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)

Peptides with opioid activity are found in pepsin hydrolysates of wheat gluten and alpha-casein. The opioid activity of these peptides was demonstrated by use of the following bioassays: 1) naloxone-reversible inhibition of adenylate cyclase in homogenates of neuroblastoma X-glioma hybrid cells; 2) naloxone-reversible inhibition of electrically stimulated contractions of the mouse vas deferens; 3) displacement of [3H]dihydromorphine and [3H-Tyr, dAla2]met-enkephalin amide from rat brain membranes. Substances which stimulate adenylate cyclase and increase the contractions of the mouse vas deferens but do not bind to opiate receptors are also isolated from gluten hydrolysates. It is suggested that peptides derived from some food proteins may be of physiological importance.
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PMID:Opioid peptides derived from food proteins. The exorphins. 37 81

Protein-calorie malnutrition (PCM) is prevalent in cancer patients. However, the effect of PCM on anti-tumor immunity is unclear and critically important in an era of improving results with adoptive immunotherapy. This study examined the effect of short- and long-term PCM on tumor-specific and natural immune effector mechanisms in a murine neuroblastoma (C1300 NRB) model. A/J mice received an isocaloric 2.5% or 24% casein diet for 3 or 8 weeks before inoculation with tumor. Three weeks later lymphocytes from tumor-bearing mice were harvested for determination of cytotoxic T lymphocyte (CTL) generation and natural killer (NK) cell cytotoxicity. Both 3 and 8 weeks of PCM significantly reduced mean total body weight by 25% (p less than 0.001) and 41% (p less than 0.001), respectively, compared with regularly nourished mice. Short-term PCM did not inhibit CTL or NK cytotoxicity, whereas long-term PCM significantly diminished CTL generation (p less than 0.001) but preserved NK cytotoxic function. These results indicate that CTL development against autologous tumor, in contrast to basal NK function, is dependent on host nutritional status. Mean tumor growth, determined by tumor-weight to carcass-weight ratio, was unchanged for both short- and long-term protein-energy deprived groups compared with results in regularly nourished mice. These findings suggest that NK function is the predominant effector mechanism inhibiting C1300 NRB growth and that NK tumoricidal capacity is preserved during PCM.
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PMID:Comparison of acute and chronic protein-energy malnutrition on host antitumor immune mechanisms. 190 Nov 2

The efficacy of systemic interleukin-2 (IL-2) immunotherapy is dependent on a competent host immune response. This study demonstrated that protein-calorie malnutrition (PCM) inhibited the generation of an antitumor response to IL-2. A/J mice received an isocaloric diet of 2.5% or 24% casein 8 weeks before inoculation with C1300 neuroblastoma cells. Three weeks later lymphocytes from tumor-bearing mice were harvested for determination of cytotoxic T-lymphocyte generation and natural killer cell cytotoxicity. PCM produced a significant reduction in total body weight (p less than 0.001) and serum albumin concentration (p less than 0.001). PCM inhibited generation of cytotoxic T lymphocytes (p less than 0.001), T-lymphocyte response in mixed lymphocyte reaction (p less than 0.001), and in vitro activation of natural killer cell cytotoxicity with IL-2 (p less than 0.001). A second experiment was performed to evaluate whether the in vitro deficits in tumor-specific and natural immunity in the animal model of PCM would diminish the efficacy of systemic high-dose IL-2 (3 x 10(6) units/kg three times daily for 5 days). The mean percent inhibition of C1300 growth with IL-2 was only 15% in mice with PCM compared with 60% in well-nourished mice (p less than 0.01). Median host survival time was greater in well-nourished animals (55 days) compared with animals with PCM (39 days) that received IL-2 (p less than 0.05). These data suggest that nutritional status is a critically important variable in tumoricidal response to systemic IL-2.
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PMID:Protein-calorie malnutrition inhibits antitumor response to interleukin-2 immunotherapy. 214 20

The nuclear protein kinase NI (NI kinase) was purified from NB-15 mouse neuroblastoma cells by phosphocellulose column and casein affinity column chromatography. The purified NI kinase exhibited (i) an apparent subunit molecular weight of about 37,000, (ii) autophosphorylation, and (iii) insensitivity to inhibition by heparin. When NI kinase was added to heat-treated neuroblastoma nuclei in the presence of [gamma-32P] ATP, two proteins with apparent subunit molecular weights of 11,000 and 10,000 were prominently phosphorylated. Other protein kinases tested including the nuclear protein kinase NII, Type I cAMP-dependent protein kinase, and protein kinase C did not catalyze the phosphorylation of these two proteins. The NI kinase-catalyzed phosphorylation of these two proteins was completely inhibited by 1 mM spermine. In contrast, 10 mM putrescine, 2 mM spermidine, 5 mM arginine, and 10 mM NH4Cl, had no inhibitory effect on this phosphorylation reaction. Our study also indicated that the phosphorylation of the 11,000- and 10,000-dalton proteins occurred in the nuclear matrix fraction but not in heterogeneous nuclear ribonucleoproteins, high mobility group proteins, or histone fractions. We have previously reported that spermine specifically inhibits the endogenous phosphorylation of an 11,000-dalton nuclear protein in various mammalian cell lines (Chen, K. Y., and Verma, R. (1984) Biochem. Biophys. Res. Commun. 118, 710-716). The present study suggests that the 11,000- and 10,000-dalton nuclear proteins may be native substrates of nuclear protein kinase NI and that their phosphorylation can be affected by physiological concentrations of spermine.
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PMID:Spermine inhibits the phosphorylation of the 11,000- and 10,000-dalton nuclear proteins catalyzed by nuclear protein kinase NI in NB-15 mouse neuroblastoma cells. 394 52

Exorphins, peptides with opioid activity, have previously been isolated from pepsin hydrolysates of alpha-casein [Zioudrou, C., Streaty, R. A., & Klee, W. A. (1979) J. Biol. Chem. 254, 2446-2449]. Analysis of these peptides shows that they correspond to the sequences 90-96, Arg-Tyr-Leu-Gly-Tyr-Leu-Glu, and 90-95, Arg-Tyr-Leu-Gly-Tyr-Leu, of alpha-casein. These peptides, as well as two of their analogues Tyr-Leu-Gly-Tyr-Leu-Glu (91-96) and Tyr-Leu-Gly-Tyr-Leu (91-95), have now been synthesized and characterized. Their opioid activity was examined by three different bioassays: (a) displacement of D-2-alanyl[tyrosyl-3,5-3H]enkephalin-(5-L-methioninamide) and [3H]dihydromorphine from rat brain membranes; (b) naloxone-reversible inhibition of adenylate cyclase in homogenates of neuroblastoma x glioma hybrid cells; (c) naloxone-reversible inhibition of electrically stimulated contractions of the mouse vas deferens. The synthetic peptide of sequence 90-96 was the most potent opioid in all three bioassays and its potency was similar to that of the isolated alpha-casein exorphins. The synthetic peptides were totally resistant to hydrolysis by trypsin and homogenates of rat brain membranes, but were partially inactivated by chymotrypsin and subtilisin. The difference in opioid activity of alpha-casein exorphins may be related to differences in conformational flexibility observed by NMR spectroscopy.
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PMID:Opioid activities and structures of alpha-casein-derived exorphins. 631 43

To evaluate the relationship between tumor burden and circulating immune complexes (IC) in children with neuroblastoma (NBL), we studied sera collected at intervals from patients with disseminated (Stage III or IV) NBL. Sera from 10 of 12 patients contained IC by the Raji cell assay at some time during the first 9 to 11 months of the study. Higher IC levels were observed in sera of female patients. Fluid-phase C1q binding tests detected IC in only 16% of sera. IC measurements by either assay did not correlate with tumor burden. However, serum IC levels, as measured by the Raji cell assay, correlated significantly with serum antibody to bovine serum albumin (BSA) (rs = 0.54; p less than 0.001, rs = r as determined by Spearman rank correlation test). Measurement of anti-BSA antibodies in sera from the 12 patients, tested serially for circulating IC, and from five additional patients revealed that these had significantly higher anti-BSA activity than was found in sera from 13 age-matched controls. Sera from females also had relatively high levels of anti-BSA. Levels of antibody to bovine gamma-globulin and casein were not abnormal. Three sera with high IC levels (greater than 800 micrograms equivalents of heat-aggregated IgG) and relatively low anti-BSA activity appeared to contain "hidden" antibodies to BSA. These were demonstrated by measuring the increase in the ability of sera to bind 125I-BSA after they had been briefly acidified and then neutralized in the presence of the labeled BSA. The possible relevance of these results to the pathophysiology of NBL is discussed in light of earlier work that reported that serum IC levels correlate with the stage of the disease in NBL.
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PMID:Correlation of immune complexes in disseminated neuroblastoma with serum antibody to bovine serum albumin. 633 61

Although the brain contains cathepsins at high concentrations which exhibit a non-specific renin-like activity at acidic pH, the presence of specific renin in the brain has been demonstrated by characterizing its specific properties. Renin was separated from cathepsin by affinity chromatography on casein-Sepharose. Brain renin showed neutral pH optima for the reaction to generate angiotensin I. The presence of inactive prorenin was also found. The isoelectric points of brain renin were significantly lower differences from that of renal or plasma renin. Immunohistochemical studies demonstrated a wide-spread localization of renin in many different regions. Angiotensin II, the final product of the prohormone-to-hormone conversion reaction mediated by renin and angiotensin converting enzyme, was found to exist in the same cell as renin by immunohistochemical studies of brain sections and with cloned and cultured neuroblastoma cells. This is the first demonstration of the mechanism of peptide hormone formation in neuronal cells. Similar intracellular formation was demonstrated in gonadotrophs of adenohypophysis. Coexistence of renin and angiotensin II was demonstrated in some cells. Electrophysiological studies have shown that angiotensin II functions to disinhibit the inhibition of neuronal response to electrical stimuli in the hippocampus.
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PMID:Brain renin. 704 40

The in vitro phosphorylation of the microtubule-associated protein tau by casein kinase II was studied. Purified human brain tau was phosphorylated by casein kinase II to a stoichiometry of 0.7 mol of 32P/mol of tau. Individual recombinant human tau isoforms were phosphorylated to stoichiometries ranging from 0.2 to 0.8 mol of 32P/mol of tau. Casein kinase II catalyzed a 4-fold greater incorporation of phosphate into the tau isoform containing a 58-amino acid insert near its amino terminus (T4L) than the isoforms without the 58-amino acid insert (T3 and T4). Phosphopeptide mapping of casein kinase II phosphorylated human tau and recombinant tau isoforms suggested that the isoforms containing an amino-terminal insert constitute the major substrates for casein kinase II within the tau family. The sites of phosphorylation on T4L were identified by digesting phosphorylated T4L with the protease Asp-N, separating the peptides by reversed phase high performance liquid chromatography, and analyzing the isolated peptides by liquid-secondary ion mass spectrometry and solid-phase amino-terminal sequencing. Thr39 was identified as the predominant phosphorylation site, which is located 5 residues from the amino-terminal insert in T4L. Phosphopeptide mapping of tau isolated from LA-N-5 neuroblastoma cells indicates that Thr39 is phosphorylated in situ. To our knowledge, this is the first demonstration of a differential phosphorylation of the human tau isoforms, with the isoforms containing the acidic amino-terminal insert being the preferred substrates of casein kinase II.
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PMID:Casein kinase II preferentially phosphorylates human tau isoforms containing an amino-terminal insert. Identification of threonine 39 as the primary phosphate acceptor. 830 7

Casein kinase II is a multifunctional protein kinase which has been implicated in the regulation of cell growth and differentiation. This enzyme is much more abundant in neurons than in any other cell type. The treatment of neuroblastoma cells with an antisense oligodeoxyribonucleotide which specifically results in the depletion of casein kinase II catalytic subunits blocks neuritogenesis. Accordingly, this enzyme may perform an essential role during neurite growth in developing neurons. Casein kinase II depletion induced by antisense oligodeoxyribonucleotide is accompanied by a site-specific dephosphorylation of microtubule-associated protein MAP1B (also referred to as MAP5, MAP1.X or MAP1.2), which is paralleled by a release of MAP1B from microtubules. We therefore propose that phosphorylation by casein kinase II may be required for the proper MAP1B functioning in the promotion of the assembly of microtubules which constitute the cytoskeletal scaffolding of growing axon-like neurites.
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PMID:Depletion of casein kinase II by antisense oligonucleotide prevents neuritogenesis in neuroblastoma cells. 846 10

A mutant of Bacillus subtilis IMR-NK1, which is used for the production of domestic "natto" in Taiwan, produced high fibrinolytic enzyme activity by solid-state fermentation using wheat bran as medium. In addition, a strong fibrinolytic enzyme was purified from the cultivation media. The purified enzyme was almost homogeneous, as examined by SDS-PAGE and capillary electrophoresis. The enzyme had an optimal pH of 7.8, an optimal temperature of 55 degrees C, and a K(m) of 0.15% for fibrin hydrolysis. The molecular mass estimated by gel filtration was 31.5 kDa, and the isoelectric point estimated by isoelectric focusing electrophoresis was 8.3. The enzyme also showed activity for hydrolysis of fibrinogen, casein, and several synthetic substrates. Among the synthetic substrates, the most sensitive substrate was N-succinyl-Ala-Ala-Pro-Phe-pNA. PMSF and NBS almost completely inhibited the activity of the enzyme. These results indicate that the enzyme is a subtilisin-like serine protease, similar to nattokinase from Bacillus natto.
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PMID:Potent fibrinolytic enzyme from a mutant of Bacillus subtilis IMR-NK1. 1095 93


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