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)

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

Terminal deoxynucleotidyl transferase (TdT) assay has proved a valuable test for distinguishing lymphoblastic from myeloblastic leukaemias, particularly in adults whose blast cells are often negative for the c-ALL antigen. The immunofluorescence assay, particularly when used in combination with antisera to surface membrane antigens, has proved a sensitive technique for detecting small numbers of lymphoblasts in extramedullary sites, for example, testis or cerebrospinal fluid, or of residual Thy-ALL blasts in the marrow, which might otherwise be difficult to recognise. Differences in concentration of several enzymes concerned in purine metabolism have been detected between the blast cells in the various acute leukaemias. Adenosine deaminase (ADA) concentrations tend to be higher in Thy-ALL than in other forms of leukaemia, but the wide overlap reduces the diagnostic value of this assay. Thy-ALL blasts, however, appear to be selectively and exquisitely susceptible to inhibition of ADA by the drug deoxycoformycin, which has now been used sucessfully in a number of other wise resistant patients with Thy-ALL to obtain a complete remission. The recently introduced technique for the production of monoclonal antibodies has substantially widened the reagents available for analysing the membrane characteristics of bone marrow stem cells and of cell lineages derived from them. These have revealed previously unsuspected heterogeneity among different cases of acute lymphoblastic leukaemia, for example, among Thy-ALL blasts from different patients, and they have also delineated minor populations of immature thymocytes from which these leukaemic cells are derived. The potential use of these antibodies to prevent graft-versus-host disease by selective removal of T-lymphocytes from donor bone marrow before allogeneic bone marrow transplantation, or to prevent recurrence of Thy-ALL and other lymphoblastic leukaemias or lymphomas by selective removal of leukaemic or lymphoma malignant cells before autologous transplantation, is reviewed.
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PMID:Enzyme and membrane markers in leukaemia: recent developments. 678 21