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)

Antibody deficiency syndromes (ADS) are defined by the inability of the organism to maintain sufficient concentrations of specific antibodies in circulation. The carriers of antibodies, the immunoglobulins, are a well-defined class of plasma proteins. Some of the pertinent knowledge on their structure and function is briefly summarized. Clinical classification of ADS may be based on different criteria: etiological and pathogenetic views are here used according to needs. Primary ADS are the result of deficient synthesis, and secondary ADS are due to increased catabolism and/or loss of antibodies. Etiological factors in primary ADS are congenital disturbances (hereditary deficiency, e.g. agammaglobulinemia), regulatory imbalances (e.g. infantile hypogammaglobulinemia) or acquired disease (e.g. malignant monoclonal lymphoma). Among the causes of acquired ADS as one example diseases leading to protein loss, are discussed. However, the whole problem may not be summarized so briefly, and this is exemplified in two illustrative examples of genetically determined diseases (hereditary deficiency of transcobalamin II and of adenosine deaminase). Patients with congenital metabolic deficiences may be considered as "experiments of nature". Their extensive study has essentially contributed to new knowledge and insights into normal physiological mechanisms. This is also true in immunology where the discovery of fundamental facts is connected with such studies.
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PMID:[Antibody-deficiency syndrome]. 30 3

A competitive radioimmunoassay for a saline-soluble human thymus-leukemia-associated antigen (HThy-L) was applied for quantitation of this antigen in leukemia and normal hematopoietic cell lines. Highly increased quantities of HThy-L were detected in all T-cell leukemia lines tested, regardless of the presence or absence of receptors for sheep erythrocytes. This elevated level of HThy-L in combination with high terminal deoxynucleotidyl transferase and adenosine deaminase activities and the presence of a T-lymphocyte-specific surface antigen appear to represent stable phenotypic characteristics of T-cell lines. Most normal B-cell lines had low quantities of HTy-L. The level of HThy-L was slightly elevated in a considerable number of lymphoma B-cell lines and in all non-T, non-B leukemia cell lines tested. No relationship existed between quantities of HThy-L and an expression of different surface immunoglobulin isotypes in B-cell lines. Low quantities of HThy-L were detected in leukemia myeloid and myeloma cell lines as well as in B-cell leukemia lines originating from patients with B-cells acute lymphoblastic leukemia. Apparently, the increased quantities of HThy-L in T-cell leukemia lines may be related to certain stages of T-cell differentiation at which leukemia cell transformation occurs.
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PMID:Quantitation of human thymus-leukemia-associated antigen in established hematopoietic cell lines by radioimmunoassay. 31 16

Adenosine deaminase (EC 3.5.4.4, ADA) has been assayed in lymphocytes, granulocytes and erythrocytes from 45 patients with haematological malignancies. Activities were uniformly low in lymphocytes from patients with chronic lymphocytic leukaemia. Variable, but abnormal activities were frequently found in multiple myeloma, untreated lymphoma and leukaemic reticuloendotheliosis. High values were observed in lymphocytes from patients with lymphoma during intensive combination chemotherapy. ADA levels in lymphocytes were not correlated with levels in granulocytes or erythrocytes. ADA was elevated in blasts of patients with acute lymphocytic and myelogenous leukaemias but the ranges of activities per cell were so similar that ADA assay is unlikely to be of major help in distinguishing the two diseases.
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PMID:Adenosine deaminase activity in peripheral blood cells of patients with haematological malignancies. 106 90

YK-176 is a newly isolated 2'-deoxycoformycin (DCF), a potent inhibitor of adenosine deaminase, produced by Aspergillus nidulans. In a cooperative phase I study, YK-176 was administered to 22 patients, comprising 18 with adult T-cell leukemia-lymphoma (ATL), two with cutaneous T-cell lymphoma (CTCL), one with lymphoblastic lymphoma of T-cell type and one with carcinoma of the uterine cervix. Doses of YK-176 ranged from 3.0 to 9.0 mg/m2 and were given intravenously for three consecutive days. General malaise, anorexia, nausea, vomiting and low grade fever were frequently encountered, but were transient and not dose-related. At all dose levels hematological toxicities were mild. Two of seven patients receiving 7.0 mg/m2 for three consecutive days developed hepatocellular enzyme elevations (grade 2) and one patient, proteinuria (grade 2). One of two patients given 9.0 mg/m2 for three consecutive days manifested a life-threatening (grade 4) disturbance of consciousness and dyspnea, presumably ascribable to the drug-related toxicity of YK-176. The results suggest that 7.0 mg/m2 i.v. for three consecutive days is the maximum acceptable dose of YK-176. Central nervous system, pulmonary and possibly renal toxicities appeared to be dose-limiting. Out of the 20 patients evaluable for therapeutic response, partial remissions were observed in four, three with ATL and one with CTCL, who received less than 7.0 mg/m2 for three consecutive days. We conclude that YK-176 is an active agent against ATL at doses that may not be associated with prohibitive toxicity. A starting dose of 5.0 mg/m2 for three consecutive days is recommended for further phase II studies on ATL.
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PMID:Phase I study of YK-176 (2'-deoxycoformycin) in patients with adult T-cell leukemia-lymphoma. The DCF Study Group. 151 64

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

We measured the activity of adenosine deaminase (ADA) in the cerebrospinal fluid of 3 patients with tuberculous meningitis, 38 with viral meningitis, 15 with bacterial meningitis, 5 with malignant lymphoma, 11 with cerebrovascular diseases and 13 with miscellaneous neurological disorders. The highest ADA activities were observed in patients with tuberculous meningitis (median 21.3 U/l, range 20.0-23.0) and lymphoma (13.0 U/l, range 4.0-25.0). The sensitivity of the test for diagnosing tuberculous meningitis was 100% and the specificity 99% when a cut-off value of 20.0 U/l was used. We conclude that determination of ADA in cerebrospinal fluid is useful for the diagnosis of tuberculous meningitis, but that high activity also can be seen in some other CNS disorders, e.g. lymphoma with meningeal involvement.
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PMID:Diagnostic value of cerebrospinal fluid adenosine deaminase determination. 158 21

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

We measured the levels of adenosine deaminase (ADA) and immunosuppressive acid protein (IAP) in 10 patients with acute myeloid leukemia (AML), 5 with acute lymphoblastic leukemia (ALL), 8 with chronic myeloid leukemia (CML), 7 with myelodysplastic syndrome (MDS), 5 with malignant lymphoma (ML), 3 with multiple myeloma (MM) and one with adult T cell leukemia. On admission, the level of IAP was abnormally high in all cases of AML and ALL 50% of CML cases, 71.4% of MDS cases, 60% of ML cases and none of MM cases. ADA was elevated in all cases of ALL, 77.8% of AML and CML cases, 57.1% of MDS cases, 60% of ML cases and 33.3% of MM cases. In 7 patients with AML, the level of IAP returned to normal when they achieved complete remission. On the other hand, the level of ADA had already returned to normal even during induction therapy. ADA showed a positive correlation with the absolute number of peripheral blasts and lactic dehydrogenase both in AML and ALL. These results suggest that ADA indicates the activity of leukemia and IAP indicates the immunocompetence of the host.
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PMID:[Combination assay of IAP and ADA in hematologic malignancies]. 238 Oct 93

Recent evidence suggests that ethanol initially causes an increase in receptor-dependent cAMP levels, followed by heterologous desensitization of receptors coupled to GS after chronic exposure. Here we investigated the role of adenosine in mediating these responses. We found that ethanol caused accumulation of extracellular adenosine in NG108-15 and S49 lymphoma cells. This adenosine activated adenosine receptors to increase intracellular cAMP levels. The addition of adenosine deaminase, to degrade accumulated extracellular adenosine, or isobutyl-methylxanthine, an adenosine receptor antagonist, completely blocked ethanol-induced increases in cAMP levels in NG108-15 cells. Chronic exposure of NG108-15 and S49 wild type cells to ethanol resulted in heterologous desensitization of adenosine receptor- and prostaglandin E1 receptor-dependent cAMP signal transduction. Coincubation of NG108-15 and S49 wild type cells with adenosine deaminase and ethanol for 48 hr prevented heterologous desensitization. Moreover, mutant S49 cells, which are unable to transport adenosine, did not accumulate extracellular adenosine after incubation with ethanol and did not develop ethanol-induced heterologous desensitization. Our results suggest that adenosine is an important mediator of both the acute and chronic effects of ethanol on cAMP signal transduction.
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PMID:Adenosine is required for ethanol-induced heterologous desensitization. 255 72


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