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

Cytotoxic T-lymphocytes (CTL's) harvested from mixed splenic lymphocyte cultures (DBA/2 + C57BL) were tested for their ability to lyse allogeneic P815 mastocytoma cells under various tumor-like assay conditions, with or without previous exposure to ionizing radiation or hyperthermia (43 degrees). There was little or no decrease of immune cytolysis when CTL's were assayed by 51Cr release under tumor-like conditions (plateau-phase target cells, low pH, or anoxia) or after irradiation, but cytolytic activity was greatly reduced when CTL's were exposed to heat; 45 min of hyperthermic treatment decreased activity by greater than or equal to 99% while reducing the apparent cell viability (as indicated by trypan blue exclusion) by only 30%. When the P815 target cells rather than the CTL's were exposed to heat their susceptibility to immune lysis was not affected even after treatment times that were lethal to the tumor cells. Despite the dissimilar heat sensitivities of CTL and P815 cells, the dose-response curves for inhibition of protein synthesis by heat, as indicated by [3H]leucine incorporation, were similar for both cell types: neither the depression of protein synthesis in heated CTL's nor the decreased cytolytic ability of these cells was reversed within 3 hr. When irradiated or heated P815 cells were incubated with CTL's, the resulting survival curves were always additive, indicating that neither irradiation nor heat treatment affected the susceptibility of the tumor cells to immune attack. The extreme heat sensitivity of cytotoxic T-lymphocytes raises important questions about the possible effects of hyperthermic treatment on the immune competence of cancer patients.
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PMID:Effects of Tumor-like assay conditions, lonizing radiation, and hyperthermia on immune lysis of tumor cells by cytotoxic T-lymphocytes. 0 45

Fourteen di- and tripeptide analogues of MIF, Pro-Leu-Gly-NH2, have been synthesized and assayed for inhibition of oxotremorine-induced tremor. Replacement of Pro by HCO-Pro or cyclopentanecarboxylic acid gave inactive analogues, while some peptides of the general structure less than Glu-Leu-Gly-NR1R2 were highly active. Thus, R1 = C3H8 and R2 = H gave 4 times the activity of MIF, R1 = I-C3H8 and R2 = H gave 13 times the activity of MIF, and R1 = R2 = CH3 gave 29 times the activity of MIF. cyclo(-Pro-Leu-), Pro-Lys-Gly-NH2, and Pro-Arg-Gly-NH2 had no activity. Apparently, small modifications in the structure of MIF can yield highly active analogues with potential clinical value, e.g., in the treatment of Parkinson's disease or mental depression.
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PMID:Tripeptide analogues of melanocyte-stimulating hormone release-inhibiting hormone (Pro-Leu-Gly-NH2) as inhibitors of oxotremorine-induced tremor. 4 28

Previous in vitro studies of the metabolism of the peripheral nerve have been based on incorporation of radioactive precursor into components isolated from whole nerve. In this study we have determined incorporation secifically into myelin components of peripheral nerve by isolating myelin after incubating whole nerves with lipid or protein precursors and by determining the specific activity of the components of that membrane. The effect of diabetes on such incorporation was also studied. In the rat, in vitro incorporation of DL-[1-14C]leucine into protein components of myelin was decreased by 30-88% in diabetic animals as compared to controls. The major polypeptide constituent of rat sciatic nerve myelin (mol st 28,000; 58.5% of total mass of proteins) was not labeled in either the diabetic or the control group. In diabetes incorporation rate into a polypeptide of mol wt 23,000, which constitutes 21% of total mass, was approximately one half that of controls. In polypeptides of mol wt 38,000-49,000, which are heavily labeled in normal animals, but constitute only about 5% of total mass of proteins, depression of incorporation was e-en more marked in the diabetics. While these marked differences in incorporation between diabetic and control animals were observed, the amount of protein and its distribution among the constituent polypeptides was the same in both groups. In young rats made diabetic with streptozotocin and young rabbits made diabetic with alloxan, there was a lower rate of incorporation of the lipid precursors, [1-14C]sodium acetate or [3H]water, into myelin components. In older animals of both species incorporation in the controls was considerably lower than in the yount animals, and the effect of diabetes was no longer apparent. In nondiabetic animals, the in vitro addition of insulin (10-7 M) stimulated incorporation of DL-[1-14C]leucine into myelin proteins 1.6-3.1 times that of controls. This stimulation by insulin in vitro was not seen in diabetic animals. In animals in which diabetes had spontaneously recovered, however, incorporation rate in the in vitro experiments approached that of controls and were significantly above that in animals whose diabetes persisted. Since myelin is the palsma membrane of the Schwann cell, these studies provide evidence that the Schwann cell is affected by insulin and that some aspects of the metabolism of myelin are altered in insulin-deficient states.
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PMID:Metabolism of peripheral nerve myelin in experimental diabetes. 12 35

Earlier results on potassium ion inhibition of amino acid incorporation into the brain proteins in vivo (spreading cortical depression) led to the hypothesis that inhibition of protein synthesis is based on ATP deficiency. In the present study we tested various aspects of the aminocylation of tRNA, an ATP-dependent process, during spreading cortical depression produced by the topical application of 25% KCl. On using a 7-min interval between the subcutaneous injection of L-[U-14C] leucine and killing the rat, incorporation into the tRNA fraction was found to be reduced by 25%. Total amino acid radioactivity in the soluble fraction was unaltered. The acceptor capacity of tRNA, measured in vitro, and the proportion of non-acylated tRNA in vivo were likewise unchanged.
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PMID:On the mechanism of the inhibitory effect of potasium ions on amino acid incorporation into rat cerebral cortex proteins in vivo. 14 13

The present report is a continuation of our previous studies on the biochemical mechanisms of carcinogenesis; studying the nature of interactions taking place between Ethylnitrosourea and DNA, RNA and protein of various stages of their synthetic activity. As a model system we chose partially hepatectomized mice live 36 hrs after surgery. Synthetic macromolecule activity in the remaining liver segment was determined by means of 3H-thymidine, 3H-uridine and 3H-leucine. We observed complete depression of DNA synthetic activity (immediately after Ethylnitrosourea administration it remained depressed almost through out the whole period of our observations) while protein synthetic activity was highly elevated. Qualitative changes of soluble proteins which were analyzed by isoelectric fractionation on 5% polyacrylamide after previous 3H- and 14C-leucine incorporation, could not be detected. Our biochemical data are correlated with histological studies and with the tumour incidence following the Ethylnitrosourea treatment of partially hepatectomized mice in the course of long-term experiments. The results provide guideline for further analysis, which should be modified according to the information concerning Ethylnitrosourea carcinogenesis induced 36 hours after partial hepatectmoy.
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PMID:Macromolecular synthetic activity in mice regenerating liver after ethylnitrosourea injection. 15 33

1 The actions of morphine, methionine and leucine enkephalin, administered electrophoretically, were studied on supraspinal neurones in the cortex and brainstem of the rat anaesthetized with urethane and on spinal Renshaw cells and dorsal horn interneurones in the cat anaesthetized with pentobarbitone.2 The majority of Renshaw cells and cortical and brainstem neurones were excited by all three compounds although some supraspinal neurones were depressed.3 Naloxone reversibly antagonized both excitatory and depressant actions of morphine and enkephalin. Acetylcholine-induced excitation but not amino acid-induced excitation was also antagonized by naloxone.4 Neither morphine nor the enkephalins had any naloxone-reversible action on dorsal horn neurones when ejected from conventional multibarrelled electrodes. However, morphine but not enkephalin, administered into the substantia gelatinosa region of the spinal cord selectively reduced responses to noxious stimuli of neurones in deeper laminae. Naloxone administered into the same region antagonized this action of morphine.5 Intravenous morphine also antagonized responses of dorsal horn neurones to noxious stimuli and subsequent intravenous naloxone reversed this effect.6 It was concluded that the excitatory and inhibitory effects of morphine and enkephalin on central neurones may be mediated by actions on different opiate receptors and that depression of noxious responses of dorsal horn neurones may be relevant to the analgesic action of morphine.
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PMID:Pharmacological and electrophysiological studies of morphine and enkephalin on rat supraspinal neurones and cat spinal neurones. 20 9

Multinucleate cells are found frequently in rheumatoid synovium. In this study, polyethylene glycol was used to fuse rabbit synovial fibroblasts. Approximately 40% of the cells developed more than one nucleus in a 24 hour period, during which time cell membranes had increased permeability. In cultures containing multinucleate cells, 3H-thymidine incorporation was depressed for 24 hours although 3H-leucine incorporation into TCA precipitable material was unaffected; autoradiography showed that depression of 3H-thymidine continued for at least 4 days. Collagenase production by cultures containing fused cells was increased more than 10-fold over control cultures during a 28 day period.
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PMID:Collagen production by cultures containing multinucleated cells derived from synovial fibroblasts. 21 86

The specific activity of glutamine synthetase in cultured Chinese hamster cells is inversely related to the concentration of glutamine in the surrounding solution. Enzyme specific activity increases 8- to 10-fold when glutamine is removed from serum-free F12 growth media. The induction of glutamine synthetase activity occurs only after glutamine removal and not after the removal of other amino acids (methionine, leucine, or isoleucine). The analysis of the glutamine-mediated decrease in glutamine synthetase activity has been simplified by the finding that depression proceeds in nutrient-free buffered saline solution (141 mM NaCl, 5.4 mM KCl and 30 mM Tricine (pH 7.4). Under these conditions, 0.1 mM cyanide blocks glutamine-mediated depression. The cyanide inhibition is reversed by the addition of 1.0 mM glucose which suggests that ATP is required for depression. Glutamine-mediated depression is temperature-dependent, occurring between 25 and 45 degrees with an optimum rate at 37 degrees. Studies of the time course of induction and depression as a function of glutamine concentration suggest that glutamine regulates the rate at which the enzyme is either modified or degraded. We have employed an antibody prepared against homogeneous Chinese hamster liver glutamine synthetase to measure the amount of glutamine synthetase protein in extracts of cells containing induced or depressed levels of enzyme activity. A highly sensitive immunoprecipitation procedure enables quantitation of nanogram amounts of glutamine synthetase protein. Glutamine synthetase in cell extracts containing induced levels of enzyme activity possesses the same molecular specific activity (ratio of activity to antigenicity) as homogeneous Chinese hamster liver glutamine synthetase. The molecular specific activity of glutamine synthetase is almost the same in extracts of cells with depressed levels of enzyme obtained by growth for short (2 hours) and long (24 hours) times in the presence of glutamine. These data suggest that glutamine-mediated depression of glutamine synthetase results from degradation of enzyme molecules.
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PMID:Immunochemical evidence for glutamine-mediated degradation of glutamine synthetase in cultured Chinese hamster cells. 23 54

The reactivity of peripheral blood lymphocytes from patients with advanced malignancy was assessed by mitogen-induced stimulation of protein synthesis as measured by 3H-leucine incorporation. It was confirmed that the lymphocyte response of patients was depressed. Furthermore, the lymphocytes of 15 out of 27 cancer patients, selected because of their low responses, inhibited the reactivity of normal lymphocytes in co-cultures. The lymphocytes from one patient with Hodgkin's disease were also inhibitory. In contrast, lymphocytes from healthy subjects, patients with chronic lymphocytic leukaemia, lymphosarcoma or multiple myeloma caused no suppression. Experiments with purified cell populations from patients with carcinoma indicated that purified T cells responded to mitogens while unseparated lymphocytes failed to respond and that the inhibitory activity was due to adherent cells, presumably monocytes. There was no evidence for B-cell-mediated suppression. However, in two cases inhibition was caused by isolated T cells of the patients and not by adherent cells. These experiments suggested that one mechanism for the depression of cell-mediated immunity seen in patients with advanced cancer may be the nonspecific suppresssion of certain T-cell functions by circulating monocytes.
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PMID:Depressed in vitro peripheral blood lymphocyte response to mitogens in cancer patients: the role of suppressor cells. 30 Nov 22

Kinetics of the transport systems common for entry of L-isoleucine, L-leucine, and L-valine in Salmonella typhimurium LT2 have been analyzed as a function of substrateconcentration in the range of 0.5 to 45 muM. The systems of transport mutants, KA203 (ilvT3) and KA204 (ilvT4), are composed of two components; apparent Km values for uptake of isoleucine, leucine, and valine by the low Km component are 2 muM, 2 to 3 muM, and 1 muM, respectively, and by the high Km component 30 muM, 20 to 40 muM, and 0.1 mM, respectively. The transport system(s) of the wild type has not been separated into components but rather displays single Km values of 9 muM for isoleucine, 10 muM for leucine, and 30 muM for valine. The transport activity of the wild type was repressed by L-leucine, alpha ketoisocaproate, glycyl-L-isoleucine, glycyl-L-leucine, and glycyl-L-methionine. That for the transport mutants was repressed by L-alanine, L-isoleucine, L-methionine, L-valine, alpha-ketoisovalerate, alpha-keto-beta-methylvalerate, glycyl-L-alanine, glycyl-L-threonine, and glycyl-L-valine, in addition to the compounds described above. Repression of the mutant transport systems resulted in disappearance of the low Km component for valine uptake, together with a decrease in Vmax of the high Km component; the kinetic analysis with isoleucine and leucine as substrates was not possible because of poor uptake. The maximum reduction of the transport activity for isoleucine was obtained after growing cells for two to three generations in a medium supplemented with repressor, and for the depression, protein synthesis was essential after removal of the repressor. The transport activity for labeled isoleucine in the transport mutant and wild-type strains was inhibited by unlabeled L-alanine, L-cysteine, L-isoleucine, L-leucine, L-methionine, L-threonine, and L-valine. D-Amino acids neither repressed nor inhibited the transport activity of cells for entry of isoleucine.
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PMID:Repression and inhibition of transport systems for branched-chain amino acids in Salmonella typhimurium. 32 Jan 86


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