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 bone marrow cells of a patient with congenital dyserythropoietic anaemia, type II, were incubated with 3H-thymidine, 3H-uridine or 3H-leucine for 1 h and studied using the technique of electron microscope autoradiography. Several of the erythroblasts which either displayed the characteristic subsurface double membranes or showed various non-specific abnormalities of the nuclear membrane were found to be actively engaged in DNA, RNA and protein synthesis. Both members of some pairs of erythroblasts which were joined together by a spindle bridge were found to be engaged in DNA synthesis, indicating that some spindle bridges persist for a period longer than the duration of the G1 phase. A small proportion of mononucleate and binucleate late (non-dividing) erythroblasts showed a marked depression or arrest of protein synthesis and some or all of such cells were presumably destined to be phagocytosed by the bone marrow macrophages.
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PMID:Electron microscope autoradiographic studies of the erythroblasts of a case of congenital dyserythropoietic anaemia, type II. 66 56

6-Thioguanine, at a dose of 40 mg/kg body weight, was administered to rats at 12 hr after partial hepatectomy; 6 hr later, liver polysomes and cell sap were isolated and utilized to measure the effects of this antimetabolite on protein synthesis in vitro. When radioactive leucine was used to label peptides synthesized in vitro, no difference was observed between polyacrylamide gradient gel scans of systems derived from control regenerating liver and those from 6-thioguanine-treated regenerating liver. However, when radioactive tyrosine was used as the tracer to monitor synthesized peptides, a depression in the 30,000-molecular weight region of scans of products synthesized in systems derived from 6-thioguanine-treated regenerating liver was observed. Recombination experiments showed this effect to be due to the polysome component of the system. When equal amounts of polyadenylic acid-containing RNA from 6-thioguanine-treated or control regenerating liver were added to a wheat germ in vitro protein-synthesizing system, polyacrylamide gel scans of the products synthesized in the presence of radioactive tyrosine showed that more peptides were synthesized from polyadenylic acid-containing RNA from 6-thioguanine-treated rats than from control polyadenylic acid-containing RNA. That this phenomenon might be the result of incorporation of the analog into RNA was shown by the finding that all types of RNA containing 6-thioguainine, with the greatest concentration occurring in polyadenylic acid-containing RNA.
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PMID:Effects of 6-thioguanine on RNA biosynthesis in regenerating rat liver. 85 43

Growth rate, plasma amino acid, and alpha-keto acid concentrations and activities of the branched-chain amino acid degradative enzymes of rats were measured. Effects of ingestion of excessive amounts of branched-chain amino acids on these variables were determined. Excessive intake of a single branched-chain amino acid led rapidly to elevated plasma concentration of both the amino acid administered and its corresponding alpha-keto acid and, if the rats had previously been fed a low protein diet, to an increase in liver branched-chain alpha-keto acid dehydrogenase activity. Only leucine caused, in addition, marked growth and food intake depression and decreased plasma isoleucine, valine, alpha-keto-beta-methylvaleric acid and alpha-keto isovaleric acid concentrations. The growth depression was associated food intake depression and could be moderated by addition of isoleucine and valine to the diet. The decreases in plasma isoleucine, valine, alpha-keto-beta-methylvaleric acid and alpha-keto isovaleric acid were not caused by increased degradation of these metabolites to carbon dioxide as branched-chain amino acid oxidation rates in vivo were unchanged by leucine loading and the degradative enzymes were unchanged in adequately fed rats. The decreased concentrations of these amino and keto acids may be the result of decreased protein degradation or increased protein synthesis, possibly mediated by insulin.
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PMID:Effects of branched-chain amino acid antagonism in the rat on tissue amino acid and keto acid concentrations. 87 Jun 54

In these studies the effects of ingested arsenic (As(+5)) on hepatic heme biosynthetic capability and hemoprotein function in adult male rats were investigated. Animals exposed for 6 weeks to 0, 20, 40, or 85 ppm sodium arsenate in the drinking water suffered depression of hepatic delta-aminolevulinic acid (ALA) synthetase and heme synthetase (ferrochelatase) activities, with maximal decreases to 67 and 55% of control levels, respectively, at 85 ppm. Concomitantly, urinary uroporphyrin levels were elevated by as much as 12 times, and coproporphyrin by as much as 9 times, control values. The rate of incorporation of (3)H-ALA into mitochondrial and microsomal hemes was depressed by 40-50% at 20 ppm but was increased with regard to controls by as much as 150% at the higher treatment levels. A similar biphasic pattern was observed in regard to (14)C-leucine incorporation into cellular membranal proteins. In contrast, the levels of ALA dehydratase, uroporphyrinogen I synthetase, aminopyrine demethylase, and cytochrome P-450 were not significantly changed in As(+5)-treated rats. These results support the hypothesis that chronic, low level, arsenic exposure results in selective inhibition of mitochondrial-bound heme biosynthetic pathway enzymes (ALA synthetase and heme synthetase) resulting in a substantial increase in urinary porphyrins, uniquely characterized by a greater increase in uroporphyrin than coproporphyrin levels. These changes occur independent of, or prior to, alterations in hepatic hemoprotein-dependent functions and may thus serve in the clinical analysis of pretoxic exposure to arsenic compounds in human populations.
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PMID:Effects of chronic arsenic exposure on hematopoietic function in adult mammalian liver. 90

The principal psychoactive component of marihuana is delta-9-tetrahydrocannabinol. This compound at 10(-5) molar concentration in the medium of human cell cultures appeared to inhibit DNA, RNA, and protein synthesis by 50, 40, and 30% respectively, as measured by incorporation of radioactive precursors into acid-insoluble cell fractions in human diploid fibroblasts, human neuroblastoma cells, and mouse neuroblastoma cells. While delta-9-tetrahydrocannabinol inhibited semiconservative DNA synthesis, it had no effect on DNA repair synthesis in human cells as assayed by the photolysis of 5-bromodeoxyuridine incorporation into DNA during repair after ultraviolet radiation damage. Delta-9-tetrahydrocannabinol also had no effect on rejoining of DNA single-strand breaks induced by gamma-rays. The nonspecificity of the inhibition of macromolecular synthesis by delta-9-THC suggested a possible interference with uptake of radioactive precursors. However, experimentation has shown that this depression of macromolecular synthesis cannot be accounted for by reduced transport of radioactive precursors into the cell because the rate of transport of these precursors into the cell is essentially the same in the presence or absence of delta-9-THC. Pool sizes of macromolecular precursors as measured radioisotopically (3H-thymidine, 3H-uridine, 14C-leucine) appear to be reduced about 50%, and this reduced pool size could fully account for the reduced macromolecular synthesis seen in the presence of delta-9-THC. We do not know what causes this apparent reduction of pool sizes in the presence of delta-9-THC.
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PMID:delta-9-Tetrahydrocannabinol: effect on macromolecular synthesis in human and other mammalian cells. 94 11

Cycloheximide depresses maximum rate of change in membrane potential observed during the rising phase of the action potential in single medullated axons of Xenopus. To,e course of depression is independent of cycloheximide concentration over a range that almost completely inhibits leucine incorporation into axonal proteins.
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PMID:The action of cycloheximide on the action potential and protein synthesis in medullated Xenopus axons. 97 43

In four experiments, the interactions of leucine, isoleucine and valine in turkey poults were studied. The additon of 1.50% excess leucine to a 22% protein starter diet, marginal in isoleucine and valine, depressed growth. This growth depression was corrected by the addition of valine and isoleucine. The addition of the excess leucine caused a decrease in plasma valine and isileucine concentrations in experiments 3 and 4, and plasma valine concentration in experiment 1. The addition of valine caused a marked linear increase in plasma valine with little or no effect on plasma isoleucine. The addition of isoleucine to the diet caused an increase in plasma isoleucine. Plasma valine, however, was decreased by the addition of isoleucine to a high-leucine diet. It is concluded that interactions exist in turkey poults between leucine-valine, leucine-isoleucine and isoleucine-valine and that the growth reduction caused by added leucine can be partly alleviated by addition of valine or by valine plus isoleucine, but not be isoleucine alone.
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PMID:Leucine, isoleucine and valine interactions in turkey poults. 99 1

The authors studied C14-leucine and S35-methionine incorporation into the brain tissue homogenates and protein from different parts of the brain of rats subjected to intrauterine hypoxia. Depression of protein synthesis in certain brain structures, particularly in the hyppocampus was observed alongside with the stimulation of the amino acid incorporation into proteins of the other parts of the brain. Changes of the amino acid penetration into tissue homogenates fialed to correlate with the rate of their incorporation into proteins in separate structures of the brain. Experimental results pointed to disfunction in the protein metabolism intensity and in the blood-brain barrier system occurring during the late ontogenesis in rats surviving the intrauterine hypoxia.
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PMID:[Changes in the incorporation of labelled amino acids into proteins and homogenates of the brains of rats that have suffered acute hypoxia in the antenatal period]. 103 1

Suspensions of human bone marrow cells were incubated with various concentrations of phenobarbitone or phenytoin sodium for 2 h, and the effects of this incubation on the subsequent incorporation of 3H-thymidine and3H-leucine into DNA and protein, respectively, were studied. Both drugs caused a depression of 3H-thymidine incorporation and this phenomenon was not prevented by the addition of 100 mug of pteroyl-glutamic acid, folinic acid or 5-methyltetrahydrofolate per ml of marrow culture. The lowest concentration of drug which caused a statistically significant depression of 3H-thymidine incorporation was 200 mug per ml for phenobarbitone and 50 mug per ml for phenytoin sodium. Both phenobarbitone and phenytoin sodium also caused an increase in the incorporation of 3H-leucine at concentrations of 50 and 20 mug per ml, respectively, suggesting the possibility that a stimulation of protein synthesis within erythropoietic cells may play an important role in the development of anticonvulsant-induced macrocytosis.
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PMID:Effects of anticonvulsant drugs on the synthesis of DNA and protein by human bone marrow cells in vitro. 108 45

The effects of hypophysectomy and short-term GH replacement on insulin release and on some aspects of glucose metabolism in isolated rat islets of Langerhans were investigated. The effects on body, pancreas and adrenal gland weights, and on the levels of blood plasma constituents were also measured. Three to four weeks after hypophysectomy the early and late phases of insulin release from islets incubated with high concentrations of glucose, but not with low concentrations of glucose or with xylitol, leucine, arginine, tolbutamide, citrate or butyrate, were significantly lowered. Short-term GH replacement partially reversed the depression in glucose-stimulated insulin release. This reversal effect was not dependent on the increase in body weight of rats after GH replacement when the fall in adrenal gland but not in pancreas weight was also reversed. Nine out of the 12 plasma constituents measured, including glucose, were maintained in the control range of levels, but albumin, inorganic phosphate and urea nitrogen levels were altered after hypophysectomy or GH replacement. Three to four weeks after hypophysectomy, total glucose oxidation and glucose utilization by the islets were slightly depressed. Hypophysectomy appeared to slow down glucose 6-phosphate utilization in the islets. However, the functional capacity of the glucose phosphorylating, glucose-6-phosphate and 6-phosphogluconate dehydrogenase activities were not changed. Short-term GH replacement caused improvements in these islet functions.
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PMID:Effects of hypophysectomy and short-term growth hormone replacement on insulin release from and glucose metabolism in isolated rat islets of Langerhans. 110 38


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