Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allogeneic bone marrow transplantation (BMT) was applied in 1968 to treat severe combined immunodeficiency disease (SCID). Almost simultaneously, marrow from an MHC-matched donor corrected the immunological deficiency of a patient with Wiscott-Aldrich Syndrome (WAS). In the first successful treatment of X-linked SCID the match was imperfect and, although SCID was cured, a graft vs. host reaction caused pancytopenia. A second BMT from the same donor successfully treated a complicating aplastic anemia. Subsequently, it has been possible to cure most patients with SCID who are in reasonably good condition at the time of BMT without other manipulation if a matched sibling donor is available. Successes are reported from Holland, France, Italy, England, Scandinavia, Japan, Germany, and from many centers in the United States. Similarly, BMT is used to correct SCID due to adenosine deaminase (ADA) deficiency or nucleoside phosphorylase (NP) deficiency, which underlie two forms of SCID. Bone marrow transplantation using HLA-matched sibling donors can now treat, successfully, at least eight genetically separable forms of SCID. Highly lethal defects of phagocytic function (including LFA-1, MO-1, CR-3 deficiencies, IL-2 and IL-1 receptor deficiencies), defects of killing after phagocytosis (as in chronic granulomatous disease, WAS, and Kostmann's Syndrome), and certain inborn errors of metabolism can be cured by BMT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone marrow transplantation for immunodeficiency diseases. 330 7

Human gene therapy for diseases involving leukocytes would be facilitated by the identification of specific promoter/enhancer sequences capable of directing high levels of tissue and stage-specific expression of the requisite cDNA when used in a retroviral vector. We tested the promoter sequences from the leukocyte integrin CD11a (LFA-1), CD11b (Mac-1), and CD18 subunits in retroviral vectors to express a reporter gene, adenosine deaminase, in the human leukocyte cell lines K562 and HL-60. The leukocyte integrins are expressed in leukocytes, and they are inducible in HL-60 cells, a model system for myeloid differentiation. Although the leukocyte integrin promoter/enhancer sequences direct the expression of reporter genes in myeloid lineage cell lines in transient transfection assays, in these studies, the leukocyte integrin promoters direct low levels of reporter gene expression following retroviral-mediated transduction in K562 and HL-60 cells and selection of stable integrants. Treatment of HL-60 cells transduced with retroviral vectors containing the leukocyte integrin promoters with retinoic acid or phorbol myristate acetate results in less than a two-fold increase in reporter gene expression. These studies indicate that: (i) expression from the leukocyte integrin promoters from stable integrants in retroviral vectors does not parallel the results observed in transient transfection assays, and (ii) additional promoter/enhancer sequences will likely be required for these promoters to direct high levels of tissue and stage-specific expression in retroviral vectors.
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PMID:Expression from leukocyte integrin promoters in retroviral vectors. 794 33