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)

Within the past 11 years, 11 patients with opsoclonus and myoclonus, with or without a history of neuroblastoma, have been admitted to Children's Memorial Hospital. Eight of the 11 children had an occult neuroblastoma. Eight children have had subsequent delayed development with motor incoordination and speech delay (7 with neuroblastoma, 1 without). Nine of 11 children initially were treated with ACTH, 1 child was treated with prednisone, and 1 was not treated. Nine of the 10 children who were treated had recurrences of symptoms during the gradual withdrawal or discontinuation of ACTH. Often the ACTH had to be restarted or increased, although several times the episodes were self-limited, not requiring treatment after ACTH was withdrawn. We found prednisone was ineffective in controlling opsoclonus-myoclonus regardless of etiology. The majority of children with opsoclonus-myoclonus, regardless of etiology, have developmental delay, more severe and at a higher rate than previously reported. When a neuroblastoma was present, tumor removal did not improve symptoms. Although limited in size, our study indicates patients with opsoclonus-myoclonus without an associated neuroblastoma have a better chance for normal neurologic development (2/3 versus 1/8).
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PMID:Outcome of children with opsoclonus-myoclonus regardless of etiology. 757 43

Adrenal scintigraphy using 131I-6-beta-iodomethyl-19-norcholesterol or 6-methyl-75Se-methyl-19-norcholesterol is a function-dependent imaging method which, in association with high-resolution spatial imaging techniques, plays an essential role in the study of adrenocortical hyperfunction. It can distinguish between bilateral cortical hyperplasia and monolateral adenoma or carcinoma and can lateralise the adenoma. In patients with Cushing syndrome, in addition to allowing a distinction to be made between ACTH-dependent forms and independent forms, adrenocortical scintigraphy is particularly appropriate to identify non-common forms of adenomatous hyperplasia. Adrenocortical scintigraphy, performed during dexamethasone administration, is an accurate mean of differentiating bilateral adrenal hyperplasia from monolateral forms (adenoma or carcinoma) in patients with Conn's syndrome. Owing to the gradual spread of high-resolution spatial imaging techniques, the problem of the diagnostic classification of so-called "incidentalomas" (clinically silent masses discovered by chance) is a subject of considerable interest. Adreno-cortical scintigraphy appears to be able to provide an important contribution to identifying the functional behaviour of these tumours. Since the early 80s meta-iodobenzyl-guanidine (MIBG), marked with 131I or 123I, with a structure similar to norepinephrine and characterized by selective tropism for sympathetic and chromaffin tissue, has been used for the scintigraphic study of adrenal medulla. MIBG scintigraphy has been found to be particularly appropriate for the study of intra- and extra-adrenal, single and multiple, benign and malignant pheochromocytomas. This method has a high overall sensitivity and specificity. Lastly, MIBG scintigraphy is useful in the study of neuroblastoma.
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PMID:[Nuclear medicine methods for the diagnosis of adrenal tumors]. 765 Dec 80

To study the putative binding sites of the neurotrophic peptide Org 2766, an analogue of ACTH(4-9) [H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH], biotinylated forms of the peptide were used. After fixation, cultures of rat spinal cord and dorsal root ganglia were incubated with 4-10 microM of biotinyl-Org 2766 (b-Org 2766). Binding of both N- and C-terminally biotinylated Org 2766 was seen to phase-bright, round cells with thin processes, but not to flat, orthogonal-shaped cells with tapering processes. The b-Org 2766 binding was displaceable by an excess of nonbiotinylated Org 2766. Light and electron microscopy showed that the biotinylated peptide binds to a cytoplasmatic component as well as to the cell membrane. Double-labeling experiments with b-Org 2766 and an antibody (RT-97) to a high molecular weight neurofilament protein in dorsal root ganglion cultures showed, using fluorescence and confocal scanning laser microscopy, that all b-Org 2766 binding cells were neurofilament positive. Biotinylated Org 2766 did also bind to the neuronally differentiated cells in cultures of the human neuroblastoma cell line SK-N-SH, but not to those differentiated into epithelial cells. The present data suggest that the neurotrophic peptide Org 2766 binds specifically to cell types with neuronal characteristics.
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PMID:Binding of a biotinylated neurotrophic ACTH(4-9) analogue, Org 2766, to neurofilament-positive cells in primary or cell line cultures. 813 2

The structure of pro-opiomelanocortin (POMC) can be divided into three main domains: an NH2-terminal domain formed by the NH2-terminal glycopeptide and the joining peptide, a central domain corresponding to the adrenocorticotropin sequences and a COOH-terminal domain containing the beta-lipotropin sequences. Expression of POMC in neuroendocrine cell lines such as the mouse neuroblastoma Neuro2A cells results in its targeting to the regulated secretory pathway of these cells. Intracellular targeting of proteins along non default pathways are widely believed to involve the recognition of specific structural features by a sorting machinery. To understand the nature of the signal involved in targeting prohormone to the regulated secretory pathway, we have constructed mutants of POMC in which sequences from the NH2-terminal, the central and the COOH-terminal domains were deleted and examined the sorting of these mutant POMC molecules in Neuro2A cells by immunofluorescence and immunoelectron microscopy. Our results indicate that POMC NH2-terminal glycopeptide or beta-LPH domain do not contain sufficient information for targeting to the regulated pathway since these peptides are not sorted to secretory vesicles when expressed in Neuro2A cells: Similarly, the ACTH domain does not contain essential targeting information since POMC mutants lacking these sequences were sorted to secretory vesicles. Mutant POMCs containing the sequences of more than one of the main protein domains were, however, correctly targeted to the regulated secretory pathway. Our results indicate that POMC is not targeted to the regulated secretory pathway through recognition of a unique continuous 'molecular address'.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Targeting of pro-opiomelanocortin to the regulated secretory pathway may involve cooperation between different protein domains. 822 24

In the past decade there have been considerable advances in basic knowledge of the renin-angiotensin system (RAS). The most important new development has been the appreciation of a tissue based RAS that can be independently regulated from the renal and vascular RAS. Greater insight into the mechanism by which angiotension-II (AII) exerts its action has been achieved through the study of molecular biology and pharmacological characterization of multiple receptor subtypes. This review summarises the features and distribution of several binding subtypes that may mediate the diverse functions of AII. Of these AT1 subtype is the most well known receptor which preferentially binds AII and AIII. The AT1 receptor site appears to mediate the classic angiotensin responses concerned with the body water balance and the maintenance of blood pressure. Less is known about the AT2 sites which also bind AII and AIII and may play a role in vascular growth. Recently, an AT3 has been discovered in cultured neuroblastoma cells and an AT4 site which preferentially binds AIV. It has been implicated in memory aquisition and retrieval and in the regulation of blood flow. Another important aspect covered is the primary and secondary messengers involved during the signal transduction after the binding of AII with receptors. A stress has also been given on the regulation of density and affinity of AII receptors by various physiological parametres as they affect the responses of RAS. Autoregulation by RAS, salt intake, development and aging and some of the hormones are important variables which could affect the AII receptors. Interactions of AII with various neuroeffector transmission involved in the regulation of water-electrolyte balance and BP regulation play an important role in the maintenance of the homeostasis. AII has been suggested to increase the NAergic transmission by enhancing synthesis, release, inhibiting reuptake by the presynaptic nerve terminals as well as enhancing cell responsiveness to the transmitter. The finding of existence of AII receptors in vagal afferent nerve terminals suggests that its baroreflex inhibitory effect is mediated by inhibiting neurotransmitter release at NTS in the baroreflex arc. Moreover, AII acts on the central receptors to stimulate AVP and ACTH secretion, drinking and peripherally increase synthesis and secretion of aldosterone. Interactions of RAS with kallikrein-kinin system and prostaglandins strongly support the existence of a balance between renal depressor and pressor substances. AII is now considered a growth promotor in cardiovascular tissues and the resultant vascular hypertrophy could contribute in the maintenance of hypertension. AII also plays a role in the kidney, not only as a regulator of hemodynamics but also in the structural changes occurring in a variety of renal disorders. In addition to the more well studied functions of RAS in RVH the review also highlights the potential contribution by the RAS to other clinically relevant syndromes such as aortoarterities induced RVH, hyperaldosteronism, heavy metal induced cardiovascular effects, diabetes mellitus and thyroid dysfunction. Although the receptor subtypes involved in these pathological states have not been definitely identified, research efforts in this direction are ongoing.
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PMID:Angiotensin II--receptor subtypes characterization and pathophysiological implications. 864 21

Melanocortins (MC), neuropeptides derived from pro-opiomelanocortin, have been implicated in enhancing neurite outgrowth via an as yet unknown mechanism. Recently, five MC receptors have been identified, three of which, the MC3-R, the MC4-R and the MC5-R, are expressed in the nervous system. In this study, alpha-MSH and the melanocortin analog [D-Phe7]ACTH (4-10) were able to stimulate neurite outgrowth in the neuroblastoma cell line Neuro 2A. ACTH (4-10), gamma2-MSH and ORG2766 were inactive. In addition, the MC4-R antagonist [D-Arg8]ACTH (4-10), inhibited the alpha-MSH effect, indicating that the MC4-R mediated stimulation of neurite outgrowth by alpha-MSH. Indeed, the presence of MC4-R mRNA in Neuro 2A cells was demonstrated by a RNase protection assay. Heterologous expression of the MC5-R in Neuro 2A cells lead to the recruitment of a responsiveness to gamma2-MSH, but did not increase the effect of alpha-MSH on neurite outgrowth. This finding indicated that the function of MC4-R can also be exerted by another MC receptor, suggesting that the coupling to Gs, which they have in common, plays an essential role in the neurite outgrowth promoting effect. This was further substantiated by the fact that forskolin treatment per se induced neurite outgrowth in a similar fashion. These data imply that the neurotrophic properties of alpha-MSH are likely to result from Gs-coupled MC receptor activity in neuronal cells.
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PMID:Melanocortin receptors mediate alpha-MSH-induced stimulation of neurite outgrowth in neuro 2A cells. 901 63

A retrospective data collection was performed on 29 children diagnosed with neuroblastoma and opsoclonus-myoclonus between 1983-1993 from Pediatric Oncology Group institutions. The aim was to describe neurologic outcome in children with neuroblastoma and opsoclonus-myoclonus. Age at diagnosis ranged from one month to 4 years (median age, 18 months). The duration of opsoclonus-myoclonus symptoms prior to the diagnosis of neuroblastoma ranged from 6 days to 17 months (median duration, 6 weeks). There was a prevalence of low stage disease according to the POG staging system: stage A (n = 18), stage B (n = 3), stage C (n = 7), stage D (n = 1). There was a predominance of paraspinal primary tumors. There was no case of Nmyc amplification (0/17), and 2/8 cases were diploid. Treatment for neuroblastoma consisted of surgery alone in 19/29 (18 stage A, 1 stage C in thorax), and surgery plus chemotherapy in 10/ 29. No patient received radiotherapy. Treatment for opsoclonus-myoclonus ranged varied. Six children received no treatment for opsoclonus-myoclonus. The following agents were used ACTH (n = 14), prednisone (n = 12), IV IgG (n = 6), immuran (n = 2), depakote (n = 1), and inderal (n = 1). Eighteen of 29 children (62%) had resolution of opsoclonus-myoclonus symptoms. The range of time for recovery was a few days to 3 years. However the majority recovered over several months. Twenty of 29 children (69%) had persistent neurologic deficits including speech delay, cognitive deficits, motor delay, and behavioral problems. Of the 9 children who had complete recovery of opsoclonus-myoclonus without neurologic sequelae, age at diagnosis and duration of symptoms were not different from the entire group. Interestingly, 6/9 children with complete recovery received chemotherapy as part of their treatment. In conclusion, persistent neurologic deficits are characteristic for children with neuroblastoma and opsoclonus-myoclonus. Treatment with chemotherapy may improve the neurologic outcome.
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PMID:Long-term neurologic outcome in children with opsoclonus-myoclonus associated with neuroblastoma: a report from the Pediatric Oncology Group. 907 25

In our previous study, xenogeneic mouse neuroblastoma cells bearing the POMC gene, the precursor of ACTH and beta-endorphin, were implanted within polymer capsules into the CSF space of rats. Although ACTH and beta-endorphin were secreted, we were not able to control the amounts or times of hormone release. A promoter that is inducible by administration of tetracycline derivatives (Tet) was linked to the POMC gene to control its gene expression (Neuro2A-Tet-On-POMC; NTP). The results showed that POMC gene expression in the implanted encapsulated NTP cells could be regulated in a dose-dependent manner by Tet administration to the hosts. However, no analysis of gene control with the Tet-On system over a long period has been performed. In this study, encapsulated NTP cells were treated in vitro with doxycycline (Dox) (1.0, 10, 100, 1000 ng/ml) continuously for a month. On day 4, the amount of ACTH secretion was dependent on the Dox dose. But in the course of the experiment, the difference of ACTH secretion among those treated with Dox 10, 100, and 1000 ng/ml was eliminated. On the other hand, NTP cells, which were treated with Dox (1000 ng/ml) just on days 7, 14, 21, and 28, secreted almost the same amount of ACTH in 24 h. From these results, for clinical use, an NTP cell line that secretes enough opiate to reduce pain sensitivity without Dox should be established, and Dox could then be administered if necessary.
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PMID:Long-term functional assessment of encapsulated cells transfected with Tet-On system. 1047 25

Opsoclonus-myoclonus syndrome (OMS) is a rare, autoimmune neurological disorder that is poorly recognized and undertreated. Neuroblastoma is found in one half of the cases. Because of the high incidence of spontaneous regression of neuroblastoma, it is unknown whether not finding a tumor means there was none. To define demographic trends and the standard of care in the first large series of OMS, 105 children were recruited over a 13-year period in a retrospective questionnaire survey. Children with and without a tumor differed little in viral-like prodrome and neurological symptoms. Earliest neurological symptoms were staggering and falling, leading to a misdiagnosis of acute cerebellitis. Later symptoms included body jerks, drooling, refusal to walk or sit, speech problems, decreased muscle tone, opsoclonus, and inability to sleep. Tumor resection alone did not provide adequate therapy for most. Adrenocorticotropic hormone (ACTH), prednisone, and intravenous immunoglobulin were used with equal frequency, but ACTH was associated with the best early response. More than one half of the children had relapses. Residual behavioral, language, and cognitive problems occurred in the majority. The delay in diagnosis (11 weeks) and initiation of treatment (17 weeks) is unacceptably long.
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PMID:Neuroepidemiologic trends in 105 US cases of pediatric opsoclonus-myoclonus syndrome. 1557 22

A 39-year-old woman who presented with typical Cushingoid appearance (moon facies, central obesity, purpura) was admitted to our hospital because of pulmonary infection. She was found to have hypertension, severe hypokalemia, and metabolic alkalosis. Endocrine data revealed elevated plasma levels of ACTH and cortisol with lack of circadian rhythm, non-suppressibility to high-dose dexamethasone, and hyperresponsiveness to CRH stimulation. Although no pituitary mass was detected by MRI of the brain, inferior petrosal sinus sampling showed a step-up of central to peripheral ACTH levels; these data are consistent with the diagnosis of Cushing's disease. She was successfully treated with metyrapone to control hypercortisolemia. Ten months later, a mass was detected in the ethmoid sinus, which was surgically removed. After resection of the ethmoid sinus tumor, her Cushingoid features and hypercortisolemia disappeared, but recurred after enlargement of a second mass in the maxillary sinus. After resection of the maxillary sinus tumor, her hypercortisolemia subsided. Histologically, the tumor tissues from both the ethmoid and maxillary sinus were identical and consistent with the diagnosis of olfactory neuroblastoma. Immunohistochemically, the immunoreactivities of ACTH and POMC were positive in the cytoplasm of tumor cells, and immunoreactive ACTH was demonstrated in both tumor tissues. Thus, this is the second rare case with ectopic ACTH syndrome caused by olfactory neuroblastoma thus far reported.
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PMID:Olfactory neuroblastoma causing ectopic ACTH syndrome. 1641 Jun 58


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