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)

Previous studies indicating the importance of catecholamine metabolism in neuroblastoma were briefly reviewed. Metabolic pathways were presented showing how the major urinary metabolites 3-methoxy-4-hydroxymandelic acid (VMA) and 3-methoxy-4-hydroxy-phenylacetic acid (HVA) are formed from norepinephrine and from dopamine plus 3,4-dihydroxyphenylalanine (DOPA), respectively. For 289 neuroblastoma patients at the time of diagnosis, the urinary excretion of VMA was significantly elevated in 75%, and HVA was elevated in 80%. Periodic assay of these metabolites during the course of the disease revealed that the excretion trends were of prognostic value with 80-90% reliability. By contrast, when the excretion in only the initial urine specimens was considered, the survival rate was the same for patients with normal, and with significantly elevated, excretion. Review of the results of tracer studies aimed at elucidating the in vivo metabolic origins of the urinary metabolites suggested that a) in neuroblastoma, the catecholamines were largely inactivated by intracellular metabolism in the tumor cells; b) there was excess production and excretion of the norepinephrine precursors, DOPA and dopamine; and c) in the tumors of most neuroblastoma patients, the initial enzyme in catecholamine synthesis, tyrosine hydroxylase, had an activity comparable with that in normal adrenal glands. The importance of the metabolism of catecholamines in patients with neuroblastoma was stressed: a) The excretion of elevated levels of urinary catecholamine metabolites were useful in diagnosis and in following the course of the disease, and b) study of the catecholamine metabolism in these patients permitted examination of possible relationships between the activity of the enzymes involved in catecholamine synthesis and the malignancy of this tumor.
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PMID:Catecholamine metabolism in neuroblastoma. 1 Apr 50

Serum samples from eleven children with neuroblastoma were drawn at diagnosis and again every 15 days or a month after the beginning of treatment over the course of 17 months observation. Twenty healthy children of the same age with no appreciable clinical manifestation were also studied as controls. Investigations included quantitative serum complement levels (total complement hemolytic activity, C3 and C4), anticomplementary serum activity and urine catecholamine levels (VMA and HVA). Complement levels of tumor patients were significantly higher than those of healthy subjects, but fluctuations were seen at different stages of the disease; patients at admission with active tumors or tumor recurrence had higher complement levels than those of patients in remission. Temporary recurrences of the disease were usually accompanied by fluctuations of urinary catecholamines, serum complement levels (mainly C3) and anticomplementary serum activity. At the terminal phase of the disease a drop in complement levels was usually seen, while urinary catecholamines were progressively increasing.
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PMID:Fluctuation of serum complement levels in children with neuroblastoma. 45 27

We describe the determination of the 4-O-methylated catecholamine metabolites 4-methoxy-3-hydroxyphenylacetic acid (iso-HVA), 4-methoxy-3-hydroxyphenylmandelic acid (iso-VMA) and 4-methoxy-3-hydroxyphenylethylene glycol (iso-MOPEG) in urine with use of mass fragmentography and deuterated internal standards. Normal values, expressed in terms of creatinine, are given as a function of age. Urinary excretion values during neuroblastoma, pheochromocytoma, and parkinsonism treated with L-DOPA, and during the intravenous administration of dopamine are discussed. For normal persons, the mean percentages (+/- SD) of 4-O-methylated metabolites relative to their 3-O-methylated analogs were 6.29 +/- 2.79% (iso-HVA/HVA), 0.70 +/- 0.57% (iso-VMA/VMA), and 0.77 +/- 0.53% (iso-MOPEG/MOPEG). We observed no significant changes in these parameters for the patients studied and conclude that the determination of 4-O-methylated catecholamine metabolites for these patients does not add information to the results obtained from their quantitatively more important 3-O-methylated analogs.
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PMID:Determination of 4-O-methylated catecholamine metabolites in urine by mass fragmentography. 47 19

We describe the determination of 3-methoxy-4-hydroxy-phenylacetic acid, 3-methoxy-4-hydroxyphenylamandelic acid, and 3-methoxy-4-hydroxyphenylethylene glycol in amniotic fluid by means of mass fragmentography, with use of deuterated internal standards. The results expressed in terms of absolute concentration and creatinine concentration, are given as a function of gestational age. In the 15th to 17th week, concentrations in amniotic fluid are a reflection of those in the mother's serum, whereas in the 32nd to 40th week, these concentrations, expressed in terms of creatinine, are similar to those found in the urine of newborns. We discuss the possible usefulness of the determination of catecholamine metabolites in amniotic fluid in the diagnosis of congenital neuroblastoma, maternal pheochromocytoma, and underdevelopment.
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PMID:Mass-fragmentographic determination of catecholamine metabolites in amniotic fluid and its possible clinical usefulness. 70 17

Homovanillic acid is an important metabolite of dopamine, and a high proportion of patients with neuroblastoma excrete increased amounts of it in their urine. When this diagnosis is suspected, both homovanillic acid and vanilmandelic acid should be measured, because such a combined measurement reportedly leads to detection of 95% of cases. Although rapid and reliable chemical methods are available for vanilmandelic acid, the same is not true for homovanillic acid. We report here a colorimetric method for homovanillic acid that reasonably fills this void and that can be used in most clinical laboratories. In addition, we present normal values determined for children of various age groups.
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PMID:Improved colorimetry of urinary 3-methoxy-4-hydroxyphenylacetic acid (homovanillic acid). 91 65

High-speed liquid chromatographic determinations of vanilmandelic acid and homovanillic acid in human urine have been made. The effects of taking refreshments on the assay were examined. HVA conjugates in urine also were hydrolyzed and determined. Urinary excretion of vanilmandelic acid, free and conjugated homovanillic acid in normal subjects and patients with neuroblastoma, phaeochromosytoma and Sipple's syndrome were determined and discussed. Urinary excretion values (mean +/- 1 S.D.) of vanilmandelic acid and homovanillic acid in 14 normal subjects were 2.0 +/- 0.7 mg/day and 4.0 +/- 1.0 mg/day, respectively.
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PMID:Urinary levels of vanilmandelic acid and homovanillic acid determined by high-speed liquid chromatography. 100 Aug 51

By means of thin-layer chromatographic methods, iso-homovanillic acid (iso-HVA), iso-vanillactic acid (iso-VLA) and iso-vanilmandelic acid (iso-VMA) were determined in the urine of 10 children with neuroblastoma. The mean excretion of iso-HVA was 10.1% of total HVA excretion. Three patients excreted VLA; in their urine no iso-VLA was detected with certainty. All patients excreted high amounts of VMA; there was no detectable excretion of iso-VMA. Those results suggest that para-O-methylation could be limited to dopamine catabolism.
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PMID:Para-O-methylation of the catecholamines in neuroblastoma. 112 41

Quantitation of the urinary metabolites of catecholamines, including VMA, HVA, and metanephrines, from six normal preschool children was performed during a normal diet, a restricted diet, and a diet with increased amounts of vanilla, vanillin, and phenolic acids. Ingestion of these substances has been suspected of producing elevated values of urinary catecholamines and their metabolites. Urine was collected on the fourth day of each diet in two consecutive 12-hour aliquots, beginning at 8:00 AM. Statistically significant diurnal variation in excretion of all three metabolites and total free catecholamines (epinephrine, norepinephrine, and dopamine) was demonstrated. Diet did not alter exceretion of total free catecholamines or any of the three metabolites. This study suggests that a three-day restricted diet is not necessary prior to screening children for neuroblastoma when using quantitative assay methods and that all screening tests should be performed on a 24-hour urine sample.
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PMID:Effect of diet on urinary excretion of VMA, HVA, metanephrine, and total free catecholamine in normal preschool children. 124 41

The properties of low (LVA) and high (HVA) voltage-activated calcium currents were investigated in rat sensory neurons and a murine neuroblastoma cell line exposed to various concentrations of intra- or extracellular monovalent ([c+]i/o) and trivalent ([c3+]i/o) cations. In neurons, when [c+]i was changed from 150 to 20 mM, positive shifts of 18-28 mV were observed in activation curves of both LVA and HVA currents, as well as in LVA inactivation curves. Extracellularly, in divalent-free solutions, [c+]o of 20-50 mM produced medium (12-22 mV) negative shifts of the LVA channel properties. These data were used to estimate, by a "screening" model, a negative surface charge density around neuron's calcium channels of 1/1,000 and 1/1,325 eA-2 at the outside or inside face, respectively. In the presence of physiological concentrations of divalent cations, [c+]o of 20-60 mM caused smaller (4-11 mV) negative shifts of the activation and inactivation curves, which can be explained by assuming a partial neutralization of negative charges by divalent cations. By applying the above procedure to LVA channels of neuroblastoma cells, the ratio of extra- to intracellular surface charge density turned out to be more than tenfold higher than in neurons. Effects produced by [c3+]i/o were not in agreement with expectations based on screening or binding models.
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PMID:Intra and extracellular surface charges near Ca2+ channels in neurons and neuroblastoma cells. 133 41

High-threshold (HVA) Ca2+ channels of human neuroblastoma IMR32 cells were effectively inhibited by noradrenaline. At potentials between -20 mV and +10 mV, micromolar concentrations of noradrenaline induced a 50%-70% depression of HVA Ba2+ currents and a prolongation of their activation kinetics. Both effects were relieved at more positive voltages or by applying strong conditioning pre-pulses (facilitation). Facilitation restored the rapid activation of HVA channels and recruited about 80% of the noradrenaline-inhibited channels at rest. Re-inhibition of Ca2+ channels after facilitation was slow (tau r 36-45 ms) and voltage-independent between -30 mV and -90 mV. The inhibitory action of noradrenaline was dose-dependent (IC50 = 84 nM), mediated by alpha 2-adrenergic receptors and selective for omega-conotoxin-sensitive Ca2+ channels, which represent the majority of HVA channels expressed by IMR32 cells. The action of noradrenaline was mimicked by intracellular applications of GTP[gamma S] and prevented by GDP[beta S] or by pre-incubation with pertussis toxin. The time course of noradrenaline inhibition measured during fast application (onset) and wash-out (offset) of the drug were independent of saturating agonist concentrations (10-50 microM) and developed with mean time constants of 0.56 s (tau on) and 3.6 s (tau off) respectively. The data could be simulated by a kinetic model in which a G protein is assumed to modify directly the voltage-dependent gating of Ca2+ channels. Noradrenaline-modified channels are mostly inhibited at rest and can be recruited in a steep voltage-dependent manner with increasing voltages.
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PMID:Voltage-dependent noradrenergic modulation of omega-conotoxin-sensitive Ca2+ channels in human neuroblastoma IMR32 cells. 133 78


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