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)

Antibodies in sera of 7 patients with neurologic manifestations of Lyme borreliosis and a monoclonal antibody (mAb H9724) to the flagellin of Borrelia burgdorferi have been shown to bind neural tissue. To identify the antibody binding site common to the B. burgdorferi flagellin and the neural tissue, we made recombinant fusion proteins expressing epitopes of flagellin. Antibodies in patients' sera and mAb H9724 bound within an 18-amino acid epitope (residues 208-225) in the central region of flagellin, whereas two other mAbs bound to epitopes mapping elsewhere in the protein. Antibodies in patients sera and mAb H9724 also bound to a human neuroblastoma cell line. Absorption of patients sera with a peptide, EGVQQEGAQQPA, corresponding to amino acids 213-224 of flagellin, inhibited binding to the neuroblastoma cell line. The data suggest that the immune response to a specific B-cell epitope within flagellin, shared by a human neuroblastoma cell line, may be involved in the pathogenesis of neuroborreliosis.
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PMID:Serologic response to the Borrelia burgdorferi flagellin demonstrates an epitope common to a neuroblastoma cell line. 767 36

A monoclonal antibody (H9724), specific for the 41-kDa flagellar protein of the Lyme disease pathogen Borrelia burgdorferi, cross-reacts with human axons and detects one major protein in human neuroblastoma cell extracts. The homologous cross-reacting protein has now been isolated from calf adrenal and identified as chaperonin-HSP60 by N-terminal sequencing.
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PMID:Molecular mimicry in Lyme disease: monoclonal antibody H9724 to B. burgdorferi flagellin specifically detects chaperonin-HSP60. 809 52

The serum of patients with Lyme neurologic disease contain antibodies that bind to human axonal antigens that cross-react with Borrelia burgdorferi. The sera also bind to SK-N-SH neuroblastoma cells, especially the neuritic processes of these cells. H9724, a murine IgG monoclonal antibody to B. burgdorferi flagellin, binds to an SK-N-SH cell protein of approximately 64,000 apparent molecular weight (M(r)). H9724 immunoprecipitates a protein of the same M(r) (p64) from the cells and from a delipidated preparation of human peripheral nerve. The Lyme disease patient sera that bind to human axons and SK-N-SH cells also bind to the immunoprecipitated p64. Immunologic cross-reactivity between borrelial and human axonal proteins may be involved in the immunopathogenesis of Lyme neurologic disease.
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PMID:Cross-reactivity between Borrelia burgdorferi flagellin and a human axonal 64,000 molecular weight protein. 850 26

Although Borrelia burgdorferi is found at the site of many manifestations of Lyme disease, local infection may not explain all features of the disease. Previous work has demonstrated that the organism's flagellin cross-reacts with a component of human peripheral nerve axon, heat shock protein 60. The cross-reacting epitope is identified by a single anti-B. burgdorferi flagellin monoclonal antibody, H9724. We now report that the spontaneous and peptide growth factor-stimulated in vitro neuritogenesis of SK-N-SH neuroblastoma cells and other neural tumor cell lines is suppressed by H9724. In contrast, changes induced by exposure of these cells to optimal and suboptimal concentrations of cyclic AMP, phorbol ester, or retinoic acid are not affected by H9724. H9724 does not decrease cell viability or the ability of the cells to anchor to the culture plate or extracellular matrix and does not block nerve growth factor binding to the cells. These findings are compatible with the premise that antiaxonal antibodies formed during the immune response to B. burgdorferi flagellin might modify axonal function in vivo and play a role in the pathogenesis of neurologic features of Lyme disease. A humoral immune response predicated on molecular mimicry could explain persistent or ongoing neurologic dysfunction occurring after elimination of the organism by appropriate antibiotic therapy.
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PMID:A monoclonal antibody to Borrelia burgdorferi flagellin modifies neuroblastoma cell neuritogenesis in vitro: a possible role for autoimmunity in the neuropathy of Lyme disease. 912 53

Opsoclonus-myoclonus is a rare neurological syndrome affecting children and adults. In children it occurs as a parainfectious process or a paraneoplastic syndrome in association with neuroblastoma. Here we report it presenting as an unusual neurological manifestation of Lyme borreliosis. To our knowledge, this is the first report which describes recovery from this syndrome in a child.
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PMID:Opsoclonus-myoclonus syndrome in a child with neuroborreliosis. 1084 Oct 99

Although Borrelia burgdorferi, the causative agent of Lyme disease, is found at the site of many disease manifestations, local infection may not explain all its features. B. burgdorferi's flagellin cross-reacts with a component of human peripheral nerve axon, previously identified as heat shock protein 60 (HSP60). The cross-reacting epitopes are bound by a monoclonal antibody to B. burgdorferi's flagellin, H9724. Addition of H9724 to neuroblastoma cell cultures blocks in vitro spontaneous and peptide growth-factor-stimulated neuritogenesis. Withdrawal of H9724 allows return to normal growth and differentiation. Using electron microscopy, immunoprecipitation and immunoblotting, and FACS analysis we sought to identify the site of binding of H9724, with the starting hypotheses that the binding was intracellular and not identical to the binding site of II-13, a monoclonal anti-HSP60 antibody. The current studies show that H9724 binds to an intracellular target in cultured cells with negligible, if any, surface binding. We previously showed that sera from patients with neurological manifestations of Lyme disease bound to human axons in a pattern identical to H9724's binding; these same sera also bind to an intracellular neuroblastoma cell target. II-13 binds to a different HSP60 epitope than H9724: II-13 does not modify cellular function in vitro. As predicted, II-13 bound to mitochondria, in a pattern of cellular binding very different from H9724, which bound in a scattered cytoplasmic, nonorganelle-related pattern. H9724's effect is the first evidence that HSP60 may play a role in peptide-hormone-receptor function and demonstrates the modulatory potential of a monoclonal antibody on living cells.
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PMID:H9724, a monoclonal antibody to Borrelia burgdorferi's flagellin, binds to heat shock protein 60 (HSP60) within live neuroblastoma cells: a potential role for HSP60 in peptide hormone signaling and in an autoimmune pathogenesis of the neuropathy of Lyme disease. 1186 Jan 86

Inflammation has long been implicated as a contributor to pathogenesis in many CNS illnesses, including Lyme neuroborreliosis. Borrelia burgdorferi is the spirochete that causes Lyme disease and it is known to potently induce the production of inflammatory mediators in a variety of cells. In experiments where B. burgdorferi was co-cultured in vitro with primary microglia, we observed robust expression and release of IL-6 and IL-8, CCL2 (MCP-1), CCL3 (MIP-1alpha), CCL4 (MIP-1beta) and CCL5 (RANTES), but we detected no induction of microglial apoptosis. In contrast, SH-SY5Y (SY) neuroblastoma cells co-cultured with B. burgdorferi expressed negligible amounts of inflammatory mediators and also remained resistant to apoptosis. When SY cells were co-cultured with microglia and B. burgdorferi, significant neuronal apoptosis consistently occurred. Confocal microscopy imaging of these cell cultures stained for apoptosis and with cell type-specific markers confirmed that it was predominantly the SY cells that were dying. Microarray analysis demonstrated an intense microglia-mediated inflammatory response to B. burgdorferi including up-regulation in gene transcripts for TLR-2 and NFkappabeta. Surprisingly, a pathway that exhibited profound changes in regard to inflammatory signaling was triggering receptor expressed on myeloid cells-1 (TREM1). Significant transcript alterations in essential p53 pathway genes also occurred in SY cells cultured in the presence of microglia and B. burgdorferi, which indicated a shift from cell survival to preparation for apoptosis when compared to SY cells cultured in the presence of B. burgdorferi alone. Taken together, these findings indicate that B. burgdorferi is not directly toxic to SY cells; rather, these cells become distressed and die in the inflammatory surroundings generated by microglia through a bystander effect. If, as we hypothesized, neuronal apoptosis is the key pathogenic event in Lyme neuroborreliosis, then targeting microglial responses may be a significant therapeutic approach for the treatment of this form of Lyme disease.
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PMID:Microglia are mediators of Borrelia burgdorferi-induced apoptosis in SH-SY5Y neuronal cells. 1991 Oct 57

A 6-week-old male infant presented with 2 days of fever, emesis, and diarrhea, associated with episodic and chaotic rapid eye movements, determined to be opsoclonus. An electroencephalogram (EEG) obtained during the events was normal. He was treated empirically for meningitis, and an initial workup for neuroblastoma including urine homovanillic acid and vanillylmandelic acid levels, abdominal ultrasonography, and computed tomography (CT) of the chest, abdomen, and pelvis was negative. Stool and blood cultures were positive for Salmonella, and antibiotic regimen was adjusted appropriately. Over the next few days, his fever, emesis, and diarrhea subsided, and the opsoclonus resolved by hospital day 6. He was back to baseline by hospital day 9. Although there have been cases of parainfectious opsoclonus associated with Lyme disease, enterovirus, Streptococcus, and West Nile virus, this represents the first reported pediatric case of opsoclonus associated with salmonellosis. Only 2 such cases in adults have been reported in the literature.
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PMID:Opsoclonus associated with salmonellosis in a 6-week-old infant. 2345 33

Outer membrane vesicles (OMVs) are spherical bodies containing proteins and nucleic acids that are released by Gram-negative bacteria, including Borrelia burgdorferi, the causative agent of Lyme disease. The functional relationship between B. burgdorferi OMVs and host neuron homeostasis is not well understood. The objective of this study was to examine how B. burgdorferi OMVs impact the host cell environment. First, an in vitro model was established by co-culturing human BE2C neuroblastoma cells with B. burgdorferi B31. B. burgdorferi was able to invade BE2C cells within 24 h. Despite internalization, BE2C cell viability and levels of apoptosis remained unchanged, but resulted in dramatically increased production of MCP-1 and MCP-2 cytokines. Elevated secretion of MCP-1 has previously been associated with changes in oxidative stress. BE2C cell mitochondrial superoxides were reduced as early as 30 min after exposure to B. burgdorferi and OMVs. To rule out whether BE2C cell antioxidant response is the cause of decline in superoxides, superoxide dismutase 2 (SOD2) gene expression was assessed. SOD2 expression was reduced upon exposure to B. burgdorferi, suggesting that B. burgdorferi might be responsible for superoxide reduction. These results suggest that B. burgdorferi modulates cell antioxidant defense and immune system reaction in response to the bacterial infection. In summary, these results show that B. burgdorferi OMVs serve to directly counter superoxide production in BE2C neurons, thereby 'priming' the host environment to support B. burgdorferi colonization.
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PMID:Effect of Borrelia burgdorferi Outer Membrane Vesicles on Host Oxidative Stress Response. 3246 66