Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Quantitative structure-activity relationships between pharmacological activities and physical properties of a series of 2,2-diphenylpropionate compounds were used to define the topography of the antagonist binding site of muscarinic receptors. XICAMM, a computer molecular modeling program, was used to calculate geometrical and topological values of the compounds. The compounds were tested for their antimuscarinic activities by: (a) inhibition of [N-methyl-3H]scopolamine binding to the muscarinic receptors of N4TG1 neuroblastoma cells, (b) inhibition of carbachol-induced alpha-amylase release from rat pancreas acini, and (c) blocking of acetylcholine-induced contraction of guinea pig ileum. To evaluate as clearly as possible only the effect of the bond distance on the potency of the synthesized antimuscarinics, the compounds contained as many constant features as possible. Neither the hydrophobic nor the ester moieties of the compounds were changed, and the rings containing the protonated nitrogen were saturated and restricted. The antimuscarinic activities obtained from the three assays were significantly correlated with each other, with the exception of two compounds, 9 and 13. The latter two compounds demonstrated specificity for the m3 muscarinic receptor subtype expressed in the pancreas. Furthermore, it was demonstrated that the antimuscarinic activities were significantly related to the bond distances between the carbonyl oxygen (constant electronegative locus) and the protonated nitrogen (center of cationic charge) of the 2,2-diphenylpropionate compounds. Parabolic relationships between the pharmacological activities and bond distances were empirically established. The shortest calculated bond distance of these compounds was approximately 4.4 A, whereas the longest was about 5.9 A. The maximum antimuscarinic potency was observed with a calculated bond distance of about 5.2 A in all three assays.
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PMID:Distance geometry of alpha-substituted 2,2-diphenylpropionate antimuscarinics. 258 91

We investigated whether polymorphonuclear leukocytes (PMN) are able to kill human neuroblastoma cells either directly or if coated with antibody MAb 14.18 that recognizes ganglioside GD2 present on the cell surface of most neuroblastoma cells. Neuroblastoma cells could not be destroyed directly, whereas in the antibody-dependent reaction (ADCC-reaction) they were easily eliminated. In order to answer the question whether reactive oxygen intermediates are involved in this process, chemiluminescence measurements were performed. Compared to the signals that could be measured using opsonized zymosan as stimulus, only weak CL-signals could be registered during the ADCC reaction. Pretreatment of PMN with granulocyte-macrophage colony stimulating factor (GM-CSF) enhanced the CL-signals, catalase and SOD reduced it; however, cell killing was only slightly influenced in the presence of catalase and superoxide dismutase. These data suggested that reactive oxygen compounds do not play a prominent role in the killing process. Definitive evidence for this suggestion could be obtained using PMN from a patient with chronic granulomatous disease (CGD): MAb 14.18 coated neuroblastoma cells could be killed effectively, but no CL-signal could be registered, either in the ADCC-reaction or using opsonized zymosan as stimulus.
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PMID:Effects of granulocytes on human neuroblastoma cells measured by chemiluminescence and chromium-51 release assay. 272 18

Suspensions of human neuroblastoma cells consume oxygen at a constant rate when the oxygen pressure is greater than approximately 11 Torr. The rate of oxygen consumption, however, becomes dependent on the oxygen pressure below this level. The falling respiratory rate at the lower pressures gives rise to an oxygen pressure for half-maximal respiration (P50) of approximately 0.8 Torr, which is consistent with the 0.5 Torr value for suspensions of isolated mitochondria in the presence of ATP (J. Biol. Chem. 263: 2712-2718, 1988). When the cellular metabolic energy state is lowered by addition of an uncoupler of mitochondrial oxidative phosphorylation, the respiratory rate increases up to fivefold, but the P50 decreases to approximately 0.6 Torr. In the cells treated with uncoupler, the P50 decreases further when the mitochondrial respiratory rate is inhibited with amobarbital (amytal), an inhibitor of the respiratory chain. The additional decrease in P50 is proportional to the decrease in respiratory rate. Thus, for cells treated with uncoupler, the P50 appears to be limited by oxygen diffusion from the external medium to the mitochondria. When the respiratory rate of the uncoupled cells is inhibited to the level of coupled cells, the P50 for the former is less than 0.15 Torr. This indicates that for coupled cells the difference in oxygen pressure from the external medium to the mitochondria is less than 0.15 Torr at half-maximal respiratory rate and does not significantly affect the P50 for oxygen that occurs at 0.8 Torr.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxygen diffusion and mitochondrial respiration in neuroblastoma cells. 273 96

In suspensions of normally respiring human neuroblastoma cells respiration has an oxygen dependence similar to that of suspensions of isolated mitochondria in a comparable metabolic state. When mitochondrial oxidative phosphorylation is uncoupled, respiration at limiting oxygen pressures is indicative of the oxygen pressure difference between the extracellular medium and the mitochondria. Diffusion gives a P50 proportional to the cellular respiratory rate, with a value of 0.15 torr for the respiratory rate of normal cells. The oxygen pressure difference between the cytoplasm and the mitochondria is probable only a few tens of millitorr.
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PMID:Contribution of diffusion to the oxygen dependence of energy metabolism in human neuroblastoma cells. 278 91

The toxicity of single and multiple fire gases is studied to determine whether the toxic effects of the combustion products from materials can be explained by the toxicological interactions (as indicated by lethality) of the primary fire gases or if minor, more obscure gases need to be considered. LC50 values for Fischer-344 rats have been calculated for the individual gases, carbon monoxide (CO), hydrogen cyanide (HCN), or decreased oxygen (O2), for 30-min exposures plus relevant postexposure periods using the NBS Toxicity Test Method. Combination experiments with CO and HCN indicate that they act in an additive manner. Synergistic effects have been found when the animals are exposed to certain combinations of CO and carbon dioxide (CO2). Five percent CO2 raised the threshold for deaths due to hypoxia and decreased the LC50 of HCN. Decreasing the O2 concentration in the presence of various mixtures of the other major fire gases increased the toxicity even further. A comparison of the concentrations of the major combustion products generated from a number of polymeric materials at their LC50 (30-min exposure plus 14-day postexposure) values with the combined pure gas results indicates that, in most cases, the observed toxicity may be explained by the toxicological interactions of the examined primary toxic fire gases. These results provide necessary information for the computer model currently being developed at the Center for Fire Research to predict the toxic hazard that people will experience under various fire scenarios.
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PMID:Effects of exposure to single or multiple combinations of the predominant toxic gases and low oxygen atmospheres produced in fires. 282 Aug 22

Tyrosine hydroxylase and tryptophan hydroxylase are widely held to be rate-limiting for the synthesis of the catecholamines and serotonin, respectively. Both enzymes are oxygen-requiring and kinetic properties suggest that oxygen availability may limit synthesis of these neurotransmitters in the brain. Using pheochromocytoma cells as a cell culture model for catecholamine synthesis, and neuroblastoma cells as a model for serotonin synthesis, enzyme activity was measured under control and hypoxic conditions. Both tyrosine hydroxylase and tryptophan hydroxylase activity increased substantially with chronic exposure but not with acute exposure. In the case of tyrosine hydroxylase, increased enzyme content with hypoxia accounts for increased activity. This suggests a mechanism for the maintenance of neurotransmitter synthesis with chronic hypoxia. Measurement of intracellular metabolites revealed no change in dopamine or norepinephrine in hypoxic pheochromocytoma cells, consistent with a simple adaptive mechanism. However, in neuroblastoma cells, hypoxia was associated with an increase in serotonin concentration. The reasons for this are still unclear.
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PMID:Adaptations of neurotransmitter synthesis to chronic hypoxia in cell culture. 288 82

6-Hydroxydopamine(6-OHDA), a specific neurotoxin against sympathetic nerve cells, is a drug already used for purging of bone marrow from neuroblastoma cells before autologous bone marrow transplantation. However, we could not detect significant differences in the toxicity of 6-OHDA against neuroblastoma and other tumor cells under the purging conditions clinically used. In contrast, bone marrow stem cells were much more resistant. The unspecific toxic effect of 6-OHDA is caused by H2O2 or H2O2-derived products which are generated by auto-oxidation in the incubation medium before a significant amount of 6-OHDA is taken up by the cells. Withdrawal of oxygen during the incubation period and subsequent incubation with an oxygen containing medium led to a more specific destruction of neuroblastoma cells which can take up 6-OHDA selectively.
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PMID:The role of reactive oxygen compounds derived from 6-hydroxydopamine for bone marrow purging from neuroblastoma cells. 299 60

The patterns of the cytolytic effects of 6-hydroxydopamine (6-OHDA), with/without ascorbate, on C-1300 and three other cloned mouse neuroblastoma cell lines (N1E-115, NS-20, N-18) were studied in vitro. The sensitivity to 6-OHDA differed and the three cloned cell lines were more sensitive than the wild type C-1300 cell line. Ascorbate synergistically potentiated the cytolytic effect of 6-OHDA to all four cell lines. The 6-OHDA cytotoxicity was eliminated by the addition of exogenous catalase but not by addition of other oxygen free radical scavengers, thereby suggesting that the hydrogen peroxide formed might influence the cells, extracellularly. In addition, the critical time for tumor cell lysis was the first 60 min of the reaction. The cytotoxicity induced by the unmasked cyclophosphamide, 4-hydroperoxycyclophosphamide, was synergistically enhanced in the presence of a nontoxic concentration of 6-OHDA and ascorbate. These data suggest that reactive oxygen intermediates may prove to be a good tool for destroying neuroblastoma cells.
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PMID:Patterns of destruction of mouse neuroblastoma cells by extracellular hydrogen peroxide formed by 6-hydroxydopamine and ascorbate. 308 96

A bioluminescent technique was used to show that murine neuroblastoma (NB) cells or cell-free extracts (H variant) were able to enhance the release of reactive oxygen intermediates (ROI) from peritoneal macrophages in vitro. L-variant NB cells were ineffective. Physiological concentrations of met-enkephalin produced the same effect in vitro but not leu-enkephalin. When both H- and L-variant cells, or their extracts, were incubated together with macrophages, ROI production was not increased. Similar findings were detectable when met- and leu-enkephalin were cultured together with macrophages. In vivo, preliminary studies gave the same results. The concentration rate of met- to leu-enkephalin was higher in H-variant than in L-variant NB cells. We conclude from our results that met-enkephalin can enhance the release of ROI from peritoneal macrophages. The difference in the effects produced by the H and L variants is due to differences in the concentrations of enkephalins released.
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PMID:Enhanced oxygen metabolism of peritoneal macrophages in the presence of murine neuroblastoma cells is partly caused by enkephalins. 317 Jul 21

The human CuZn superoxide dismutase (superoxide dismutase 1) a key enzyme in the metabolism of oxygen free-radicals, is encoded by a gene located on chromosome 21 in the region 21 q 22.1 known to be involved in Down's syndrome. A gene dosage effect for this enzyme has been reported in trisomy 21. To assess the biological consequences of superoxide dismutase 1 overproduction within cells, the human superoxide dismutase 1 gene and a human superoxide dismutase 1 cDNA were introduced into mouse L cells and NS20Y neuroblastoma cells. Both cell types expressed elevated levels (up to 3-fold) of enzymatically active human superoxide dismutase 1. These human superoxide dismutase 1 overproducers, especially neuronal cell lines, showed an increased activity in the selenodependent glutathione peroxidase. These data are consistent with the possibility that gene dosage of superoxide dismutase 1 contributes to oxygen metabolism modifications previously described in Down's syndrome.
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PMID:Expression of transfected human CuZn superoxide dismutase gene in mouse L cells and NS20Y neuroblastoma cells induces enhancement of glutathione peroxidase activity. 333 51


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