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

Plasma concentrations of neuropeptide Y, analysed in 112 healthy children, decreased significantly with age, while sex, discomfort induced by the sampling procedure or induction of general anaesthesia did not have a significant influence. An age-adjusted upper reference limit was established and proved to be useful when tested prospectively in 56 children with tumours. Two of 18 children with preliminary diagnosis of rhabdomyosarcoma had elevated plasma neuropeptide Y; both showed malignant ectomesenchymoma (p < 0.01), a mixed tumour with neural crest features. Among 38 children with neural crest derived tumours, all 7 with benign ganglioneuromas had plasma neuropeptide Y concentrations below the reference limit, while 13 of 31 with neuroblastoma had elevated concentrations (p < 0.05). Only neuroblastoma patients with elevated plasma neuropeptide Y had a poor outcome; 10 of 13 died, whereas all with normal concentrations are alive after 3-74 months of follow-up (p < 0.001).
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PMID:Plasma neuropeptide Y in healthy children: influence of age, anaesthesia and the establishment of an age-adjusted reference interval. 802 3

The cellular mechanisms underlying the clinical effects of volatile anaesthetics remain unknown, although the plasma membrane and its associated proteins are likely targets. One such protein is the enzyme phospholipase C (PLC), which catalyses the formation of the second messenger inositol(1,4,5)triphosphate [Ins(1,4,5)P3]. Using SH-SY5Y human neuroblastoma cells we have demonstrated that halothane (0.50, 0.75 and 1.00%) enhances basal Ins(1,4,5)P3 mass formation approximately 1.8-fold. Halothane also caused a dose-dependent enhancement of carbachol-stimulated biphasic Ins(1,4,5)P3 formation at both the peak (half-maximal stimulation, EC50 = 0.76%) and plateau (EC50 = 0.74%) phases. At 1%, halothane did not alter the affinity for carbachol at either the peak (IC50: air = 9.4 +/- 1.5, halothane = 12.7 +/- 1.0 microM) or plateau (EC50: air = 11.7 +/- 1.2, halothane = 11.6 +/- 1.0 microM) phase, but did increase the maximum Ins(1,4,5)P3 response at both phases (air vs halothane: peak, 79.9 +/- 0.5 vs 124.8 +/- 2.5; plateau, 33.2 +/- 0.5 vs 47.9 +/- 0.6 pmol/mg protein). Isoflurane (2%) also enhanced basal and carbachol-stimulated Ins(1,4,5)P3 formation 2-fold and 1.5-fold, respectively. In summary, clinically relevant doses of the volatile anaesthetics halothane and isoflurane enhance basal and carbachol-stimulated Ins(1,4,5)P3 formation. Thus, activation of PLC, and subsequent potential Ins(1,4,5)P3-mediated rises in intracellular calcium, could play a part in the cellular mechanisms of volatile agent-induced anaesthesia.
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PMID:Halothane and isoflurane enhance basal and carbachol-stimulated inositol(1,4,5)triphosphate formation in SH-SY5Y human neuroblastoma cells. 814 13

While the ability of increased pressure to reverse anaesthesia has been well documented, the cellular or molecular mechanism(s) responsible for their mutual antagonism have remained elusive. Previous work in our laboratory, using diverse cell types, has indicated several processes requiring Ca2+ are affected in opposite directions by hydrostatic pressure [as represented by helium (He)], narcotic gases, and some anesthetics. Here we report on the effects of elevated pressures of He, and of 1 atm abs of the anesthetic gas nitrous oxide (N2O), when present alone and in combination, on calcium mobilization in the human neuroblastoma cell line SK-N-SH. Cytosolic-free Ca2+ ([Ca2+]i) was monitored by fluorescence spectrophotometry in cell suspensions loaded with the intracellular Ca2+ indicator fura-2. N2O reversibly depressed the carbachol-stimulated increase in [Ca2+]i (P < 0.01). The application of both 18 and 35 atm abs He attenuated this N2O-induced depression of carbachol-stimulated increase in [Ca2+]i. These findings support the hypothesis that pressure/anesthetic antagonism may be due in part to effects on neuronal [Ca2+]i and its regulation.
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PMID:Pressure antagonism of nitrous oxide depression of intracellular calcium in a neuroblastoma cell line. 865 62

Most neuroblastoma identified by mass screening are clearly different from the clinically diagnosed tumors with respect to biology, epidemiology, and outcome. Because the neuroblastomas detected by mass screening have favorable biological features (97% survival rate at 5 years), aggressive surgery may not be appropriate for such tumors. Laparoscopic adrenalectomy was performed on a 9-month-old boy and two 8-month-old girls who had suitable lesions. The tumors were small (< 20 mm in diameter). With the patients under general anesthesia, five trocars were placed in the abdomen. The abdominal wall traction method was used in addition to pneumoperitoneum. Intraabdominal pressure was maintained at below 4 mm Hg. The adrenal tumors were well encapsulated and completely excised, placed into a plastic bag, and removed through one of the 10-mm trocar sites. No lymphadenopathy was observed. The postoperative course was uneventful. The tumors were of favorable Shimada histology and had no N-myc gene amplification. The patients have survived, with no evidence of recurrence or metastasis, through the follow-up period of 17 to 22 months.
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PMID:Laparoscopic surgery for neuroblastoma identified by mass screening. 870 8

A three-year-old girl who underwent an operation for adrenal neuroblastoma was anaesthetized with sevoflurane and epidural analgesia. In the immediate recovery period she had convulsions. The convulsions were successfully treated with thiopentone and sevoflurane, there were no neurological sequelae. The convulsions were considered to be a manifestation of mepivacaine toxicity because of a high plasma mepivacaine concentration. Complications of paediatric regional analgesia and manifestations of mepivacaine toxicity under sevoflurane anaesthesia are discussed.
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PMID:Convulsions associated with epidural analgesia during sevoflurane anaesthesia. 936 77

Interest in umbilical cord blood as an alternate source of hematopoietic stem cells is growing rapidly. Umbilical cord blood offers the clinician a source of hematopoietic stem cells that is rarely contaminated by latent viruses and is readily available. Moreover, the collection of umbilical cord blood poses no risk to the donor; there is no need for general anesthesia or blood replacement, and the procedure causes no discomfort. Whether cord blood lymphocytes are as likely to cause GVHD as lymphocytes from older individuals is unknown. Current clinical experience would suggest that the incidence may be low. Few of the patients transplanted with umbilical cord blood thus far have developed clinically significant GVHD, including recipients of HLA-disparate grafts. These results and associated laboratory findings pose intriguing possibilities for the future of umbilical cord blood stem cells in the setting of unrelated transplantation. With the marked incidence of grade 2-4 acute GVHD that is currently observed after unrelated bone marrow transplantation, a reduction in incidence or severity would be a major advancement in this field. In the setting of autologous trans-plantation, there are other intriguing possibilities; for example, cord blood may be an optimal source of pluripotential stem cells for gene therapy. The large-scale collection and storage of cord blood stem cells has become a reality. Pilot programs for the banking of unrelated umbilical cord blood have already begun in the United States and Europe. Not only is there the potential for reducing the time from search initiation to the time of donor stem cell acquisition but also there is the potential for reducing the risks associated with unrelated bone marrow transplantation. There is also the hope of remedying the shortage of donors from ethnic and racial backgrounds that are currently underrepresented in most unrelated donor programs. Even with the creation of such banks, it should not be forgotten that the collection of umbilical cord bloods should at least be considered when a child with leukemia, lymphoma, neuroblastoma, marrow failure syndrome, immunodeficiency state, or inborn error of metabolism has a mother who is pregnant. The clinical results to date in small recipients would suggest that it is at least as good as bone marrow; but additional patients and more time will be needed to finalize this conclusion.
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PMID:Allogeneic umbilical cord blood transplantation. 907 4

We have examined the effects of the volatile general anaesthetic agent, halothane, on K+ and carbachol stimulated [3H]noradrenaline release and associated increases in intracellular Ca2+ in a cultured human neuroblastoma cell line, SH-SY5Y. K+ (but not carbachol) stimulated [3H]noradrenaline release, and the increase in intracellular Ca2+ concentration was entirely extracellular Ca2+ dependent. Halothane produced a dose-dependent reduction in K+ evoked release of [3H]noradrenaline with significant inhibition (17%) occurring from 1.26 atm%. Basal and carbachol evoked release were unaffected. Halothane also produced a dose-dependent reduction in K+ evoked increases (measured at the peak) in intracellular Ca2+ with significant inhibition (29%) occurring from 0.88 atm%. K+ plateau, basal and carbachol evoked increases in intracellular Ca2+ were unaffected. These data suggest that halothane reduced Ca2+ entry through voltage-sensitive Ca2+ channels and implicate this important class of ion channel in the mechanism of anaesthesia.
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PMID:Effect of halothane on K+ and carbachol stimulated [3H]noradrenaline release and increased [Ca2+]i in SH-SY5Y human neuroblastoma cells. 930 93

Minimally invasive surgery (MIS) for cancer patients has become widely accepted in general surgery, however, it has not completely replaced the standard open operative procedures in pediatric oncology. The aim of this study was to evaluate the host relationship following MIS in a murine model of retroperitoneal neuroblastoma (NB) Immature, 5- to 7-week-old male A/J mice weighing 18-23 g were inoculated with either C1300 or TBJ NB in the left retroperitoneal space. At 4 days (early stage) or 11 days (late stage) following tumor inoculation, the animals underwent a laparotomy or pneumoperitoneum with carbon dioxide under general inhalational anesthesia. Animal survival, tumor growth, and postoperative changes in body weight were observed. In the model of subcutaneous TBJ NB, distant metastases following the laparotomy or MIS technique were also evaluated. Each surgical group had a sample size > or = 12, and data were statistically analyzed by ANOVA and the chi-square test where appropriate. P < 0.05 was considered to be significant. There were no significant differences in animal survival, tumor growth, or distant metastases among surgical groups in any combination of type and stage of tumor. The only salutary influence of MIS was seen in a model of early-stage NB, where the decrease in body weight on postoperative day 7 was preserved when compared to post-laparotomy weight loss. We conclude that when compared to conventional laparotomy, the MIS access technique does not influence the outcome in a model of retroperitoneal murine NB.
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PMID:Minimally invasive surgery does not improve the outcome in a model of retroperitoneal murine neuroblastoma. 956 30

This study presents the results of fine needle aspiration cytology in a series of 26 consecutive children with neuroblastic tumours. The cytological spectrum varied from undifferentiated small tumour cells to mature ganglion cells in a fibrillar background. In 24 children with neuroblastic tumours at onset the cytological diagnosis was correct in 21 cases, whereas two aspirates yielded nondiagnostic necrotic material and a fibrillar material without tumour cells, respectively. One necrotic lymph node aspirate was initially incorrectly diagnosed as lymphoma, but the diagnosis was later revised to neuroblastoma. Suspected signs of disease progression or relapses were confirmed (n = 9) or ruled out (n = 1) using aspiration cytology. The diagnostic accuracy in the complete series was 97% (31/32) in cases with adequate smears. Immunocytochemistry confirmed the cytological diagnosis in 14 of 15 cases and was decisive in one. Elevated catecholamine metabolites in urine was detected in all children with a cytological diagnosis of neuroblastoma. General anaesthesia was only performed when coincidental invasive investigations (n = 13) were to be carried out or if the aspiration was intrathoracic (n = 6). It is concluded that aspiration cytology in conjunction with immunocytochemistry offers a safe, rapid and accurate diagnostic method which may be useful, together with analyses of catecholamine metabolites in urine, in the clinical management of children with neuroblastic tumours.
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PMID:The clinical use of fine needle aspiration cytology for diagnosis and management of children with neuroblastic tumours. 971 4

Current understanding of the molecular mechanisms of anaesthesia entails multiple molecular sites of anaesthetic action, each more or less important for a specific anaesthetic drug used. For some molecular anaesthetic targets such as the GABA(A), and acetylcholine receptors as well as potassium channels, large differences in anaesthetic effects and sensitivity between different receptor subtypes have been found. Voltage-gated sodium channels have been shown to be affected at clinical concentrations of pentobarbital. However, these results were obtained in an expression system, and anaesthetic sensitivity may be dependent on sodium channel subtype and subunit composition, too. Therefore, we compared the sensitivity of voltage-gated sodium channels to pentobarbital in human (SHSYSY) and mouse (N1 E-115) neuroblastoma cell lines as well as an HEK293-cell expression system with previously reported data with other sodium channel subtypes. Remarkably, for all sodium channel subtypes studied as well as all subtypes reported in the literature, pentobarbital had qualitatively identical effects with some quantitative differences, and at potentials near the action potential threshold sodium currents were significantly reduced by clinical concentrations of pentobarbital.
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PMID:Sodium channels (from rat, mouse, and man) in neuroblastoma cells and different expression systems have similar sensitivities to pentobarbital. 1032 19


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