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)

The bacillary population described in tuberculous pleuritis is small, and its most likely pathogenetic mechanism is essentially immunologic. This explains why, until now, the diagnostic identification of tuberculous pleuritis (TP) has been based on the presence of granulomas in pleural biopsy. Correcting this diagnostic deficiency through other parameters related to the specific pathogenetic mechanism has been widely studied. The determination of the levels of adenosine deaminase (ADA) in pleural fluid offers high performance in its discriminating capacity to identify TP (sensitivity 87 to 100%, specificity 81 to 97%). Adenosine deaminase expresses the sum of two isoenzymes (ADA1 and ADA2). ADA1 is ubiquitous in all cells, including lymphocytes and monocytes, whereas ADA2 is found only in monocytes. Analysis and determination of these isoenzymes have shown that ADA in TP increases particularly at the expense of ADA2 and that the ADA1 /ADAp activity ratio improves performance in terms of sensitivity, specificity, and efficacy (100%, 92 to 97%, and 98%, respectively) in correcting all false-negative and false-positive results except 1 to 9% of nonlymphoproliferative malignancies. Only the high performance of ADA in the identification of TP allows it to be assumed that pleural biopsy can be obviated, especially in patients aged less than 35 years of age or having a lymphocyte-to-neutrophil proportion of more than 0.75 in regions of high prevalence. Quick determination and low cost justify its routine use in exudates. The ADA1 /ADAp activity ratio improves performance even more and could be used in cases with uncertain diagnoses or in regions with low prevalence of tuberculosis.
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PMID:The use of adenosine deaminase and adenosine deaminase isoenzymes in the diagnosis of tuberculous pleuritis. 1091 30

The present study investigated serum adenosine deaminase (ADA) activity and the patterns of two ADA isoenzymes, ADA1 and ADA2, and to evaluate the possible role of cell-mediated immunity as causes of the changes in ADA activity in pre-eclampsia. We measured serum activities of total ADA, ADA1 and ADA2 in pre-eclampsia (n = 22) and normal pregnancy (n = 22). Peripheral blood monocyte counts and neopterin levels, reflecting the activation of the monocyte-macrophage cell system, were also measured. In pre-eclampsia, serum total ADA and ADA2 activities were significantly increased compared with normal pregnancy (p < 0.05), which were accompanied by increases in serum neopterin levels. These results suggest that increased total ADA activity reflects increases in ADA2 activity, which may be in part related to enhanced cell-mediated immunity during pre-eclampsia.
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PMID:Serum adenosine deaminase activity in women with pre-eclampsia. 1257 39

A prospective study was undertaken to assess the usefulness of leukocyte count, serum C-reactive protein (CRP), procalcitonin (PCT), and the activities of total adenosine deaminase (tADA) and its isoenzymes ADA1 and ADA2, in the aetiological diagnosis of pneumonia in children. The study included three groups. Group A consisted of 23 children with bacterial pneumonia, group B of 50 children with viral and mycoplasmal pneumonia and group C of 46 healthy children. On the first day of admission in the clinic, blood samples were collected before the start of antimicrobial treatment, for culture, serological tests, leukocyte count and for the determination of CRP and PCT levels as well as tADA activity and its isoenzymes ADA1 and ADA2. According to our results, the mean leukocyte count and the mean concentrations of PCT and CRP were significantly higher in the children of group A than those in groups B and C. The admission serum PCT concentration has a higher sensitivity, specificity and positive predictive value for bacterial pneumonia than either CRP or the leukocyte count. The mean serum tADA, ADA1 and ADA2 activity in children of group A was not significantly different from those in group C, while the difference between groups B and C was statistically significant. In conclusion, we found that CRP is a good marker for screening various infectious diseases, but it cannot be used to distinguish between bacterial and viral infections. Serum PCT measurement might be a useful tool for the physician for the aetiological diagnosis of pneumonia in children. Measurements of serum tADA and ADA2 activity may provide useful additional diagnostic information on the aetiology of pneumonia so that appropriate antibiotic therapy can be given promptly. Further studies with larger patients groups are required to confirm our results.
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PMID:Serum procalcitonin, adenosine deaminase and its isoenzymes in the aetiological diagnosis of pneumonia in children. 1259 Aug 74

Adenosine deaminase (ADA) can aid in the diagnosis of tuberculous pleural effusions, but false-positive findings from lymphocytic effusions have been reported. The purpose of this study is to assess the ADA levels in nontuberculous lymphocytic pleural effusions (lymphocyte count > 50%) of different aetiologies. Altogether, 410 nontuberculous lymphocytic pleural fluid samples were consecutively selected. These included malignant effusions (n = 221), idiopathic effusions (n = 76), parapneumonic effusions (n = 35), postcoronary artery bypass graft surgery effusions (n = 6), miscellaneous exudative effusions (n = 21) and transudative effusions (n = 51). The ADA level reached the diagnostic cut-off for tuberculosis (40 U x L(-1)) in seven of the 410 cases (1.71%). The negative predictive value of ADA for the diagnosis of pleural tuberculosis was 99% (403 of 407 cases) in the group of lymphocytic pleural effusions. In five of these seven patients ADA1 and ADA2 were measured, and in all these cases (100%) ADA1/ADA(p) correctly classified these lymphocytic effusions as nontuberculous (ratio < 0.42). This prospective study provides additional evidence that adenosine deaminase levels in nontuberculous lymphocytic pleural effusions seldom exceed the cut-off set for tuberculous effusions. The pleural fluid adenosine deaminase levels were significantly higher in different types of exudative effusions than in transudates. An adenosine deaminase level < 40 IU x L(-1) virtually excluded a diagnosis of tuberculosis in lymphocytic pleural effusions. Adenosine deaminase1/adenosine deaminase(p) correctly classified all nontuberculous lymphocytic pleural effusions with high adenosine deaminase levels.
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PMID:Diagnostic value of adenosine deaminase in nontuberculous lymphocytic pleural effusions. 1260 33

Tuberculosis is the most frequent cause of death due to infectious diseases. In Europe, it is one of the most frequent types of pleural effusions in young patients. Tuberculosis is caused by the rupture of a pulmonary subpleural caseous focus, which releases mycobacterium into the pleural cavity, thereby triggering an immune response involving mainly macrophages, CD4+ T lymphocytes, and the cytokines released by these cells (especially interleukin 1, interleukin 2, and ?-interferon). In recent years, classical microbiological and histological methods of diagnosis have been joined by biochemical analyses of pleural fluid, which are faster and can be more sensitive. In particular, tuberculous effusions have high adenosine deaminase (ADA) activity, apparently due to high levels of the ADA isoenzyme ADA2, which is only found in monocytes and macrophages (although certain data suggest the possible involvement of activated T cells, too). It has been recommended that treatment for tuberculosis be initiated if analysis of pleural fluid shows high ADA activity, a lymphocyte/neutrophil ratio greater than 0.75, and no malignant cells. Another highly efficient marker is ?-interferon, which is released by activated CD4+ T cells, but its high price is an obstacle to its routine determination in clinical practice. Identification of mycobacterial DNA by means of the polymerase chain reaction (PCR) is less efficient, apparently because its sensitivity depends heavily on mycobacterium concentration. No other biochemical parameters currently appear to be of marked relevance for the diagnosis of tuberculous pleural effusion (TPE). TPE responds well to the standard treatment for tuberculosis. However, 50% of TPE patients have a thickened pleura as a result of the accumulation of fluid, and in 16% the quantity of effusion increases during treatment, even if corticosteroids are administered. It therefore seems reasonable for treatment with antituberculous drugs to be preceded by therapeutic thoracocentesis to remove as much fluid as possible.
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PMID:Tuberculous pleural effusions. 1271 23

Serum activity of the adenosine deaminase (ADA) isozyme, ADA2, has been reported to be elevated during various disease states. Macrophages have been suggested as the cellular source of extracellular ADA activity because they are one of the only cell types in which intracellular ADA2 activity has been measured, but extracellular secretion has never been demonstrated. Rat primary peritoneal macrophages (PPMs) and peripheral blood monocytes (PBMs) were harvested and incubated for 18 h in RPMI supplemented with horse serum. PPM and PBM lysates were assayed for intracellular ADA activity (ammonia production). In vitro and in vivo extracellular ADA activities were measured in media and rat serum, respectively. Activity of ADA1 was confirmed by selective inhibition with erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA). ADA2 activity was inhibited by 2'-deoxycoformcin only, and was increased at a low pH (6.5). Activity of both ADA isozymes was found in PPMs and PBMs, and their media. In a separate group of rats, peritonitis was induced by ip insertion of 400 mg/kg caecal slurry. PPMs were harvested 24 h later and incubated for 18 h. In PPMs from rats with peritonitis both isozymes were elevated by a similar proportion. In contrast, media from these PPMs had a lower ADA1 and a higher ADA2 activity compared to PPMs from nonseptic rats. This resulted in a greater proportion of ADA2 in media. The isozyme proportions in serum from septic rats more closely resembled that of the PPM media. The response of PBM was small relative to that of PPM. These results suggest that macrophages are a significant source of extracellular ADA isozymes, the activity of which increases during an inflammatory response. Because extracellular isozymes profiles differ from cellular concentrations, the data also suggest differential release of each isozyme from PPMs.
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PMID:Macrophages are a source of extracellular adenosine deaminase-2 during inflammatory responses. 1537

Adenosine deaminase (ADA) is an unique enzyme which catalyzes conversion of adenosine and 2'-deoxyadenosine to inosine and 2'-deoxyinosine respectively. One of physiological roles of this enzyme is modulation of its substrate--adenosine concentration (both intracellular and extraectocellular). In presented work the influence of acetylsalicylic acid, metoprolol, simvastatin, isosorbide mononitrate and molsidomine on total activity of adenosine deaminase and its isoenzymes--ADA1 and ADA2 in vivo was studied. We have affirmed that simvastatin decreased of tADA activity by 50%, acetylsalicylic acid by 34%, metoprolol by 29.1% and isosorbide mononitrate by 19.3%. Only after molsidomine administration were no significant changes in ADA activity observed. The result showed that the decline of ADA activity was mainly due to marked decrease in ADA2 isoenzyme.
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PMID:[Inhibition of adenosine deaminase activity by drugs influencing the cardiovascular system]. 1550 88

Two distinct isoenzymes of ADA (adenosine deaminase), ADA1 and ADA2, have been found in humans. Inherited mutations in ADA1 result in SCID (severe combined immunodeficiency). This observation has led to extensive studies of the structure and function of this enzyme that have revealed an important role for it in lymphocyte activation. In contrast, the physiological role of ADA2 is unknown. ADA2 is found in negligible quantities in serum and may be produced by monocytes/macrophages. ADA2 activity in the serum is increased in various diseases in which monocyte/macrophage cells are activated. In the present study, we report that ADA2 is a heparin-binding protein. This allowed us to obtain a highly purified enzyme and to study its biochemistry. ADA2 was identified as a member of a new class of ADGFs (ADA-related growth factors), which is present in almost all organisms from flies to humans. Our results suggest that ADA2 may be active in sites of inflammation during hypoxia and in areas of tumour growth where the adenosine concentration is significantly elevated and the extracellular pH is acidic. Our finding that ADA2 co-purified and concentrated together with IgG in commercially available preparations offers an intriguing explanation for the observation that treatment with such preparations leads to non-specific immune-system stimulation.
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PMID:Human ADA2 belongs to a new family of growth factors with adenosine deaminase activity. 1592 89

Adenosine deaminase (ADA; EC 3.5.4.4) activity is elevated in the synovial fluid (SF) of rheumatoid arthritis (RA) patients. Since the anti-inflammatory effect of methotrexate is reportedly associated with increased levels of extracellular adenosine, the study was undertaken to clarify the role of two ADA isozymes (ADA1 and ADA2) in the pathogenesis of RA. The activities of ADA1 and ADA2 were measured in SF from RA and osteoarthritis (OA) patients, sera from RA patients, and lysates prepared from mononuclear and polymorphonuclear cells from RA-SF, peripheral blood from RA patients, and fibroblast-like synoviocytes (FLS) from RA and OA patients. Also investigated were the effects of proinflammatory cytokines on ADA1 activity and ADA mRNA expression in RA-FLS by the real-time PCR assay. The adenosine concentration in RA-SF was determined using a radioimmunoassay. The adenosine concentration in RA-SF ranged from 0.027 microM to 0.508 microM (mean+/-SD, 0.156+/-0.132). At these concentrations, ADA1 is expected to be functionally dominant due to its higher affinity for adenosine. ADA1 activity in RA-SF (14.4+/- 8.5 IU/l) was significantly higher than in OA-SF(3.0+/- 1.1 IU/l) or RA-sera (3.0+/-0.6 IU/l), suggesting they are the major source of ADA1 in RA-SF. Proinflammatory cytokines failed to affect ADA1 activity or ADA mRNA expression in RA-FLS. Taken together, these findings suggest that the elevated ADA1 activity is an intrinsic characteristic of RA-FLS, which likely contributes to the pathogenesis of RA by neutralizing the anti-rheumatic properties of endogenous adenosine.
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PMID:[Aberrant over-expression of adenosine deaminase and its significance on rheumatoid arthritis]. 1619 Mar 61

Measurement of pleural adenosine deaminase activity (ADA) is a useful diagnostic tool for tuberculous pleurisy, but false-positive findings from non-tuberculous effusions have been reported. In order to improve diagnostic value of ADA it is recommended to estimate activity of both ADA1 and ADA2 izoenzymes or 2'-deoxyadenosine/adenosine activity ratio. In order to evaluate ADA as a diagnostic parameter total ADA, with adenosine as a substrate, and 2'-deoxyadenosine/adenosine activity ratio were measured in tuberculous and malignant pleural effusions. Altogether, 26 pleural exudates (11 tuberculous and 15 malignant) were selected. ADA either with adenosine or 2'-deoxyadenosine was determined by colorimetric method of Giusti. Each pleural fluid sample was diluted prior to the assay (1:8) to avoid enzyme inhibition which was observed in nondiluted pleural effusions. The ADA level reached the diagnostic cut-off set for tuberculous effusions (40 U/L) in every 11 tuberculous exudates with the mean value of 85,3+/-47,1 U/L; in 9 of these the 2'-deoxyadenosine/adenosine ratio was less than 0,45. In the malignant group of patients, no one ADA level exceed 40 U/L, being estimated at 10,6+/-7,7 U/L (p<0,001). In 10 of these 15 exudates the 2'-deoxyadenosine/adenosine ratio was undetectable, in four it was less than 0,45 and only in one it was over 0,45. We concluded that ADA measured by the Giusti method proceeded by the dilution 1:8 of the pleural effusion samples very good differentiates tuberculous from malignant pleurisy, without the necessity to determine the 2'-deoxyadenosine/adenosine ratio. The investigation needs to be continued on the more numerous groups of patients.
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PMID:[Adenosine deaminase activity in tuberculous and malignant pleural effusions]. 1717 68


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