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)

In an investigation of the role of trace elements in gallstone formation and of minor and trace elements in gallstone and bile, samples from five patients were analysed using three different techniques for cross-verification: NAA, PIXE, and XRF. In addition, certified standards of bovine liver and oyster tissue from the NBS, Washington, were re-analysed using the different techniques to confirm the accuracy of the experimental procedures. NAA of five gallstones was used for the quantitative analysis of 19 elements with Z greater than 11. The concentrations of Cl, K + Ca, Mn, Fe and Cu + Zn were determined by PIXE and those of Mg, P, S, K and Ca by XRF. In most cases the concentrations were in the range of a few PPB to a few hundred PPM. The spatial distribution of the component elements was obtained using XRF with a scanning electron microscope and the results demonstrated that calcium was present centrally in all the stones. The analysis of gallbladder bile from four patients showed that the calcium concentration was much greater than normal, indicating that calcium and other elements play an important role in stone formation. Infrared spectroscopy showed that the calcium salts were present in gallstones in three compound forms: calcium carbonate, calcium phosphate and calcium bilirubinate. Reasons for the cause of calcium precipitation are discussed.
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PMID:Analysis of minor and trace elements in gallstones by induction of characteristic ionising radiation. 670 Nov 97

The N-CAMs are a group of surface glycoproteins involved in adhesive interactions of neurones. Related molecules of the mouse nervous system, identified in our laboratory, have been called BSP-2 and shown to act as ligands in adhesion of neuroblastoma cells. Results presented in this report show that they are immunochemically identical with N-CAM. A monoclonal anti-(N-CAM) antibody, that recognized a determinant accessible only after permeabilization of intact cells, was used to define the mode of association of the N-CAMs with the plasma membrane. This antibody bound a 35 000-Mr fragment in lysates of trypsin-treated neuroblastoma cells. It is concluded that the antibody reacts with a transmembrane or cytoplasmic domain of the molecules. The same antibody recognized the Mr-180 000 and Mr-140 000 proteins but not the Mr-120 000 chain, which co-purify from adult mouse brain. The latter polypeptide was detected in the cytosol and could be partially released from brain membranes by osmotic shock. Part or all of the Mr-120 000 protein may thus lack a transmembrane segment. Our conclusion that the N-CAM forms of higher Mr are transmembrane proteins was further corroborated by our finding that they contain phosphoserine residues, which can be labeled with (32P)phosphate in intact neuroblastoma cells.
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PMID:Studies on the transmembrane disposition of the neural cell adhesion molecule N-CAM. A monoclonal antibody recognizing a cytoplasmic domain and evidence for the presence of phosphoserine residues. 674 67

A simple and rapid method is described for the determination of lead in foods. The samples are digested in HNO3, HF, and HClO4 and then the lead is determined by atomic absorption spectrophotometry using an electrothermal atomizer with the L'vov platform. Interferences and ways to improve the precision and accuracy of the analysis were studied. Matrix modification using 1% ammonium phosphate alleviated most interferences encountered. The precision and accuracy of the method was evaluated using NBS SRM 1570 Spinach and SRM 1566 Oyster Tissue. The values obtained are in good agreement with the certified values.
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PMID:Innovations in atomic absorption spectrophotometry with electrothermal atomization for determining lead in foods. 711 9

Frequent antihistaminic side effects noted during treatment of depression by tricyclic drugs, as well as the high affinity of tricyclic antidepressants for H1 receptors in mouse neuroblastoma cells, suggest possible useful antihistaminic properties. We investigated the antipruritic activity of topically applied 5% solutions of doxepin hydrochloride (Adapin; Sinequan) and amitriptyline hydrochloride (Elavil) and compared such activity to that of a 5% solution of diphenhydramine and vehicle alone. Test solutions were applied to 25-cm2 areas on the flexor forearms of forty subjects, and the development of itch to single drops of eight dilutions of histamine phosphate instilled in each area was reported over a 3-minute period. The lowest concentration of histamine able to elicit unequivocal itching in each treated area was the histamine itch threshold (HIT). Doxepin, amitriptyline, and diphenhydramine all produced significantly higher mean and median HITs (p less than 0.01 than did vehicle control. Sixty-eight percent of subjects had a HIT greater than or equal to 2 x 10(-4) mg/ml in doxepin-treated areas versus 58% for amitriptyline, 53% for diphenhydramine, and 25% for vehicle. Our data suggest that tricyclic antidepressants are effective topical antipruritic agents.
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PMID:Inhibition of histamine-induced pruritus by topical tricyclic antidepressants. 729 24

Diisopropylfluorophosphate has been reported to cause an early inhibition of proteosynthesis in the spinal ganglia of cats. If organophosphorus compounds can cause a partial blockage of protein synthesis, normal turnover of neuronal proteins could establish conditions similar to those which ocur in Wallerian degeneration. In this study neuroblastoma 2-A cells, a homogenous cell system which exhibits many of the functional properties of normal neurons, was used to establish dose-response relationships of three organophosphorus compounds: Tri-o-tolyl-phosphate (TOTP), Diisopropylfluorophosphate (DFP) and dicrotophos. The incorporation of 14C from glucose was used as an indicator of metabolic activity and the incorporation of L-leu-cine-14C as an indicator of proteosynthetic activity. The rates of incorporation of labeled precursors as effected by three dose levels of each organophosphorus compound were measured in logarithmically growing cells and in cells in a stationary growth phase in media without serum. The cells were also observed under phase-contrast microscopy. The organophosphorus compounds caused the neurites to have a shrunken, rough and irregular appearance. Swelling along the length of the neurites were also observed, especially with the DFP-treated cells. All three compounds caused a dose-related reduction in the accumulation of 14C activity from glucose which was probably a measure of cytotoxicity. DFP and TOTP caused an inhibition of the uptake of leucine-14C while dicrotophos did not. The results suggest that neurotoxic organophosphate compounds depress the rate of protein synthesis which may be responsible for the degenerative syndrome.
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PMID:Organophosphate cytotoxicity: the effects on protein metabolism in cultured neuroblastoma cells. 744 Oct 94

Cross-regulation from the stimulatory phospholipase C to the adenylyl cyclase pathways was explored in neuroblastoma-glioma NG-108-15 cells in culture. Activation of protein kinase C by phorbol myristic acid resulted in a markedly attenuated activation of the inhibitory adenylyl cyclase response to delta-opiate agonists and epinephrine but not to the muscarinic agonist carbachol. The ability of okadaic acid to mimic the effects of phorbol myristic acid on the inhibitory response suggested a role for protein phosphorylation. Adenylyl cyclase activity from cells in which protein kinase C had been activated demonstrated a loss in the inhibitory adenylyl cyclase response at the level of the G-protein. Activation of protein kinase C prompted a 2-4-fold increase in phosphorylation of G1 alpha 2 in cells metabolically labeled with [32P]orthophosphate. The phosphate content of Gi alpha 2 was determined to be approximately 0.5 mol/mol subunit in the unstimulated cells and approximately 1.5 mol/mol subunit for cells in which protein kinase C was activated. The effects of okadaic acid, 4-alpha-phorbol, and calphostin C on inhibition of adenylyl cyclase in cells treated with phorbol myristic acid correlate with the effects of these agents on phosphorylation of Gi alpha 2. The time courses for attenuation of inhibitory adenylyl cyclase and that for phosphorylation of Gi alpha 2 were similar in cells challenged with phorbol myristic acid. These data argue for cross-regulation from the stimulatory protein kinase C to inhibitory adenylyl cyclase pathways at the level of Gi alpha 2 via protein phosphorylation.
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PMID:Phosphorylation of Gi alpha 2 attenuates inhibitory adenylyl cyclase in neuroblastoma/glioma hybrid (NG-108-15) cells. 751 3

The novel, synthetic, adenophostin A analogue 2-hydroxyethyl-alpha-D-glucopyranoside-2,3',4'-trisphosphate [Glu(2,3',4')P3] was synthesized to probe the structure-activity relationship at the D-myo-inositol-1,4,5-trisphosphate [Ins(1,4,5)P3] receptor [Ins(1,4,5)P3R]. This study was stimulated by the recent observation that the fungal isolates adenophostins A and B were very potent, metabolically resistant, Ins(1,4,5)P3R agonists [J. Biol. Chem. 269:369-372 (1994)]. Gluc(2,3',4')P3 can be visualized as a truncated version of adenophostin A, in which the 2'- and 3'-carbons of the ribose ring, with their terminal phosphate groups, are retained and the remainder of the adenosine residue is excised. Gluc(2,3',4')P3 specifically displaced [3H]Ins(1,4,5)P3 from pig cerebellar Ins(1,4,5)P3 binding sites, with an affinity (IC50 = 130 nM) only 5-fold weaker than that of Ins(1,4,5)P3 (IC50 = 27 nM). Gluc(2,3',4')P3 was also a full agonist for Ca2+ release, being only 10-12-fold less potent than Ins(1,4,5)P3 in saponin-permeabilized SH-SY5Y neuroblastoma cells [EC50 = 647 nM; Ins(1,4,5)P3 EC50 = 52 nM] and Madin-Darby canine kidney cells [EC50 = 2484 nM; Ins(1,4,5)P3 EC50 = 247 nM]. Gluc(2,3',4')P3 did not significantly interact with recombinant Ins(1,4,5)P3 3-kinase and 5-phosphatase enzymes and was also poorly metabolized by saponin-permeabilized SH-SY5Y cells. However, Gluc(2,3',4')P3 was a considerably weaker ligand (approximately 500-fold) and agonist (approximately 1000-fold) than adenophostin A, suggesting that the partial excision of the adenosine residue compromised structural motifs that have favorable interactions with the Ins(1,4,5)P3R. Indeed, molecular dynamics simulations revealed that the potencies of the three compounds show a correlation with the relative distance of the two vicinal ring phosphates from the remaining phosphate. Gluc(2,3',4')P3, with its alpha-glucoside ring, is the first synthetic Ins(1,4,5)P3 analogue that is not structurally based on a phosphorylated inositol isomer and that exhibits potent activity at the Ins(1,4,5)P3R. This, combined with the metabolic resistance of Gluc(2,3',4')P3, thus affords a novel approach for the investigation of the cellular role of Ins(1,4,5)P3 and its receptor.
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PMID:2-Hydroxyethyl-alpha-D-glucopyranoside-2,3',4'-trisphosphate, a novel, metabolically resistant, adenophostin A and myo-inositol-1,4,5-trisphosphate analogue, potently interacts with the myo-inositol-1,4,5-trisphosphate receptor. 760 61

In this study, the in situ phosphorylation and subsequent calcium-activated proteolysis of tau protein were examined in human neuroblastoma (LA-N-5) cells, which were differentiated into a neuronal phenotype. The phosphorylation of tau was increased by treating the cells with forskolin and rolipram, which elevate cyclic AMP levels, by treating with the phosphatase inhibitor okadaic acid, or by treating with a combination of both treatments. Phosphorylated tau migrated slightly slower on sodium dodecyl sulfate-polyacrylamide gels than tau from untreated cells. Immunostaining with the phosphate-sensitive monoclonal antibody Tau-1 was also decreased in cells treated with okadaic acid, indicating an increase in the phosphorylation of specific Ser-Pro motifs within the molecule. Calcium-dependent, in situ proteolysis of tau protein was induced by treating the cells with the calcium ionophore A23187. Tau protein was proteolyzed to a significantly lesser extent in cells treated with forskolin and rolipram, okadaic acid, or both than in cells in which phosphorylation was not increased. Partially purified tau protein from cells treated with a combination of forskolin, rolipram, and okadaic acid was also more resistant to proteolysis by calpain in vitro compared with tau isolated from control cells. These data suggest a possible role for phosphorylation in the regulation of tau metabolism and in pathological conditions in which the balance between protein kinases and phosphatases is disrupted.
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PMID:Phosphorylation of tau in situ: inhibition of calcium-dependent proteolysis. 761 52

The monoclonal antibodies SMI-31 and SMI-34 react with phosphate-dependent epitopes of the high molecular mass (200 kDa) neurofilament protein (Hphos). Determination of whether or not these monoclonals react with different epitopes would assist in interpretation of post mortem immunocytochemical analyses in neurodegenerative disorders and in normal aging. We therefore examined the relative immunoreactivity of these antibodies against Triton-insoluble (cytoskeleton-associated) and Triton-soluble Hphos variants in NB2a/d1 neuroblastoma and post-natal mouse brain in immunoblot analysis. Densitometric analysis yielded a 'reactivity ratio' (soluble Hphos/insoluble Hphos) for each antibody. This ratio was approximately 44% and 87% less for SMI-34 than for SMI-31 in neuroblastoma and brain, respectively. These findings confirm that the SMI-34 epitope is distinct from that recognized by SMI-31, and, in these systems, is preferentially associated with the cytoskeleton.
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PMID:Evidence that the monoclonal antibodies SMI-31 and SMI-34 recognize different phosphorylation-dependent epitopes of the murine high molecular mass neurofilament subunit. 768 97

Protein phosphorylation and subsequent dephosphorylation was studied in digitonin-permeabilized neuroblastoma SH-SY5Y cells by measuring the incorporation of [32P]phosphate into myelin basic protein (MBP). 1,2-Dioctanoyl-sn-glycerol (DOG) and calcium synergistically induced phosphorylation of MBP, which was inhibited by the protein kinase C (PKC) pseudosubstrate peptide (PKC19-36). The phosphorylation increased for 10 min when a net dephosphorylation started to appear. The dephosphorylation was inhibited by okadaic acid. Regardless of calcium concentration, the presence of DOG was necessary for significant effects of okadaic acid on MBP phosphorylation. H7 and staurosporine dose-dependently inhibited the phosphorylation of MBP, induced by DOG and calcium in the presence of okadaic acid. Different PKC pseudosubstrate peptides were applied and all showed an inhibitory effect on the phosphorylation of MBP under these conditions. These results demonstrate the presence, in SH-SY5Y cells, of a protein phosphatase, possibly protein phosphatase 2A, with a high basal activity that counteracts PKC-induced phosphorylation.
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PMID:An okadaic acid-sensitive protein phosphatase counteracts protein kinase C-induced phosphorylation in SH-SY5Y cells. 768 46


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