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

A1 adenosine-receptor-antagonist drugs such as 8-cyclopentyl-1,3-dipropylxanthine (CPX) and xanthine amine congener (XAC) are found to activate the efflux of 36Cl- from CFPAC cells. These cells are a pancreatic adenocarcinoma cell line derived from a cystic fibrosis (CF) patient homozygous for the common mutation, deletion of Phe-508. The active concentrations for these compounds are in the low nanomolar range, consistent with action on A1 adenosine receptors. In addition, drug action can be blocked by exogenous agonists such as 2-chloroadenosine and also can be antagonized by removal of endogenous agonists by treatment with adenosine deaminase. Cells lacking the CF genotype and phenotype, such as HT-29 and T84 colon carcinoma cell lines, appear to be resistant to activation of chloride efflux by either drug. CFPAC cells transfected with the CF transmembrane regulator gene, CFTR, are also resistant to activation by CPX. We conclude that, since these antagonists are of relatively low toxicity and appear to act somewhat selectively, they might be considered as promising therapeutic candidates for CF.
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PMID:A1 adenosine-receptor antagonists activate chloride efflux from cystic fibrosis cells. 137 23

The concentration of gamma interferon (IFN gamma) and adenosine deaminase (ADA) activity were measured in the pleural fluid of 162 patients to compare their diagnostic significance and to establish a possible correlation between both tests. The IFN gamma levels in tuberculous pleural effusions were quite variable, with a mean of 93 U/ml and a median of 48 U/ml. They were higher than 2 U/ml in all cases, whereas no case of nontuberculous effusion showed higher values. ADA activity was higher than 43 U/l in all tuberculous effusions, with a mean value of 80 U/l, higher than in any other group except lymphoma. In three pleural effusions associated with lymphoma, one with mesothelioma, one with adenocarcinoma and four with empyema, ADA activity was higher than 43 U/l. In these patients, IFN gamma levels were low. There was no correlation in the whole series or in any group between IFN and ADA. Both parameters can be very useful for the diagnosis of tuberculous pleuritis. The measurement of IFN gamma is more specific, although the experience with this test is more limited than with ADA. It has the additional shortcoming of a high cost and it requires facilities for radionuclide use. Therefore, we think that ADA measurement should be considered as a routine test while IFN gamma measurement should be reserved for reference institutions.
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PMID:[Gamma interferon and adenosine deaminase in pleuritis]. 211 Jun 5

In a prospective study of 118 patients with pleural effusion admitted to four medical wards in Muhimbili Medical Center between January and August 1991, Dar es Salaam, Tanzania, tuberculosis (TB) was diagnosed in 112. In 84 patients the diagnosis of TB was made by detection of acid-fast bacilli by stain (auramine, Ziehl-Neelsen) or by culture of mycobacteria (Lowenstein-Jensen medium) in pleural fluid or pleural tissue obtained by closed biopsy or by the presence of caseating granulomas in histological sections. In 28 patients the diagnosis of TB was considered probable, based on good response to anti-tuberculous therapy. In the remaining 6 non-TB patients adenocarcinoma (1), bacterial infection (2), and aspecific inflammation (3) were diagnosed. 58% of the TB and 3 of the non-TB patients were infected with HIV. The diagnostic procedures were evaluated in 75 patients. The highest diagnostic yield was obtained by histology (85%), followed by culture of pleural biopsy (37%), and pleural fluid culture (36%). Pulmonary tuberculosis was found in 8 (4 HIV-positive) patients and dissemination of TB to other sites in 25 patients, of whom 20 were HIV-positive. By logistic regression analysis, two independent diagnostic markers for TB pleuritis were identified: pleural fluid protein 50 g/l (odds ratio [OR] 12.1) and pleural fluid adenosine deaminase level of 10 U/l (OR 11.08). The sensitivity of these two diagnostic tests was 82% and 97.3%, and the specificity was 83.6% and 50%, respectively. TB was the underlying cause in nearly all patients who presented with pleural effusion (94.9%). TB was confirmed in 75% of these using the referral hospital. Conventional facilities of a referral hospital are sufficient to diagnose tuberculous pleuritis as well as disseminated tuberculosis irrespective of HIV infection. However, in regions with overburdened health facilities and high prevalence of tuberculous pleurisy in patients with pleural effusion, a simplified diagnostic approach is suggested based on exclusion of other causes of pleural effusion by simple use of these diagnostic markers.
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PMID:Diagnosis of tuberculosis in patients with pleural effusion in an area of HIV infection and limited diagnostic facilities. 785 15

We have investigated the hypothesis that adenosine, a purine nucleoside produced within hypoxic regions of solid tumors, may interfere with the recognition of tumor cells by cytolytic effector cells of the immune system. We measured the adhesion of murine spleen-derived anti-CD3-activated killer (AK) lymphocytes to syngeneic MCA-38 colon adenocarcinoma cells in a model system. Adenosine, in the presence of the adenosine deaminase inhibitor coformycin to prevent the breakdown of adenosine, inhibited adhesion by up to 60%. The inhibitory effect of adenosine was exerted on the AK cells and not on the MCA-38 targets. The response to adenosine was generated at the cell surface, since the inhibition of adhesion was not abrogated by S-(4-nitrobenzyl)-6-thioinosine or dipyridamole, which block adenosine uptake. The inhibition of adhesion due to adenosine was not blocked by either the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine or the A2 receptor antagonist 3,7-dimethyl-1-propargylxanthine. This suggested that a non-A1, A2 receptor might be involved. The relative order of potencies of adenosine and common analogues was: 5'-N-ethylcarboxamidoadenosine = adenosine = (R)-phenylisopropyladenosine > N6-cyclopentyladenosine > 2-chloro-N6-cyclopentyladenosine = 2-p-(2- carboxyethyl)phenethylamino-5'-N-ethyl-carboxamidoadenosine. This agonist potency profile was again inconsistent with either the A1 or the A2 receptor subtype but indicated that the recently described A3 receptor subtype might be responsible for the inhibition of adhesion. Consistent with this suggestion, aminophenylethyladenosine, an adenosine analogue that binds with high affinity to A3 receptors, inhibited the adhesion of AK cells to MCA-38 tumor cells with high potency (50% inhibitory concentration approximately 1 nM). Adenosine, therefore, interferes with the AK cell recognition of colorectal tumor targets by acting through an A3 receptor on the effector cells. We suggest that this mechanism of immunosuppression, secondary to tissue hypoxia, may be important in the resistance of colorectal and other solid cancers to immunotherapy.
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PMID:Adenosine inhibits the adhesion of anti-CD3-activated killer lymphocytes to adenocarcinoma cells through an A3 receptor. 801 76

Up to now, only 2 cases of benign asbestos pleural effusion have been described in Spain. We report our experience of 15 patients diagnosed of benign asbestos pleural effusion (BAPE). Between 1980 and January 1995, 15 patients were diagnosed of BAPE according to the following criteria: a) evidence of pleural effusion; b) previous asbestos exposure, and c) exclusion of other etiologies of last during 3 years of follow-up. Retrospective review of diagnostic and evolutive data from the patients' clinical records. Asbestos exposure was intense in 8 patients and slight in 7. There were 11 effusions on the left side and 4 on the right side. All effusions were exudative, with a pleural adenosine deaminase level lower than 43 U/l. Eleven patients had a lymphocytic pleural fluid. All patients had nonspecific pleural histology, and asbestos bodies were detected in one case. Eleven patients achieved a radiographic resolution in less than 3 months, and 3 patients presented relapses. Fourteen patients had a good outcome, and one patient presented a lung adenocarcinoma after 5 years of follow-up. Benign asbestos pleural effusions are predominant on the left side, have a tendency to relapse and the exposition can be occasional. The outcome is good in most of the cases.
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PMID:[Benign asbestos pleural effusion. Report of a first series in Spain]. 899 13

Several lines of evidence suggest that extracellular adenosine interacting with specific cell surface receptors may influence cell growth and differentiation of cancer cells in culture. The data presented here demonstrate that various treatments of human colonic adenocarcinoma HT29 cells in the presence of exogenously added adenosine deaminase, which converts extracellular adenosine into inosine, resulted in a significant decrease of the proliferation. Cell growth inhibition was also observed in the presence of adenosine A1 receptor antagonists. These various treatments also induced a significant elevation of basal intracellular cAMP levels. This strongly indicated that extracellular adenosine was maintaining low intracellular cAMP levels in HT29 cells. A partial pharmacological characterization of the binding of the adenosine A1 receptor agonist [3H]CCPA (2-chloro-N6-cyclopentyl[2,3,4,5-(3)H]adenosine), and the adenosine A1 receptor antagonist [3H]DPCPX (cyclopentyl-1,3-dipropyl[2,3-(3)H]xanthine), to HT29 cells is also provided. Together the data support the idea that A1-adenosine receptors are expressed in HT29 cells and might mediate part of the above described effects of adenosine on cell proliferation.
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PMID:Adenosine modulates cell proliferation in human colonic adenocarcinoma. I. Possible involvement of adenosine A1 receptor subtypes in HT29 cells. 954 51

In a previous study, we provided evidence that extracellular adenosine modulates growth of the poorly differentiated colonic adenocarcinoma cells HT29 and proposed that adenosine A1 receptors might mediate proliferative effects. We now extend our investigations to a group of colonic adenocarcinoma cells at different stages of enterocytic differentiation. In HT29, DLD-1, Caco-2 and SW403, proliferation was decreased in the presence of adenosine deaminase (5 or 10 U/ml), 5'-N-ethylcarboxamido-adenosine (NECA; 1 microM), xanthine amine congener and 8-phenyltheophylline (both at 1 nM or 1 microM). NECA stimulated cAMP accumulation in all cell lines except for HT29. In the presence of forskolin (adenyl cyclase activator) cAMP accumulation was inhibited at sub-nanomolar concentrations of NECA and stimulated at micromolar concentrations in all four cell lines. The inhibitory response disappeared in the presence of 50 nM cyclopentyladenosine (CPA). The binding of [3H]cyclopentyl-1,3-dipropylxanthine and [3H]NECA was also investigated in the four cell lines. Results of displacement experiments were consistent with the idea that poorly differentiated cells with high proliferation rates (e.g. HT29) express mainly adenosine A receptors. In contrast, displacement curves with more differentiated cells exhibiting low proliferation rates (e.g. Caco-2, DLD-1, SW403) displayed two components. The high-affinity component was no longer seen in competition experiments performed in the presence of [3H]NECA and 50 nM CPA. Together, our results further support the idea that extracellular adenosine stimulates cell proliferation in colonic adenocarcinoma cells. The effects might involve cAMP-coupled adenosine receptors.
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PMID:Adenosine modulates cell proliferation in human colonic carcinoma. II. Differential behavior of HT29, DLD-1, Caco-2 and SW403 cell lines. 954 52

HT29 cells display an undifferentiated phenotype in culture. However, numerous treatments are able to induce both epithelial differentiation and cell growth inhibition. We have previously demonstrated that adenosine and its analogues act through specific adenosine receptors to modulate cell proliferation in HT29 and other human colon adenocarcinoma cell lines. Among the treatments tested, the most potent inhibition of HT29 cell growth was induced by deprivation of extracellular adenosine using adenosine deaminase. Here, we investigated the capacity of adenosine deaminase to initiate epithelial differentiation. After 1 month of daily addition of 10 U/ml adenosine deaminase to the culture medium, HT29 cells were cloned by limited dilution. Among the clones obtained, we focused our attention on clone 13. Microscopic visualization and proliferation studies indicated that cells from this clone grew very slowly and in a pseudo-monolayer, in marked contrast with the situation observed in the mother HT29 cell line. In addition, clone 13 cells displayed epithelial features that mimic the enterocytic differentiation of Caco-2 cells. These modifications were accompanied by dramatic changes in the activity of adenosine receptors, as demonstrated by pharmacological studies. In contrast to the original HT29 cells, clone 13 as well as Caco-2 cells displayed (i) a very low number of adenosine A(1) receptors, and (ii) increases in intracellular cAMP levels when challenged with adenosine analogues. It is hypothesized that a loss of adenosine A(1) receptors, with no change or a concomitant increase in adenosine A(2) receptors, results in the emergence of adenosine A(2) receptor-mediated differentiation and inhibition of proliferation, through a cAMP-dependent pathway.
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PMID:Extracellular adenosine deprivation induces epithelial differentiation of HT29 cells: evidence for a concomitant adenosine A(1)/A(2) receptor balance regulation. 1072 Jun 31

The extra-enzymic function of cell-surface adenosine deaminase (ADA), an enzyme mainly localized in the cytosol but also found on the cell surface of monocytes, B cells and T cells, has lately been the subject of numerous studies. Cell-surface ADA is able to transduce co-stimulatory signals in T cells via its interaction with CD26, an integral membrane protein that acts as ADA-binding protein. The aim of the present study was to explore whether ADA-CD26 interaction plays a role in the adhesion of lymphocyte cells to human epithelial cells. To meet this aim, different lymphocyte cell lines (Jurkat and CEM T) expressing endogenous, or overexpressing human, CD26 protein were tested in adhesion assays to monolayers of colon adenocarcinoma human epithelial cells, Caco-2, which express high levels of cell-surface ADA. Interestingly, the adhesion of Jurkat and CEM T cells to a monolayer of Caco-2 cells was greatly dependent on CD26. An increase by 50% in the cell-to-cell adhesion was found in cells containing higher levels of CD26. Incubation with an anti-CD26 antibody raised against the ADA-binding site or with exogenous ADA resulted in a significant reduction (50-70%) of T-cell adhesion to monolayers of epithelial cells. The role of ADA-CD26 interaction in the lymphocyte-epithelial cell adhesion appears to be mediated by CD26 molecules that are not interacting with endogenous ADA (ADA-free CD26), since SKW6.4 (B cells) that express more cell-surface ADA showed lower adhesion than T cells. Adhesion stimulated by CD26 and ADA is mediated by T cell lymphocyte function-associated antigen. A role for ADA-CD26 interaction in cell-to-cell adhesion was confirmed further in integrin activation assays. FACS analysis revealed a higher expression of activated integrins on T cell lines in the presence of increasing amounts of exogenous ADA. Taken together, these results suggest that the ADA-CD26 interaction on the cell surface has a role in lymphocyte-epithelial cell adhesion.
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PMID:Regulation of epithelial and lymphocyte cell adhesion by adenosine deaminase-CD26 interaction. 1177 92

Lactate dehydrogenase (LDH), adenosine deaminase and thymidine phosphorylase activity was analyzed in the blood serum, primary tumor and adjacent uninvolved breast tissues from 49 women with adenocarcinoma and from 10 ones with benign adenofibroma. The LDH activity was increased in both cancerous and adjacent tissues. Serum LDH level reflects cell membrane alterations not only in the tumor node cells but also to a greater extent--in the surrounding unmalignant tissues. The discovered changes in nucleosides catabolic enzyme's activity in patients with breast cancer are correlated with LDH activity and its level in the blood serum.
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PMID:[Lactate dehydrogenase, adenosine deaminase and thymidine phosphorylase activity of blood and tissues in breast cancer]. 2038 38


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