Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the nervous systems and tumors of five patients with anti-Hu-positive paraneoplastic encephalomyelitis/sensory neuronopathy (PEM/PSN) to determine if the autoantibody found in the serum and CSF was also present in those tissues. Immunohistochemical studies of the nervous system revealed the presence of IgG bound predominantly to the nuclei of most of the neurons and the cytoplasm of some glial cells. IgG was also present to a lesser degree in the neuropil. In brains of patients who died of cancer without the paraneoplastic syndrome, IgG was present in the immediate perivascular areas and to a very limited degree in the neuropil. There was no IgG in neurons, and in only some of the controls a few glial cells showed IgG immunoreactivity in the cytoplasm. The amount of anti-Hu IgG relative to total IgG in various brain regions and tumor was determined by quantitative Western blot analysis. The proportion of anti-Hu IgG was greater in some areas of the brain and tumor than in serum and CSF. Control brains did not contain anti-Hu IgG. There was a limited correlation among (1) the principal clinical symptoms, (2) regions of major tissue injury, and (3) the quantitative anti-Hu IgG distribution. We conclude that although the role of the antibody in the pathogenesis of the disease is still uncertain, its specific localization in the nervous system and tumor suggests an immunologic etiology of this paraneoplastic syndrome.
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PMID:Detection of the anti-Hu antibody in specific regions of the nervous system and tumor from patients with paraneoplastic encephalomyelitis/sensory neuronopathy. 194 5

Using immunohistochemistry, we studied the IgG subclass distribution of the anti-Hu antibody in serum, nervous system, and tumor of patients with anti-Hu-associated paraneoplastic encephalomyelitis/sensory neuropathy (PEM/PSN). The nervous system was also examined for deposits of complement and the distribution and type of inflammatory cells. IgG1 and IgG3 were the predominant isotypes of the anti-Hu IgG in serum, nervous system, and tumor. A few patients also had anti-Hu IgG2, but this isotype was not consistently present in all the regions of the nervous system studied. There was no correlation between neurologic symptoms and specific anti-Hu isotype, nor was there evidence that different anti-Hu isotypes recognized specific brain regions. Although IgG1 and IgG3 can activate complement, only weak complement reactivity was found, and that only in a few areas of the nervous system. This finding, in addition to the absence of natural killer (NK) cells, suggested that complement-mediated toxicity and antibody-dependent cell cytotoxicity mediated by NK cells are not pathogenic in PEM/PSN. Inflammatory infiltrates included CD19+ (B cells) and CD4+ (helper/inducer) cells in the perivascular spaces, and lymphocytes bearing CD8+CD11b- markers (cytotoxic T cells) in the interstitial spaces. Infiltrates of EBM11+ (monocyte/macrophage) cells were identified in the perivascular spaces (macrophage phenotype) and in those interstitial regions (microglial phenotype) with severe pathologic changes. The ability of the IgG1 and IgG3 isotypes to bind Fc receptors may have played a role in the recruitment of these monocyte/macrophage cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of the IgG subclass distribution and inflammatory infiltrates in patients with anti-Hu-associated paraneoplastic encephalomyelitis. 829 49

Symptoms of anti-Hu associated paraneoplastic encephalomyelitis (PEM) and sensory neuropathy (PSN) are usually severe and irreversible. Two patients are reported whose symptoms improved spontaneously, and in one of them they resolved after resection of an inflammatory lesion of the lung. Spontaneous neurological improvement, although rare, should be considered in the evaluation of therapies for PEM/PSN.
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PMID:Spontaneous neurological improvement in anti-Hu associated encephalomyelitis. 906 85

HuD, one of the Hu antigens (HuD and HuC), was recognized in the sera of small cell lung cancer (SCLC) patients with antibody-associated paraneoplastic encephalomyelitis/peripheral sensory neuropathy (PEM/PSN). Three forms of HuD mRNA, 197, 156, 110 nucleotides are made by alternative splicing at 868-909 residues and an additional 3'-splice site. To determine the diagnostic value of the HuD expression for small cell lung cancer, we examined 4 SCLC cell lines, 9 surgically resected SCLCs, and 12 surgically resected non-SCLCs using the reverse transcriptase-polymerase chain reaction with the HuD-specific primer pairs that spanned the putative alternative 3'-splicing site and direct DNA sequencing. None of the patients were associated with PEM/PSN. A single RNA transcript (156 nucleotides) among three forms (110, 156, 197 nucleotides) of the HuD gene was an alternatively spliced at 868-909 residues in SCLC cell lines. Expression of the HuD gene was stronger in three classic cell lines, but not in a variant cell line. Two of 9 SCLCs (22%) and 3 of 12 non-SCLCs (25%) expressed only the major RNA transcript (156 nucleotides) of the HuD gene, which was alternatively spliced in the same fashion as the cell line. These results revealed that no aberrant alternative splicing occurred in SCLC not associated with PEM/PSN and the expression of HuD gene was not specific for a particular histologic subtype of human lung cancer.
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PMID:Expression of HuD (a paraneoplastic encephalomyelitis antigen) mRNA in lung cancer. 928 29

Patients with low titers of anti-Hu, the paraneoplastic encephalomyelitis/sensory neuronopathy (PEM/PSN) antibody, have a better tumor prognosis that those who do not harbor these antibodies. Accordingly, we examined the effects of serum from patients with anti-Hu antibodies on human tumor cell lines, in order to determine: (1) if the serum was toxic (growth inhibition or cytolysis) to tumor cells with or without complement, and (2) if anti-Hu antibodies contributed to tumor toxicity. The serum of 14 patients with anti-Hu associated PEM/PSN, 22 patients with small-cell lung cancer (SCLC) without anti-Hu antibodies, and 20 normal individuals were studied. Three cell lines (NT-2, BE(2)-C, and SH.SY5Y) that express Hu proteins, and one cell line (SAOS-2) that does not, were studied. We examined the effects of whole serum, IgG-depleted serum, and purified IgG in the presence or absence of complement. A higher percentage of anti-Hu sera were toxic (71%) compared with sera from anti-Hu negative SCLC patients (23%) (p < 0.0001). No correlation existed between the titer of anti-Hu antibodies and toxicity. The toxic effects were observed in all tumor cell lines including the cell line that does not express Hu antigens. Toxicity persisted in serum depleted of IgG. Purified anti-Hu IgG in the presence and absence of complement, was not toxic. Our findings indicate that anti-Hu serum is toxic for human tumor cell lines, but this toxicity does not appear to be mediated by anti-Hu antibodies.
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PMID:Paraneoplastic anti-Hu serum: studies on human tumor cell lines. 939 93

Previous study has shown that the anti-Hu antibody titre of serum samples from patients with paraneoplastic encephalomyelitis/paraneoplastic sensory neuronopathy (PEM/PSN) was significantly higher than that from patients with small cell lung cancer without neurological disturbances (non-PEM/PSN). The aims of this study were (1) to identify the fine epitopes on HuD recognised by the anti-Hu antibody, (2) to determine if the pattern of epitopic reactivity differed between antibodies from patients with and without PEM/PSN, and (3) to determine if the pattern of epitopic reactivity correlated with the clinical features. Recombinant full length HuD and nine deletion fragments were constructed and immunoreacted by western blot analysis with 14 anti-Hu serum samples from eight patients with PEM/PSN and six without PEM/IPSN. All anti-Hu serum samples reacted with the deletion fragments containing amino acids (aa) 90-101 or aa 171-206. Some anti-Hu samples reacted with the deletion fragments containing aa 223-234, aa 235-252, or aa 354-373. There was no difference in the pattern of epitopic reactivity between patients with and without PEM/PSN. There was no correlation between the pattern of epitopic reactivity and the clinical features. The anti-Hu antibody titre from patients with PEM/ PSN was significantly higher than from patients without PEM/PSN, but there was overlap of their titre concentrations. In conclusion, aa 90-101 and aa 171-206 are the major epitopes with which all anti-Hu serum samples react, and aa 223-234, aa 235-252, and aa 354-373 are the minor epitopes with which only some anti-Hu serum samples react. The analyses suggested that the pattern of epitopic reactivity of the anti-Hu antibody on HuD was not a critical factor for the development or clinical features of PEM/PSN.
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PMID:Pattern of epitopic reactivity of the anti-Hu antibody on HuD with and without paraneoplastic syndrome. 988 63

Paraneoplastic syndromes are disorders associated with cancer but without a direct effect of the tumor mass or its metastases on the nervous system. Small cell carcinoma of lung associated with paraneoplastic sensory neuronopathy and/or paraneoplastic encephalomyelitis with the presence of anti-Hu antibodies has been termed "anti-Hu syndrome." Anti-Hu associated PSN-PEM is an immune disorder in which both cell-mediated and humoral mechanisms are involved. Patients are considered affected by Anti-Hu associated PSN-PEM when they develop clinical signs and symptoms of CNS dysfunction and/or sensory neuropathy not caused by metastases or other disorders, and serum or cerebrospinal fluid is positive for Hu abs. SCLC is found in more than 90% of patients with cancer and positive Hu abs. Individual patients with Hu abs associated to SCLC may suffer PSN-PEM, limbic encephalitis, brainstem encephalopathy, opsoclonus-myoclonus, paraneoplastic cerebellar degeneration or myelopathy. Hu abs have a specificity of 99% and sensitivity of 82% in detecting paraneoplastic neurological syndromes. There are two types of treatment: the first is to treat the cancer, the second is to suppress the immune reaction with the use of corticosteroids, cyclophosphamide, azathioprine, plasma exchange, intravenous immunoglobulin and immunoadsorption; however, treatment of paraneoplastic syndromes is generally unsatisfactory.
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PMID:Paraneoplastic syndromes associated with anti-Hu antibodies. 1134 32

n-ELAV (neuronal-Embryonic Lethal, Abnormal Vision)-like genes belong to a family codifying for onconeural RNA-binding proteins, also called Hu antigens. Anti-Hu-antibodies (anti-Hu-Ab) are typically associated with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/PSN), and low titres of anti-Hu-Ab were found in neural/neuroendocrine neoplasms, especially small cell lung cancer (SCLC). To date, few studies have been published focused on the genetic causes of their involvement in the pathogenesis of neuroendocrine tumors (NE). Here we analyzed 20 primary human neuroendocrine lung tumor tissues for somatic mutations in the HuD gene. Two inactivating mutations (a frameshift and a stop codon mutation) and 11 nucleotide changes were detected in the coding sequence of HuD gene in 7 different lung tumors. Our results on SCLC and carcinoid tissues support the hypothesis that alterations of nELAV genes could be involved in the onset and/or progression of a subset of neuroendocrine lung tumors.
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PMID:Molecular analysis of the HuD gene in neuroendocrine lung cancers. 1941 Mar 29