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)

Clinical and analytic data of 64 patients with firm etiologic diagnosis of pleural effusion with adenosine deaminase (ADA) present, were analyzed retrospectively. The patients had entered our hospital over a 40-month period. ADA activity in pleural fluid was analyzed by the Blake and Berman kinetic method. Mean ADA activity of the total sample was 32 U/l (SD:23.9). In patients with tuberculous pleural effusion ADA activity was higher than in the remaining patients (47.7, SD:21.4, versus 15.5 SD: 13.2; p < 0.0001). In the group of patients with tuberculous pleuritis diagnosed by pleural biopsy (22 cases) the presence of necrotizing granulomas was associated with slightly higher ADA activity although the difference was not statistically significant (49.2 SD 10.1 versus 41.3 SD 8.9; p = 0.07). Among only patients with tuberculous pleuritis or neoplasia with lymphocytic exudate, a cut off point greater than 23 U for ADA predicted a diagnosis of tuberculous pleuritis with a sensitivity of 0.96, specificity of 1, positive predictive value of 1, negative predictive value of 0.94, and a confidence limit of 0.97. In conclusion, ADA activity greater than 23 U determined by the kinetic method in pleural fluid with signs of lymphocytic exudate is strongly suggestive of pleural tuberculosis based on our sample of patients with pleural effusion.
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PMID:[Adenosine deaminase activity in the pleural effusion. A study of 64 cases]. 814 81

Adenosine deaminase is one of the key enzymes in purine nucleotide degradation. This enzyme exists in most of the human tissues and the activity is high in lymphatic tissues, especially in T lymphocytes. Elevated adenosine deaminase activity in T cell leukemia has been reported, and its inhibitor, deoxycoformycin, has been developed as an antitumor agent. In some types of leukemia, serum adenosine deaminase activity increases in accordance with the severity of the disease. Although mycosis fungoides rarely involves peripheral blood, tumor cells do invade the skin. In order to evaluate the clinical significance of adenosine deaminase in mycosis fungoides, adenosine deaminase activity was measured in sera of 15 patients with mycosis fungoides at various stages. The mean enzyme activity was 23.2 IU/l, which was high with statistical significance compared with healthy controls (P < 0.001). Nine of twelve patients in the plaque stage (T2N0M0, IB) showed higher adenosine deaminase activity than did the normal population. The mean adenosine deaminase activity in sera in the patients in the plaque stage (T2N0M0, IB) was as high as 19.0 IU/l (range 13.7-21.4) with statistical significance compared with healthy control (P < 0.001). Three tumor stage patients without visceral involvement (T3N0M0, IIB) showed higher levels of adenosine deaminase activity (19.7, 21.5, 24.4 IU/l). An erythrodermic patient (T4N0M0, III) also had a high adenosine deaminase activity 28.4 IU/l. Two tumor stage patients with organ involvement (T3N0M1, IVB) exhibited extremely high adenosine deaminase activity (60.9, 32.2 IU/l). The adenosine deaminase activity in sera showed a tendency to become higher with the extension of the stages.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical significance of serum adenosine deaminase activity in patients with mycosis fungoides. 840 19

The effect of 3'-deoxyadenosine N(1)-oxide (3'-dANO) on Ehrlich ascites tumor and a human squamous lung cell carcinoma was investigated. The 3'-dANO concentration that inhibited the cell growth 50% (IC(50)) in Ehrlich ascites tumor cells in vitro was 0.15 mM, and the killing efficiency concentration (concentration of the drug that kills all cells) was 1 mM. By simultaneous administration of 3'-dANO and the adenosine deaminase inhibitor erythro-9-(2-hydroxyl-3-nonyl) adenine (EHNA), the IC(50) of 3'-dANO was unchanged, but the killing efficiency concentration of 3'dANO was reduced to 0.3 mM. When mice bearing Ehrlich ascites tumor were treated i.p. with 3'-dANO doses of 200 mg/kg daily for 4 days, the mean increased life span (ILS) was 200%. 3'-dANO in combination with EHNA did not further increase the life span of the tumor-bearing mice. The specific growth delay (SGD) of the Ehrlich tumor and of a human squamous lung cell carcinoma growing subcutaneously in 3'-dANO-treated mice were calculated from Gomperts tumor growth curves. The Ehrlich tumor-bearing mice received 3'-dANO i.p. at doses of 250 mg/kg daily for 4 days, and the nude mice bearing human carcinoma received 3'-dANO i.p. at doses of 225 mg/kg daily for 5 days. The SGD for the investigated tumors were calculated to be 1.0 and 1.1, respectively.
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PMID:The effect of 3'-deoxyadenosine N(1)-oxide on growth in vitro and in vivo on Ehrlich ascites tumor and on a human squamous lung cell carcinoma xenograft in nude mice. 859 87

Because of the difficulty in isolating the causative organism, pericardial tuberculosis is rarely diagnosed. Adenosine deaminase activity measured in the pericardial fluid of 108 patients was initially of undetermined origin. Subsequently, we classified five sources: (1) tuberculosis (20 cases); (2) idiopathy (82 cases); (3) neoplasia (three cases); (4) purulent bacterial infection (two cases); and (5) radiotherapy (one case). The highest mean adenosine deaminase value (126 +/- 16.68 U.l(-1) was found in group 1; other values were 29.4 +/- 8.9, 27 +/- 7.21, 29.5 +/- 13.4, 26 U.l(-1) in the idiopathy, neoplasia, purulent bacterial infection and radiotherapy groups, respectively. there was a statistically significant difference between group 1 and the other groups (P less than 0.001), indicating that the adenosine deaminase value has 100% sensitivity and 91% specificity. In addition, there was a positive correlation between high adenosine deaminase values and the development of constrictive pericarditis. In this study, two patients required pericardectomy. Therefore, the adenosine deaminase value is a significant prognostic indicator for the development of constrictive pericarditis in tuberculous pericarditis.
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PMID:The diagnostic and prognostic value of adenosine deaminase in tuberculous pericarditis. 866 76

Newcastle disease virus (NDV) has received much attention recently because of its non-specific immune stimulating potential and its various anti-tumor activities. Here we describe that NDV induces synthesis of NO and causes an activation of nuclear factor-kappa B (NF-kappa B) in murine macrophages. These reactions were part of an activation process which included also stimulation of adenosine deaminase and inhibition of 5'-nucleotidase. NDV-mediated NO synthesis and NF-kappa B activation were blocked by an antioxidant (butylated hydroxyanisole), by an inhibitor of protein tyrosine kinase (genistein) and of protein kinase A (H-89), but not by an inhibitor of protein kinase C (staurosporin). These data suggest that signalling requirements of NF-kappa B activation and NO production in NDV-treated macrophages are similar.
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PMID:Induction of NO synthesis in macrophages by Newcastle disease virus is associated with activation of nuclear factor-kappa B. 867 35

Adenosine deaminase activity was studied in tissue slices taken endoscopically from gastric mucosa of patients with the intestinal type of gastric carcinoma. The enzyme activity was measured in mucosal homogenates by determination of ammonia liberated from substrate during 10-min incubation. It was found that: (1) the enzyme activity of de novo gastric cancer was significantly lower than that of recurrent cancer of the gastric remnant; and (2) the enzyme activity of uninvaded gastric mucosa surrounding the neoplastic lesion of non-operated stomach was significantly lower than of the gastric mucosa of partially resected stomach due to malignancy. Since the enzyme activity in gastric cancer and surrounding uninvaded gastric mucosa correlated well with the advance of neoplastic disease estimated by ultrasonography examination, we speculate that some systemic factors associated with tumor progression might be implicated in the regulation of adenosine deaminase activity.
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PMID:Adenosine deaminase activity in patients with the intestinal type of gastric carcinoma. 902 Sep 21

The purine nucleoside adenosine (9-beta-D-ribofuranosyladenine) inhibits a number of lymphocyte functions in vitro, including the ability of activated T lymphocytes and natural killer cells to adhere to and kill tumor targets. Solid tumors, such as adenocarcinomas of the lung and colon, are frequently hypoxic and are, therefore, likely to exhibit increased adenine nucleotide breakdown through the 5'-nucleotidase pathway, yielding adenosine. We examined whether the concentration of adenosine in the extracellular fluid of such tumors is adequate to cause immunosuppression. Murine tumors grown in syngeneic hosts or human tumors grown in immunodeficient nu/nu mice were subjected to microdialysis, and adenosine levels in the microdialysate were measured by high-performance liquid chromatography. Treatment of the tumor microdialysates with adenosine deaminase eliminated the adenosine peak. Recovery of adenosine ranged from 15 to 29%, depending on the microdialysis probe, and concentrations of adenosine in tumors ranged from 0.2 to 2.4 microM with a mean of 0.5 microM. In contrast, the adenosine concentration measured s.c. at the same location was 30 +/- 5 nM (mean +/- SE). Inclusion of the adenosine deaminase inhibitor coformycin (10 microM) and the adenosine kinase inhibitor 5'-iodotubercidin (0.1 microM) in the microdialysis perfusion buffer increased extracellular adenosine concentration in tumors to as high as 13 microM. These data show that extracellular adenosine levels in solid tumors are sufficient to suppress the local antitumor immune response and that interference with pathways of adenosine metabolism causes marked increases in tumor extracellular adenosine concentration.
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PMID:The extracellular fluid of solid carcinomas contains immunosuppressive concentrations of adenosine. 920 63

Identification of A1 adenosine receptors (A1Rs) in a tumor cell line derived from rat pituitary (GH4 cells) was performed by ligand binding and immunological experiments. Subsequently, the involvement of A1Rs in the regulation of calcium conductance was studied in these cells. The agonist N6-(R)-(2-phenylisopropyl)adenosine (R-PIA) did not modify the intracellular calcium basal levels, whereas it inhibited the increase produced by 15 mM KCl depolarization. The antagonist 1,3-dipropyl-8-cyclopentylxanthine led to the opening of voltage-dependent cell surface calcium channels in the absence of exogenous KCl. The channels were of the L type because the effect was abolished by calciseptine and by verapamil. These results suggest that endogenous adenosine exerts a tonic inhibitory effect on calcium transport. This was confirmed by the high adenosine concentration found in cell supernatants (up to 1 microM) and by the calcium mobilization produced by exogenously added adenosine deaminase. In depolarizing conditions, the calcium peak in the presence of adenosine deaminase was reduced when cells were preincubated with R-PIA, thus suggesting that A1R activation regulates the intensity of depolarization. These results demonstrate that adenosine is an important regulator of the physiological state of pituitary tumor cells by modulating, in an autocrine manner, the activity of L-type voltage-dependent calcium channels.
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PMID:Regulation of L-type calcium channels in GH4 cells via A1 adenosine receptors. 937 88

Host-cell reactivation (HCR) of UV-C-irradiated herpes simplex virus type 1 (HSV-1) has been determined in skin fibroblasts from the following hereditary cancer-prone syndromes: aniridia (AN), dysplastic nevus syndrome (DNS), Von Hippel-Lindau syndrome (VHL), Li-Fraumeni syndrome (LFS) and a family with high incidence of breast and ovarian cancer. Cells from AN, DNS or VHL patients were found to exhibit heterogeneity in HCR. Cells from individuals belonging to an LFS family show reduced HCR in all cases where the cells were derived from persons carrying one mutated p53 allele, whereas cells derived from members with two wild-type alleles show normal HCR. LFS cells with reduced HCR also reveal reduced genome overall repair, and a slower gene-specific repair of the active adenosine deaminase (ADA) gene, but little if any repair of the inactive 754 gene. In the breast/ovarian cancer family, reduced HCR is observed in skin fibroblasts derived from both afflicted and unaffected individuals. In addition, these cells display lower survival after exposure to UV-C and exhibit higher levels of SCEs than those in normal cells. These observations indicate that various hereditary cancer-prone syndromes, carrying mutations in different tumor-suppressor genes, exhibit an unexplained impairment of the capacity to repair UV-damaged DNA.
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PMID:Impaired DNA repair capacity in skin fibroblasts from various hereditary cancer-prone syndromes. 963 47

T cells are important effector cells in natural antiviral and anticancer immunity. It is important to reveal the cellular and molecular requirements for T cell differentiation and effector functions. We explored the idea that the final outcome of antigen receptor-driven immune processes is at least partially determined by physiologically abundant small signaling molecules in extracellular environment of lymphocytes in different tissues. Extracellular purines (ATP and adenosine) and their (purinergic) receptors were studied as an example of such molecules. Studies of functional effects of extracellular ATP and adenosine in immunoregulation have evolved in studies of individual molecules of purinergic receptors and of phosphorylation of extracellular domains of functionally important proteins. ATP-gated membrane pore, p2x 7(formerly p2z receptor) and A2a adenosine receptors are found to be predominantly expressed in T cells. The Gs-protein coupled A2a receptors activate cAMP-dependent protein kinase which was shown to have dual role in regulation of T cells functions. The results of our recent studies of adenosine receptors indicate that A2a receptors on T cell surface may play immunosuppressive role in conditions which lead to accumulation of extracellular adenosine. These conditions include pharmacological intervention with widely used anti-inflammatory drugs (methotrexate and sulfasalazine) and extracellular environment near large solid tumors. Hypoxic conditions in such tumors are known to cause accumulation of extracellular adenosine, which, in turn, as we have shown, could inhibit incoming antitumor cytotoxic T-lymphocytes from destroying the tumor. Normal development and functions of immune cells require adenosine deaminase (ADA) activity. Absence or low levels of ADA in humans result in severe combined immunodeficiency (SCID), which is characterized by hypoplastic thymus, T lymphocyte depletion, and autoimmunity. ADA SCID is currently explained only by intracellular lymphotoxicity of accumulated adenosine. We propose that T cell depletion, immunodeficiency, and autoimmunity could also be due to extracellular adenosine-induced signaling, which inhibits the antigen receptor (TCR) signaling and therefore affects the TCR-driven positive and negative selection of thymocytes. This, in turn, may lead to changes in antigen receptor repertoires and to immunodeficiency, Such properties of adenosine receptors suggest an expanded understanding of pathogenesis of ADA SCID as being due to two independent (intracellular and extracellular) mechanisms of adenosine action. It was conclusively demonstrated that functionally important T cell surface proteins including T cell receptor- are constitutively Ser/Thr phosphorylated on their ectodomains. We identified the major ecto-protein kinase activity in T-lymphocytes as casein kinase II-like (CKII-like) protein kinase. Consensus phosphorylation sites for serine and threonine protein kinases were found to be strongly evolutionary conserved in both alfa and beta TCR chains constant region. We have shown that ecto- or releasable by T-cells protein phosphatase has properties of PP1 and PP2a class protein phosphatase. Such covalent modifications of ectodomains may change T cells cognate interactions by e.g. affecting TCR-multimolecular complex formation and antigen binding affinity. It is suggested that TCR ectodomain phosphorylation could serve as a potential mechanism for regulation of TCR-mediated T-lymphocytes response.
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PMID:Extracellular purines and their receptors in immunoregulation. Review of recent advances. 980 87


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