Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Simultaneous infection of primary rabbit kidney cells with HSV type 1 TK+ and a TK- strain results in a mutual influence of both viruses on the induction of thymidine kinase (TK). TK+ virus has an enhancing and TK- virus a depressing effect on TK induction by a superinfecting TK+ virus. The enzyme induction depends on the ratio of multiplicities of both viruses. The mutual influence on TK induction depends further on the time of addition of the superinfecting virus: the effect of the second virus can still be observed when given 6 hours after primary infection. Identical phenomena can be observed using combinations with HSV type 2 or Pseudorabies viruses. The ability of HSV to induce TK is progressively inactivated with increasing the time of UV-irradiation. The depressing effect of a TK- strain and the stimulating effect of a TK+ strain on superinfecting TK+ strains is UV-sensitive: after 6 minutes of UV-irradiation neither inhibition nor stimulation of TK induction by a superinfecting TK+ strain can be observed. Infection by long-term (20 minutes) UV-irradiated TK+ strains results in a depression of TK induction by a superinfecting TK+ virus. Long-term irradiation of the TK- virus does not show this effect. Cytosine-arabinoside has no effect on the mutual influence of TK induction by TK+ and TK-strains; the phenomenon of mutual depression therefore has to be considered an early process.
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PMID:Influence of double infections on the induction of thymidine kinase by UV-irradiated herpes simplex virus types 1 and 2 and pseudorabies virus. 17 20

Reserpine, a well-known CNS depressant which depletes central monoamine stores, was found to produce in the brains of 11-day-old rats a severe depression in cell proliferation in terms of the rate of [3H]thymidine incorporation into DNA. The effect was studied in detail 12 h after ther administration of the drug (2.5 mg/kg, s.c.) when the rate of in vivo DNA synthesis in the forebrain was about one-third of control: the decrease was less marked in the cerebellum (rate about two-thirds of control). It was possible to exclude side effects of the drug, such as restricted food intake, hypothermia and an elevation of the level of blood corticosteroids being responsible for the reduction of [3H]thymidine incorporation into DNA. Kinetic studies showed that reserpine had no marked effect on the entry of [3H]thymidine from blood to brain, but it caused some retardation in the rate of [3H]thymidine conversion into [3H]thymidine nucleotides. Nevertheless, the severe depression of DNA labelling was evident even after correcting the values on the basis of [3H]thymidine nucleotide concentrations. In contrast to these effects, thymidine kinase activity was normal in the brain of reserpine-treated animals.
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PMID:Effect of reserpine on cell proliferation in the developing rat bran: a biochemical study. 88 5

L5178Y mouse lymphoma cells normally appear to possess two functional thymidine kinase alleles (TK+/+). TK-deficient (TK-/-) clonal lines can be derived from these cells by treatment with EMS or other mutagens. Mezger-Freed [12] has argued that such stable phenotypic variants do not arise as the result of gene mutations but instead represent epigenetic events such as normally occur during differentiation without any permanent gene alteration. If this be so, then rare TK+/- revertants arising in TK-/- cultures should possess TK enzyme identical with one of those present in the original TK+/+ cells, since only depression of the TK gene is involved. Our studies show that this is not the case. Among the mutant TK enzymes analyzed in vitro (those from parental TK+/- lines, each derived in turn from separate TK-/- lines) differences were found in (1) solubility in saline; (2) solubility in 3 M LiCl; (3) Km's; and (4) ATP-Mg2+ requirements. These findings were incompatible with a non-mutational model for the production of these stable variants and, in conjunction with reversion-rate data, they tended to favor either direct structural gene modifications or mutations affecting the expression of adult and fetal enzymes.
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PMID:Evidence for chemically-induced structural gene mutations at the thymidine kinase locus in cultured L5178Y mouse lymphoma cells. 89 58

Damage to the lung may be caused by chemicals that gain access to the alveolar zone by inhalation or via the pulmonary circulation. Several agents toxic to the lung have recently been found to bind covalently to pulmonary macromolecules or to disrupt certain metabolic reactions. However, it has also been observed that extensive chemical lung injury is not necessarily preceded by a depression of pulmonary metabolic reactions. One possible explanation for this might be that biochemical changes due to cell death are often masked and/or compensated for by changes associated with lung tissue repair. Substantial cell proliferation as a response to toxic lung damage is a common phenomenon in lung pathology. This makes it necessary to develop models that permit analysis of the biochemical events triggering and accompanying cell growth in lung. We have recently examined some aspects of cell proliferation in mouse lung. Intraperitoneal injection of the antioxidant butylated hydroxytoluene (BHT) produces within 3-5 days extensive hypertrophy, hyperplasia, and general disorganization of the cellular components of the lung. Total lung weight and total DNA per lung almost double within this time and are accompanied by proportional increases in protein and lipids. RNA accumulates at a faster rate than DNA. The changes in lung composition are accompanied by dose-dependent increases in the in vivo incorporation of thymidine into DNA and of leucine into protein. The activities of several enzymes (thymidine kinase, DNA polymerase, uridine kinase, glucose-6-phosphate dehydrogenase, and 5'-nucleotidase) increase substantially after BHT. Administration of BHT to mice seems to offer a convenient tool to study cell growth in the lungs of mice.
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PMID:Biochemical pathology of lung damage produced by chemicals. 124 36

This study compared the function of reduced grafts prepared in situ or ex vivo and transplanted immediately or after 4 hr of cold storage. Measurements of acid/base balance, plasma electrolytes, albumin, and urea showed no differences between groups. There was no difference between the increase and decline of plasma AST in recipients of grafts transplanted immediately after either ex vivo or in situ reduction; the increase in plasma AST of recipients of stored grafts was up to 10-fold and persisted until the end of the study at 7 days, with some decline. Plasma fibrinogen decreased intraoperatively but levels were restored within 24 hr in all groups; plasma prothrombin and partial thromboplastin times were not significantly disturbed. The patterns of decline and return of tissue adenine nucleotides were similar in all groups. While the regenerative response measured by tissue thymidine kinase and mitotic figures was not different between the groups, comparison with results from a group of partially hepatectomized animals showed a 3-4-fold depression in response in reduced liver grafts. The contributions of the effects of ischemia, flushing, and preservation to the depressed regenerative response of reduced liver grafts need to be determined. The present studies suggest however, that with regard to functional assessment, results are not affected either by ex vivo or in situ reduction of the graft, or by cold storage for 4 hr.
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PMID:Ex vivo versus in situ resection of segmental liver grafts in pigs--a comparison in immediate and four-hour-stored grafts. 158 63

An overview was presented of our approach of inhibition of de novo and salvage pathways in pyrimidine and purine metabolism. 1. Combination of acivicin, an inhibitor of de novo biosynthesis, and dipyridamole, a transport inhibitor, provided synergistic cytotoxicity in hepatoma and colon carcinoma cells. 2. AZT, a competitive inhibitor of the salvage enzyme, thymidine kinase, and 5-FU or MTX provided synergistic cytotoxicity in hepatoma 3924A. In human colon carcinoma HT-29 cells AZT and methotrexate yielded synergistic cytotoxicity and thymidine and hypoxanthine together provided protection from the action of these drugs. 3. These observations are significant because in rat hepatoma 3924A and in human cell lines HT-29, HL-60 and K562 thymidine kinase activity was 16- to 67-fold higher than that of dTMP synthase. Therefore, inhibition of dTMP synthase activity alone may provide poor responses because the salvage pathways can circumvent this block. 4. In leukemic patients treated with tiazofurin, an inhibitor of IMP dehydrogenase, the rate-limiting enzyme of GTP biosynthesis, and with allopurinol, which inhibits GPRT activity through raising plasma hypoxanthine levels, synergistic therapeutic results were obtained. The responses in sensitive patients entailed a decrease in IMP dehydrogenase activity and GTP concentration in leukemic cells and down-regulation of the ras and myc oncogenes. The down-regulation of the ras oncogene by tiazofurin through the decrease of GTP concentration has now been shown in K562, HL-60 and hepatoma cells and in patients with chronic granulocytic leukemia in blast crisis. Tiazofurin may be useful in studies on selective depression of the expression of the ras oncogene. 5. In 27 consecutive patients 50% responded positively to tiazofurin treatment. From this group, 10 out of 12 patients (83%) with chronic granulocytic leukemia in blast crisis responded to tiazofurin treatment.
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PMID:Regulation of de novo and salvage pathways in chemotherapy. 187 99

The safety of an Aujeszky's disease virus vaccine based on strain 783, a deletion mutant which does not express glycoprotein I and thymidine kinase, was assessed in pigs, calves and sheep. Four-day-old piglets which were inoculated intranasally and intramuscularly with 10(7) plaque forming units (PFU) developed only slight depression and fever. The virus was transmitted to a sentinel piglet. Six weeks after inoculation, the pigs were injected with high doses of corticosteroids in an attempt to reactivate the vaccine virus. The pigs did not shed Aujeszky's disease virus, did not develop a rise in virus neutralising antibody titres and sentinel pigs remained seronegative to Aujeszky's disease virus. Strain 783 was passaged in two series of three- to five-day old piglets, but after the third and fourth passages virus could no longer be recovered. Pregnant sows were inoculated with 10(7) PFU of virus strain 783 around day 35 or on day 85 of pregnancy, and their fetuses and piglets were assayed for Aujeszky's disease virus and antibodies against Aujeszky's disease virus. No evidence was found for transplacental transmission of the virus. Calves and sheep were given 10(7) PFU of virus strain 783 intranasally or intramuscularly; they survived and did not develop clinical signs of Aujeszky's disease. All the sheep and the calves inoculated intramuscularly developed neutralising antibodies to Aujeszky's disease virus.
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PMID:Safety of an Aujeszky's disease vaccine based on deletion mutant strain 783 which does not express thymidine kinase and glycoprotein I. 217 88

The administration of the lipophilic 3,7-bis-(4-trifluoromethylphenyl)- 1,5,3,7-dioxadiazocane (TFMPD) to rats induced the following effects on the biosynthesis of DNA in the liver, kidney, thymus and spleen: (a) The utilization of [3H]thymidine for the synthesis of liver DNA thymine was decreased after the administration of a single dose of the drug. The depression of the specific activities of DNA pyrimidines of liver DNA in experimental groups was observed also after an injection of [14C]orotic acid. (b) A decreased incorporation of labeled thymidine had occurred also in the spleen during the prereplicative period. Thereafter the specific activity of DNA thymine was higher than in the control group. (c) The observed mitogenic response in the spleen showed a protracted effect; after the administration of a single dose of the drug the specific activity of DNA thymine as well as the thymidine kinase activity of spleen cytosol have been rising up to the ninth day. The same holds true for DNA thymine of the thymus; the activity of thymidine kinase was not affected. (d) Both the single and repeated doses of TFMPD had no marked effect on the levels of microsomal cytochromes P-450 and b5 in the liver and kidney.
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PMID:Effect of 3,7-bis-(4-trifluoromethylphenyl)-1,5,3,7-dioxadiazocane on pyrimidine and DNA synthesis in rat organs. 238 45

The increases in the activities of hepatic thymidylate synthetase and thymidine kinase were significantly suppressed at 24 h after 70% partial hepatectomy in rats which had been administered a microtubule disrupter, colchicine or vincristine. The decrease of these enzymic activities was accompanied by a reduction of DNA content in 24 h regenerating liver. The immunoblotting assay showed that the depression of the thymidylate synthetase activity by the injection of colchicine or vincristine was due to the decrease of the enzyme protein. These results indicate that colchicine and vincristine inhibit the DNA synthesis during liver regeneration by inhibiting the induction of the key enzyme in DNA synthesis.
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PMID:Effect of colchicine and vincristine on DNA synthesis in regenerating rat liver. 280 79

The influence of a strong homogeneous and stationary magnetic field (SMF) on the activity of the enzyme thymidine kinase (TdR-K) in bone marrow cells, and as a consequence of this on the incorporation of 125I-labelled 5-iodo-2-deoxyuridine (125IUdR) into DNA of mice and into isolated bone marrow cells in vitro, was assayed after exposure of immobilized mice. No effect could be elicited in moving mice, in cells in suspension or in enzyme in solution. The response depended on the body temperature during exposure: at 27 degrees C and 29 degrees C there was an increase and at 37 degrees C and a depression of enzyme activity. The TdR-K activity at low temperature increased with the field strength ranging from 0.2 to 1.4T. Thirty minutes were required for full expression of the effect at 1.4T; 5-10 min were needed after exposure for a return to base-line levels. Mice were given total-body irradiation at a dose of 0.1 Gy 137Cs gamma rays and then exposed immediately to a magnetic field at 1.4T for 30 min at a body temperature of 27 degrees C; gamma irradiation no longer inhibited the enzyme. Exposure to the magnetic field further removed from the time of gamma irradiation, did not negate the inhibitory effect of gamma irradiation. The observed responses to given challenges in this complex system support the hypothesis that the magnetic field affects TdR-K activity by way of a mediating structure, such as a membrane.
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PMID:In vivo enzyme control through a strong stationary magnetic field--the case of thymidine kinase in mouse bone marrow cells. 330 98


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