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)

A rapid, reliable method for the simultaneous separation of adenosine deaminase, adenylate kinase, and carbonic anhydrase II by agarose gel electrophoresis is presented. This method uses a double origin sample application system. Unreduced sample extracts for adenylate kinase analysis are applied 13.0 cm from the anode. Reduced sample extracts for the remaining proteins of interest are applied 7.0 cm from the anode. The use of applicator foils and an increased voltage gradient result in superior resolution, linearity, and band sharpness of the allozyme patterns. Further, there is no masking of the adenylate kinase 2 band as a result of the use of a reducing agent, and carbonic anhydrase II is resolved without interference from hemoglobin as has been observed with other multisystem methods.
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PMID:A double origin electrophoretic method for the simultaneous separation of adenosine deaminase, adenylate kinase, and carbonic anhydrase II. 302 23

Contemporary molecular techniques including gene cloning, DNA sequencing, and gene transfer permit precise and comprehensive analysis of genetic disorders. For example, the molecular basis of hemoglobin synthesis disorders (the thalassemias) can now be ascribed to more than 30 different specific mutations. These affect virtually all aspects of gene expression. The more recent capacity to reintroduce cloned genes into mammalian cells in a functional form has raised the prospect of gene therapy, that is, the replacement of an abnormal gene with its normal counterpart or merely the introduction of a normal gene into a cell containing a defective copy. Genetic correction of enzyme-deficiency disorders whose effects are manifest in bone-marrow-derived cells seems most likely to be amenable to "somatic" (as opposed to germ line) gene therapy. Treatment of severe combined immunodeficiency due to adenosine deaminase (ADA) deficiency may be a suitable model for this approach. This report will review the molecular genetics of ADA, the methods by which ADA gene sequences may be transferred into various cells, and goals for current and future research.
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PMID:Molecular genetics and potential gene therapy. 352 68

A large pedigree containing a child with severe combined immunodeficiency disease (CID) associated with adenosine deaminase (ADA) deficiency was investigated to ascertain if heterozygotes could be detected by measuring red cell ADA activity. 9 of 17 individuals in three generations who were at risk for being heterozygous had decreased red cell ADA activity. This genetic information establishes one form of CID as an autosomal recessive disorder. The identified heterozygote population had a mean ADA value of 19.2 U/g hemoglobin (0.95 confidence interval; 14.0 to 24.4 U/g hemoglobin), which was approximately one-half the mean, 36.1 U/g hemoglobin, of a randomly selected control population (0.95 confidence interval; 22.5-58.1 U/g hemoglobin). Statistical comparisons of the heterozygotes to the normal population indicates that within a high-risk family heterozygotes may be identified with 90% confidence.
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PMID:Detection of the carrier state in combined immunodeficiency disease associated with adenosine deaminase deficiency. 481 83

Abnormalities of adenosine deaminase, a critical enzyme of the purine salvage pathway, have been reported in association with immune dysfunction, acute leukemia, and hereditary hemolytic anemia. We report data showing that erythrocyte adenosine deaminase activity is also abnormal in congenital hypoplastic anemia (the Diamond-Blackfan syndrome). Adenosine deaminase activity in erythrocytes from 12 patients (mean +/- S.D., 2.20 +/- 0.77 IU per gram of hemoglobin) was substantially greater than that observed in 50 controls (0.62 +/- 0.13 IU per gram). Enzyme activity in affected patients was also greater than that seen in cord blood or in erythrocytes from patients with hemolytic anemia, acquired aplastic anemia, Fanconi's hypoplastic anemia, acquired pure red-cell aplasia, or transient erythroblastopenia of childhood. These observations indicate that erythrocyte adenosine deaminase activity may be a unique marker for identifying congenital hypoplastic anemia.
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PMID:Elevated erythrocyte adenosine deaminase activity in congenital hypoplastic anemia. 664 73

The adenosine analog xylosyladenine is a potent inducer of hemoglobin synthesis in Friend virus-infected murine erythroleukemia (MEL) cells. In cultures treated with 0.1 microM xylosyladenine and an inhibitor of adenosine deaminase, 80% of the cells accumulated hemoglobin. Under these conditions, cell growth was inhibited by 50%. No effect was observed in the absence of adenosine deaminase inhibition. An adenosine kinase-deficient MEL subline was isolated and was found to be resistant to induction by xylosyladenine. Treated cells accumulated substantial amounts of the xylofuranosyl analogs of ATP, S-adenosylmethionine, and S-adenosylhomocysteine, indicating that metabolites of xylosyladenine participate in S-adenosylmethionine-mediated transmethylation reactions. Measurements of in vivo nucleic acid methylation showed that xylosyladenine causes a marked inhibition of 2'-O-methyluridine, 2'-O-methylcytidine, 5-methyluridine, and 5-methylcytidine formation in the RNA of treated cells. DNA methylation was not inhibited. These data suggest that the xylofuranosyl analogs of S-adenosylmethionine and/or S-adenosylhomocysteine can inhibit intracellular RNA methylation in MEL cells while having little or no such effect on DNA methylation.
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PMID:Induction of hemoglobin synthesis by xylosyladenine in murine erythroleukemia cells. Metabolism of xylosyladenine and effects on transmethylation. 730 32

Three isomers of trifluoromethylaniline (TFMA) were investigated for their possible different toxic effects on the hematopoietic system in male Wistar rats. The effects of isomeric 2-, 3- and 4-TFMA were compared with those of aniline, the prototypic drug. Strong leukocytosis manifested by considerable increase in the number of all respective white blood elements was observed in the peripheral blood 1 day after the administration of 4-TFMA. In contrast, erythropoiesis, as ascertained by erythrocyte count and hemoglobin concentration, was inhibited by 4-TFMA. The determination of the ED50 revealed lymphocytes to be the most responsive elements towards 4-TFMA administration. Besides hyperemic and proliferative splenomegaly the histological changes in maturation of immunocompetent cells following the 4-TFMA administration were found also in thymus. In accord with an enhanced incorporation of [3H]thymidine, the specific activity of thymidine kinase (TdK) in spleen was increased after a single dose of 4-TFMA. Activities of the catabolic enzymes adenosine deaminase (ADA) and inosine phosphorylase (IP) decreased in both organs with the exception of IP activity in thymus. The effects evoked by the 3-TFMA isomer were regularly less pronounced, and 2-TFMA was nearly inactive.
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PMID:Effects of trifluoromethylaniline isomers on enzyme activities in lymphatic organs and hematology of the rat. 794 May 66

The use of polymers for delivering peptide and protein drugs is described. Soluble-polymer technology attempts to bind a polymer to all sites on therapeutic protein molecules that cause the body to recognize the molecules as foreign. Goals include a stable linkage, water solubility, low immunogenicity, prolonged half-life, and intact biological activity. Polyethylene glycol (PEG)-adenosine deaminase (ADA), or pegademase bovine, has FDA-approved labeling as replacement therapy for ADA deficiency in patients with severe combined immunodeficiency disease who are not suitable candidates for bone marrow transplantation. Pegademase bovine reverses the toxic accumulation of adenosine and deoxyadenosine in adenosine deaminase-deficient cells, restoring the immune system. PEG-asparaginase (pegaspargase) has shown promise in patients with acute lymphocytic leukemia; allergic reactions have been minimal. Animal studies suggest that superoxide dismutase has potential use in conditions in which the body's ability to remove oxygen free radicals is reduced, such as burns and myocardial infarction; coupling with PEG may greatly increase the protein's half-life. Other PEG-conjugated proteins under investigation include PEG-catalase, PEG-uricase, PEG-honeybee venom, PEG-hemoglobin, and PEG-modified ragweed pollen extract. Dextran, albumin, DL-amino acids, and polyvinyl pyrrolidone have also been studied as protein carriers; most of the products created thus far have not shown much promise. The coupling of polymers to proteins has yielded protein drugs with intact biological activity and reduced immunogenicity, but much remains to be learned about this technology.
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PMID:Polymers for delivering peptides and proteins. 816 Jun 72

Adenosine deaminase (ADA) activity was studied in red blood cells of patients suffering from multiple sclerosis treated with adrenocorticotropic hormone (ACTH). ADA activity in hemolysates was determined according to the method of Hopkinson and calculated as units per g of hemoglobin. Activity of adenosine deaminase in healthy subjects was 0.871 +/- 0.251 U/g Hb. In patients with multiple sclerosis, before treatment ADA activity was 0.765 +/- 0.131 U/g Hb and was about 15.2% lower than in the control group (p < 0.02). After treatment with ACTH, ADA activity increased to 1.005 +/- 0.211 U/g Hb (p < 0.001). We have suggested that increased activity of adenosine deaminase in red blood cells of patients suffering from multiple sclerosis after treatment with ACTH is caused by diminution of superoxide generation, and therefore its sparing effect on cell membrane and enzyme is connected with membranes.
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PMID:Activity of adenosine deaminase in red blood cells of patients suffering from multiple sclerosis treated with adrenocorticotropic hormone. 886 75

We report on a 4-month-old Japanese infant girl with Diamond-Blackfan anemia (DBA) as shown by congenital macrocytic pure red cell hypoplasia with marked reduction of erythroid precursors in bone marrow, reticulocytopenia, increased fetal hemoglobin, and elevated adenosine deaminase activity in peripheral blood. She responded poorly to conventional doses of corticosteroids, however, with high-dose corticosteroids she responded with reticulocytosis and an elevation of hemoglobin level above 12 g/dL. Erythrophagocytosis was noted during the tapering period of prednisone when her hemoglobin level declined to 7.6 g/dL and reticulocyte level to 0.4%. At that time, the erythrophagocytosis was noted in about 60% of marrow histiocytes. These findings were not observed prior to or during the high dose prednisone therapy. We speculate that one of the causes of pure red cell aplasia and reticulocytopenia in DBA is mediated by erythrophagocytosis.
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PMID:Transient erythrophagocytosis in Diamond-Blackfan anemia. 936 62

To approach the goal of consistent long-term erythropoietin (Epo) expression in vivo, we developed an implantation procedure in which transduced autologous vascular smooth muscle was introduced into rats in a chamber created from a polytetrafluoroethylene (PTFE) ring placed under the serosa of the stomach. The implant became vascularized and permitted the long-term survival of smooth muscle cells expressing Epo. Hematocrits of treated animals increased rapidly and monitored over 12 months gave a mean value of 56.0 +/- 4. 0% (P < .001; n = 9), increased from a presurgery mean of 42.3 +/- 1. 6%. Hemoglobin levels rose from a presurgery mean of 15.2 +/- 0.4 g/dL and for 12 months were significantly elevated with a mean value of 19.5 +/- 1.3 g/dL (P < .001; n = 9). The hematocrit and hemoglobin levels of control animals receiving human adenosine deaminase (ADA)-expressing cells were not significantly different from baseline (P > .05; n = 5). In response to tissue oxygenation, kidney, and (to a lesser extent) liver are specific organs that synthesize Epo. Treated animals showed downregulation of endogenous Epo mRNA in kidney over a 12-month period. The PTFE implant provides sustained gene delivery, is safe, and is minimally invasive. It allows easy engraftment of transduced cells and may be applied generally to the systemic delivery of therapeutic proteins such as hormones and clotting factors.
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PMID:Stomach implant for long-term erythropoietin expression in rats. 968 Mar 56


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