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)

The sequence divergence of mitochondrial DNAs (mtDNA) from rat, mouse, guinea pig, monkey, and chicken has been examined by DNA-DNA hybridization. mtDNAs, isolated as closed circular molecules by propidium iodide-CsCl centrifugation, were labeled in vitro by use of Escherichia coli DNA polymerase I, and renatured (Tm-35 degrees) in the presence of a 2500-fold excess of heterologous mtDNA. Single-stranded and duples DNA were separated by hydroxylapatite chromatography. The thermal stability of heteroduplexes was compared to the homoduplex by thermal elution chromatography on hydroxylapatite columns. Heteroduplex fromation between the tritiated myDNAs and a 2500-fole excess of rar mtDNA were 70, 59, 37, and 22%, respectively, for mouse, guinea pig, monkey, and chicken. Similar results were obrained in reciprocal hybridizations where one of the other mtDNAs was present in excess. Considerable mismatching of sequences in all the heterohybrids was indicated by a 18-24 degrees depression in the te50 of the heteroduplexes compared with the homoduplex. There was no apparent change in heteroduplex formation when the concentration ratio of driving DNA in excess to [3H]mtDNA was varied between 1250 and 7500. Furthermore, a second renaturation with excess driving DNA after completion of the first reaction resulted in no detectable augmenting of heteroduplex formation. Similar sequences appear to be conserved preferentially in different organisms, since the presence of two of fouf different heterologous mtDNAs in excess resulted in only moderate and nonadditive increases in heteroduplex formation. Evolutionary divergence of mtDNA sequences appears to have occurred at rates similar to that for unique sequences nuclear DNA.
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PMID:Sequence homology between mitochondrial DNAs of different eukaryotes. 114 57

Events preceeding the cortisol inhibition of uridine utilization by corticoid-sensitive P1798 lymphocytes have been investigated. When tumor cells were incubated with 1 muM cortisol for 15 min and then washed free of steroid and reincubated in the absence of hormone, the expected decrease of uridine uptake failed to appear 1.5 hr later. In contrast, the removal of cortisol after 30 or 60 min did not prevent subsequent development of the steroid effect. Addition of actinomycin D with cortisol, or 15 min after hormone treatment was started, blocked steroid action. However, when actinomycin D was added 30 or 60 min after the initial exposure to cortisol, hormone-induced depression of uridine uptake was no longer prevented. To study the role of protein synthesis, cycloheximide was added to the tumor cell suspensions at various times after cortisol treatment was started. Cortisol suppression of uridine utilization was blocked when cycloheximide was added with the hormone or 30 min after the start of hormone treatment. Cycloheximide added together with cortisol and washed out with the steroid after 30 min did not prevent subsequent appearance of decreased nucleoside uptake. Hydroxyurea, an inhibitor of DNA synthesis, did not prevent cortisol action, even when present throughout a 2 hr exposure to the steroid. Hormone removal or actinomycin D addition after 1.5 to 2 hr (when uridine uptake was already inhibited about 25%) did not prevent intensification of the steroid effect during a subsequent 1.5- to 2-hr incubation period, while addition of cycloheximide at this time completely prevented its progression. These results suggest aht: (a) cortisol inhibition of uridine uptake by P1798 lymphocytes involves an early irreversible step and appears to require continuing RNA but not protein synthesis during the first 15 to 30 min of hormone action; (b) protein synthesis but not RNA synthesis is required between 30 and 60 min; and (c) continuing protein synthesis but not RNA synthesis or hormone presence is necessary for the preestablished cortisol effect to progress.
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PMID:Sequential irreversible, actinomycin D-sensitive, and cycloheximide-sensitive steps prior to cortisol inhibition of uridine utilization by P1798 tumor lymphocytes. 114 29

A simple and accurate method for the detection of Deoxyribonucleases is described. The DNA substrate (3H-labeled) is bound to DNA-binding sites in the "wells" of plastic depression plates either directly of via anti-DNA antibodies. Following incubation with the appropriate enzyme, the radioactivity released from the wells or left bound to the wells is determined. The method is suitable for enzymes which attack native DNA, single stranded DNA and modified DNA (e.g., u.v.-irradiated) as substrates.
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PMID:A new assay of deoxyriboucleases using as a substrate radioactively labelled DNA bound either directly or through anti-DNA antibodies to plastic depression plates. 117 May 55

Using radioautographic technique actinomycin D at a concentration of 0.08 mug/ml was shown to inhibit selectively ribosomal RNA (rRNA) synthesis in monolayer cultures of Chinese hamster cells. The treatment with actinomycin D of cells synchronized by mitotic selection in the beginning of the G1 period causes a delay in the onset of DNA synthesis. However, a similar treatment in the late G1 period does not prevent cells from entering the S-period. The same effect has been produced by 9 mug/ml lucanthone, another inhibitor of rRNA synthesis. The experiments demonstrate a pronounced difference in cell reaction to the depression of rRNA synthesis in early and late G1 period. The data imply that the formation of rRNA, essential for the initiation of DNA synthesis, is accomplished in the first half of the G1 period, while part of rRNA has been already formed in the previous cycle.
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PMID:[Inhibition by actinomycin D of ribosomal RNA synthesis in the presynthesis period of the mitotic cycle of Chinese hamster cell cultures]. 117 11

The effect of chlorambucil on the colony-forming ability of HeLa cells following either treatment for 1 h or continuous treatment has been measured. Concentrations of chlorambucil which had only minimal effects on cell survival inhibited the rate of DNA but not RNA and protein synthesis within 1 h of treatment. Nevertheless, cells continued to synthesize DNA for many hours after this treatment in the absence of cell division. Synchronous populations of HeLa cells treated prior to DNA synthesis, in the G1 phase of the cell cycle, were not delayed in their progression into the S phase where they exhibited a marked dose-dependent inhibition of the rate of DNA synthesis. Cells in which DNA synthesis had been depressed showed a prolongation of the S phase and this was accompanied by a corresponding dose-dependent mitotic delay. Treatment during the G2 phase of the cell cycle did not induce any delay or block in the next mitosis, but did inhibit the rate of DNA synthesis in the following cell cycle in a dose-dependent manner; this depression of DNA synthesis was followed by a delay in the next mitosis. Cross-linking of either isolated DNA or DNA present in treated HeLa cells was demonstrated, and in the latter case calculated to be of the same order as that which occurred with other difunctional agents at comparable toxic concentrations.
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PMID:Inactivation of the DNA template in HeLa cells treated with chlorambucil. 117 97

Isolated filaments of Funaria hygrometrica have been treated by whole-cell UV irradiation (265 nm) as well as by microirradiation of the nucleus. 4 to 5 hrs thereafter the cells showed a depression in length growth. The intensity of this depression remarkably depends on the absorbed energy only. It does not matter whether the nucleus and its environcence or the whole cell are irradiated. The effect does not show photoreactivation and is rather independent from the cell cycle and hence from the DNA content of the nucleus. After X-irradiation supplying the same amount of absorbed energy no damage is detectable. The authors conclude that the site of the primary radiation effect is situated mainly outside the nucleus and that it may be a damage of the m-RNA, r-RNA or of membranes.
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PMID:[Extranuclear sites of action in UV-irradiated Fumaria hygrometrica (author's transl)]. 117 29

The potent skin tumor promoter (12-O-tetradecanoyl phorbol-13-acetate (TPA) stimulates epidermal macromolecular synthesis as well as proliferation, but little is known of specific functional aberrations produced by TPA. This report presents results of a study on the effects of TPA on epidermal histidase (L-histidine ammonia lyase), an enzyme found in normal epidermis but not in dermis or in mouse squamous cell carcinomas. Histidase activity was assayed on postmitochondrial supernatants obtained from hairless mouse epidermis after removal by keratotome. Topical TPA treatment at doses active in tumor promotion (1.7 to 17.0 nmoles/application) produced dose-dependent decreases in epidermal histidase specific activity at 19 hr posttreatment. The onset of the decrease occurred at 12 hr with recovery to control level specific activity by 5 days, showing kinetics similar to those obtained for stimulation of DNA synthesis. This decrease in histidase could not be attributed to a general inhibition of soluble protein synthesis or to the appearance of an inhibitor of histidase activity. The strong promoter TPA produced a greater histidase decrease than did the moderate promoter and mitogen 12,13-didecanoyl phorbol at equimolar dose, while phorbol, a nonpromoter and nonmitogen, produced no effects on histidase. The relationship of this histidase depression to tumor promotion and not initiation is further indicated by the finding that (a) Tween 60, a structurally unrelated tumor promotor, also produced a decrease in histidase; and (b) the tumor initiator urethan and an initiating dose of 9,10-dimethybenz(a)anthracene showed no effects on histadase activity.
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PMID:Decrease of epidermal histidase activity by tumor-promoting phorbol esters. 118 5

When tumour cells (line L cells) were grown in culture with syngeneic normal non-immune C3H/He mouse spleen cells or in the cell free supernatant of these spleen cells they incorporated less tritiated thymidine (3H-Tdr) than when grown by themselves. Despite this effect there was no depression in either cell growth or DNA synthesis. Autoradiographic studies revealed that the decrease of 3H-Tdr incorporation into tumour cells in the presence of spleen cells was not due to inhibition of cell entry into S phase but due to the amount of 3H-Tdr the tumour cells incorporated. Since the medium of spleen cell cultures was found to contain DNA and the addition of calf thymus DNA to fresh growth medium also resulted in decreased 3H-Tdr uptake by the tumour cells, it was concluded that line L cells utilize DNA released by spleen cells into the medium for de novo DNA synthesis. On the basis of these findings, it is suggested that caution be used in interpreting decreased 3H-Tdr uptake as determined by scintillation counting as evidence for a cytostatic effect exerted by lymphoid cells or their supernatants in vitro.
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PMID:The effect of normal spleen cells on 3H-thymidine uptake by target cells in vitro. 119 18

Hepatic protein synthesis was investigated using a postmitochondrial supernatant system derived from the livers of rats that were given injections of a single dose of dimethylnitrosamine (DMN), 30 mg/kg. The time course and extent of DMN-induced inhibition in vitro were identical to those reported for the incorporation of amino acids into liver proteins in vivo, maximum inhibition being about 70% at 5 hr. Addition of specific inhibitors of chain initiation (polyinosinic acid and aurin tricarboxylic acid) to the postmitochrondrial supernatant system from DMN-treated rats caused only a slight additional inhibition, indicating that DMN predominantly affects translation by a block of initiation. Treatment with cystamine prior to DMN administration completely abolished the depression of protein synthesis and reduced by more than 90% the methylation by [14C]DMN of purine bases in liver DNA. Pretreatment with pregnenolone-16alpha-carbonitrile stimulated protein synthesis in controls but had no preventive effect in DMN-treated rats and did not reduce the extent of DNA alkylation in vivo.
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PMID:Dimethylnitrosamine-induced inhibition of hepatic protein synthesis in vitro and the effect of pretreatment with cystamine or pregnenolone-16alpha-carbonitrile. 119 27

In a system that yields 100% incidence of renal mesenchymal tumors and a 30 to 40% incidence of renal cortical epithelial neoplasms, the proliferative activity of renal epithelial and mesenchymal cell subpopulations following a single dose of dimethylnitrosamine (DMN) was traced by autoradiographic analysis of [methyl-3H]thymidine uptake during the 3 weeks immediately posttreatment. The initial response to DMN was a depression in DNA synthesis and mitosis to near 0 levels in all segments of the nephron and in attendant mesenchymal cells for a period of 1 to 3 days. Following the period of inhibition, increased DNA synthetic activity was observed in certain subpopulations of both epithelium and mesenchyme and these patterns were matched by equivalent mitotic activity. A stimulation of DNA synthesis was observed in cells of the proximal and distal tubules of Zones 1 and 2 but in no other epithelial segments. The increased activity was most intense in Zone 1 epithelium reaching a peak at the 10th day after DMN injection 4 days after epithelial cell necrosis had commenced. In renal mesenchyme, the major response involved only the interstitial cells of Zones 1 and 2. At Day 3, there was a wave of increased DNA-synthetic and mitotic activity in the free interstitial cells of the cortex, followed by a 2nd, more intense peak of activity at Day 6. The cells responding at Day 3 appeared to involve the resident population of cortical fibrocytes while the major contribution to the Day 6 peak came from infiltrating mononuclear inflammatory cells, although resident fibrocytes and capillary endothelium also contributed. A significant wave of increased activity involved the intestitial cells of Zone 2, but the peak, although of equivalent intensity to the response in Zone 1, was single and occurred 3 days later at Day 9. Apart from a small, brief, and variable wave of activity in interstitial cells of Zone 3 from Days 8 to 10, no toerh mesenchymal cell populations in the kidney were stimulated by the injection of DMN.
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PMID:Autoradiographic analysis of proliferative activity in rat kidney epithelial and mesenchymal cell subpopulations following a carcinogenic dose of dimethylnitrosamine. 119 32


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