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Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lymphoblastoid cell lines from a patient with adenosine deaminase (ADA) deficiency and his parents were established by Epstein-Barr virus (EBV). ADA activity in the lymphoblastoid cells from the patient was not detectable, while the enzyme activity in the cells from his parents was approximately a half level of the controls'. No inhibitor to ADA could be detected in the lymphoblastoid cells from the patient.
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PMID:A lymphoblastoid cell line from an adenosine deaminase deficient patient established by Epstein-Barr virus. 22 40

Induction of Epstein-Barr virus (EBV) capsid antigen synthesis in 59.6% of P3HR-1 cells was followed by a decrease to 70% in adenosine deaminase (ADA) activity. In Daudi cells synthesizing EBV early antigen, ADA activity did not decrease.
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PMID:Adenosine deaminase activity in relation to the appearance of early and late Epstein-Barr virus antigens induced in lymphoblastoid cells. 166 42

Extrachromosomal elements are common early intermediates of gene amplification in vivo and in cell culture. The time at which several extrachromosomal elements replicate was compared with that of the corresponding amplified or unamplified chromosomal sequences. The replication timing analysis employed a retroactive synchrony method in which fluorescence-activated cell sorting was used to obtain cells at different stages of the cell cycle. Extrachromosomally amplified Syrian hamster CAD genes (CAD is an acronym for the single gene which encodes the trifunctional protein which catalyzes the first three steps of uridine biosynthesis) replicated in a narrow window of early S-phase which was approximately the same as that of chromosomally amplified CAD genes. Similarly, extrachromosomally amplified mouse adenosine deaminase genes replicated at a discrete time in early S-phase which approximated the replication time of the unamplified adenosine deaminase gene. In contrast, the multicopy extrachromosomal Epstein-Barr virus genome replicated within a narrow window in late S-phase in latently infected human Rajii cells. The data indicate that localization within a chromosome is not required for the maintenance of replication timing control.
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PMID:Replication timing control can be maintained in extrachromosomally amplified genes. 167 57

B-lymphoblastoid cell lines (LCL) transformed by Epstein-Barr virus (EBV) were established from a patient with severe combined immunodeficiency (SCID) caused by adenosine deaminase (ADA) deficiency, from his mother and from a normal volunteer. ADA activities of the patient's and mother's LCL were about 0.5% and 25% of that of the normal LCL, respectively. Proliferation of these three LCL was related to the ADA activity. The patient's LCL grew well in medium containing fetal bovine serum (FBS), but slowly in medium with the ADA inhibitor 2'-deoxycoformycin-treated FBS, horse serum, or without serum. Proliferation of the patient's LCL was markedly inhibited in serum-free medium containing 2'-deoxyadenosine.
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PMID:Comparative characterization of B-lymphoblastoid cell lines in adenosine deaminase deficiency and its heterozygote. 261 47

The subject of this investigation was an 11-month-old infant girl who presented with a pathological fracture of the right femur due to a metastasis from an abdominal immunoblastic sarcoma. Her past history included recurrent, intractable bacterial and fungal infections. Investigations of her immune status revealed low numbers of T-lymphocytes, a reversed T-helper (TH)/T-suppressor (TS) cell ratio, no response of her peripheral blood lymphocytes to pokeweed mitogen, phytohemagglutinin, concanavalin A, and Candida albicans, and an inability of her cells to react in a mixed lymphocyte culture. Serum levels of IgG, IgM, and IgA were all below normal. No thymic shadow was visible on the chest radiograph. There was no evidence of adenosine deaminase or nucleoside phosphorylase deficiencies. The tumor cells exhibited both surface IgM and IgG, and many of the cells contained large amounts of cytoplasmic IgM. Light chain specificity was restricted to lambda chain for both surface and cytoplasmic immunoglobulin. Ultrastructural study of the tumor cells revealed the presence of both intranuclear and cytoplasmic virions in roughly 1% of the tumor cells. These viral particles strongly resembled herpes viruses. DNA-hybridization studies on the neoplasm revealed the presence of 7-10 genome equivalents of Epstein-Barr virus-DNA per tumor cell.
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PMID:Demonstration of Epstein-Barr virus in immunoblastic sarcoma of B-cells arising in a child with primary immunodeficiency disease. 282 Feb 54

Cultured human T-cell leukemia lymphocytes have enhanced sensitivity to growth inhibition by deoxyadenosine. We have used flow cytometry to investigate the mechanism of deoxyadenosine toxicity in cultured T-leukemic cells. Comparative studies on deoxyadenosine-resistant Epstein-Barr virus-transformed B-lymphocyte cell lines were also performed. After exposure of T-cells to low concentrations of deoxyadenosine (3 microM), in the presence of an adenosine deaminase inhibitor (erythro-9-[3-(2-hydroxynonyl)]adenosine), accumulation of cells of cells with a G1 DNA content was demonstrated. In contrast, B-cell lines showed a similar degree of growth inhibition after exposure to 200 to 400 microM deoxyadenosine but were blocked in S phase. The T-cell G1 block was associated with a rise in the deoxyadenosine triphosphate pool, and both these phenomena were prevented by the addition of deoxycytidine. The biochemical mechanism of this G1 block induced by deoxyadenosine in T-cells is not understood.
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PMID:G1-phase arrest of cultured human leukemic T-cells induced by deoxyadenosine. 627 90

Adenine arabinoside (ara-A) at a concentration of 5-10 micrograms/ml inhibited the multiplication of two Epstein-Barr virus (EBV) producer lymphoblastoid cell lines B . 95-8 and P3HR-1. The nonproducer EBV genome carrier cell line, Raji, and the EBV negative cell line, Ramos, were not significantly affected. The cytotoxicity of ara-A to Ramos, Raji and P3HR-1 cells increased in the presence of 1 . 10(-5)M erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), an inhibitor of adenosine deaminase. EHNA alone was noncytotoxic and even had a mild stimulatory effect on cell multiplication. The level of adenosine deaminase in Raji and Ramos cells was similar to that observed in human cord blood lymphocytes, as determined by starch gel electrophoresis. A low level of adenosine deaminase was detected in P3HR-1 cells and the enzyme was absent from B . 95-8 cells. These findings indicate that in the absence of adenosine deaminase, ara-A cytotoxicity increased. Ara-A (5 micrograms/ml) and EHNA (1 . 10(-5)M) had no effect on human cord blood lymphocytes stimulated by phytohemagglutinin as measured by (3H) thymidine uptake, but had some effect on protein A-stimulated lymphocytes. Ara-A, however, inhibited the transformation of human cord blood lymphocytes by EBV, which EHNA did not inhibit. The synthesis of EBV capsid antigen in B . 95-8 cells was also inhibited by ara-A and slightly stimulated by EHNA.
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PMID:Cytotoxicity of arabinofuranosyladenine and erythro-9-(2-hydroxy-3-nonyl) adenine to Epstein-Barr virus producer and nonproducer lymphoma cells in culture. 630 55

The metabolism of 8-14C-labelled 2'-deoxyadenosine (dAR) and 2'-deoxyguanosine (dGR) has been investigated using lymphocytes in long-term culture transformed by Epstein-Barr (EB) virus (B-cells) from eight patients with different inherited purine enzyme defects. The use of such lines enabled accurate mapping of the route of metabolism by acting as a 'trap' for the radiolabel at specific points. With either substrate (25 microM) most of the label was recovered in the medium. Using dAR, less than 30% of the radiolabel was incorporated into cellular nucleotides. For dGR, values were less than 18%. Studies with dAR alone confirmed the principal route of metabolism was to hypoxanthine, with further metabolism (by lines with intact salvage pathways) to ATP and GTP in the ratio of approximately 4:1. Lack of accumulation of deoxyinosine in the purine nucleoside phosphorylase (PNP) deficient line, or hypoxanthine in the hypoxanthine guanine phosphoribosyltransferase (HGPRT) deficient line, using dAR together with the adenosine deaminase (ADA) inhibitor 2'-deoxycoformycin (dCF) at 10 microM, confirmed the effectiveness of ADA inhibition. Nevertheless, some ATP was still formed by all lines in the presence of dCF by a route as yet unknown. Only the ADA deficient lines formed dATP with dAR alone. However, some dATP was formed by all lines in the presence of dCF. A partially HGPRT deficient line formed extremely high dATP levels, well in excess of those formed by the T-cell line CEM. Studies with dGR revealed some interesting differences, a large proportion of the substrate being metabolized predominantly to xanthine by most enzyme deficient lines. In the PNP deficient line most of the substrate remained unmetabolized, but some dGTP was formed. No other enzyme deficient line formed any dGTP--with or without the PNP inhibitor 8-aminoguanosine (8-NH2GR)--with one exception. Again this was the partially HGPRT deficient line, which with the inhibitor again formed more dGTP than the T-cell line. Within the cells most of the substrate was metabolized to GTP, except in the PNP, and totally HGPRT deficient lines. Levels of GTP formed were not altered by the inhibitor, reflecting the lack of effective PNP inhibition by 8-NH2GR. Some counts were also found in ATP and IMP, confirming the existence of this route in mammalian cells of lymphoid origin. The results also support previous studies by us using cell lines with intact purine pathways, which demonstrated that, contrary to current beliefs, some B-cell lines are capable of accumulating high levels of deoxynucleotides.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Metabolism of deoxynucleosides by lymphocytes in long-term culture deficient in different purine enzymes. 642 79

A 4-kb HindIII fragment that supported the efficient autonomous replication of plasmid vector pDY-, a replication-defective construct based on Epstein-Barr virus sequences, in human K562 cells was rescued from amplified double-minute chromosomes containing the murine adenosine deaminase locus. Polymerase chain reaction assays of size-fractionated nascent strands demonstrated that replication initiation occurred within the same 1- to 2-kb region of this fragment in autonomously replicating plasmids containing the sequence in either orientation, in double-minute chromosomes, and in the single-copy locus at its normal chromosomal location. The complete sequence of this fragment was determined; it contains a 248-bp polypurine tract and consensus binding site sequences for several putative transcription and replication factors.
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PMID:Analysis of a replication initiation sequence from the adenosine deaminase region of the mouse genome. 841 98

In the past year, a number of human gene therapy trials involving the adoptive transfer of genetically modified T lymphocytes have been reported. These include trials of adenosine deaminase gene transfer in children with severe combined immunodeficiency syndrome, a gene-marking study of Epstein-Barr virus-specific cytotoxic T cells, and trials of gene-modified T cells expressing suicide or viral resistance genes in patients infected with HIV. Additional strategies for T-cell gene therapy currently being pursued in the clinic involve the engineering of novel T-cell receptors that impart antigen specificity for virally infected or malignant cells.
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PMID:T-cell gene therapy. 893 44


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