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)

The availability of a human lymphoma cell line deficient in adenosine deaminase, adenosine kinase and methylthioadenosine phosphorylase enabled us to compare the effects of nucleoside transport inhibitors on the excretion of endogenously generated adenosine, deoxyadenosine and 5'-methylthioadenosine. The nucleoside transport inhibitors nitrobenzylthioinosine and dipyridamole blocked the efflux of adenosine, but not deoxyadenosine or 5'-methylthioadenosine. The inhibitors also prevented the uptake of exogenous adenosine, but not deoxyadenosine or 5'-methylthioadenosine, by human lymphoblasts. The results show (i) that the transport inhibitors modify adenine nucleoside efflux and influx similarly, and (ii) that the effects of the compounds on the excretion and uptake of these three physiologically important adenine nucleosides are distinctly different.
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PMID:Modulation of adenine nucleoside excretion and incorporation in adenosine deaminase deficient human lymphoma cells. 642 10

Enzyme activity measurements are of great relevance to the classification and biochemical characterization of the various types of leukemias, but they have been much less studied in solid lymphoid tumors. The authors report investigations in human lymphomas. The levels of the following enzymes were determined: terminal deoxynucleotidyl transferase (TdT), deoxyribonucleic acid polymerase alpha (DP alpha), adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), thymidine and uridine kinases (TK and UK, respectively), and thymidine phosphorylase (ThPh). Moreover, cytochemical investigations were done in the group of Burkitt's lymphoma (BL) and lymphoblastic lymphoma (LL), and ultrastructural studies were performed in seven of the nine LL of this series. These results were obtained: (1) TdT (90 cases) was highly specific for LL; eight of nine LL were positive, and all other histologic types were negative; the only TdT-, acid esterase (AcE) positive, nonconvoluted LL was probably related to TdT- normal medullary thymocytes, and had an unfavorable clinical course with resistance to a vincristine-and-prednisone-including treatment; (2) ADA (61 cases) could distinguish clearly between the high levels of LL and the low levels found in any other group of lymphomas; among LL, the highest values were found in T-cell-derived neoplasias, and the lowest value in a periodic acid-Schiff (PAS) positive, acid phosphatase negative case that showed the presence of large nucleoli at the ultrastructural analysis, a finding that is unusual for LL and possibly related to a more immature differentiation stage; (3) PNP (39 cases) values alone were not clinically relevant, but together with ADA levels, a subset of T-LL with high ADA:PNP ratio could be selected among LL; (4) DP alpha (61 cases), and TK and UK (37 cases) were found in concentrations reflecting the malignancy of the non-Hodgkin's lymphoma, and were more elevated in the high-grade malignant lymphomas; (5) ThPh (34 cases) was always elevated in Hodgkin's disease, but low in Burkitt's lymphoma and LL; thus, they had a high TK:ThPh ratio that could be useful in predicting clinical response to thymidine treatment. The authors think that taken together, multiple enzyme determinations could be useful in the characterization of human lymphomas.
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PMID:Multienzymatic analyses of human malignant lymphomas. Correlation of enzymatic data with pathologic and ultrastructural findings in Burkitt's and lymphoblastic lymphomas. 642 36

Neoplastic lymphocytes from a horse with lymphosarcoma and IgM deficiency were analyzed for ability to grow in culture; surface and cytoplasmic IgM; functional activity in blastogenesis, cytoxicity, and suppressor assays; and activities of six enzymes involved in purine and pyrimidine metabolism. The cells lacked surface and cytoplasmic IgM. They had elevated activity of adenosine deaminase and reduced activity of purine nucleoside phosphorylase. Neoplastic cells were nonresponsive in blastogenesis assay and did not kill allogeneic lymphocyte target cells or YAC-1 targets in a lectin-dependent cytotoxicity assay, however, the cells were active in a suppressor assay. They were grown for 16 weeks in cultures supplemented with interleukin 2, during which time the cells retained suppressive activity. These results are consistent with a T cell lymphoma of suppressor cell origin, and may explain the deficiency of IgM observed in some horses with lymphoreticular neoplasms.
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PMID:Biochemical and functional characterization of lymphocytes from a horse with lymphosarcoma and IgM deficiency. 654 49

The adenosine deaminase-resistant purine deoxynucleoside 2-chloro-2'-deoxyadenosine (CdA) is markedly toxic in vitro to nondividing and proliferating normal human lymphocytes and to many leukemia cell specimens. The CdA is also effective against mouse L1210 leukemia in vivo. The present investigations have examined the pharmacology, chemotherapeutic activity, and toxicity of CdA in nine patients with advanced hematologic malignancies refractory to conventional therapy. When administered by continuous intravenous infusion, the deoxyadenosine analog was well tolerated. As monitored by radioimmunoassay, plasma CdA levels rose gradually during the infusions. The CdA was not deaminated significantly. In all patients with leukemia, the CdA lowered the blast count by at least 50%. In one patient with a T-cell leukemia-lymphoma, and in another patient with chronic myelogenous leukemia in blast crisis, the CdA infusion eliminated all detectable blasts from the blood and bone marrow. In a patient with a diffuse lymphoma complicated by severe autoimmune hemolytic anemia, CdA treatment quickly terminated the hemolytic process. Bone marrow suppression represented the dose-limiting toxicity, and was related to plasma CdA levels, cumulative drug dosage, and the rapid release of CdA that accompanied tumor cell lysis.
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PMID:Antileukemic and immunosuppressive activity of 2-chloro-2'-deoxyadenosine. 658 95

A prospective study was done to assess the clinical utility of terminal deoxynucleotidyl transferase (TdT) and adenosine deaminase (ADA) assays in adult leukemia with a lymphoid phenotype. The study population consisted of 58 patients with adult lymphoblastic leukemia (ALL) at onset, 12 with lymphoblastic lymphoma, 15 with acute unclassifiable leukemia (AUL), and 30 with lymphoid or mixed acute phase of Philadelphia chromosome-positive (Ph' +) chronic myelogenous leukemia (CML). TdT was present in all cases of T-ALL, in 90% of non-T, non-B ALL, and absent in B-ALL; the ADA activity was significantly higher (P less than .01) in T-ALL. TdT was found in 75% of lymphoblastic lymphomas, in 78% of lymphoid, and in 50% of mixed CML transformations; higher ADA activity correlated with TdT positivity in AUL and CML blastic transformations (P less than .001). TdT-positive ALL had a better chance of response to therapy than TdT-negative ALL (P less than 0.01), but survival was not statistically different. TdT was undetectable in the peripheral blood of patients with ALL in complete remission and within the normal range in bone marrow (0.1%-8% of nucleated cells); median ADA activity was as in control subjects. Relapsing ALL patients had TdT and ADA enzymatic activities as before therapy; TdT immunofluorescence test (IF) was positive in 69% of bone marrow and in 100% of CNS relapses. Twenty percent of TdT-positive ALL at onset became TdT-negative in bone marrow at relapse. TdT IF test was instrumental in detecting meningeal leukemia but neither TdT nor ADA could be used as indicators of complete remission or impending relapse because TdT-positive cells were present in normal marrows and wide fluctuations of TdT IF values and of ADA activity were observed in remission.
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PMID:Clinical utility of terminal deoxynucleotidyl transferase and adenosine deaminase determinations in adult leukemia with a lymphoid phenotype. 658 63

Neoplastic thymocytes from rat thymic lymphoma-leukemias induced by the rat-adapted Gross-leukemia virus (RAGV) were analyzed for a variety of differentiation markers to define their differentiation state and possible cellular origin. A majority of thymocytes from leukemic rats had the phenotypic characteristics of subcapsular cortical thymocytes that are the most ancestral of the thymocytes. These cells exhibited readily detectable levels of Thy-1 and histocompatibility antigens on their surfaces, they contained terminal deoxynucleotidyl transferase (TdT) and they contained low adenosine deaminase (ADA) and high purine nucleoside phosphorylase (PNP) specific activity. The leukemic thymocytes also contained a sub-band of the LDH-5 isozyme (LDH-5') that was not detected in normal thymocytes but that was present in lymphocyte-rich fractions of postnatal bone marrow, fetal and prepubertal spleen, and fetal and neonatal liver. The tissue distribution and ontogeny of LDH-5'-containing cells is similar to prethymic TdT+ cells in the rat and both TdT and LDH-5' are enriched in a subset of bone marrow "null" cells. These results suggest that TdT+ thymocyte progenitors or their precursors are the targets of leukemic transformation of RAGV.
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PMID:Evidence for the cellular origin of Gross virus-induced leukemia in the rat: description of a unique LDH isozyme sub-band in leukemic lymphoid cells and lymphohemopoietic precursor cells. 677 89

A fourteen-year old female presented with a mediastinal mass and pleural effusion. A diagnosis of a poorly differentiated lymphocytic lymphoma was made from a lymph node biopsy. Fluid from a pleural tap contained numerous lymphoblasts; 91.5% of these lymphoblasts had a thymus leukemic antigen. At presentation, although morphologically normal, no adenosine deaminase (ADA) activity could be demonstrated in her peripheral blood lymphocytes. Lysates of her lymphocytes mixed with lysates of lymphocytes with known ADA activity resulted in ADA activity that was greater than expected. With disappearance of tumor following the institution of therapy, ADA activity appeared in her lymphocytes and the above phenomenon disappeared.
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PMID:Transient stimulatory adenosine deaminase activity in peripheral lymphocyte lysates from a case of T-cell lymphoma. 689 85

A deficiency of adenosine deaminase, an enzyme important in purine nucleoside catabolism, is associated with a severe combined immunodeficiency disease in children. Inhibition of this enzyme in vitro and in vivo results in an impairment in lymphoblast proliferation. We have investigated the pharmacologic inhibition of this enzyme by 2'-deoxycoformycin in 15 patients with hematologic malignancies. Biochemical consequences of the administration of this agent were closely monitored in erythrocytes, nucleated peripheral blood and bone marrow cells, serum, and urine. A marked rise in erythrocyte dATP was accompanied by a depletion of ATP in those patients exhibiting toxicity. Most patients excreted large amounts of deoxyadenosine but not adenosine in the urine. Serum deoxyadenosine rose in patients demonstrating a marked decrease in cell mass. The biochemical disturbances and clinical toxicity, including hepatic, renal, and conjunctival abnormalities, were usually reversible. Central nervous system toxicity, which potentially was the most serious consequence, was associated with high erythrocyte dATP/ATP ratios and high levels of cerebrospinal fluid deoxyadenosine. In patients with lymphoma and leukemia, objective responses were observed but were short-lived. Patients with chronic lymphocytic leukemia receiving weekly low doses of the drug demonstrated minimal toxicity and some efficacy. The chemotherapeutic potential o 2'-deoxycoformycin, as either a single agent or in combination with Ara-A, merits further exploration.
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PMID:The biochemical and clinical consequences of 2'-deoxycoformycin in refractory lymphoproliferative malignancy. 697 50

The importance of humoral immune defects and of the antibody deficiency syndrome, respectively, at adult age was examined on 69 patients. As immunological methods the estimation of the immunoglobulins G, A, M, D with Mancini's technique, of IgA-antibodies with Ouchterlony's technique, of T-lymphocytes with the sheep erythrocyte rosette test, of B-lymphocytes with direct immunofluorescence and mouse erythrocyte rosette test were used. The enzyme adenosine deaminase was determined in the plasma, the erythrocytes and the lymphocytes. 31 patients with primary antibody deficiency syndrome, of them 22 patients with selective IgA-deficiency could be diagnosed. 38 patients with secondary antibody deficiency syndrome came from groups of patients with lymphoproliferative diseases (non-Hodgkin-lymphoma and plasmocytoma), chronic dialysis and other haematological diseases. In 80% of the patients clinical symptoms of an immune defect could be proved. Chronically relapsing infections of the respiratory tract are in the first place. Familial accumulation, allergic reactions, antibodies against IgA, statistically significant accumulation of gastric and duodenal ulcers set off the anyway large group of patients with selective IgA-deficiency. An antibody deficiency syndrome with IgA-deficiency could be proved in 5 of 16 patients undergoing the dialysis programme, but clinically it is perhaps insignificant. Disturbances of the cell-mediated immune reaction occurred in a child with teleangiectatic ataxia and lymphoproliferative diseases. A deficiency of adenosine deaminase, which is of importance in combined immune defects syndrome at adult age, but it is to be proved in the plasmocytoma and the non-Hodgkin-lymphoma. The necessity of the knowledge of forms of the antibody deficiency syndrome at adult age results from the increasingly immunosuppressively acting therapeutic measures, correct and well-timed diagnosing as well as the necessity of aimed consultation of the physician in institutions specialised in immunology.
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PMID:[Humoral immune defects in adults]. 711 11

Pentostatin, a potent inhibitor of adenosine deaminase, is an antineoplastic agent which has been studied in the treatment of a variety of lymphoproliferative disorders. It is particularly effective in the treatment of hairy cell leukaemia, achieving complete remissions in 33 to 92% of patients, and has useful activity in treating B cell chronic lymphocytic leukaemia, prolymphocytic leukaemia, adult T cell leukaemia/lymphoma and cutaneous T cell lymphoma refractory to conventional chemotherapy. Initial results suggest that in the treatment of hairy cell leukaemia pentostatin achieves a more rapid response and higher frequency of complete remission with longer duration than interferon-alpha 2a, although it is still not known if some patients experiencing complete remission have been cured. The drug has yet to be directly compared with other promising purine analogues such as cladribine and fludarabine, and results of such comparisons are required before the ultimate role of pentostatin in the treatment of hairy cell leukaemia can be clearly established. However, pentostatin does produce a substantial response in a difficult therapeutic area and should be considered for initial treatment of hairy cell leukaemia.
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PMID:Pentostatin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in lymphoproliferative disorders. 750 51


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