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)

Neuropeptide Y (NPY) and peptide YY (PYY) are structurally related peptides that primarily function as neurotransmitter and gastrointestinal hormone, respectively. Previous functional and binding data have indicated the existence of at least three distinct receptor types, Y1, Y2, and Y3, for NPY and/or PYY in mammals. We describe here a human Y1 cDNA clone, hY1-5, isolated from a fetal brain library. The human Y1 receptor consists of 384 amino acids and has seven putative transmembrane domains like other members of the G-protein-coupled superfamily of receptors. In the region spanning the transmembrane domains, the Y1 receptor displays 29% sequence identity to human tachykinin receptors, but it only shows 21% and 23% homology with proposed bovine (LCR1) and Drosophila (PR4) NPY receptor clones, respectively. Northern blot analysis of a human neuroblastoma cell line, SK-N-MC, previously used by many investigators as a model system for studies on the Y1 receptor, revealed a single 3.5-kilobase mRNA species. Reverse transcriptase-polymerase chain reaction analysis indicated expression also in human cultured vascular smooth muscle cells, supporting the view that the Y1 receptor is associated with NPY/PYY-evoked vasoconstriction. When expressed in COS1 cells, hY1-5 conferred specific 125I-PYY binding sites with displacement patterns characteristic of the Y1 receptor, i.e. PYY greater than or equal to NPY greater than or equal to [Leu31,Pro34]NPY much greater than NPY2-36 greater than C2NPY greater than pancreatic polypeptide greater than NPY13-36 greater than NPY18-36. Moreover, in the Y1 receptor-transfected COS1 cells, but not in type 1 angiotensin II receptor-transfected control cells, NPY and PYY accelerated 45Ca2+ influx and inhibited forskolin-stimulated cAMP accumulation, both phenomena being characteristic of the mammalian Y1 receptor.
 ...
PMID:Cloning and functional expression of a human neuropeptide Y/peptide YY receptor of the Y1 type. 131 48

Infectivity of human T-lymphotropic virus type I (HTLV-I) to human nervous tissue cells was explored using co-cultivation with X-irradiated, HTLV-I-producing MT2 cells. Examined cells included normal cerebellar cells, brain tumor cells (astrocytoma, medulloblastoma, meningioma, hemangioblastoma, and schwannoma), and various cell lines (astrocytoma, ependymoma, oligodendroglioma, medulloblastoma, and neuroblastoma). Successful HTLV-I infection was confirmed immunohistochemically using monoclonal antibodies to HTLV-I p19, p24, and pX product. All cell lines and primary cultures from normal cerebellar tissues and brain tumors could be infected with HTLV-I. Double immunostaining showed that glial fibrillary acidic protein-, S-100 protein- or vimentin-positive cells were susceptible to infection. Neurofilament- or neuron-specific enolase-positive cells in medulloblastoma could also be infected. Reverse-transcriptase assay revealed the productive infection in U251-MG (astrocytoma) and KG-IC (oligodendroglioma) lines. Co-cultivated U251-MG cells formed syncytial polykaryons after serial passages, and polymerase chain reaction assay detected HTLV-I genome in U251-MG syncytial polykaryons and p19+ mononuclear cells. HTLV-I viral RNA was also detected in infected U251-MG cells by in situ hybridization. These data show that HTLV-I may have a wide spectrum of infectivity in human nervous tissues.
 ...
PMID:Infectivity of human T-lymphotropic virus type I to human nervous tissue cells in vitro. 138 59

Six temperature-sensitive (ts) mutants of vesicular stomatitis virus (VSV) isolated from the central nervous system (CNS) following injection with ts G31 (III) all possessed a post-transcriptional defect, not found in the initial virus, that affects the stability of viral RNA transcripts. Examination of viral RNA metabolism in mouse neuroblastoma (N-18) cells revealed that RNA synthesis of the CNS isolates was decreased considerably at elevated temperatures (up to 80 or 90% at 39 degrees C). In addition, analysis of the RNA transcripts suggested that little if any normal-sized transcripts were made in cells infected with these CNS isolates at either 37 degrees C or 39 degrees C. The RNA deficiencies did not appear to be the result of a temperature-sensitive lability of virion transcriptase as examined by in vitro transcriptase assays. However, when N-18 cells infected with one of the CNS isolates, ts G31 BP, were first preincubated at the permissive temperature of 31 degrees C for 3 h and then shifted to 39 degrees C, RNA synthesis proceeded at a rate comparable to that of 31 degrees C. The viral mRNA species synthesized following the temperature shift also contained normal sized tracts of poly(A) RNA, suggesting that neither the viral transcriptase nor its polyadenylate synthetase was thermally labile. However, for any of the six CNS isolates, all species of viral RNA synthesized in cells that were first preincubated at 31 degrees C degraded rapidly when the cells were shifted to 39 degrees C. In contrast little or no RNA degradation of either 42S progeny RNA or mRNA species was detected in the wild-type VSV, ts G31 or three other VSV mutants that are defective in some aspect of viral RNA metabolism: [ts G11 (I), ts G22 (II), ts G41 (IV)]. The apparent phenotype alteration in the stability of viral RNA in all of these CNS isolates is discussed in terms of the possible genotypic changes that may have occurred as well a the unique CNS disease that accompanies infection by these viruses.
 ...
PMID:RNA degradation defect in central nervous system isolates of vesicular stomatitis virus. 616 98

Plasmacytomagenesis provides a murine model to decipher progressive genetic events culminating in a B-cell neoplasia. Activation of the c-myc protooncogene by chromosomal translocation is considered an initiating event. Intracisternal A-type particles (IAPs) are defective retroviral-like structures present in the endoplasmic reticulum of plasmacytomas (PCTs). IAP proviral insertions have been documented to engender negative or positive effects on the expression of nearby cellular genes. We have isolated a gene, PANG (plasmacytoma-associated neuronal glycoprotein), that is ectopically transcribed in a number of PCTs due to IAP long terminal repeat (LTR) activation. A full-length PANG cDNA was isolated from an MPC-11 plasma cell tumor cDNA library and encodes a polypeptide of about 113 kDa with six immunoglobulin C2-like and four type III fibronectin-like domains. PANG bears a striking resemblance to axonal glycoproteins TAG-1 and F11 known to function in neuronal outgrowth. An extensive survey revealed a predominant 3.6-kb PANG transcript in 60% (30 of 50) of PCTs as well as unique smaller and larger species. All other normal and transformed lymphoid and nonlymphoid cell lines and normal tissues were negative for PANG expression except for the brain, wherein unique 4.0- and 6.1-kb transcripts were detected. Reverse transcriptase PCR analysis revealed IAP LTR fusion to PANG mRNAs in five PCTs and in a neuroblastoma line. The 5' end of a mouse brain PANG cDNA was identical to the MPC-11 PANG transcript except for the precise replacement of its 5' LTR sequence.
 ...
PMID:PANG, a gene encoding a neuronal glycoprotein, is ectopically activated by intracisternal A-type particle long terminal repeats in murine plasmacytomas. 810 13

Neuroblastoma (NB) is a major-histocompatibility-complex(MHC)-negative neuroectodermal tumour that is often infiltrated with lymphocytes. A detailed characterization of NB-associated tumour-infiltrating lymphocytes (TIL) has never been carried out. Here we have investigated the immunophenotype and the cytotoxic activities of TIL from nine and seven NB patients respectively. Furthermore, the T cell receptor (TcR) variability and the patterns of cytokine gene expression of fresh versus recombinant (r) interleukin (IL)-2-cultured TIL were studied in four NB cases. The results obtained showed the following: (1) freshly isolated TIL were comprised of a mixture of CD4+ and CD8+ T cells partially expressing HLA-DR and/or CD25. The CD4/CD8 ratio ranged from 0.5 to 5 in the different cases. Upon culture of TIL with rIL-2, an increased proportion of CD56+ and CD8+ lymphocytes was consistently observed; (2) IL-2-expanded TIL lysed natural-killer(NK)sensitive and lymphokine-activated-killer(LAK)-sensitive target cell lines; (3) reverse-transcriptase/polymerase-chain-reaction (RT-PCR) experiments showed that most TcR V beta genes were expressed both in fresh and in cultured TIL, suggesting that such cell populations were polyclonal; (4) interferon gamma, IL-4, IL-5, tumour necrosis factor (TNF) alpha, IL-8, IL-10 mRNA and, to a lesser extent, IL-2 mRNA were expressed by cultured TIL, as assessed by RT-PCR; the corresponding tumour samples consistently contained TNF alpha, IL-8 and IL-10 mRNA, whereas IL-2 and IFN gamma mRNA were faintly expressed in some NB tumours and IL-4 and IL-5 mRNA were never detected. A total of 90 clones were subsequently raised from IL-2-expanded TIL from six NB patients; 87/90 clones were of T cell lineage with a CD4+ or CD8+ immunophenotype, whereas the 3 remaining clones were of NK cell origin. Upon triggering of the CD3-TcR complex, 64% CD4+ and 77% CD8+ T cell clones killed the murine P815 mastocytoma cell line. Virtually no T cell clone lysed a LAK-sensitive NB cell line whereas 15% CD4+ and 17% CD8+ clones mediated NK-like activity against the K562 cell line. Finally, the patterns of cytokine production by CD4+ clones were roughly consistent with those of a T helper (TH) 1 profile and similar to those observed in CD8+ clones.
 ...
PMID:Functional and molecular characterization of tumour-infiltrating lymphocytes and clones thereof from a major-histocompatibility-complex-negative human tumour: neuroblastoma. 864 Aug 45

Mouse neuroblastoma Neuro-2a cells were examined for the expression of pro-enkephalin mRNA, protein, and Met-enkephalin ([Met]-Enk) peptide. Reverse transcriptase/polymerase chain reaction (RT/PCR) and in situ hybridization demonstrated the presence of pro-enkephalin mRNA in these cells. Immunocytochemistry using an antibody which recognizes pro-enkephalin and high pressure liquid chromatography (HPLC) followed by radioimmunoassay indicated that pro-enkephalin was synthesized in these cells and processed to yield the bioactive pentapeptide, [Met]-Enk. Furthermore, release studies showed that the [Met]-Enk was secreted from these cells with high K+ stimulation. Using double labeling, in situ hybridization combined with immunocytochemistry, we demonstrated that prohormone convertase 2 (PC2) mRNA is colocalized with pro-enkephalin in the same Neuro-2a cells, suggesting that this enzyme may be responsible for processing this precursor. we also showed the presence of vasopressin mRNA and arginine-vasopressin peptide in these cells using in situ hybridization and immunocytochemistry, respectively. Thus, the Neuro-2a cells are a multiple neuropeptide-producing cell line and an excellent model for studying the mechanisms involved in the synthesis, intracellular targeting and processing of endogenous pro-enkephalin and pro-vasopressin, as well as other transfected neuropeptide precursors.
 ...
PMID:The Neuro-2a neuroblastoma cell line expresses [Met]-enkephalin and vasopressin mRNA and peptide. 867 23

CD24 is a glycoprotein with an unusual structure consisting of a small protein core extensively glycosylated and linked to the outer surface of the plasma membrane by a glycosylphosphatidylinositol (GPI) lipid anchor. Its murine homolog mCD24 is transiently expressed during the development and differentiation of the hematopoietic and neural cell lineages. We have searched for the expression of CD24 in the developing and in the mature human brain as well as in a wide range of neuroectodermal tumors. Neuroblastomas, a subgroup of tumors able to maturate from undifferentiated features towards mature ganglioneuromas, were more extensively studied. Immunohistochemical studies demonstrated that CD24 is transiently expressed by neurons during human brain development. In neuroectodermal tumors, CD24 is a marker of neuronal tumors. Furthermore, in neuroblastomas, CD24 expression decreases as tumors differentiate. In non-neuronal neuroectodermal tumors, CD24 expression is mostly absent. When present, it correlates with the emergence of anaplastic histological features. Reverse transcriptase -polymerase chain reaction (RT-PCR) demonstrated the presence of an unique transcript identical in both hematopoietic, developing and tumoral nervous tissue. RT-PCR and in situ hydridization techniques showed that CD24 expression is transcriptionally regulated. Interestingly, Western blot analysis demonstrated differential CD24 isoforms according to the tissue (hematopoietic versus nervous), the differentiation status, and the origin of neuroblastomas likely reflecting variations in the extent of glycosylation. This indicates an additional level of regulation of CD24 involving post-translational modifications.
 ...
PMID:CD24, a glycosylphosphatidylinositol-anchored molecules is transiently expressed during the development of human central nervous system and is a marker of human neural cell lineage tumors. 892 17

All the angiotensin peptides originate from angiotensinogen, a glycoprotein synthesized by several tissues, including the brain and the anterior pituitary. In the rat, immunohistochemistry has been used to localize angiotensinogen in gonadotropes and in uncharacterized cells surrounding sinusoids. Both cell types are capable of secreting angiotensinogen in cell culture; only the gonadotropes contain angiotensin II (AngII) and are capable of secreting it in culture. It has been asserted that the perisinusoidal cells are the only source of angiotensinogen for the generation of AngII by gonadotropes. Our current data favor the existence of a complete intracellular renin-angiotensin system (RAS) in gonadotropes and a separate extracellular system which utilizes the high concentration of angiotensinogen from perisinusoidal cells. Furthermore, we postulate that gonadotrope AngII serves mainly reproductive functions, while the proximity of angiotensinogen-secreting cells to folliculostellate cells, and their access to the intercellular sinusoidal and follicular spaces, places the extracellular RAS in a strategic position to affect pituitary growth and the mediation of acute-phase immune responses. In the rat brain, angiotensinogen is expressed by the 16-18th day of fetal life and by areas generally concerned with vasopressor, electrolyte, and fluid homeostasis. Antisense deoxyoligonucleotides to angiotensinogen mRNA lower blood pressure in hypertensive rats and inhibit in vitro growth of neuroblastoma cells, indicating a significant role for angiotensinogen in mitogenic and homeostatic functions. It is commonly agreed that astrocytes express angiotensinogen. Neuronal angiotensinogen has also been demonstrated by immunohistochemistry, as a secretion from neuronal cell cultures, and by reverse-transcriptase polymerase chain reaction. The fate of secreted astrocytic and neuronal angiotensinogen remains obscure. Angiotensinogen is regulated in a tissue-specific manner with smaller or absent responses observed for brain tissue. By using astrocyte and neuronal cultures the actions on angiotensinogen production of growth hormone, IGF-1, inflammatory lipopolysaccharide, and phorbol ester have been examined. Recent observations show that angiotensinogen is regulated positively or negatively by glucocorticoids and that a positive synergism between cAMP and glucocorticoids exists. On the basis of analogous systems for other proteins, a scheme involving glucocorticoid receptors, CREB, and AP-1 transcription factors is formulated to explain glucocorticoid-cAMP interactions. These transcriptional interactions may form a significant functional link between the RAS and adrenergic mechanisms.
 ...
PMID:Novel perspectives on pituitary and brain angiotensinogen. 910 Dec 59

One of the loci for neuroblastoma suppressor genes is chromosome 18q21 where the DPC4 tumor suppressor gene, as well as the DCC and MADR2 genes, is located. DPC4 is a molecule of the TGF-beta signal which regulates differentiation of the neural crest precursor cells from which neuroblastoma originates. During the search for the significance of DPC4 as a candidate neuroblastoma suppressor gene, we found that there are at least two variant forms of the DPC4 transcripts by using the reverse-transcriptase-PCR procedure. The subsequent sequencing analysis has revealed that one is missing exons 5 and 6 and the other is missing exons 4-6. Both splice variants were frequently observed in neuroblastomas and at low levels in normal tissues. Though the functional role of the DPC4 splice variants is unknown, they might be important in regulating the TGF-beta signaling not only in neuroblastomas but also in other tumors and normal tissues.
 ...
PMID:DPC4 splice variants in neuroblastoma. 946 9

In this study, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 10(-3) to 10(-4) M for 2 to 5 days) increased the expression of microtubule-associated tau protein in both the supernatant and pellet fractions of lysed SH-SY5Y human neuroblastoma cells. The western blot using anti-tau-1 antibodies demonstrated that the cells contained at least six isoforms of tau proteins, five with molecular weights from 45 to 62 kD. Reverse transcriptase polymerase chain reaction (RT-PCR) using primers coding whole length tau protein further confirmed the presence of tau in SH-SY5Y cells. The PCR product of tau in SH-SY5Y cells had approximately 1050 base pairs. MPTP caused an increased expression of the PCR product of tau, suggesting that the toxicant caused an increase in mRNA coding the tau protein. The expression of cytoskeletal tau protein may, therefore, provide a marker for MPTP neurotoxicity in SH-SY5Y cells.
 ...
PMID:Alterations of cytoskeletal tau protein of SH-SY5Y human neuroblastoma cells after exposure to MPTP. 949 23


1 2 3 Next >>