Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities of thymidine kinase and uridine kinase (enzymes for pyrimidine salvage pathway) in phytohemagglutinin (PHA)--prestimulated lymphocytes were inhibited by arginase in a similar pattern to the inhibition on thymidine incorporation. Further study revealed that arginase did not directly affect the activities of these enzymes in the cell-free system. Thymidine kinase and uridine kinase activities of PHA-prestimulated lymphocytes were inhibited by arginase making their activities as low as that cultured in arginine-free RPMI-1640 medium. These results suggest that arginine-depletion in the culture medium is the primary mode of action of arginase on the inhibition of mitogen-stimulated lymphocyte proliferation.
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PMID:Inhibition of lymphocyte proliferation by liver arginase. 143 81

We have found that human lymphoblastoid cell line RPMI-6410t is a biochemical mutant for gene of thymidine kinase and has chromosome markers in the karyotype. Thus, this cell line can be used as a partner in somatic hybridization, in particular for producing hybridomas, synthesizing human monoclonal antibodies. We have discovered that line RPMI-6410t carries HLA-A2, -B7 and -B12 antigens of human histocompatibility complex on the cell surface. The cell membrane of this cell line contains immunoglobulins of M and D classes. RPMI-6410t cells secrete IgM molecules. It is demonstrated that induction of the switch of immunoglobulin heavy-chain classes by the factors of foetal calf serum takes place in the cells of RPMI-6410t line. Thus, the corresponding stage of B-lymphocytes differentiation in vivo is reproduced in 6410t line in vitro.
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PMID:[Induction of the switch in the synthesis of immunoglobulin classes in the RPM 1-6410t lymphoblast cell line and its clones as affected by fetal calf serum factors]. 309 62

A study was made of the properties of human lymphoid cell line RPMI-6410 derived from peripheral blood of a patient with acute myeloblastic leukaemia. The lymphoblastoid cell line was found to be resistant to 5-brom-deoxyuridine and to have a low thymidine kinase activity. The modal chromosome number for RPMI-6410 is 46-47 XY. The karyotype includes marker chromosomes: two large submetacentrics --M1 and M2, and two small acrocentrics--M3 and M4. Ways of marker chromosome formation are discussed. The properties of RPMI-6410 line make it possible to use it for somatic cell hybridization, in particular, for obtaining hybridoma synthesizing human monoclonal antibodies.
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PMID:[Biochemically labelled human lymphoblastoid cell line. I. Its karyotypic, growth and physiological characteristics]. 385 83

The Epstein Barr nuclear antigen (EBNA) and the rheumatoid arthritis nuclear antigen (RANA) develop in human B lymphocytes that have been infected and transformed by Epstein Barr virus (EBV). Antibodies to RANA and EBNA are found only in individuals with prior exposure to EBV. The purpose of the present studies was to determine the relation of the 2 antigens to each other and to EBV genetic material, in human-rodent somatic cell hybrids. Cultured human B lymphoblastoid cells, Raji, Daudi, and RPMI 4098 were fused with thymidine kinase-deficient mouse or hamster fibroblasts. After selection and cloning in ouabain-HAT medium, the hybrid nature of the surviving cells was confirmed by isozyme analysis. The hybrid clones were analyzed for EBNA by anti-complement im,munofluorescence, and for RANA by anti-immunoglobulin immunofluorescence and immunodiffusion. The results showed that RANA and EBNA segregated entirely independently of each other in the hybrid clones. Two methods were used to detect the presence of EBV DNA sequences in the intracellular DNA of hybrid clones. The 1st method relied on the hybridization of labeled cRNA prepared from virion DNA with DNA from 8 hybrid clones affixed to nitrocellulose filters. The 2nd approach was to hybridize labeled intracellular DNA from 3 hybrid clones to Southern blots of cloned fragments of EBV DNA. These results suggested that the presence of EBV DNA was not sufficient for the expression of either antigen. One stable RANA-positive hybrid cell line contained at least 80% of the EBV genome in the absence of detectable EBNA.
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PMID:Discordant expression of 2 Epstein-Barr virus-associated antigens, EBNA and RANA, in man-rodent somatic cell hybrids. 626 53

Drug-resistance in cell lines and in malignant human tumours is associated with dysregulation of several genes including mdr1, MRP1, GST-pi, bcl-2, DNA topoisomerase II alpha and beta, and thymidine kinase I. mRNA expression was evaluated by quantitative RT-PCR coupled with HPLC in three human tumour cell lines and drug-resistant (DR)-sublines. DR sublines from RPMI-8226 and KB cells specifically overexpressed the mdr1 gene without major changes observed in other putative DR-associated genes. In contrast, the DR-H69 cells exhibited a 34-fold overexpression of the MRP gene accompanied by significant down-regulation of both DNA topoisomerase II alpha and bcl-2 mRNA gene expression, by factors of 43 and 13 respectively. These results demonstrate the concomitant down regulation of topoisomerase II alpha and bcl-2 genes in response to DR. Furthermore, differential patterns of gene dysregulations appear to vary depending upon both the drug used to select resistance and cellular origin.
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PMID:Assessment of drug-induced dysregulations among seven resistance-associated genes in human tumour cell lines. 904 17

Adenoviruses are efficient gene delivery agents for a variety of neoplasms. In the present study, we have investigated the use of adenoviruses for the delivery of the thymidine kinase (tk) gene into multiple myeloma (MM) cells. We first demonstrated that MM cell lines and MM patient cells express both adenovirus receptors as well as the DF3/MUC1 protein, thus providing a rationale for using adenoviruses to selectively deliver genes under the control of the DF3 promoter. By using an adenoviral construct containing beta-galactosidase (beta-gal) gene driven by the DF3 promoter (Ad. DF3-betagal), we demonstrate greater than 80% transduction efficiency in OCI-My5 and RPMI 8226 MM cell lines at a multiplicity of infection of 1 to 100. Importantly, transduction with the tk gene driven by the DF3 promoter (Ad.DF3-tk) followed by treatment with 50 micromol/L ganciclovir (GCV) purged >/=6 log of contaminating OCI-My5 and RPMI 8226 MM cells within bone marrow mononuclear cells. In contrast, normal human hematopoietic progenitor cell number was unaffected under these conditions. Selectivity of DF3/MUC1 promoter was further confirmed, because Ad.DF3-betagal or Ad.DF3-tk did not transduce MUC1-negative HeLa cervical carcinoma cells. In addition, GCV treatment of Ad.DF3-tk-transduced RPMI 8226 MM cells did not induce a significant bystander effect. These findings demonstrate that transduction with Ad vectors using a tumor-selective promoter provides a highly efficient and selective approach for the ex vivo purging of MM cells.
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PMID:Adenovirus vector-based purging of multiple myeloma cells. 984 25

The activity of thymidine kinase (TK - EC 2.7.1.21) was measured in human thyroid tissue homogenates incubated in vitro. This enzyme functions as a part of the pyrimidine salvage pathway involved in DNA synthesis. The thyroid tissue was obtained from the thyroids of patients thyroidectomized at the Department of Endocrine Surgery, Medical University of lodz because of: 1. non-toxic nodular goiter (NTNG): tissue macroscopically unchanged, woman 46 yrs; 2. non-toxic adenoma (NTA), woman 37 yrs; 3. toxic adenoma (TA), woman 45 yrs. The tissue was incubated for 4 hours in RPMI 1640 medium (Gibco), containing Hepes buffer, 15 % FCS and the examined substance - epidermal growth factor (EGF) - used in five different concentrations (0.1 ng/ml, 1 ng/ml, 10 ng/ml, 100 ng/ml, 1000 ng/ml). The TK activity was measured according to Cheng and Prusoff (1974) as modified by Greger and Draminski (1989). The reaction products were separated by ascending chromatography. It was found that: 1. TK activity in thyroid tissue from NTNG and NTA did not significantly differ from control incubations without EGF, while it was significantly higher in the thyroid tissue from TA; 2. in the range of concentrations from 1 ng/ml to 1000 ng/ml, EGF increased TK activity in the macroscopically unchanged tissue from NTNG; 3. the incubation of the tissue from NTA with EGF resulted in the increase of TK activity in a concentration-dependent manner; 4. EGF stimulated TK activity in the tissue from TA, but the difference was significant only after the lowest EGF concentration. The obtained results suggest a possible role of EGF in the pathogenesis of NTNG, as well as of NTA and TA in humans.
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PMID:Thymidine Kinase (EC 2.7.1.21) Activity in Homogenates of Human Thyroid Tissue, Following the Exposure to Epidermal Growth Factor (EGF) in vitro. 1040 65