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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three infants with congenital neuroblastoma received a primary series of diptheria-pertassis-tetanus (DPT) immunizations during and after courses of chemotherapy with immunosuppressive medications. Serum IgG, IgA and IgM levels and antidiphthria and antitetanus antibody responses were measured and compared with those of normal infants of similar age. Protective levels of antibody were achieved by the study patients as well as by the control group. These results support the view that children with malignancies who are receiving chemotherapy should not be denied immunization with inactivated vaccines.
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PMID:Antibody responses in normal infants and in infants receiving chemotherapy for congenital neuroblastoma. 19 94

The primary interaction of tetanus toxin and toxoid with mouse neuroblastoma cells (C 1300, clone NB2A) in tissue culture was studied using direct immunofluorescence. Experiments were done in standard routine cultures and also those influenced by chemical modulators. There is a difference in the characteristic binding response between the growth culture cells (grown in presence of fetal calf serum) and differentiating culture cells (grown in absence of serum). Exposure to the toxin gives no visible effect on the cell division or viability in growth cultures; whereas in differentiating cells the processes are shortened and the adherence to the glass is diminished without involving significant cell death. The toxoid did not bind at all under the same experimental conditions. Since there was no biological effect in growth cultures we have called this binding ineffective, and in the case of the differentiating cells, effective binding. Stimulation of pinocytosis increases the uptake of toxin in both cultures. Presence of some surface bound toxin still remaining on the differentiating cells indicates the possibility of another sort of mechanism for internalization. Pre-treatment of the cells with neuraminidase or beta-galactosidase to alter the membrane gangliosides eliminates binding in growth cultures but not in differentiating cultures. From these results we suggest that even though the toxin may well bind to gangliosides, at least in the differentiating cultures they are not solely responsible for the fixation. The morphologically observed effective binding is probably that not related to gangliosides.
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PMID:Interaction of tetanus toxin and toxoid with cultured neuroblastoma cells. Analysis by immunofluorescence. 32 Apr 89

Possible effects of tetanus toxin (TeTox) on voltage-activated Ca2+ channels of the mouse neuroblastoma cell line N1E-115 and of the neuroblastoma x glioma hybrid cell line NG108-15 have been investigated using the whole-cell voltage clamp technique. Similar to N1E-115 cells, differentiated NG108-15 cells express transient (T-type) as well as long-lasting (L-type) Ca2+ channels. Using various treatment protocols N1E-115 and NG108-15 cells were exposed to TeTox externally and by internal dialysis. In the cells treated with TeTox normal Ca2+ channel activity was present, as measured by the voltage-activated Ba2+ currents under voltage clamp conditions. In addition, intracellular microelectrode recordings showed that TeTox did not block the Ca2+ action potential in N1E-115 cells. It is concluded that TeTox, in contrast to previously reported results, does not affect voltage-activated T- and L-type Ca2+ channels in cultured neuronal cell lines. The results also indicate that Ca2+ channel block is unlikely to be an explanation for the block of neurotransmitter release by TeTox in vivo.
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PMID:L- and T-type calcium channels in cultured neuronal cell lines are insensitive to tetanus toxin. 166 81

There is considerable literature on the pathogenesis of tetanus toxin poisoning; however, the mechanism of action and intracellular substrate of this toxin have not been defined. It was demonstrated that the NG-108 neuroblastoma x glioma cell line is a suitable model in which to study the mechanism of tetanus toxin action, from binding of the toxin to inhibition of transmitter release. Further, it has been shown that tetanus toxin pretreatment attenuates the ability of phorbol myristate acetate to mobilize cytosolic protein kinase C (PKC) in this cell line. In the present study a 4-hr tetanus toxin pretreatment (10(-10)-10(-13) M) completely inhibited the mobilization of cytosolic PKC induced by a 30-min exposure to 10 microM neurotensin. Pretreatment with 10(-10) M tetanus toxin for periods as short as 1 hr was sufficient to attenuate the ability of neurotensin to mobilize cytosolic PKC; however, a 30-min pretreatment had no significant effect. At a concentration of 10(-11) M, it was necessary to pretreat the cells for greater than 1 hr to significantly attenuate neurotensin-mobilized PKC activity. The exact role that PKC plays in the secretory process is not yet known; however, these findings suggest that the effect of tetanus toxin on neurotransmitter release is accompanied by an alteration in PKC metabolism in differentiated NG-108 cells.
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PMID:Tetanus toxin inhibits neurotensin-induced mobilization of cytosolic protein kinase C activity in NG-108 cells. 181 11

Although the pathology of tetanus toxin poisoning has been linked to an inhibition of neurotransmitter release, the mechanism of this inhibition is unknown. The neuroblastoma x glioma hybrid cell NG-108 is an emerging model in which to study the biochemical effect of tetanus toxin on acetylcholine secretion. In differentiated as well as undifferentiated NG-108 cells, a 4 hr tetanus toxin (10(-8) M) pretreatment had no effect on basal levels of cyclic AMP or cyclic GMP. In addition, toxin pretreatment did not affect agonist induced increases in either cyclic nucleotide. Treatment of NG-108 cells for 4 hr with 10(-10) M tetanus toxin had no effect on the subsequently measured activity of cytosolic protein kinase C. However, a 4 hr pretreatment of undifferentiated or differentiated cells with tetanus toxin (10(-8) or 10(-10) M respectively) significantly attenuated the ability of phorbol myristate acetate to mobilize cytosolic protein kinase C. Direct addition of tetanus toxin (10(-7)-10(-10) M) to isolated protein kinase C did not alter the ability of the enzyme to phosphorylate histone protein. These results suggest that one manifestation of tetanus toxin poisoning may be a disruption in protein kinase C metabolism.
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PMID:Tetanus toxin attenuates the ability of phorbol myristate acetate to mobilize cytosolic protein kinase C in NG-108 cells. 215 77

Experiments have been conducted that deal with the structure and biological activity of clostridial toxins. Studies have dealt mainly with botulinum neurotoxin, but work has also been done with tetanus toxin and with the binary toxin. Structural studies indicate that proteolytic processing of botulinum neurotoxin induces two major outcomes: activation and aging. The first is associated with a marked increase in toxicity and with conversion from a single chain to a dichain structure. The second is associated with nominal changes in toxicity and with molecular rearrangements in the dichain structure. Immunological studies have resulted in isolation and characterization of a monoclonal antibody that neutralizes tetanus toxin. Monoclonal antibodies have also been raised against botulinum neurotoxin, and these antibodies have been used to demonstrate that: i) activation is not due to marked conformational changes in the relevant epitopes, ii) binding of the toxin to cholinergic nerve endings does not produce detectable conformational changes, and iii) all functional domains of the toxin appear to be internalized simultaneously. Immunological studies done in vivo and in vitro suggest that certain antibodies may enter cholinergic nerves and neutralize subsequently internalized toxin. Additional work on clostridial toxins has produced the following results: i) the ligand binding assay typically used with tetanus toxin (i.e., low pH and ionic strength) is of questionable biological significance, ii) the binary toxin, like the clostridial neurotoxins, enters cells by receptor-mediated endocytosis, and iii) tetanus toxin can alter the disposition of protein kinase C in one neuroblastoma cell line.
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PMID:The study of clostridial and related toxins. The search for unique mechanisms and common denominators. 229 Jan 29

A one-step direct monoclonal antibody rosetting technique is described for removal of neuroblastoma cells from bone marrow. Two monoclonal antibodies (MoAbs) (BW 575, BW 625) were directly coupled to ox red blood cells by use of CrCl3. The IgG1 antibody BW 575 detects a 95-kD neuroblastoma cell-associated glycoprotein and the IgG3 antibody BW 625 recognizes the ganglioside GD 2. After coupling MoAbs to the erythrocytes, specific strong and stable rosettes were formed with neuroblastoma cells and effectively separated from mononuclear cells using density gradient centrifugation. A total of 1.5% IMR5 neuroblastoma cells were reliably removed from mononuclear cells beyond the limit of detection (less than 0.01%) as judged by tetanus toxin labeling. No impairment of stem cell growth (CFU-GM, BFU-E, CFU-GEMM, CFU-M) was observed. Recovery rate of mononuclear cells ranged between 35 and 69%. A red blood cell/nucleated cell ratio more than 50:1 resulted in increased loss of mononuclear cells and a ratio less than 30:1 in incomplete neuroblastoma cell removal. Using indirect rosettes the purging efficacy was lower and the mononuclear cell loss higher. We conclude that the direct monoclonal antibody rosetting technique may be a technically simple and effective alternative purging method for neuroblastoma patients, which is applicable even in cases demonstrating weak expression of one antigen.
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PMID:Removal of neuroblastoma cells from bone marrow by a direct monoclonal antibody rosetting technique. 265 12

Indirect immunofluorescence studies were compared with conventional smear cytology in 82 paired bone marrow samples from children with neuroblastoma using monoclonal antibodies (MAbs) BW 575 (neuroblastoma-associated 95 kD glycoprotein) and BW 625 (ganglioside GD2) and tetanus toxin labeling. Congruent results were obtained in 70 of 82, or 85% (positive/positive; negative/negative). In 12 of 82 (15%) patients, bone marrow infiltration was demonstrated by immunofluorescence but not by conventional cytology. As few as 0.01% neuroblastoma cells were reliably detected--in some cases even fewer. Because of antigen heterogeneity, false negative results were obtained in five cases with MAb BW 625, in two cases with MAb BW 575, and in no case with tetanus toxin. No antibodies showed any cross-reactivity to hematopoietic cells in either bone marrow of infants or during regeneration after chemotherapy. We conclude that this panel of antibodies is highly sensitive and specific to detect minimal disease in bone marrow of neuroblastoma patients, which has major implications for the staging procedure, monitoring treatment, early detection of relapse, and assessment of bone marrow status before autologous bone marrow transplantation.
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PMID:Detection of minimal disease in bone marrow of neuroblastoma patients by immunofluorescence. 270 75

Differentiated neuroblastoma x glioma hybrid cells NG 108-15 express on their surface specific binding sites for tetanus toxin. 450 sites/cell with a KD of 2 x 10(-11) M were found under "physiological" conditions of pH and salt concentrations. A Hill coefficient of 1.1 indicated noncooperative binding. Specific binding of 125I-toxin to its sites could be prevented either by preincubation of the toxin with a neutralizing monoclonal antibody or by pretreatment of the cells with neuraminidase (Vibrio cholerae). To quantify the action of tetanus toxin on the stimulated release of 14C activity from differentiated cells preincubated with [14C]choline, a new type of perfusion device was designed which could be filled with cells growing in monolayers on Cytodex-3 microbeads. Tetanus toxin inhibited the stimulated 14C release in a time- and dose-dependent manner. A greater than 50% inhibition was found after 2 h of incubation with 10(-12) M toxin. The inhibitory action of tetanus toxin could be prevented with a monoclonal antibody to the toxin or with neuraminidase treatment of the cells. These results suggest that the neuraminidase-sensitive 2 x 10(-11) KD receptors are the productive receptors for tetanus intoxication in differentiated NG 108-15 cells. The possible chemical composition of these receptors is discussed. Differentiated NG 108-15 cells provide a useful model in which picomolar tetanus concentrations produce both measurable saturable binding and inhibition of potassium-evoked, acetylcholine release under physiological conditions of pH and salt concentrations.
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PMID:Tetanus toxin binds with high affinity to neuroblastoma x glioma hybrid cells NG 108-15 and impairs their stimulated acetylcholine release. 282 18

Gangliosides are shed in substantial amounts by some tumors, including human neuroblastoma, and these molecules modulate experimental tumor formation in vivo. We now demonstrate that neuroblastoma tumor gangliosides have potent immunoregulatory activity. Gangliosides of every one of 17 tumors studied were highly inhibitory for the normal in vitro human lymphoproliferative responses to the soluble antigen, tetanus toxoid; 30 nmol ganglioside/ml caused 43% to greater than 99% inhibition and the mean concentration causing 50% inhibition was only 17.3 nmol/ml. Furthermore, gangliosides isolated from clinically more aggressive tumors (Stage III or IV) were up to twice as immunosuppressive as those of the generally less aggressive tumors (Stage I or II) (p less than 0.05). Taken together with the lack of immunosuppressive activity of normal plasma gangliosides, the potent activity of neuroblastoma gangliosides supports the hypothesis that one mechanism by which these shed molecules may act to enhance tumor formation in vivo is through abrogation of the host cellular immune response at the site of tumor formation.
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PMID:Immunosuppressive activity of human neuroblastoma tumor gangliosides. 291 Aug 32


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