, extent of rash, and overall clinical stage of GvHD is most useful during the first 40 d after BMT in formulating the prognosis of early acute GvHD in allogeneic BMT patients receiving cyclosporin.
J Invest Dermatol 1992 Oct
PMID:Clinical, laboratory, and histopathologic indicators of the development of progressive acute graft-versus-host disease. 140 96

Toxic epidermal necrolysis (TEN) is a severe life-threatening disorder which has many features in common with graft-versus-host disease. However, immunosuppression with steroids gives disappointing results and is possibly detrimental. We treated two patients who had TEN with a combination of cyclosporin and steroids which resulted in an apparent halt to the evolution of the disease, and a further relapse was aborted using cyclosporin in one of these patients. We feel that the use of this drug in the early treatment of TEN where it is used as a specific therapy aimed at the primary immunopathological events and is used in conjunction with the supportive care patients require, needs to be further evaluated.
Clin Exp Dermatol 1992 Jul
PMID:Toxic epidermal necrolysis treated with cyclosporin. 145 17

When immunocompetent cells are transferred to an allogeneic, immunologically compromised host a complex series of cellular events are initiated, referred to as graft versus host disease. This results in widespread organ damage with fibrosis being a prominent feature. The pathologic fibrosis may result from an increase in fibroblast numbers, an increase in collagen produced from individual fibroblasts, or a combination of the two processes. The relative contribution of fibroblast replication to the pathologic fibrosis seen in graft versus host disease has not been directly determined previously, and this is the main object of this paper. Graft versus host disease was induced by the transfer of lymphoid cells from B10D2 mice to irradiated Balb/c recipients. In order to study the mitotic activity of dermal cells following bone marrow transplantation, a thymidine anologue, bromo-deoxyuridine (BrDU), was administered to mice using an osmotically driven, implantable infusion device. The labeled cells were visualized immuno-histochemically and studied at weekly intervals. There is intense mitotic activity in the basal layer of the epidermis and the acrosyringal epithelium from the second week. Evidence of increased mitotic activity in the epidermis persisted until the fifth week post-transplantation. Fibroblast replication was seen from the end of the third post-transplant week. Dermal collagen deposition also occurred at this time. Peak mitotic activity was present at the end of the fourth week and was less pronounced by the fifth week. It was especially evident in the upper dermis where the developing collagen layer was being deposited. To our knowledge this is the first direct demonstration of fibroblast proliferation in an immunologically mediated fibrotic disorder. It is concluded that fibroblast replication is an important mechanism leading to the pathologic fibrosis seen in graft versus host disease and, by analogy, probably other types of immunologically mediated fibrosis.
J Invest Dermatol 1992 Dec
PMID:Mitotic activity in the dermis of mice during graft versus host disease: the role of fibroblast replication in dermal fibrosis. 146 92

Ultraviolet B radiation initiates a suppression of the delayed-type hypersensitivity response accompanied by a generation of antigen-specific suppressor cells and an alteration of antigen-presenting function. In previous studies we and other investigators could achieve a prolongation of graft survival by a treatment of the recipient with UVB light or 8-methoxy-psoralen plus UVA light (PUVA). One of the mediators of the systemic immunomodulatory effects of ultraviolet light or PUVA may be urocanic acid, which is isomerized in the skin by ultraviolet light from its cis- to the trans-isomer. In this work we present evidence that cis-urocanic acid, generated in vitro by a treatment with UVB light or PUVA, is able to prolong the survival of allogeneic MHC disparate skin grafts in mice. In contrast, the rejection of second set grafts was not suppressed. Unirradiated (trans-urocanic acid) had no effect on allograft rejection. In a murine model cis-, but not trans-urocanic acid, prevented or delayed an acute lethal graft-versus-host disease. These experiments demonstrate the potent systemic immunomodulatory effects of cis-urocanic acid in vivo.
J Invest Dermatol 1992 Apr
PMID:Inhibition of skin allograft rejection and acute graft-versus-host disease by cis-urocanic acid. 154 29

Acute graft versus host disease (GVHD) is a major complication of bone marrow transplantation. This study was undertaken to characterize the histopathologic alterations in early lesions of GVHD and to improve our understanding about the disease process. Histopathologic and immunoperoxidase studies of skin tissue were carried out in 20 patients of GVHD. Sixty percent had grade II histopathologic changes in the skin, grade I and III changes were observed in 35% and 5% respectively. Follicular involvement could be observed in all cases beyond grade I. Immunoperoxidase study revealed OPD4 (+) (T-helper) cells in dermis and OPD4 (-) (probably cytotoxic/suppressor) cells in epidermis.
Int J Dermatol 1992 Apr
PMID:Acute cutaneous graft versus host disease: a clinicopathologic and immunophenotypic study. 163 93

We performed an immunohistochemical analysis of skin biopsies from 13 allogeneic bone marrow transplant (BMT) recipients, undergoing either acute graft-versus-host-disease (aGVHD, n = 8) or chronic GVHD (cGVHD, n = 5). A panel of different monoclonal antibodies (MoAb) was employed including anti-CD2, -CD3, -CD4, -CD8, -CD11b, -CD16, -CD56, and -CD57, as well as a recently described reagent (HP-3B1) specific for a novel natural killer (NK)-associated cell-surface antigen (Kp43). Our data indicate that in aGVHD lesions the proportions of CD2+ cells often exceeded those detected with anti-CD3 MoAb. Double labeling confirmed the presence of CD2+ CD3- lymphocytes and suggested the coexpression in some cells of CD2 and CD11b. When MoAb specific for non-lineage-restricted NK-associated markers were employed, anti-CD56 and -CD57 occasionally stained variable numbers of lymphocytes (means = 14.6% of mononuclear cells in 0.05 mm2, range less than 1-48% and means = 10.3%, range 2-25%, respectively), whereas no CD16+ lymphocytes were observed. In contrast, most samples consistently displayed substantial proportions of Kp43+ cells (means = 32.8%, range 12-63%), which appeared CD3- and were mainly located at the dermoepidermal junction. On the other hand, sections from most (four of five) cGVHD lichenoid lesions analyzed displayed lower proportions of Kp43+ and CD56+ cells. Our data point out the interest of the anti-Kp43 MoAb to identify NK cells in aGVHD lesions, suggesting their pathogenetic participation.
J Invest Dermatol 1991 Oct
PMID:Identification of natural killer (NK) cells in lesions of human cutaneous graft-versus-host disease: expression of a novel NK-associated surface antigen (Kp43) in mononuclear infiltrates. 168 91

We describe a 20-year-old man with chronic graft-versus-host disease and progressive cutaneous changes. His skin became more lichenified despite therapy with azathioprine, prednisone, and cyclosporine. Although it was initially thought that lichenoid graft-versus-host disease had developed, it was subsequently discovered that the patient had crusted (Norwegian) scabies.
J Am Acad Dermatol 1991 Nov
PMID:Crusted scabies in a patient with chronic graft-versus-host disease. 172 27

Polymyositis developed in a patient who had had bone marrow transplants for the treatment of acute myeloid leukemia. There was no previous evidence of graft-versus-host disease. Polymyositis has previously been reported to be associated with graft-versus-host disease; this article suggests that polymyositis may represent its sole manifestation.
J Am Acad Dermatol 1991 Sep
PMID:Polymyositis: a manifestation of chronic graft-versus-host disease. 191 95

Graft-versus-host disease (GVHD) is an immunologically mediated disease occurring most frequently after allogeneic bone marrow transplantation. The aim of this study was to evaluate the contribution of immunohistochemistry in the diagnosis of cutaneous GVHD. Patients transplanted for either leukemia or beta-thalassemia were included in the study. Skin lesions of acute and chronic GVHD were examined both by direct immunofluorescence to detect immunoglobulin deposits and by an avidin-biotin-peroxidase complex technique to evaluate the inflammatory cell infiltrate. Epidermal and dermal fluorescent bodies (IgG and IgM) were frequently found in both acute and chronic GVHD. Most of the infiltrating cells were CD3+ T lymphocytes, with CD8+ cells representing the major cell population invading the epidermis both in acute GVHD and in chronic lichenoid GVHD. A small proportion of the dermal cells were CD14+ macrophages; no B cells were detected. HLA-DR, but not HLA-DQ antigens, were variably expressed by keratinocytes in all cases of acute GVHD and in chronic lichenoid GVHD. KL-1, a monoclonal antikeratin antibody specific for the 56.5 KD acidic polypeptide usually present in suprabasal keratinocytes, stained all epidermal layers, including the basal layer. Langerhans cells were dramatically reduced in number in the epidermis of both acute and chronic lichenoid GVHD. It is concluded that immunohistologic analysis may be supportive in the diagnosis of acute and early chronic lichenoid cutaneous GVHD.
J Dermatol 1991 Jun
PMID:Immunohistochemistry of cutaneous graft-versus-host disease after allogeneic bone marrow transplantation. 193 60


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