Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of recombinant retroviral vectors to transfer genetic sequences into hematopoietic stem cells (HSC) is one approach to somatic gene therapy. Two limitations of such retroviral vectors are the degree of efficiency of transfer into the reconstituting hematopoietic stem cells and the loss of reconstituting ability of hematopoietic stem cells when manipulated in vitro during infection and selection. We have investigated the effects on the efficiency of gene transfer of prestimulation of hematopoietic stem cells by growth factors prior to infection. Prestimulation of bone marrow cells in WEHI-3b-conditioned media improved the efficiency of gene transfer into CFU-S stem cells. The majority of animals transplanted with bone marrow infected after prestimulation with a simplified retrovirus, Zip PGK ADA, demonstrated long-term and stable expression of human adenosine deaminase (ADA) after full hematopoietic reconstitution. In separate experiments, retroviral vectors have been used to transfer the SV40 large T antigen sequences into stromal cells making up the hematopoietic microenvironment. Stromal cells expressing large T antigen are immortalized, and some support the maintenance of day 12 CFU-S (CFU-S12) and reconstituting hematopoietic stem cells in vitro for up to 4 weeks. Such immortalized stromal cell lines provide an in vitro hematopoietic microenvironment which may allow prolonged in vitro manipulations during infection and selection of hematopoietic stem cells without loss of reconstituting ability. We are using immortalized stromal cell lines resistant to deoxycoformycin (dCF) to select transduced murine HSC containing human ADA in vitro. The use of recombinant retroviral vectors provides a promising approach to correction of human diseases involving bone marrow cells.
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PMID:Gene transfer into murine hematopoietic stem cells and bone marrow stromal cells. 229 66

We have examined alterations in terminal deoxynucleotidyl transferase (TdT) immunofluorescence (IF) in MOLT-4 cells during changes in growth conditions. Subsequently, we used cells from 48 human hematopoietic cell lines of different cell lineages and maturation stages to compare the IF and biochemical assays for expression of TdT. In addition, we have attempted to correlate the expression of TdT, adenosine deaminase (ADA), thymidine phosphorylase (TP) and immunological markers with maturation stages in these different cell lines. The results indicate that TdT positive cells remain TdT positive when assayed by either the biochemical or IF tests during growth or early plateau phase, but that cells under poor growth conditions, such as in old cultures, may give a negative TdT IF reaction. Otherwise, biochemical and IF assays for TdT gave comparable results in the 48 cell lines tested, testifying to the reliability of the IF test. Based on the comparisons of the various cell lines studied, it appears that both ADA and TdT decrease progressively as maturation of T cells from Blast I to Blast IV to mature T cells increases. TP was deficient in all T-cell lines compared to normal peripheral blood T cells, which in turn had lower activity compared to normal peripheral blood B cells. Pre-B cells, although indistinguishable from each other by immunological markers and all having low TP and ADA activity, showed heterogeneity, with TdT activity high in some and low in others. All non-T, non-B lines had high TdT activity, but low ADA and TP activity. B- and myelocytic cell lines had low ADA and TdT activity, and showed an increase in TP activity as the maturation of cells increased. These results indicate that the TdT IF test is a reliable procedure for detecting TdT positive cells, and that TdT, ADA and TP could be useful markers for studying the differentiation of human hematopoietic cells.
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PMID:Terminal transferase immunofluorescence, enzyme markers and immunological profile of human leukemia-lymphoma cell lines representing different levels of differentiation. 635 Jul 28

Acute lymphoblastic leukemia with hand-mirror cells (HMC) was diagnosed in nine adult patients. Blast HMC were seen only in the bone marrow (12-57% range). Cytochemical studies revealed a positive reaction to tartrate-sensitive acid phosphatase in the tail portion of the cells in seven cases, with a strong, localized cytoplasmic reaction in four. Leukemic cells lacked surface immunoglobulins and were E rosette negative in all cases. Normal levels of adenosine deaminase activity (ADA) were found in five of the seven patients. Electron microscope studies confirmed the hand-mirror shape of the cell. These HMC contained large numbers of mitochondria and microspikes in the handle portion of the cell. The patients failed to respond to initial conventional ALL chemotherapy, but the prolonged survival with passable health of the majority of these, despite their lack of complete remission, is emphasized.
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PMID:Acute lymphoblastic leukemia hand-mirror cells. Study of nine cases. 657 58

The activity of thymidine kinase, thymidine phosphorylase, adenosine deaminase and 5'-nucleotedase of AMP was studied in tissues, blood serum and lymphocytes of 60 healthy females and 50 females with fibrocavernous mastopathy aged 23-70. It was revealed that age-related changes in the activity of thymidine kinase in blood serum reflect the analogous changes in enzyme activity in tissues of healthy women. A direct correlation was established between thymidine kinase activity and age both in healthy females and those with mastopathy. A significant decrease in activity of thymidine phosphorylase was demonstrated in blood serum of patients with mastopathy aged 46-60. Determined 4-fold increase in activity of adenosine deaminase in serum was accompanied by decreased enzyme activity in lymphocytes and decreased Lymphocyte Blast Transformation Index in the same age range. The revealed metabolic changes in DNA-precursors' metabolism in patients with mastopathy aged 46-60 might be one of the reasons of increased risk of oncological diseases in this age group.
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PMID:[Age-related changes in metabolism of DNA precursors in patients with mastopathy]. 931 43

The activity of thymidine kinase, thymidine phosphorylase, adenosine deaminase and 5'-nucleotidase of AMP was studied in tissues of 39 healthy females, as well as blood serum and lymphocytes of 60 healthy females, as well as in 50 patients with fibrocavernous mastopathy aged as 23-70. Comparative determination of adenosine metabolism enzymes activity in lymphocytes was carried out simultaneously with studying some immunological indexes in the organism of the same-aged healthy females and ones with mastopathy. It was revealed that age-related changes in the activity of thymidine kinase in blood serum reflected the analogous changes in enzyme activity in tissues of the healthy women. A direct correlation was established between thymidine kinase activity and age both in the healthy females and those with mastopathy. A significant decrease in activity of thymidine phosphorylase was demonstrated in blood serum of the patients with mastopathy in the age 46-60. Determined 4-fold increase in the activity of adenosine deaminase in serum was accompanied by decreased enzyme activity in lymphocytes and decreased Lymphocyte Blast Transformation Index in the same age range. Changes of immunological status are more expressed in T-system of immunity. The revealed metabolic changes in DNA-precursors metabolism in the patients with mastopathy aged as 46-60 might be one of the reasons of increased risk of oncological disease in this age group.
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PMID:[Metabolism of adenosine and thymidine in healthy females of different ages and females with mastopathies]. 1060 30