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)

The minimum inhibitory concentration (MIC) of adenine arabinoside (ara-A) in rabbit kidney microtiter tissue cultures (RK-13) to a prototype strain of herpes simplex virus, type 1 (E115) based upon inhibition of cytopathic effects is 1.5 mug/ml. In this system, the MIC of arabinosylhypoxanthine (ara-Hx), the major in vivo metabolic derivative of ara-A, is 75 mug/ml. Inhibition of cytopathic effects of herpes simplex virus, type 1 (HSV-1) in microtiter wells of RK-13 cells varies directly with the concentrations of ara-A or ara-Hx, and inversely with residual HSV-1. The MIC of ara-A for HSV-1 in RK-13 cells is 5-20 times lower than similar measures with vero renal, mouse embryo, or human foreskin cultures. With RK-13 tissue cultures in microtiter plates, an assay for "ara-A equivalents" in human body fluids was developed which compares in sensitivity with high pressure liquid chromatography and has the advantage of simultaneously measuring combined antiherpesvirus effects of ara-A and its major metabolic derivative, ara-Hx. In vitro checkerboard studies in RK-13 cells confirmed that ara-A and ara-Hx in combination had antiviral effects which are synergistic. The total of the fractional MIC of ara-A plus ara-Hx in combination also varies inversely with residual HSV-1 in microtiter wells. Because virus adsorption is complete at 2 h before specimens to be tested are added in this assay, and because human interferon is not measured in rabbit cells, the antiviral assay is not affected by the presence of type-specific antiherpesvirus antibody or human interferon.Antiviral activity (AVA) was assayed as ara-A equivalents in sera and urines from 10 patients with serious herpesvirus infections who received 2.5-20 mg/kg daily of ara-A by intramuscular or intravenous routes. When a dosage schedule of 10 mg/kg per day or more was used, sustained concentrations of AVA that ranged from 0.8 to 14.4 mug/ml were found. When an inhibitor of adenosine deaminase (covidarabine) was not added to the specimens, mean serum concentrations were congruent with3.0 mug/ml (10 mg/kg per day, i.v.), and 4.1 mug/ml (20 mg/kg per day). However, in a single patient given 20 mg/kg of ara-A daily with covidarabine immediately added to the sera, the mean concentration of AVA was 12.9 mug/ml. Urines contained even higher AVA. Assays of 19 sera were performed both by microbiologic assay for AVA and by high pressure liquid chromatography for ara-A and ara-Hx. AVA was greater by microbiologic assay, and was greater than that which could be accounted for by stoichiometric chromatographic measures of ara-A and ara-Hx. These results with sera of treated patients are consistent both with the in vitro synergy of ara-A and ara-Hx found by checkerboard titrations, and with the beneficial responses to ara-A of patients with herpesvirus infections reported here and elsewhere.
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PMID:Antiherpesvirus activity in human sera and urines after administration of adenine arabinoside: in vitro and in vivo synergy of adenine arabinoside and arabinosylhypoxanthine in combination. 21 24

A practical process is described for the large-scale isolation of pentostatin, an adenosine deaminase inhibitor used clinically for the treatment of interferon-refractory hairy cell leukemia. The identities of minor components in the fermentation beer, including 2'-deoxyguanosine, are also reported.
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PMID:Improved production of pentostatin and identification of fermentation cometabolites. 149 Aug 83

2',5'-oligoadenylate synthetase (2-5OAS) has been studied in peripheral blood mononuclear cells from nine patients with hairy cell leukaemia (HCL) receiving therapy with the adenosine deaminase inhibitor deoxycoformycin (dCF) or alpha interferon (alpha-IFN). 2-5OAS mRNA was assayed by dot-blot hybridization. Increase of 2-5OAS mRNA level was seen in six patients with HCL treated with dCF and in one patient treated with alpha-IFN who responded to therapy. A patient with a variant form of HCL treated with dCF and the second patient treated with alpha-IFN did not show an increase of 2-5OAS mRNA and neither responded to therapy. The 15 other patients with T or B-chronic lymphoblastic leukaemia (CLL), T-acute lymphoblastic leukaemia (ALL), adult T-cell leukaemia lymphoma (ATLL), non-Hodgkins lymphoma (NHL), Sezary and T or B-prolymphocytic leukaemia (PLL) treated with dCF did not show an increase in 2-5OAS, though four patients, all with T-cell tumours, responded clinically. 2-5OAS activity is known to be stimulated by alpha-IFN and recent work suggests that this rise in 2-5OAS may result in increased cleavage of mRNA for tumour necrosis factor (TNF) and other cytokines on which autocrine growth and proliferation of the tumour cells are dependent. By analogy, we suggest that one mechanism of action of dCF in hairy cell leukaemia may be to break down an autocrine growth loop for TNF or other cytokines. An alternative explanation for these observations is that cytokines released from hairy cells in the bone marrow killed by dCF induce a rise in 2-5OAS in circulating leucocytes.
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PMID:Increase in 2',5'-oligoadenylate synthetase caused by deoxycoformycin in hairy cell leukaemia. 155 Jul 76

The value of ascites gamma interferon concentration and ascites adenosine deaminase activity in distinguishing tuberculosis from other causes of ascites was examined in a prospective study of 86 patients with ascites, including 16 with tuberculous peritonitis. Gamma interferon concentration was higher in tuberculous peritonitis than in the other causes of ascites (p less than 0.0001), and a cut-off between 3 and 9 u/ml reached a sensitivity and a specificity of 100%. The mean (+/- SD) gamma interferon level in tuberculous ascites was 39.3 +/- 18.3 u/ml in patients seronegative for HIV and 14.2 +/- 4.7 u/ml in patients with AIDS (p = 0.01). Adenosine deaminase activity in tuberculous ascites was also higher than in the other causes of ascites (p less than 0.0001), and a cut-off of 40 u/l reached a sensitivity of 100% and a specificity of 97%. The two false positives for adenosine deaminase test were true negatives for the gamma interferon test. There was no significant correlation between gamma interferon concentration and adenosine deaminase activity either in tuberculous ascitis or in any other group. This study suggests that ascites gamma interferon determination may be very useful in the screening of tuberculous peritonitis, but its cost makes it advisable to use adenosine deaminase activity as a routine test, at least in areas where tuberculosis is endemic.
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PMID:Diagnostic value of ascites gamma interferon levels in tuberculous peritonitis. Comparison with adenosine deaminase activity. 177 79

Pentostatin, a novel inhibitor of adenosine deaminase, has shown activity in various lymphoid malignancies of both the T and B cell lineage. This agent has unique side effects and in general myelosuppression has been mild. Interferon has both antiviral and antineoplastic properties. This agent has shown activity in hairy cell leukemia, chronic granulocytic leukemia, low grade lymphoma, and myeloma. Side effects from interferon are in general dissimilar to those that have been seen with pentostatin and in particular myelosuppression has not been a major toxicity with low doses of interferon. This current trial explored the combination of pentostatin and interferon in hematologic malignancies. Fifteen patients were enrolled in this phase I trial at a fixed dose of pentostatin of 4 mg/m2 biweekly and interferon at doses of 0.5, 1, 2, or 4 million units/m2 of interferon. At the first three dose levels of interferon nausea and vomiting were the predominant toxicity and appeared to worsen with time on study. Fatigue also was seen at the lowest level of interferon and was severe enough to cause two individuals to discontinue the study medications. At higher dose levels of interferon, myelosuppression, nausea and vomiting, and fatigue were the predominant toxicities. One patient with hairy cell leukemia had a complete response and a second patient with T cell cutaneous lymphoma had a partial response which lasted for 6 to 7 weeks. The maximum tolerated dose of interferon with pentostatin in this patient population was four million units/m2.
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PMID:A phase I trial of alpha-interferon in combination with pentostatin in hematologic malignancies. 205 72

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

The combined effects of interferon (IFN) and 2'-deoxycoformycin (DCF) on 2',5'-oligoadenylate (2-5A) synthetase and adenosine deaminase (ADA) activity were examined in vitro in peripheral blood mononuclear cells from patients with hairy cell leukemia (HCL) and chronic lymphocytic leukemia (CLL). In HCL cells, the effects of IFN and DCF on both OAS and ADA activity were strictly antagonistic. Antagonism in inducing OAS activity was also observed in CLL cells, although, in general, little interaction between DCF and IFN occurred in these cells. If OAS and ADA are important in the antitumor effects of IFN and DCF, our results suggest that combination therapy with IFN and DCF could be counterproductive.
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PMID:Combined effects of interferon and 2'-deoxycoformycin on 2',5'-oligoadenylate synthetase and adenosine deaminase in hairy cell and chronic lymphocytic leukemia cells. 227

The adenosine deaminase inhibitor 2'-deoxycoformycin and interferon are highly effective in the treatment of hairy-cell leukemia. In this study, a patient with type 2 hairy-cell leukemia was treated with one cycle of 2'-deoxycoformycin (4 mg/m2, i.v. weekly for 3 weeks), which was repeated at 9 wk. No toxicity was observed, and the hairy cell count fell from 72,000/mm3 to 5,000/mm3 in 3 mo, with a concomitant 50% decrease in the spleen size. The erythrocyte deoxyadenosine triphosphate content increased to 13.6 pmol/10(6) cells following the initial three weekly treatments, but there was no decrease in the adenosine triphosphate pool size and no evidence of hemolysis. The hairy cell adenosine deaminase activity was inhibited by greater than 95% 24 h following the first 2'-deoxycoformycin injection and returned to the pretreatment value at Day 8, although there was a linear decline in peripheral hairy cell count (50%) during this period. No ultrastructural changes were observed in the hairy cells following 2'-deoxycoformycin to suggest lymphocytotoxicity or cellular differentiation. The antitumor activity of 2'-deoxycoformycin could not be attributed to alterations in the hairy cell deoxyadenosine triphosphate/adenosine triphosphate levels or to the induction of DNA strand breaks. Additionally, the plasma levels of interferon did not change during therapy, making it unlikely that 2'-deoxycoformycin exerts its activity by inducing endogenous interferon synthesis.
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PMID:Biochemical changes induced in hairy-cell leukemia following treatment with the adenosine deaminase inhibitor 2'-deoxycoformycin. 241 65

Hairy cell leukemia (HCL) is a rare chronic lymphoproliferative disorder which has been extensively studied over the past decade. Much has been learned regarding the diagnosis, natural history, biology, and treatment of this unique neoplasm. The disease most commonly affects middle aged men and characteristic clinical features include splenomegaly, cytopenias, and usually the presence in the peripheral blood of distinctive 'hairy cells' with irregular cytoplasmic projections. Diagnosis can usually be confirmed by bone marrow biopsy. Although the natural history can be extremely variable among patients, complications are usually referable to the cytopenias, with anemia and infection being most frequent. In addition to pyogenic infections, patients are susceptible to unusual organisms including atypical mycobacterium, legionella, and fungi. The requirement of red blood cell transfusion, severe granulocytopenia or thrombocytopenia, frequent infections, or painful splenomegaly are all indications for treatment. Splenectomy is the standard initial treatment of choice. However, in the past few years there have been exciting major advances in the therapeutic modalities for HCL. Recombinant alpha-interferon is highly effective, with beneficial responses occurring in close to 90% of patients. The Food and Drug Administration has recently approved the use of interferon for HCL. This represents the first time a biological response modifier has been approved for the treatment of human disease. In addition, preliminary results with the adenosine deaminase inhibitor, 2'deoxycoformycin (dcf), have been encouraging. Further clinical trials are required in order to determine the optimal sequential treatment strategy for HCL. The exact mechanisms of action of both interferon and dcf in HCL remain to be elucidated. A better understanding of the unusual features of the hairy cell and the underlying biological effect of these two agents in HCL may have important applications in other hematologic and non-hematologic malignancies.
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PMID:Hairy cell leukemia: clinical features and therapeutic advances. 244 91

It has been found that both adenosine deaminase (ADA) and gamma-interferon (r-IFN) are higher in tuberculous pleural effusions than in other types of pleural effusion. Both mechanisms may be related to the T-lymphocytes in effusions. We studied 39 pleural effusions: 19 tuberculous and 20 malignant [The ADA was determined according to the Giusti method and r-IFN by ELISA]. We compared the ADA and r-IFN levels in both groups of effusions and tried to determine if there was any correlation between them. The results showed: (1) The ADA enzyme level was significantly higher in tuberculous effusions than in malignant effusions as was expected (133.0 +/- 50.4 vs 32.0 +/- 17.7 U/L). (2) The r-IFN was also significantly higher in tuberculous effusions than in malignant effusions (30.4 +/- 17.4 vs 2.9 +/- 2.8 U/ml). (3) The coefficients of regression for the ADA and r-IFN levels were poor. In conclusion, both tests for measuring ADA and r-IFN levels are excellent methods for differentiating tuberculous and malignant effusions, and especially measurement of the r-IFN level could serve as a more specific test for differentiating malignant pleural effusions with high ADA levels. However, no strong correlation was found between the ADA and r-IFN levels.
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PMID:Diagnostic value of adenosine deaminase and gamma-interferon in tuberculous and malignant pleural effusions. 251 12


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