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)

Human blood lymphocytes can be separated into two populations according to the presence of surface complement receptors. Lymphocytes containing complement receptors (CR+) were found to have a high rate of RNA synthesis or turnover accompanied by increased protein synthesis. Lymphocytes not containing complement receptors (CR-) while maintaining a low profile in RNA synthesis, had a 10-12-fold greater activity in adenosine deaminase enzyme which is believed to be related to lymphocyte-immune responses and cell-mediated immunity. These two biochemical characteristics can be useful tools for future studies in lymphocyte functions. By using these two biochemical markers, we found that CLL lymphocytes were predominantly of the CR+ type, had high active RNA synthesis, and very low adenosine deaminase level. Lymphocytes from two patients with X-linked agammaglobulinaemia showed a picture opposite to that of CLL.
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PMID:Two biochemical markers in lymphocyte subpopulations. 99 Jan 93

Fludarabine (9-beta-D-arabinofuranosyl 2-fluoro-adenine monophosphate) is a fluorinated analogue of adenine which is relatively resistant to deamination by adenosine deaminase. Phase I clinical trials disclosed significant antitumor activity in lymphoid malignancies. Fludarabine has been used in the treatment of CLL since March, 1985, at a dose of 25-30 mg/m2/day x 5 days each 3-4 weeks by short intravenous infusion. Sixty-eight previously treated patients with CLL are evaluable for response. The median age was 60 years, 50 were male the median number of prior chemotherapy regimens was 2, and the median time from initial chemotherapy to fludarabine was 45 months. Forty-three (63%) were Rai stages 3 and 4, 31 (46%) were Binet Stage C. Twenty patients (29%) obtained a complete remission (CR), defined as peripheral lymphocytes less than 4,000/microliters, no clinical evidence of disease, less than 30% of lymphocytes in the bone marrow (with no residual nodules), or a nodular partial remission, NPR (CR except for residual lymphoid nodules), and 19 (28%) a partial remission (less than 50% reduction in tumor in nodes, liver, spleen and bone marrow and greater than 1 log reduction in the lymphocyte count). The complete remission rate for the various involved sites were blood (69%), liver (52%), spleen (55%), and nodes (48%). The bone marrow was the least responsive site with 16% CR and 44% PR. The number of prior regimens did not have a significant response rate or survival. The serum albumin , alkaline phosphatase, platelet and hemoglobin level all were associated with survival from the start of fludarabine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fludarabine therapy in chronic lymphocytic leukemia (CLL). 246 94

The activities of the key glycolytic enzymes phosphofructokinase (PFK), pyruvate kinase (PK) and hexokinase in addition to adenosine deaminase, purine nucleoside phosphorylase (PNP) and lactate dehydrogenase (LDH) have been measured in lymphocytes from 39 cases with B-chronic lymphocytic leukaemia (B-CLL). According to the percentage of circulating large non-granular atypical lymphocytes (AL) the B-CLL cases were classified as: typical (less than 10% of AL; 28 cases) and atypical (10-25% AL; 11 cases). In both groups the median lymphocyte volume (MLV) was assessed and correlated with the correspondent enzyme activities. The MLV of B-CLL lymphocytes was significantly (p less than 0.001) decreased (149.9 +/- 19.4 fl) as compared to normal B lymphocytes (175.1 +/- 14.5 fl) and it was significantly (p less than 0.001) lower in typical B-CLL (141.8 +/- 12.2 fl) than in atypical B-CLL (172.0 +/- 17.2 fl). Furthermore, in patients with typical B-CLL, all enzyme activities when expressed as U/10(9) cells were, with the exception of PFK, significantly decreased compared to normal B lymphocytes. However, when the results were expressed as U/ml cells, only PK, PNP and LDH remained significantly low. These findings demonstrate that the determination of MLV in addition to morphology may be a useful tool to distinguish the two previously described morphological B-CLL variants (typical and atypical) and that these two different B-CLL groups are also distinguishable on the basis of three enzyme activities, PK, PNP and LDH which have been shown to be less dependent on cell size than the other enzymes, also studied here.
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PMID:Relationship between lymphocyte size and enzyme activities in two morphological variants of B-chronic lymphocytic leukaemia. 252 63

Investigations of the purine degradative enzymes adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and ecto-5'-nucleotidase (5'NT) have been shown to be of value in defining subsets of lymphoid malignancies. We have studied the activities of these enzymes in the circulating malignant cells of 35 patients with chronic B lymphocytic leukaemia and have correlated the biochemical data with immunological phenotypes. Classification of the cases into those without evidence of secretory activity ('true' CLL, 14 patients) and those with cytoplasmic immunoglobulin (CIg) ('immunocytoma'; 21 patients) revealed that immunocytomas are phenotypically and biochemically associated with more mature features. Malignant cells without CIg were characterized by low activities of ADA, PNP and 5'NT. In malignant cells with evidence of secretory activity (immunocytoma), low activity of ADA was also observed, but the activities of PNP and 5'NT were relatively high and approached the range of normal B lymphocytes. The differences in PNP (P less than 0.05) and in 5'NT (P less than 0.01) between these two groups were significant. Phenotypically the cells without CIg were predominantly associated with IgM (+k light chains) as surface membrane immunoglobulin (SmIg) whereas expression of IgG was more often observed in the leukaemic cells with CIg. No correlation between enzyme patterns and the stage of the disease was apparent. Thus both biochemical and immunological criteria show that cases of CLL vary within a range of maturity and that those with CIg might be more mature in the B cell axis. The present study emphasizes the value of purine enzyme studies in defining subsets of B cell neoplasia.
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PMID:Purine degradative enzymes and immunological phenotypes in chronic B-lymphocytic leukaemia: indications that leukaemic immunocytoma is a separate entity. 300 40

Differences in activities of the purine degradative enzymes, adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5'-nucleotidase (5'NT), have been observed among different classes of lymphoid malignancies. Recent studies have shown that hairy cell leukemia (HCL) may respond to treatment with the ADA inhibitor, 2-deoxycoformycin. This study demonstrates that the cells of HCL have significantly lower levels of ADA and 5'NT (P always less than 0.01) when compared to levels in normal B- or T-lymphocytes, but have higher levels of PNP (P less than 0.001 for both comparisons). Recent studies have shown that when treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), cells of B-cell chronic lymphatic leukemia (B-CLL) acquire phenotypic characters of HCL. The authors have therefore also investigated the changes in enzyme pattern of B-CLL after incubation with TPA B-CLL cells are characterized by low levels of ADA, PNP, and 5'-NT, but TPA caused a marked increase in PNP activity (P less than 0.001, t test for paired samples), a pattern similar to HCL. The results from biochemical studies are thus in accordance with the hypothesis that HCL cells are more mature than B-CLL cells. The special enzyme profile of HCL suggests that a PNP inhibitor might also be effective in the treatment of this disease.
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PMID:Enzymes of purine metabolism in hairy cell leukemia. 301 Dec 39

Previous reports have shown that the purine degradative enzymes adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and ecto-5'-nucleotidase (5'NT), play an important role in the normal development of lymphocytes and that investigations of these enzymes are of value in defining subsets of lymphoid malignancies of T-cell origin. Pharmacological inhibition of one of these enzymes has been found to be an effective treatment for a few lymphatic neoplasia. We have studied the activities of the above enzymes in the circulating malignant cells of 25 patients with B-chronic lymphatic leukemia (B-CLL), four patients with B prolymphocytic leukemia (PLL), seven patients with leukemic centrocytic lymphoma (CC), 18 patients with hairy cell leukemia (HCL) and 16 patients with immunocytoma (IC). For comparison, the blasts of nine patients with 'common' acute lymphatic leukemia (cALL) and normal T (n = 12) and B (n = 8) cells were simultaneously investigated. Despite morphologic similarity, the leukemic cells of the chronic B cell malignancies demonstrate different enzyme patterns. B-CLL is characterized by very low activities of all the enzymes ADA, PNP and 5'NT. In the cells of HCL the highest values of PNP are found. The leukemic cells of IC are characterized by low levels of ADA but moderate levels of PNP and high levels of 5'NT. Thus some of the entities of B malignancies show typical enzyme patterns which might be of importance in defining maturation stages of the disease. The differences in these enzyme patterns can also be made use of in therapy with enzyme inhibitors such as deoxycoformycin.
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PMID:Purine degradative enzymes in circulating malignant cells of patients with chronic B cell neoplasia. 303 62

Promising results in the treatment of indolent lymphomas have been reported with the use of 2'deoxycoformycin. This antimetabolite, an adenosine deaminase inhibitor, also shows particular efficacy in hairy cell leukemia. Of 65 patients treated to date, 44 have achieved complete and lasting remission after a limited course of deoxycoformycin. While results are not as striking as those in hairy cell leukemia, deoxycoformycin may also be a valuable adjunct to alkylating agents in the treatment of CLL. The drug also is being studied in the treatment of mycosis fungoides and other lymphoid neoplasms. Side effects in all neoplasms are dose- and schedule-dependent.
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PMID:Deoxycoformycin: an active new drug for indolent lymphomas and hairy cell leukemia. 307 30

The levels of adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), lactic dehydrogenase (LDH), and LDH isoenzyme patterns (LD1 to LD5) have been measured in lymphocyte extract from 28 patients with B-chronic lymphocytic leukemia (B-CLL). The activities of ADA, PNP, and LDH have been correlated with two morphological groups of B-CLL classified according to the percentage of large, nongranular, atypical lymphocytes (AL) in peripheral blood: "typical" B-CLL (less than 10% of AL, 21 cases) and "atypical" B-CLL (10-25% of AL, seven cases). Patients with atypical B-CLL had significantly (P less than 0.001) higher activities of ADA (0.46 +/- 0.17 U/10(9) cells), PNP (1.74 +/- 1.0 U/10(9) cells), and LDH (48.3 +/- 9.7 U/10(9) cells) than patients with typical B-CLL (ADA, 0.29 +/- 0.1 U/10(9) cells; PNP, 0.58 +/- 0.23 U/10(9) cells; and LDH, 29 +/- 10 U/10(9) cells). In addition, the "treatment-free period" was also significantly (P less than 0.025) shorter in the group of atypical B-CLL compared with the typical B-CLL group. No clear-cut statistical differences in lymphocyte surface markers or in several other prognostic factors between the two subgroups of B-CLL were found. The present study supports the idea that in B-CLL the simultaneous determination of ADA, PNP, and LDH might be helpful in better understanding the pathophysiology, prognosis, and natural history of the disease.
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PMID:Combined assay of adenosine deaminase, purine nucleoside phosphorylase, and lactate dehydrogenase in the early clinical evaluation of B-chronic lymphocytic leukemia. 312 50

The relationship between the intracellular levels of DNA polymerase alpha (DP-alpha), adenosine deaminase (ADA) and lactate dehydrogenase (LDH) and the degree of malignancy of human lymphomas was investigated. Twelve non-neoplastic lymph nodes and 88 malignant lymphomas were examined. For non-Hodgkin's lymphomas (NHL) the low or high grade of malignancy was established according to three classifications: the Rappaport, the Kiel and the Working Formulation for Clinical Usage, with the latter also recognizing an intermediate grade group. Non-neoplastic lymph nodes had significantly lower levels of all the three enzymes than those found in high-grade malignant NHL (the P value ranged from less than 0.02 to less than 0.001). Hodgkin's disease, a slowly evolving neoplasia, showed lower levels of DP-alpha (P less than 0.001) and ADA (P less than 0.001), but not of LDH, than high-grade NHL. Among NHL, whatever classification was used, the low-grade malignant lymphomas had significantly lower levels than the high-grade ones for all the three enzymes (P less than 0.005 or P less than 0.001). The intermediate-grade group of the Working Formulation differed from the high-grade group for DP-alpha (P less than 0.01) and ADA (P less than 0.02) but not for LDH. It differed from the low-grade group only for ADA (P less than 0.005). Lymphoblastic and Burkitt's lymphomas were the groups with the highest levels of the three enzymes. Among low-grade lymphomas very low values were found in the histological entities defined as DLWD in the Rappaport classification, CLL and lymphoplasmacytoid immunocytoma in the Kiel classification and small lymphocytic (group A) in the WF. The levels of all enzymes in these histotypes were always significantly different from the other low-grade histotypes, and from the intermediate-grade ones of the WF. In the Kiel classification polymorphous lymphoplasmacytoid lymphoma, recently recognized as a group with a quite aggressive clinical course, was characterized by high levels of all three enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relation between enzymatic activities and the degree of malignancy of human lymphomas. 404 77

In order to study if enzymes of purine metabolism could be used as cell markers in B-chronic lymphocytic leukemia (B-CLL), the activities of adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5'-nucleotidase (5'N) were repeatedly measured in blood mononuclear cells from B-CLL patients and were compared to those obtained in normal controls. Enzyme activities in patients were also compared to other biological parameters indicative of B-CLL to activities of ADA and PNP in erythrocytes. Results show that B-leukemic cells display abnormal enzyme patterns: subnormal ADA activity is characteristic; 5'N activity is depressed in 60% of the cases but increased in 15%. An inverse relationship between PNP activity and corresponding lymphocytosis is observed in leukemic but not in normal cells. The enzymatic anomalies seem to be linked to the presence of an unusual peripheral lymphocytic population, induced by the leukemic process. Indeed, ADA and PNP are not abnormal in erythrocytes. In untreated nonevolutive patients, the enzyme profile tends to remain stable throughout the course of the illness; normalization of enzyme patterns in treated patients occurs only when therapy induces improvement in T and B cell distribution.
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PMID:Enzymes of purine metabolism in B-chronic lymphocytic leukemia. 633 Nov 55


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