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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)

Analysis of human adenosine deaminase (ADA) gene transcription in four different cell lines indicated that a high density of RNA polymerase II complexes is present at the 5' end of the gene and that the extent of transcription elongation beyond the promoter-proximal region governs gene expression. To determine the sequence requirements for a potential transcription arrest site in the promoter-proximal region, genomic clones containing the ADA promoter, exon 1, and various lengths of intron 1 were injected into Xenopus laevis oocyte germinal vesicles. Transcription analysis indicated that nascent ADA transcripts were highly represented at the promoter-proximal region of the injected templates, suggesting that transcription arrest occurred in the oocyte transcription system. Analysis of the transcription products indicated that ADA transcription initiated at the authentic start site and that the most prominent, short ADA transcripts were 105 nucleotides in length. The 3' end of these transcripts mapped within exon 1, 10 nucleotides downstream of the translation initiation codon. Deletion analysis demonstrated that sequences within exon 1 were sufficient to specify the synthesis of the 105-nucleotide transcripts. Taken together, these data suggest that a transcription arrest mechanism operates in the promoter-proximal region of the human ADA gene and that regulation of elongation beyond this point plays a major role in regulating ADA gene expression.
Mol Cell Biol 1990 Sep
PMID:Identification and characterization of transcriptional arrest sites in exon 1 of the human adenosine deaminase gene. 169 31

Adenosine deaminase activity was measured in cerebrospinal fluid of patients with confirmed tuberculous and bacterial meningitis. The values were compared with those of control subjects without meningitis. A statistically significant increase in the level of this enzyme was noted in the two types of meningitis, but no definite demarcation in the levels was observed between the two types. Therefore increases in adenosine deaminase activity may not be of such diagnostic significance as reported elsewhere.
Tubercle 1991 Sep
PMID:Adenosine deaminase levels in cerebrospinal fluid in tuberculosis and bacterial meningitis. 757 24

The value of ascites gamma interferon concentration and ascites adenosine deaminase activity in distinguishing tuberculosis from other causes of ascites was examined in a prospective study of 86 patients with ascites, including 16 with tuberculous peritonitis. Gamma interferon concentration was higher in tuberculous peritonitis than in the other causes of ascites (p less than 0.0001), and a cut-off between 3 and 9 u/ml reached a sensitivity and a specificity of 100%. The mean (+/- SD) gamma interferon level in tuberculous ascites was 39.3 +/- 18.3 u/ml in patients seronegative for HIV and 14.2 +/- 4.7 u/ml in patients with AIDS (p = 0.01). Adenosine deaminase activity in tuberculous ascites was also higher than in the other causes of ascites (p less than 0.0001), and a cut-off of 40 u/l reached a sensitivity of 100% and a specificity of 97%. The two false positives for adenosine deaminase test were true negatives for the gamma interferon test. There was no significant correlation between gamma interferon concentration and adenosine deaminase activity either in tuberculous ascitis or in any other group. This study suggests that ascites gamma interferon determination may be very useful in the screening of tuberculous peritonitis, but its cost makes it advisable to use adenosine deaminase activity as a routine test, at least in areas where tuberculosis is endemic.
Tubercle 1991 Sep
PMID:Diagnostic value of ascites gamma interferon levels in tuberculous peritonitis. Comparison with adenosine deaminase activity. 177 79

The rates of glycerol release in adipocytes isolated from nine identified adipose depots of sedentary or exercised guinea-pigs were measured in the presence of adenosine deaminase and 10(-9) to 10(-5) M noradrenaline and/or 1-1000 muunit/ml of bovine insulin. Twenty minutes of exercise increased the basal noradrenaline-stimulated rates of lipolysis in all depots, but these effects, and their interactions with in vitro application of the neurotransmitter differed between depots, showing that the long-lasting effects of exercise and the response to acute application of NA involve different mechanisms that may occur separately or together in different adipose depots. In general, large depots had the highest resting rates of lipolysis and the lowest responses to both noradrenaline and insulin, and lipolysis was only slightly different from the basal rate in adipocytes incubated with mixtures of the two agents. The two small intermuscular depots had the lowest unstimulated rates of lipolysis, but the fastest change and greatest maximum response to both agents. Noradrenaline-stimulated lipolysis was most effectively inhibited by small quantities of insulin in these depots. Different combinations of these properties were demonstrated in two smaller superficial depots, the mesenteric and omental depot, and in the cardiac depots. The data demonstrate the physiological inhomogeneity of both 'subcutaneous' and 'intra-abdominal' depots, and are consistent with the hypothesis that intermuscular adipose tissue interacts locally with adjacent muscle. Noradrenaline-stimulated lipolysis was more effectively inhibited by 100 muunit/ml insulin in adipocytes from the mesenteric and omental depot in those from any other site. A possible role for this property in the enlargement of this depot in hyperinsulinaemia in humans is proposed.
Int J Obes 1991 Sep
PMID:The effects of noradrenaline and insulin on lipolysis in adipocytes isolated from nine different adipose depots of guinea-pigs. 183 17

The effects of adenosine and the nonmetabolizable adenosine analogue N6-(L-2-phenylisopropyl)adenosine (PIA) on glucose transport or metabolism were determined in purified myocardial sarcolemmal vesicles, isolated cardiocytes, and perfused hearts. Adenosine (100 microM) did not affect hexose transport in myocytes. Also, adenosine deaminase, added to metabolize adenosine to inosine, did not alter transport of hexose into myocytes regardless of whether or not insulin was present. In contrast, PIA effectively inhibited 3-O-methyl-D-glucose uptake in myocytes even during insulin stimulation. PIA inhibited D-glucose-specific transport in both rat and bovine cardiac sarcolemmal vesicles (Ki = 26 microM at [D-glucose] = 5 mM). However, insulin did not affect glucose transport in sarcolemmal vesicles, which implies that receptor-coupled processes probably are not intact in this preparation. Thus, inhibition of PIA may not be receptor mediated. Also, PIA inhibited binding of cytochalasin B to bovine cardiac sarcolemmal vesicles, which supports the idea that PIA inhibits glucose flux by binding to the glucose transporter. To determine if adenosine altered glucose metabolism rather than transport, we measured the rate of 3H2O production from metabolism of D-[2-3H]glucose in paced rat hearts ([D-glucose] = 5.5 mM, [pyruvate] = 0.2 mM) perfused with a range of PIA or adenosine concentrations with or without 0.01 microM insulin. Adenosine (0.01-100 microM) in the presence or absence of insulin increased coronary flow but did not change glycolytic rates. Similar results were obtained with PIA (no insulin) rather than adenosine in the perfusate. However, with glucose as the only exogenous substrate, 100 microM PIA inhibited glycolysis by approximately 50%.(ABSTRACT TRUNCATED AT 250 WORDS)
Circ Res 1991 Sep
PMID:Myocardial glucose utilization. Failure of adenosine to alter it and inhibition by the adenosine analogue N6-(L-2-phenylisopropyl)adenosine. 187 73

The murine adenosine deaminase (ADA) gene has a (G + C)-rich promoter that can support diverse tissue-specific gene expression. By using deletion and mutation analyses, we have identified a cis-acting "repressor" element located immediately upstream of the proximal Sp1 binding site in the ADA gene promoter. This repressor element was localized to a binding site for the immediate-early, serum-responsive, DNA binding factor Zif268. This Zif268 binding site partially overlaps a binding site for the general transcription activator Sp1. Disruption of the Zif268 binding site without disturbing the Sp1 binding motif abolished Zif268 binding and resulted in significantly elevated promoter function. Conversely, disruption of the proximal consensus Sp1 binding motif without disturbing the Zif268 binding site resulted in a loss of Sp1 binding at that region and greatly reduced promoter activity. Our results suggest that one function of Zif268 may be to down-regulate this type of mammalian gene promoter by competing with Sp1 for binding to the overlapping binding motif.
Proc Natl Acad Sci U S A 1991 Sep 01
PMID:Functional significance of an overlapping consensus binding motif for Sp1 and Zif268 in the murine adenosine deaminase gene promoter. 188 92

Deoxyadenosine triphosphate (dATP) is present in adenosine deaminase (ADA)-deficient or ADA-inhibited human red cells and in the red cells of the opossum Didelphis virginiana. In order to investigate the functions of dATP in the red cell, red cells were treated with 2'-deoxycoformycin (dCf), a powerful inhibitor of ADA, and incubated with phosphate, deoxyadenosine and glucose. These red cells in which ATP was almost completely replaced by dATP, had the same shape, lactate production, nucleotide consumption, stability of reduced glutathione, osmotic fragility and cell deformability as red cells containing ATP. Cells merely depleted of ATP showed reduced viability. This indicates that dATP compensates well for the absence of ATP and acts as an energy-transferring molecule to maintain cell viability. These results indicate that the accumulation of dATP or the reduction of ATP is not the cause of the hemolysis observed after dCf administration.
Biochim Biophys Acta 1991 Sep 24
PMID:Deoxyadenosine triphosphate acting as an energy-transferring molecule in adenosine deaminase inhibited human erythrocytes. 191 76

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.
J Cell Biochem 1991 Sep
PMID:Adenosine deaminase deficiency due to heterozygous abnormality consisting of a deletion of exon 7 and the absence of enzyme mRNA. 193 66

The developmental toxicity of the potent adenosine deaminase (ADA) inhibitor, pentostatin (2'-deoxycoformycin), was investigated in pregnant rats and rabbits administered daily iv doses during organogenesis. Rats received 0, 0.01, 0.10, or 0.75 mg/kg on gestation days 6-15 and rabbits received 0, 0.005, 0.01, or 0.02 mg/kg on gestation days 6-18 and maternal and fetal parameters were evaluated on gestation day 21 (rats) or 30 (rabbits). Live fetuses were examined for external, visceral, and skeletal malformations and variations. In rats, maternal body weight gain and food consumption were significantly suppressed at doses of 0.10 and 0.75 mg/kg during the treatment period but returned to control levels during posttreatment. Increased postimplantation loss and decreased numbers of live fetuses, litter size, and fetal body weight were observed at 0.75 mg/kg. A statistically significant increase in the incidence of vertebral malformations occurred at 0.75 mg/kg. The incidence of certain skeletal variations (extra presacral vertebrae, extra ribs, hypoplastic vertebrae) was also increased at 0.75 mg/kg. Ossification of cervical centra was reduced at 0.75 mg/kg compared with controls. In rabbits, marked maternal toxicity (death, body weight loss, and decreased food consumption) and reproductive toxicity (abortion and premature delivery) occurred in all pentostatin-treated groups. However, there were no significant effects on number of live fetuses, pre- or postimplantation loss, litter size, or fetal body weights in the animals with live litters. There was also no apparent increase in the incidence of malformations or variations in the live fetuses of pentostatin-treated rabbits. Thus, these studies demonstrate developmental toxicity of pentostatin in rats and rabbits, and teratogenicity in rats, at maternally toxic doses.
Teratology 1991 Sep
PMID:Developmental toxicity of pentostatin (2'-deoxycoformycin) in rats and rabbits. 194 67

Amphotropic recombinant retroviruses were generated carrying sequences encoding human adenosine deaminase (ADA). Transcription of the human ADA gene was under control of a hybrid long terminal repeat in which the enhancer from the Moloney murine leukemia virus was replaced by an enhancer from the F101 host-range mutant of polyoma virus. Hemopoietic stem cells in murine bone marrow were infected with this virus under defined culture conditions. As a result, 59% of day-12 colony forming unit spleen (CFU-S) stem cells became infected without any in vitro selection. Infected CFU-S were shown to express human ADA before transplantation and this expression sustained upon in vivo maturation. Mice transplanted with infected bone marrow exhibited human ADA expression in lymphoid, myeloid, and erythroid cell types. Moreover, human ADA expression persisted in secondary and tertiary transplanted recipients showing that human ADA-expressing cells were derived from pluripotent stem cells. These characteristics of our amphotropic viruses make them promising tools in gene therapy protocols for the treatment of severe combined immunodeficiency caused by ADA deficiency. In this respect it is also relevant that the viral vector that served as backbone for the ADA vector was previously shown to be nonleukemogenic.
J Exp Med 1990 Sep 01
PMID:Expression of human adenosine deaminase in mice transplanted with hemopoietic stem cells infected with amphotropic retroviruses. 197 14


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