Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.4.17 (adenosine deaminase)
 5,206 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat pial arteries were observed through a closed cranial window during hypercapnic and hypoxic episodes whilst the cerebral cortex was superfused at 37 degrees C first with artificial cerebrospinal fluid (CSF) and subsequently with adenosine deaminase (ADA, 0.5-2.0 U/ml) in CSF. The results indicate that ADA attenuated hypercapnic and hypoxic dilatatory arteriolar responses by 64% and 56% respectively. Recovery was obtained by superfusing with ADA-free CSF for 1 h. We conclude that adenosine is involved in hypercapnia- and hypoxia-evoked dilation of pial arteries.
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PMID:Adenosine deaminase reduces hypoxic and hypercapnic dilatation of rat pial arterioles: evidence for mediation by adenosine. 193 88

Analyses of pairwise associations between several erythrocyte genetic systems were performed on a sample from a Brazilian trihybrid population. The present paper confirms the association between the ACP1 and ADA loci, the acid phosphatase 1 and adenosine deaminase systems. The results indicate that both selection and racial admixture may influence this association.
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PMID:Association between the acid phosphatase 1 and adenosine deaminase systems in a Brazilian sample. 193 87

An adenosine deaminase (ADA;EC 3.5.4.4)-deficient B lymphoblastoid cell line BADO5 derived from a Japanese patient with severe combined immunodeficiency disease and two B lymphoblastoid cell lines, BAMO5 from his mother and BAFO5 from his father, were characterized. To identify mutations affecting ADA activity, we prepared cDNAs to ADA mRNAs of the BADO5 cell line for nucleotide sequencing. Sequence analysis of one of the BADO5 ADA cDNA clones revealed deletion of exon 7, and one point mutation of base 629 from G to A that did not affect the amino acid sequence. All clones of the BADO5 cell line so far examined showed the absence of exon 7 by Southern blotting analysis. Ribonuclease protection assay with an RNA probe spanning from exon 5 to exon 11 showed that the BADO5 ADA mRNA had a deletion of exon 7, the BAMO5 mRNA had normal length, and the BAFO5 mRNA had two species with a deletion of exon 7 and with normal length. Consequently, the patient's ADA genes resulted from one allele of the BAMO5 ADA gene that did not produce a detectable mRNA, and the other allele of the BAFO5 ADA gene producing an aberrant mRNA without exon 7.
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PMID:Adenosine deaminase deficiency due to heterozygous abnormality consisting of a deletion of exon 7 and the absence of enzyme mRNA. 193 66

The effect of polyethylene glycol-adenosine deaminase (PEG-ADA) therapy on biochemical, immunological and clinical abnormalities in an ADA-deficit child with severe combined immunodeficiency has been studied. Following PEG-ADA therapy, total lymphocytes, lymphocyte subsets (CD3, CD4 and CD8) and the response of lymphocytes to non specific mitogens increase significantly. The improvement of immunological functions is closely related to a decrease of erythrocyte deoxyadenosine triphosphate (dATP) concentrations. This study shows that PEG-ADA therapy is sufficiently effective to reduce and to maintain erythrocyte dATP levels at values compatible with normal immune functions. PEG-ADA represents an important progress for the treatment of ADA deficiency associated with severe combined immunodeficiency disease.
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PMID:[Polyethylene glycol-adenosine deaminase: a new adenosine deaminase deficiency therapy. Value of deoxyadenosine triphosphate determination for therapeutic monitoring]. 194 9

Lymphocytes can be readily transduced with retroviral vectors and the gene-modified lymphocytes will stably express the inserted genes in vitro for long periods. As a prelude to studies in humans, we evaluated the survival of gene-modified T lymphocytes and the expression of the introduced genes in nonhuman primate T lymphocytes both in vitro and in vivo to determine if lymphocytes could be a potential cellular gene therapy vehicle. Rhesus peripheral blood T-lymphocytes and/or lymph node lymphocytes were transduced with a retroviral vector that contained a bacterial neomycin resistance (NeoR) gene or both NeoR and the human adenosine deaminase (hADA) genes. The cells were then selected for NeoR expression by growth in the neomycin analogue G418 and the autologous gene-modified T cells were reintroduced into the donor animals. T lymphocytes were periodically regrown from the blood and selected in G418. Gene-modified cells persisted in 1 animal for 727 days as detected by analysis for vector DNA by polymerase chain reaction (PCR). Evidence for expression of the human ADA or NeoR genes has also been detected up to 727 days after cell infusion. These findings suggest that gene-modified T lymphocytes can survive and circulate for long periods in vivo and can continue to express the introduced genes.
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PMID:In vivo expression and survival of gene-modified T lymphocytes in rhesus monkeys. 196 96

Plasma concentrations of the two isoenzymes of adenosine deaminase (ADA, E.C. 3.5.4.4), adenosine deaminase1 (ADA1) and adenosine deaminase2 (ADA2), were measured in a cohort of ambulatory patients infected with the human immunodeficiency virus (HIV) and controls. A sensitive isoenzyme-specific radioisotopic assay system was developed for these studies. Among 22 HIV-infected patients, plasma ADA2 was significantly elevated as compared with 16 control subjects (p less than 0.01) and 6 uninfected subjects having a risk factor for HIV infection (p less than 0.01). Plasma ADA2 was not associated with the stage of disease as defined by clinical status (p greater than 0.05) or helper (CD4) lymphocyte count (p greater than 0.05). Available evidence suggests that elevated plasma ADA2 could be a useful surrogate marker for HIV infection that occurs early in the disease process.
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PMID:Plasma adenosine deaminase2: a marker for human immunodeficiency virus infection. 198 54

A series of 6-(hydroxylamino)purine and -1-deazapurine nucleosides were synthesized and tested for their antitumor and adenosine deaminase inhibitory activity. All the examined molecules displayed an in vitro activity comparable to that of the reference compounds 6-(hydroxylamino)-9-beta-D-ribofuranosylpurine (HAPR) and ara-A, their ID50 ranging from 0.9 microM to approximately 100 microM. The 6-hydroxylamino derivatives of 1-deazapurine 9, 12, and 17 and also the blocked compound 13 are inhibitors of ADA whereas the purine derivatives 4 and 6 and the nitro compounds 11 and 16 are resistant to the enzyme. 7-(Hydroxylamino)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3H-imi dazo[4,5- b]pyridine, the less cytotoxic but the most active ADA inhibitor in the series (Ki = 2.7 x 10(-7)), greatly potentiates the antitumor activity of ara-A in vitro.
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PMID:Purine and 1-deazapurine ribonucleosides and deoxyribonucleosides: synthesis and biological activity. 206 96

Retroviral-mediated gene transfer of human adenosine deaminase (hADA) provides a model system for the development of somatic gene therapy as a therapy for diseases of bone marrow-derived cells. We have previously demonstrated that hADA can be observed in all hematopoietic lineages in a minority of mice transplanted with bone marrow cells infected with a simplified retroviral vector, ZipPGK-ADA. Here we report a majority of mice (six of eight) demonstrate expression of hADA in the peripheral blood at least 6 months after transplantation with bone marrow infected with this simplified retroviral vector, which contains no selectable marker. The failure to express hADA in two of eight mice was associated with the absence of the recombinant retroviral provirus in DNA prepared from bone marrow cells of these mice apparently due to failure to efficiently infect the reconstituting hematopoietic stem cell. In an effort to preselect bone marrow stem cells containing proviral integrations, we incorporated the selectable marker neo phosphotransferase (NEO) into a retroviral vector encoding hADA, N2/ZipPGK-ADATKNEO, and used G418 selection of infected bone marrow cells before transplantation. In contrast to the simplified retroviral vector, hADA expression in these recipients was short lived (less than 8 weeks), despite the continued presence of intact provirus in DNA prepared from bone marrow of these mice. To determine whether the preselection of bone marrow using G418 was responsible for the lack of sustained hADA expression, we repeated the infection with the N2/ZipPGK-ADATKNEO vector but omitted the G418 selection step. Again, the majority of recipient mice failed to express hADA long term, although the continued presence of provirus in DNA prepared from peripheral blood cell mononuclear cells was clearly demonstrated. Finally, we demonstrate clonal fluctuation of infected stem cells, and observe a temporal correlation between cessation of expression of hADA and the emergence of a dominant stem cell clone between 14 and 20 weeks posttransplantation in one recipient. These data suggest that inclusion of a second transcriptional unit that includes neo phosphotransferase sequences in this simplified vector is associated with decreased expression of the nonselectable ADA sequences.
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PMID:Retroviral gene transfer of human adenosine deaminase in murine hematopoietic cells: effect of selectable marker sequences on long-term expression. 207 69

We have studied the expression of mRNA encoding adenosine deaminase (ADA; EC 3.5.4.4), purine nucleoside phosphorylase (PNP; EC 2.4.2.1), and terminal deoxynucleotidyltransferase (TdT; EC 2.7.7.31) in different leukemic cell lines of B- and T-cell lineage. Incubation of leukemic cells in the presence of the phorbol esters, 12-O-tetradecanoyl-phorbol-13-acetate or phorbol 12,13-dibutyrate, resulted in reduction of ADA and TdT mRNA levels, while PNP mRNA levels increased under the same treatment. The effect of TPA on the activity of these enzymes correlated well with its effects on their mRNA levels. TPA caused a 40% decrease in ADA and a 60% decrease in TdT enzyme activity, after 6 h of treatment. In contrast, PNP activity increased up to 200% after 12 h of incubation with the phorbol ester. The changes induced by the phorbol esters in the levels of mRNA of ADA, PNP, and TdT, and their enzyme activities in human leukemic cell lines mimic the changes in the activities of these enzymes in developing T-lymphocytes during differentiation in vivo, suggesting a role for protein kinase C in the regulation of ADA, PNP, and TdT gene expression during lymphoid cell differentiation.
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PMID:Phorbol esters induce changes in adenosine deaminase, purine nucleoside phosphorylase, and terminal deoxynucleotidyl transferase messenger RNA levels in human leukemic cell lines. 211 May 2

A novel fluorescent competitive inhibitor of adenosine deaminase (EC 3.5.4.4) (ADA), 1-N6-etheno-[erythro-9-(2-hydroxy-3-nonyl)] adenine (epsilon-EHNA), is protonated at the active site of the enzyme. In epsilon-EHNA [K1 = (4.06 +/- 1.00) 10(-6) M] part of the competitive inhibition of EHNA is combined with spectroscopic properties of etheno-adenines. Computer subtraction of the fluorescence excitation spectrum of ADA from that of its equimolar complex with epsilon-EHNA yielded the corrected excitation spectrum of epsilon-EHNA at the active site of the enzyme. This spectrum mimics that of epsilon-EHNA at pH 5.5 in buffer solution and is suggested to indicate a shift in protonation equilibrium at the active site.
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PMID:The protonated form of 1-N6-etheno-[erythro-9-(2-hydroxy-3-nonyl)] adenine is identified at the active site of adenosine deaminase. 215 76


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