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)

5.7-Dinitro-quinoxaline-2.3-dione (MNQX) displaced [3H]glycine binding to cortical membranes but had no effect n [3H]3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid ([3H]CPP) binding. MNQX potently antagonized N-methyl-D-aspartate (NMDA)-evoked release of [3H]GABA from cultured cortical neurones, NMDA evoked spreading depression and NMDA depolarizations in the rat neo-cortex. All of these responses were reversed by addition of glycine to the perfusion media. These results suggested that MNQX is an antagonist at the strychnine-insensitive glycine receptor associated with the NMDA receptor/ionophore complex. Furthermore the compound was found to antagonise audiogenic seizures in DBA-2 mice indicating the potential of glycine antagonists of this type in anticonvulsant therapy.
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PMID:A potent antagonist of the strychnine insensitive glycine receptor has anticonvulsant properties. 256 Sep 79

Benzene affects hematopoietic progenitor cells leading to bone marrow depression and genotoxic effects such as micronucleus formation. Progenitor cell proliferation and differentiation are inhibited by prostaglandins produced by macrophages. Administration of benzene to DBA/2 or C57BL/6 mice caused a dose-dependent bone marrow depression and a significant increase in marrow prostaglandin E level and both were prevented by the coadministration of indomethacin and other inhibitors of the cyclooxygenase component of prostaglandin H synthase. Levels of benzene that decreased bone marrow cellularity also caused genotoxic effects measured as increased micronucleated polychromatic erythrocytes in peripheral blood, which was also prevented by the coadministration of indomethacin. These results suggest a possible role for prostaglandin synthase in benzene myelotoxicity; a mechanism by which this might occur is presented.
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PMID:Prevention of benzene-induced myelotoxicity by nonsteroidal anti-inflammatory drugs. 279 51

The effects of the kappa-opioid receptor agonists tifluadom, bremazocine and U-50,488 on locomotor activity (test: toggle-floor box) and memory (test: passive avoidance) were assessed in C57BL/6 (C57) and DB/2 (DBA) mice. The drugs administration resulted in activity depression in both strains, the effect was higher in DBA mice and was enhanced by pretreatment with haloperidol and with muscimol. Memory impairment was observed in DBA mice following posttraining administration of all drugs. This effect was enhanced by immobilization stress and decreased by familiarization with the apparatus. Memory improvement was evident in C57 mice (U-50,488 experiments). In a research carried out with CD1 mice, amygdaloid lesions decreased the memory impairing effect of U-50,488. The results are compared with those previously obtained with mu agonists and, as concerns memory, are discussed in terms of the involvement of emotional factors in mice responses to kappa agonists administration.
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PMID:Effects of kappa-opioid receptor agonists on locomotor activity and memory processes in mice. 285 67

Previous studies have shown that the progressive growth of the M-1 fibrosarcoma in DBA/2J mice is associated with the activation of suppressor cells which inhibit both mitogen-induced proliferative responses and antibody synthesis. In this study, we have analyzed the effect of tumor growth on NK cell activity. Mice in the advanced stages of tumor growth did have a significant depression in NK activity, and this depression could not be overcome by the injection of the interferon inducer, polyinosinic-polycytidylic acid (Poly I:C). The decline in NK activity was associated with the presence in the spleens of suppressor cells capable of inhibiting the NK activity of spleen cells from Poly I:C-treated syngeneic mice. In order to characterize the suppressor cells, we used a combination of negative selection procedures and kinetic analysis. These studies demonstrated that the spleens of tumor-bearing mice contained two distinct populations of suppressor cells which were not evident in normal mice. One population was non-adherent to nylon wool, Thy-1-, non-phagocytic, did not bind target cells, and had a non-competitive mechanism of suppression. The second population was adherent, Thy-1-, phagocytic, and had a competitive mechanism of suppression. In addition, the spleens of both normal and tumor-bearing mice contained an adherent, non-competitive suppressor cell population which was enriched following negative selection procedures removing T cells or phagocytic cells.
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PMID:Kinetic analysis of the inhibition of natural killer (NK) activity by multiple populations of tumor-activated suppressor cells. 287 55

Natural resistance against the proliferation of splenic colony-forming units (CFU-S) is seen in certain combinations of bone marrow donors and irradiated hosts. In order to examine the early events following bone marrow transplantation and to determine whether genetically determined CFU-S repression is due to elimination of the transplanted cells from the spleen or to inhibition of their proliferation, we labeled proliferating cells in freshly isolated bone marrow or long-term bone marrow cultures (LTBMC) with radioactive I-iododeoxyuridine prior to injection. A heterogeneous mixture of cells was labeled in both freshly isolated marrow and LTBMC; CFU-S precursors were among the cells labeled as indicated by reduction of CFU-S numbers in the radiolabeled cell population. Radiolabeled cells from C57BL/6J, DBA/2J, and B6D2F1 mice were injected into syngeneic, semisyngeneic, and allogeneic irradiated mice that were killed at various times after injection to determine the amount of radioactivity remaining and the organ distribution of the labeled cells; additional mice were killed 7-8 days later to count CFU-S. Retention of label in the spleen was predictive of subsequent CFU-S numbers, suggesting that killing or elimination of the transplanted cells from the spleen is the cause of CFU-S depression in resistant animals. Further genetic analysis of the survival of the radiolabeled cells in the spleen indicated that mismatching of H-2 homozygous donor cells with the host at H-2D was a prerequisite for resistance and that H-2 heterozygous cells were not resisted in spite of H-2 mismatching. Although natural killer (NK) cell-deficient beige mice were able to resist H-2-nonidentical bone marrow cells, pretreatment of the host with anti-asialo GM-1 antibodies completely abrogated natural resistance as assessed by splenic survival or radiolabeled cells. The findings that splenic survival or radiolabeled bone marrow cells reflects the immunogenetic specificity of CFU-S repression and that abrogation of CFU-S repression increases the splenic survival of the labeled cells strengthen the postulate that repression of CFU-S proliferation involves events occurring within the first 24 hr after injection.
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PMID:Early events in natural resistance to bone marrow transplantation. Use of radiolabeled bone marrow cells. 287 42

Injection of (C57BL/6 X DBA/2)F1 mice with Corynebacterium parvum (CP), iv, resulted in a depression of splenic natural killer (NK) cell activity 7-17 days after treatment. This decline in reactivity was accompanied by an increase in splenic tumor-binding cells and a decrease in cytotoxic tumor-binding cells as evaluated in a single-cell assay. Morphologic analysis indicated that the increased tumor-binding cells following CP injection were due to erythroblasts binding to YAC-1 tumor cells. With the use of a double-fluorescent binding technique, nonlytic tumor-binding cells of CP-treated mice inhibited NK cytotoxicity of normal syngeneic mice by competing with effectors for binding to tumor cells. Removal of erythroblasts by hypotonic shock treatment eliminated this competition and significantly improved the lytic capacity of CP-treated mice, thus indicating that erythroblasts contributed to the suppression of NK activity in these mice. The presence of a second inhibitory mechanism in CP-treated mice was found following asialo GM1 treatment or Percoll density gradient separation of erythroblast-depleted CP splenocytes; this inhibitory population was identified as Thy 1.2+ lymphocytes. Further analysis of the mechanism of suppression indicated that it was mediated by a soluble factor. In addition to the presence of suppressor cells, CP-treated mice displayed a decrease in splenic large granular lymphocyte content, which may also contribute to their NK deficiency.
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PMID:Mechanism of decline of natural killer cell activity in Corynebacterium parvum-treated mice: inhibition by erythroblasts and Thy 1.2+ lymphocytes. 288 87

Benzene is a myelotoxin which affects hemopoietic progenitor cells leading to bone-marrow depression as well as a genotoxin which causes chromosomal abnormalities including micronucleus formation. We have demonstrated previously that benzene administered to DBA/2 or C57B1/6 mice causes bone-marrow depression and increased prostaglandin E2 levels in bone marrow; both of these effects can be prevented by the coadministration of indomethacin, a selective inhibitor of prostaglandin synthase. We report, herein, that benzene (400-600 mg/kg body weight), under conditions where it depresses bone-marrow cellularity, also induces an increase in the frequency of micronucleus formation in polychromatic erythrocytes of C57B1/6 mice which is also prevented by the coadministration of indomethacin at levels that do not inhibit cytochrome P450 or myeloperoxidase. In Swiss Webster wild-type mice doses of benzene from 400 to 1000 mg/kg were without effect on marrow cellularity, but did induce the formation of micronucleated polychromatic erythrocytes which could be prevented by indomethacin. In contrast, DBA/2 mice, a strain highly sensitive to benzene, exhibited significant bone-marrow depression at a dose of benzene of 100 mg/kg body weight. Even at this low dose, benzene is too toxic toward developing erythrocytes to allow the evaluation of micronucleus formation. The frequency of induction of micronucleated polychromatic erythrocytes by benzene thus depends on the strain of mouse used. Furthermore, micronucleus formation appears to be an early and very sensitive indicator of benzene toxicity. A possible role for prostaglandin H synthase in the geno- and myelo-toxicity of benzene is discussed.
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PMID:The prevention of benzene-induced genotoxicity in mice by indomethacin. 292 13

In previous structure-activity studies, we have demonstrated that attachment of a glucose molecule to the chloroethylnitrosourea cytotoxic group produces a compound with reduced murine bone marrow toxicity and retention of full antitumor activity. To further define this protective role conferred by the glucose moiety in bone marrow cells, we have replaced the nitrosourea cytotoxic group with another class of alkylating agent, a bifunctional nitrogen mustard. In a detailed structure-activity analysis, we have now characterized four analogues, with the mustard cytotoxic group positioned at carbon 2 [1,3,4,6-tetra-O-acetyl-2-(di-2-chloroethyl)amino-2-deoxy-D-glucopyranos e (TGM)], carbon 6, or carbon 1 (D- and L-isomers) of the aminoglucose molecule. On a molar basis, TGM was most toxic to normal BALB/c X DBA/2 F1 mice, with a 10% lethal dose (LD10) of 3.8 mumol/kg. The D- and L-isomers of 2,3,4,6-tetra-O-acetyl-N,N-bis(2-chloroethyl)glucopyranosylamine (C-1) were the least toxic, with an LD10 of 73 mumol/kg for both. Optimal antitumor activity against the murine P388 leukemia (single i.p. administration of the LD10) did not differ significantly among the four analogues, with increased life span ranging from 83-86%. P388 antitumor activity for nitrogen mustard (HN2) was significantly less, 60% increased life span (P = 0.01), while p-di(2-chloroethyl)amino-L-phenylalanine produced an increased life span of greater than 101%. An LD10 of 6-bis-(2-chloroethyl) amino-6-deoxy-D-glucose (C-6) or TGM produced significantly less depression of WBC counts than did an equitoxic dose of the C-1 isomers, HN2, or p-di(2-chloroethyl)amino-L-phenylalanine. The mean nadir WBC count for C-6 equaled 86% of control, and for TGM, 80% of control. Consistent with this sparing effect on the peripheral WBC, C-6 and TGM produced significantly less in vivo murine bone marrow DNA synthesis depression, 77 and 64% of control, respectively, as compared to the depression nadir produced by HN2 (27% of control), the D-isomer of C-1 (17%), the L-isomer of C-1 (18%), and p-di(2-chloroethyl)amino-L-phenylalanine (2%). These structure-activity studies demonstrate that conjugation of the mustard cytotoxic group to carbon 6 or carbon 2 of glucose produces an analogue that retains P388 antitumor activity significantly greater than that of HN2, with a concomitant reduction in murine bone marrow toxicity.
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PMID:Antitumor activity and bone marrow toxicity of aminoglucose mustard anticancer agents in mice. 293 28

Effects of morphine on the rectal temperature and respiratory rate, and [3H]naloxone binding to brain membranes from seven brain regions were compared among six strains of male mice, including DBA/2N, C57BL/6N, BALB/c, C3H/HeN, A/J and ICR. The administration of 10 and 20 mg/kg doses of morphine HCl to these strains of mice decreased rectal temperature and respiratory rate. However, there was a significant strain difference in these two measures of the effect of morphine. The DBA/2N strain was the most sensitive in both measures of morphine action. The magnitude of hypothermia was positively correlated with respiratory depression among six strains of mice after the administration of 10 and 20 mg/kg morphine HCl, suggesting common mechanisms. Strain difference in naloxone binding in the brain regions could not explain that of the morphine responses, because there was no correlation between the intensity of morphine-induced hypothermia or respiratory depression and the regional [3H]naloxone binding for the mouse strains.
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PMID:Strain difference in the effects of morphine on the rectal temperature and respiratory rate in male mice. 309 May 93

The ability of seven lectins to bind to newt epidermal cells and influence their motility was examined. Of the seven fluoresceinated lectins applied to frozen sections containing intact newt skin and migrating epidermis (wound epithelium), only Con A (concanavalin A), WGA (wheat germ agglutinin), and PNA (peanut agglutinin) produced detectable epidermal fluorescence. Con A and WGA each heavily labeled all layers of intact epidermis, but PNA bound only to the more superficial layers. In contrast to a single population of labeled cells in migrating epidermal sheets after treatment with Con A, there were both labeled and unlabeled cells after exposure to either WGA or PNA. The wound bed was labeled by both Con A and WGA, but not by PNA. DBA (Dolichos bifloris agglutinin), RCA I (Ricinus communis agglutinin), and UEA (Ulex europaeus agglutinin), did not produce significant fluorescence with either migrating or intact epidermis. In general, inhibitory effects on epidermal motility correlated with the binding studies. Thus, Con A, WGA, and PNA, the lectins which clearly bound to the epidermis, all produced a concentration-dependent depression in the rate of epidermal wound closure. RCA was somewhat paradoxical in that it was moderately inhibitory despite showing essentially no binding. The effects of SBA and UEA were equivocal. DBA had no effect. These results indicate that the inhibition of motility produced by Con A that we have described previously is not peculiar to this mannose-binding lectin, but is shared by at least one lectin with an affinity for D-GlcNAc (WGA), and one with an affinity for B-D-Gal(1-3)-D-GalNAc (PNA).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lectin binding to newt epidermis: fluorescent localization and effects on motility. 309 58


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