Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Experiments in vitro were made to study adenosine deaminase (ADA) and 5'-nucleotidase (5-N) activity in NK after their treatment with interferon inductor--Newcastle disease virus (NDV) or with prostaglandin E2 (PGE2). It has been established that treatment of human NK with NDV leads to increasing of their cytotoxic activity (CTA), which is accompanied by rising of ADA activity and reducing of 5-N activity in these cells. Decrease of CTA under the influence of PGE2 occurs together with reduction of ADA activity and increase of 5-N activity in human NK. Changes in NK activity under the influence of various exogenous or endogenous factors may be due to the modification of activity of adenosine metabolism enzymes in these cells.
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PMID:[Enzyme activity of adenosine metabolism in human natural killers (NK cells) during the activation and suppression of their cytotoxic activity]. 254 32

2'-Deoxycoformycin (pentostatin [dCF]), a potent inhibitor of adenosine deaminase (ADA), was administered in a biweekly low-dose (2 to 4 mg/m2) intravenous (IV) schedule to patients with advanced hairy cell leukemia. Twenty-three patients were treated, including 12 patients previously treated by splenectomy and five patients treated with interferon. Twenty-one of 23 patients had objective responses, including 20 who achieved a complete remission (CR). Responses occurred rapidly, with an average time to CR of 5.4 months. Treatment was not continued once CR was achieved, and 15 of 20 patients remain in remission with an average duration of 12.6 months. CRs were achieved in both patients previously treated with interferon (three of five) and patients with marked splenomegaly (three of three). Relapses, when seen, have occurred in the bone marrow alone and the one patient who required retreatment was reinduced into CR. Toxicity has been mild and reversible, with nausea and vomiting, conjunctivitis, and skin rash as the main complications of treatment. dCF is the most effective single agent in the treatment of hairy cell leukemia, inducing a high percentage of CRs in all subgroups. Two multiinstitutional trials are now underway to compare its effectiveness v alpha interferon.
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PMID:Pentostatin in the treatment of advanced hairy cell leukemia. 278 31

The in vitro effect of short-term culture as well as the effect of retinol (ROH), retinoic acid (RA), muramyl dipeptide [( Abu']MDP), lipopolysaccharide (LPS), and gamma interferon (IFN-gamma) on the induction of the purine metabolic enzymes, adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5'nucleotidase (5NT) in human peripheral blood monocytes (HPBM) was examined. HPBM isolated by centrifugal elutriation were cultured for up to 96 h. Following an initial time lag of 24 h, mean ADA activity from seven separate experiments as measured in nmoles/10(6) cells/h increased from a baseline of 31.3 +/- 9.3 to 57.8 +/- 16.4 (P less than 0.005) at 72 h and to 72 +/- 21.5 (P less than .025) by 96 h. 5NT activity increased from a baseline of 2.2 +/- 0.9 to a maximum of 44 +/- 10.1 by 72 h and then declined to 29 +/- 18 (P less than 0.005) by 96 h, while no significant change in PNP activity was observed. HPBM incubated for 3 d with optimal concentrations of LPS, RA, and IFN-gamma had increases in ADA and 5NT activity ranging from three- to 10-fold compared to HPBM cultured in media alone, whereas no effect was observed with ROH and [Abu']MDP. RA, but not ROH, significantly enhanced ADA activity in a monocytic leukemia cell (THP-1) line. Addition of RA or the tumor promoter, phorbol 12-myristic 13-acetate (PMA), to HPBM or THP-1 cells resulted in significant increases in 5NT activity with opposite effects on ADA activity. These findings suggest that the biological mechanisms associated with differentiation in normal and malignant monocytes seem to be related and that the sequence and degree to which the various differentiation agents induce the enzyme elevations are also related to the mechanisms of activation/differentiation.
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PMID:Induction of adenosine deaminase and 5' nucleotidase activity in cultured human blood monocytes and monocytic leukemia (THP-1) cells by differentiating agents. 284 22

Laboratory and clinical data relating to the use of 2'-deoxycoformycin in human disease are reviewed. Pentostatin is an inhibitor of adenosine deaminase, an enzyme that is important for purine metabolism, but more than one mechanism may be involved in its cytotoxic action. Early studies with dCF employed large doses and for the most part were conducted in patients with acute lymphocytic leukaemia: responses were brief and relatively few, and severe renal, hepatic, and central nervous system toxicity were encountered, leading to temporary abandonment of clinical trials. More recently, it has been shown that dCF is effective in much smaller doses, with considerably less toxicity. It has proved to be more effective in low-grade lymphoid malignancies (chronic leukaemias, indolent lymphomas) than in more undifferentiated neoplasms (acute leukaemias, lymphoblastic and immunoblastic lymphomas), and is outstandingly effective in hairy cell leukaemia, both as initial therapy and after failure of splenectomy and interferon. Pentostatin is profoundly immunosuppressive: generally this is considered a disadvantage but its potential therapeutic exploitation merits investigation. Despite extensive knowledge of its biochemical effects, the optimal dose regimen of dCF and the value of combining it with purine antagonists remain to be defined.
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PMID:The role of pentostatin (2'-deoxycoformycin, dCF) in the management of lymphoproliferative malignancies. 333 90

A 6,474-nucleotide human cDNA clone designated K88, which encodes double-stranded RNA (dsRNA)-specific adenosine deaminase, was isolated in a screen for interferon (IFN)-regulated cDNAs. Northern (RNA) blot analysis revealed that the K88 cDNA hybridized to a single major transcript of approximately 6.7 kb in human cells which was increased about fivefold by IFN treatment. Polyclonal antisera prepared against K88 cDNA products expressed in Escherichia coli as glutathione S-transferase (GST) fusion proteins recognized two proteins by Western (immunoblot) analysis. An IFN-induced 150-kDa protein and a constitutively expressed 110-kDa protein whose level was not altered by IFN treatment were detected in human amnion U and neuroblastoma SH-SY5Y cell lines. Only the 150-kDa protein was detected in mouse fibroblasts with antiserum raised against the recombinant human protein; the mouse 150-kDa protein was IFN inducible. Immunofluorescence microscopy and cell fractionation analyses showed that the 110-kDa protein was exclusively nuclear, whereas the 150-kDa protein was present in both the cytoplasm and nucleus of human cells. The amino acid sequence deduced from the K88 cDNA includes three copies of the highly conserved R motif commonly found in dsRNA-binding proteins. Both the 150-kDa and the 110-kDa proteins prepared from human nuclear extracts bound to double-stranded but not to single-stranded RNA affinity columns. Furthermore, E. coli-expressed GST-K88 fusion proteins that included the R motif possessed dsRNA-binding activity. Extracts prepared either from K88 cDNA-transfected cells or from IFN-treated cells contained increased dsRNA-specific adenosine deaminase enzyme activity. These results establish that K88 encodes an IFN-inducible dsRNA-specific adenosine deaminase and suggest that at least two forms of dsRNA-specific adenosine deaminase occur in human cells.
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PMID:Expression and regulation by interferon of a double-stranded-RNA-specific adenosine deaminase from human cells: evidence for two forms of the deaminase. 756 88

Treatment of human amnion U cells with interferon increased the steady state level of mRNA encoding the double-stranded (ds) RNA-specific adenosine deaminase (AdD) as measured by Northern gel-blot analysis. A single major dsRNA-specific AdD transcript of approximately 6.7 kb was detected; the transcript was induced by both interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma). Likewise, Western immunoblot analysis revealed that a 150-kDa protein recognized by antiserum prepared against recombinant dsRNA-specific AdD was increased in the human amnion U and neuroblastoma SH-SY5Y cell lines treated with interferon. Both IFN-alpha and IFN-gamma induced the 150-kDa protein. These results, which establish that dsRNA-specific AdD is an IFN-inducible protein in human cells, have implications regarding the possible role of interferon in persistent viral infections.
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PMID:Mechanism of interferon action: double-stranded RNA-specific adenosine deaminase from human cells is inducible by alpha and gamma interferons. 761 88

The gamma interferon (gamma-IFN) concentration and the adenosine deaminase (ADA) activity were evaluated in 30 patients with tuberculous peritonitis, 21 patients with ascites due to a malignant disorder, and 41 patients with cirrhosis. The gamma-IFN concentrations were significantly higher (p < 0.0001) in tuberculous peritonitis patients (mean: 6.70 U/ml) than in the malignant (mean: 3.10 U/ml) and cirrhotic (mean: 3.08 U/ml) groups. Use of a cut off value of > or = 3.2 U/ml gave the assay a sensitivity of 93% (25 of 27), a specificity of 98% (54 of 55), positive (P+) and negative (P-) predictive values of 96% and a test accuracy of 96%. The ADA activity was significantly (p < 0.0001) higher in the tuberculous peritonitis group (mean: 101.84 U/l) than in the control groups (cirrhosis (mean: 13.49 U/l) and malignancy (mean: 19.35 U/l)). A cut off value of > 30 U/l gave the ADA test a sensitivity of 93% (26 of 28) a specificity of 96% (51 of 53), a (P+) value of 93%, a (P-) value of 96%, and a test accuracy of 95%. There was a significant (p < 0.0001) correlation (r = 0.72) between ADA activity and gamma-IFN values in patients with tuberculous peritonitis. These results show that a high concentration of gamma-IFN in ascitic fluid is as valuable as the ADA activity in the diagnosis of tuberculous peritonitis. Both are rapid non-invasive diagnostic tests for tuberculous peritonitis.
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PMID:Ascitic fluid gamma interferon concentrations and adenosine deaminase activity in tuberculous peritonitis. 769 2

Since the introduction of adenosine deaminase analogues the vast majority of patients with Hairy cell leukemia obtain lasting complete remission. In this report we describe our experience with 2 CdA in 18 patients with Hairy cell leukemia (HCL). Ten of these had failed previous interferon therapy, 6 were splenectomized before and of these, 4 had also received interferon. Sixteen of the 18 patients receiving 2 CdA achieved complete remission (CR), 1 patient is in good partial response (GPR) and 1 patient has relapsed. These results are in keeping with those reported from other larger centers and confirm the efficacy of 2-CdA. In this report IL-2 receptor (sIL-2R) levels were performed in most of the patients and found to be an accurate indicator of disease activity. Mean levels prior to therapy were 17200 U/ml (+/- 2500) and after successful therapy 970 U/ml (+/- 160). We confirm that 2-CdA treatment is the treatment of choice in HCL and suggest that sIL-2 levels be used as a parameter of disease activity.
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PMID:Hairy cell leukemia: results of 2-chlorodeoxyadenosine therapy in Jerusalem. 782 44

The level of tumor necrosis factor (TNF)-alpha, soluble TNF receptors p75 (sTNFR-75) and sTNFR-55, interferon (IFN)-gamma, and interleukin (IL)-10 and IL-12 were measured in 59 cerebrospinal fluid (CSF) samples from 15 patients with tuberculous meningitis (TBM). TBM was associated with elevated concentrations of TNF-alpha, sTNFR-75, sTNFR-55, IFN-gamma, and IL-10, while CSF IL-12 was undetectable in all TBM patients. A significant correlation between cytokines and CSF adenosine deaminase activity was also found. The levels of TNF-alpha did not decrease over time, being still detectable in the CSF 16 months after starting antibiotic therapy, whereas IFN-gamma along with anti-inflammatory mediators sTNFR-75, sTNFR-55, and IL-10 remained elevated in the CSF for 4-8 months. The chronic release of cytokines in the CSF compartment was related neither to the TBM stage nor to the clinical outcome of the disease, thus suggesting the presence of a continuous activity of the inflammatory process at the site of infection.
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PMID:Cerebrospinal fluid cytokines in patients with tuberculous meningitis. 924 49

The virus-associated VAI RNA of adenovirus is a small highly structured RNA that is required for the efficient translation of cellular and viral mRNAs at late times after infection. VAI RNA antagonizes the activation of the interferon-inducible RNA-dependent protein kinase, PKR, an important regulator of translation. The RNA-specific adenosine deaminase, ADAR, is an interferon-inducible RNA-editing enzyme that catalyzes the site-selective C-6 deamination of adenosine to inosine. ADAR possesses three copies of the highly conserved RNA-binding motif (dsRBM) that are similar to the two copies found in PKR, the enzyme in which the prototype dsRBM motif was discovered. We have examined the effect of VAI RNA on ADAR function. VAI RNA impairs the activity of ADAR deaminase. This inhibition can be observed in extracts prepared from interferon-treated human cells and from monkey COS cells in which wild-type recombinant ADAR was expressed. Analysis of wild-type and mutant forms of VA RNA suggests that the central domain is important in the antagonism of ADAR activity. These results suggest that VAI RNA may modulate viral and cellular gene expression by modulating RNA editing as well as mRNA translation.
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PMID:Adenovirus VAI RNA antagonizes the RNA-editing activity of the ADAR adenosine deaminase. 963 58


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