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)

Pre-implantation embryos were infected with the retroviral vector MMCV-neo, which carries the neomycin resistance (neo) gene and the v-myc gene. Three transgenic substrains (M-TKneo 1-3) were derived which stably transmit a single intact copy of the vector. In all of the substrains, expression of the neo gene from the internal thymidine kinase (TK) promoter was detected, with two of the substrains expressing the gene in all tissues analysed. In the third substrain, the vector had integrated on the X chromosome and neo expression varied between different tissues. A second series of transgenic mice were obtained with the retroviral vector SAX, in which the human adenosine deaminase cDNA (ADA) is under the control of an internal SV40 promoter. Four substrains (M-SAX 1-4) were analysed; however, no expression of the ADA cDNA was detected. In all mice, no expression was found of the genes under the control of the viral 5' long terminal repeats (LTRs). In the M-TKneo substrains the vector was hypomethylated irrespective of its expression whereas in the M-SAX mice the vector was hypermethylated. These results demonstrate for the first time that the TK promoter can apparently express a gene in all tissues of adult mice and that retroviral vectors with internal promoters may provide an alternative to DNA injection for the efficient expression of genes in transgenic mice.
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PMID:Expression of retroviral vectors in transgenic mice obtained by embryo infection. 303 88

Multiple replication-defective retrovirus vectors were tested for their ability to transfer and express human adenosine deaminase in vitro and in vivo in a mouse bone marrow transplantation model. High-titer virus production was obtained from vectors by using both a retrovirus long terminal repeat promoter and internal transcriptional units with human c-fos and herpes virus thymidine kinase promoters. After infection of primary murine bone marrow with one of these vectors, human adenosine deaminase was detected in 60 to 85% of spleen colony-forming units and in the blood of 14 of 14 syngeneic marrow transplant recipients. This system offers the opportunity to assess methods for increasing efficiency of gene transfer, for regulation of expression of foreign genes in hematopoietic progenitors, and for long-term measurement of the stability of expression in these cells.
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PMID:Expression of human adenosine deaminase in murine hematopoietic cells. 307 74

Some biochemical mechanisms underlying the impairments of cellular immunity were studied in C3Ha mice in the course of growth of transplantable and induced (ortoaminoazotoluol) solid hepatomas. During intensive hepatoma growth, the adenosine deaminase activity in host thymocytes was shown to be drastically (6 times) reduced, resulting in the elevation of dATP and dGTP concentrations (6- and 7-fold, respectively), the potential inhibitors of ribonucleoside diphosphate reductase. Consequently, the rate of DNA synthesis was reduced as can be evidenced by the decrease of (a) thymidine kinase activity, (b) 14C-thymidine incorporation into DNA, and (c) dTTP and dCTP pools. By the terminal period of hepatoma growth (both transplantable and induced one), the serum corticosterone content increased 3- and 8-fold, respectively. At the same time, specific binding of [3H]triamsinolone acetonide by thymocytes was augmented and the activity of terminal deoxynucleotidyl transferase increased the latter alterations, which can be regarded as a reflection (including other parameters mentioned) of the arrest of T-lymphocyte differentiation at the level of immature cortex thymocytes.
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PMID:[Changes in the lymphoid cells of DNA and purine nucleotide synthesis and sensitivity to glucocorticoids associated with impairment of differentiation and immune function during tumor growth in mice. Thymocytes]. 308 74

Biochemical impairments in spleen immunocompetent cells (T- and B-lymphocytes) were revealed in host (C3HA mice) of transplantable and ortoaminoazotoluol-induced hepatomas in the course of their growth. As soon as hepatoma emerged (chemical carcinogenesis), the activity of adenosine deaminase and purine nucleoside phosphorylase in T- and B-lymphocytes were found to be reduced 2-6 and 7-10-fold, respectively in parallel with the impairment of their immune system. These alterations were accompanied by the increase in concentrations of dGTP in T-lymphocytes (5.4-fold) and of dATP in B-lymphocytes (4-fold) as well as with the inhibition of DNA synthesis, predominantly in T-lymphocytes. In both T- and B-lymphocytes, the dCTP pool was decreased. In the spleen, T- and B-lymphocytes of mice carrying transplantable 22 hepatoma 22 by the moment of its maximal growth (5th day), the DNA synthesis was inhibited as revealed by the reduction of (a) thymidine kinase activity, (b) rate of the labeled thymidine incorporation into DNA, and (c) intracellular dTTP and dCTP concentrations. In latter periods (from 8th day up to the moment of death), drastic stimulation of DNA synthesis in spleen T- and B-lymphocytes was observed irrespective of the impairments in the immune function and the decrease of the adenosine deaminase activity. In the course of growth of both transplantable and induced solid hepatomas in host spleen T- lymphocytes, the activity of the CTP-dependent thymidine kinase isoenzyme increased, coinciding in time with the activation of antigen-specific T-suppressors in the same organ.
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PMID:[Changes in DNA and purine nucleotide synthesis in lymphoid cells and sensitivity to glucocorticoids associated with the impairment of differentiation and immune function in mice during tumor growth. Spleen T- and B-lymphocytes]. 308 34

Chemical and enzymatic procedures have been employed for the preparation of various phosphorylated derivatives of the acyclonucleoside 9-(1,3-dihydroxy-2-propoxymethyl)adenine, an analogue of the active antiviral agent 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG). In combination with the previously reported 2',3'-seco nucleosides and their phosphates and cyclic phosphates (Stolarski et al., Z. Naturforsch. 41c, 758-770, 1986), this made available a broad class of acyclonucleosides and nucleotides, the acyclic moieties of which are capable of mimicking the ribose and 2'-deoxyribose rings. The solution conformations of the foregoing were determined with the aid of 1H, 13C and 31P NMR, and compared with those of DHPG and 9-(hydroxyethoxymethyl)guanine (Acyclovir, ACV). Particular attention was devoted to conformations about C-O bonds in different acyclic fragments, which demonstrated well-defined differences between 2',3'-seco derivatives on the one hand (conformational "rigidity") and derivatives with DHP and AC acyclic chains on the other (rotation about the C(1')-O(4') bond). The overall results are in good general agreement with reported crystal structures, and are compared with those obtained by quantum mechanical calculations. The conformational features of the various compounds are also discussed in relation to their substrate and/or inhibitor properties in a number of enzyme systems, including adenosine deaminase, phosphodiesterases, nuclease P1,3'-nucleotidase and herpes virus type 1 thymidine kinase.
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PMID:Solution conformations of some acyclo nucleoside and nucleotide analogues of antiviral acyclonucleosides, and their substrate/inhibitor properties in several enzyme systems. 338 56

In thymocytes of C3HA mice carrying the transplantable and ortoaminoazotoluene induced hepatomas at the time of their intense growth a drastic decrease in adenosine deaminase activity set in and 3-4-fold augmentation of intracellular concentration of dATP and dGTP, potential inhibitors of ribonucleoside diphosphate reductase was observed, leading to the reduction of the DNA synthesis. The latter event was evidenced by a suppressed 14C-thymidine incorporation into thymocytes DNA in vitro, decreased thymidine kinase activity, intracellular dTTP and depletion of dCTP pools. Only in the terminal period of hepatocarcinogenesis (12 months) a 4-fold increase in the corticosterone serum concentration was observed. As for the mice carrying transplantable 22a hepatoma, serum hormone levels augmented 4-fold as early as 24 h after tumor implantation and thereafter kept increased two fold. An elevated activity of terminal deoxynucleotidyl transferase in mouse thymocytes has been shown to be characteristic of the late periods of tumor growth reflecting the arrest of the immature cortical thymocyte differentiation. By the time hepatomas emerged in the course of hepatocarcinogenesis in spleen T and B lymphocytes a significant drop in the activity of adenosine deaminase (3-4-fold) and purine nucleoside phosphorylase (2-8-fold) was noted--the events directly correlated with the weakening of cell immune functions. The disorders described were accompanied by the accumulation of dGTP in spleen T lymphocytes, dATP in B lymphocytes and inhibition of DNA synthesis, predominantly in T lymphocytes. In the latter instance the pool of dCTP was found to be depleted. In spleen T and B lymphocytes of mice carrying solid 22a hepatoma when the peak of its growth was reached (day 5) the rate of DNA synthesis dropped. Later on (from day 8 to the animal death), however, in spite of the suppression of immune function and the decrease in adenosine deaminase activity a drastic stimulation of DNA synthesis in spleen T and B lymphocytes was observed. The increase in spleen T suppressor activity in the course of intense growth of the both types of hepatomas coincided in the time with the stimulation of the CTP-dependent thymidine kinase isoenzyme activity in total T lymphocyte population of the same organ.
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PMID:Some biochemical mechanisms underlying the impairment of T and B cell immunity in C3HA mice during hepatoma growth. 349 9

To evaluate the effect of aging upon the small intestine, the distribution, content, and concentration of epithelial cell enzymes at different levels along the crypt-villus column were measured in aging and young adult, male, Fisher 344 rats. Specific activities of sucrase, maltase, lactase, and adenosine deaminase in mucosal homogenates were lower in the upper intestines of aging than in young animals, whereas the specific activity and content of thymidine kinase was higher. Enzyme activities were measured in cells obtained by cryostat sectioning from villus tip to crypt base. Sucrase and maltase activities were fully expressed nearest the crypt, alkaline phosphatase in cells higher on the villus, and adenosine deaminase higher still, whereas thymidine kinase activity was limited to the crypts. The ordered pattern of enzyme expression was maintained in aging rats but the initiation and duration were delayed. Because peak specific enzyme activities were similar in young and aging animals, the reduced specific activities in mucosal homogenates from aging animals were due to an increase in the proportion of relatively undifferentiated villus epithelial cells. These findings are of importance in explaining altered intestinal function during aging without a concomitant change in intestinal structure.
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PMID:Delayed enzyme expression: a defect of aging rat gut. 393 Mar 40

We have confirmed the localization of human acid alpha-glucosidase (GAA) to 17q21----q25 and of adenosine deaminase (ADA) to 20q13----20qter by examination of hybrid clones derived from a fusion between a human cell line carrying a 17/20 balanced translocation (17pter----17q25::20q13----20qter;20pter-- --20q13::17q25----17qter) and a mouse line deficient in thymidine kinase. These hybrids were constantly maintained in HAT selective media in order to select for the presence of the human thymidine kinase gene on the intact chromosome 17 (17q21----22) or the 17/20 (17pter----17q25::20q13----20qter) translocation chromosome. We detected human GAA by rocket immunoelectrophoresis, using a heterologous antibody raised against human acid alpha-glucosidase. A clone which contained the 17/20 translocation and no intact chromosome 17 was still positive for GAA. This finding confirms the exclusion of GAA from 17q25----17qter reported by Nickel et al. (1982). Combined with earlier results (Weil et al. 1979), GAA can be assigned to 17q21----17q25. A clone which contained only the 17/20 translocation chromosome and no intact chromosome 20 contained ADA. This confirms the previous localization of ADA to 20q13.2----qter by gene dosage studies (Philip et al. 1980).
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PMID:Confirmation of the regional localization of the genes for human acid alpha-glucosidase (GAA) and adenosine deaminase (ADA) by somatic cell hybridization. 637 91

Deoxyadenosine toxicity toward lymphocytes may produce immune dysfunction in patients with adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) deficiency. The relationship between endogenous deoxynucleoside synthesis in adenosine deaminase-deficient cells and sensitivity to adenosine and deoxyadenosine toxicity is unclear. The human histiocytic lymphoma cell line (DHL-9) naturally lacks adenosine deaminase, and has minimal levels of thymidine kinase. Dividing DHL-9 cells excrete deoxyadenosine and thymidine into the extracellular space. The present experiments have analyzed nucleoside synthesis and excretion in a mutagenized clone of DHL-9 cells, selected for increased resistance to deoxyadenosine toxicity. The deoxyadenosine-resistant cells excreted both deoxyadenosine and thymidine at a 6-7-fold higher rate than wild-type lymphoma cells. The deoxyadenosine overproduction was accompanied by a reduced ability to form dATP from exogenous deoxyadenosine, and a 2.5-fold increase in ribonucleotide reductase activity. The pace of adenosine excretion, the growth rate, and the levels of multiple other enzymes involved in deoxyadenosine and adenosine metabolism were equivalent in the two cell types. These results suggest that the excretion of deoxyadenosine and thymidine, but not adenosine, is exquisitely sensitive to alterations in the rate of endogenous deoxynucleotide synthesis. Apparently, small changes in deoxynucleotide synthesis can significantly influence cellular sensitivity to deoxyadenosine toxicity.
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PMID:Deoxynucleoside overproduction in deoxyadenosine-resistant, adenosine deaminase-deficient human histiocytic lymphoma cells. 637 66

The levels of the purine catabolic enzymes, adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP), together with the pyrimidine activities, thymidine phosphorylase (TP) and thymidine kinase isozymes (TK) have been determined for cells obtained from solid lymphoid tissue of 38 patients with non-Hodgkin's lymphoma (NHL) and 14 individuals exhibiting benign reactive lymphoid hyperplasia. Within each NHL histological group subtyped according to the Rappaport classification, and in the reactive hyperplasia group, there was considerable variation in these activities. However, higher levels of TK and TP activities occurred in cells of the histologically unfavourable prognostic NHL groups compared with those of favourable histology or reactive hyperplasia. There was an inverse relationship between survival and elevated TK isozyme 1 and TP levels, which was independent of histological classification and clinical staging. These results indicate that, in addition to morphology, estimations of TK and TP of involved lymphoma cells in NHL is of clinical relevance.
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PMID:Pyrimidine and purine activities in non-Hodgkin's lymphoma. Correlation with histological status and survival. 642 90


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