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)

A sandwich ELISA assay has been formatted from two commercially available murine monoclonal antibodies, URO-4 and URO-4a, directed against a 120,000 dalton glycoprotein, the adenosine deaminase binding protein (ABP), found on the brush border of the renal proximal tubular epithelial cell. Untimed urine samples from 37 normal individuals and urinary ABP less than 0.1 AU; 37 patients with pure glomerular disease had ABP less than 0.4 AU (with 29, or 76% less than 0.2 AU); 10 patients with pre-renal azotaemia had ABP less than 0.6 (with 8, or 80% less than 0.3 AU). In contrast, 79 patients with post-ischaemic acute tubular necrosis had ABP greater than 0.6 AU. Acute renal failure due to myoglobinuria, contrast dye, and aminoglycoside toxicity were all associated with urinary ABP greater than 1.0 AU. In addition, all six patients with acute bacteraemic pyelonephritis had ABP greater than 0.7 AU, as opposed to ABP less than 0.2 AU in the urines of 12 women with acute cystitis. We conclude that this monoclonal antibody based urinary assay is a sensitive measure of renal proximal tubular injury, reliably distinguishes acute tubular from glomerular disease, and may be helpful in differentiating forms of urinary tract infection.
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PMID:Diagnosis of renal proximal tubular injury by urinary immunoassay for a proximal tubular antigen, the adenosine deaminase binding protein. 288 57

Traditional methods of noninvasively evaluating patients for renal injury do not accomplish the following tasks: reliably distinguish potentially treatable forms of acute renal failure from acute tubular necrosis; provide a sensitive indicator of early allograft rejection in renal transplant recipients, particularly those in the pediatric age group; provide an early warning of incipient drug-induced nephrotoxicity; or serve as an adequate screening test for renal injury due to exposure to occupational or environmental toxins, especially heavy metals. Because of this, considerable effort has been devoted to the development of assays to satisfy these needs. Three approaches include measurement in the urine of low-molecular-weight plasma proteins such as beta 2-microglobulin; a variety of kidney-derived enzymes, such as L-alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase; and specific renal antigens using immunologic detection. The first two of these have not proved to be adequately sensitive or specific, complicated by the frequent loss of activity associated with the physicochemical characteristics of the urine or the presence of pyuria. Despite this, useful information has been obtained. In particular, assays of beta 2-microglobulin urinary excretion and retinol binding protein appear to have clinical utility that should be pursued. Recent experience with a monoclonal antibody-based assay for a unique proximal tubular antigen, the adenosine deaminase binding protein, suggests that a battery of such assays, each directed against an antigen localized to a particular segment of the nephron, may be particularly useful.
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PMID:Noninvasive renal diagnostic studies. 290 37

2-Deoxycoformycin (DCF) was added to an intensive Pediatric Oncology Group protocol (#8303) for children with T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma in first relapse. Twenty-seven patients received one or more courses of DCF at 15 mg/m2/day as a 3-day continuous infusion immediately after achieving a second remission with a four-drug reinduction regimen. Renal and neuromuscular toxicities were frequent and occasionally severe despite the provision of a source of adenosine deaminase by means of a packed red cell transfusion 1 day following the infusion of DCF. Hepatic toxicity, manifested by transaminase elevations, accompanied 62% of the courses. The median duration of the second complete remission was 4 months (range 2-16+ months), with only two of the 27 patients still in remission at 13+ and 16+ months. Plasma concentrations of deoxyadenosine (dAdo) and the ratio of red cell deoxyadenosine triphosphate to adenosine triphosphate (dATP:ATP) were measured prior to the DCF infusion and on day 4. A dATP:ATP ratio of 1.0 or greater was seen in two patients with acute renal failure. There was no apparent correlation between toxicity or response and the plasma dAdo concentrations. DCF administered according to this dose and schedule was excessively toxic and did not appreciably prolong the duration of the second complete remission in children with T-cell lymphoblastic malignancies.
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PMID:Deoxycoformycin treatment for childhood T-cell acute lymphoblastic leukemia early in second remission: a Pediatric Oncology Group Study. 326 63

Acute renal failure (ARF) is a frequent problem in the intensive care unit and is associated with a high mortality. Early recognition could help clinical management, but current indices lack sufficient predictive value for ARF. Therefore, there might be a need for biomarkers in detecting renal tubular injury and/or dysfunction at an early stage before a decline in glomerular filtration rate is noted by an increased serum creatinine. A MEDLINE/PubMed search was performed, including all articles about biomarkers for ARF. All publication types, human and animal studies, or subsets were searched in English language. An extraction of relevant articles was made for the purpose of this narrative review. These biomarkers include tubular enzymes (alpha- and pi-glutathione S-transferase, N-acetyl-glucosaminidase, alkaline phosphatase, gamma-glutamyl transpeptidase, Ala-(Leu-Gly)-aminopeptidase, and fructose-1,6-biphosphatase), low-molecular weight urinary proteins (alpha1- and beta2-microglobulin, retinol-binding protein, adenosine deaminase-binding protein, and cystatin C), Na+/H+ exchanger, neutrophil gelatinase-associated lipocalin, cysteine-rich protein 61, kidney injury molecule 1, urinary interleukins/adhesion molecules, and markers of glomerular filtration such as proatrial natriuretic peptide (1-98) and cystatin C. These biomarkers, detected in urine or serum shortly after tubular injury, have been suggested to contribute to prediction of ARF and need for renal replacement therapy. However, excretion of these biomarkers may also increase after reversible and mild dysfunction and may not necessarily be associated with persistent or irreversible damage. Large prospective studies in human are needed to demonstrate an improved outcome of biomarker-driven management of the patient at risk for ARF.
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PMID:Biomarkers of acute renal injury and renal failure. 1691 49

Acute tubular necrosis is a clinical problem that lacks specific therapy and is characterized by high mortality rate. The ischemic renal injury affects the proximal tubule cells causing dysfunction and cell death after severe hypoperfusion. We utilized a cell-based screening approach in a hypoxia-reoxygenation model of tubular injury to search for cytoprotective action using a library of pharmacologically active compounds. Oxygen-glucose deprivation (OGD) induced ATP depletion, suppressed aerobic and anaerobic metabolism, increased the permeability of the monolayer, caused poly(ADP-ribose) polymerase cleavage and caspase-dependent cell death. The only compound that proved cytoprotective either applied prior to the hypoxia induction or during the reoxygenation was adenosine. The protective effect of adenosine required the coordinated actions of adenosine deaminase and adenosine kinase, but did not requisite the purine receptors. Adenosine and inosine better preserved the cellular ATP content during ischemia than equimolar amount of glucose, and accelerated the restoration of the cellular ATP pool following the OGD. Our results suggest that radical changes occur in the cellular metabolism to respond to the energy demand during and following hypoxia, which include the use of nucleosides as an essential energy source. Thus purine nucleoside supplementation holds promise in the treatment of acute renal failure.
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PMID:Identification of agents that reduce renal hypoxia-reoxygenation injury using cell-based screening: purine nucleosides are alternative energy sources in LLC-PK1 cells during hypoxia. 2210 Jul 4