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

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.
 ...
PMID:Paraneoplastic anti-Hu serum: studies on human tumor cell lines. 939 93

Antibodies against the HuD antigen expressed in small-cell lung cancer (SCLC) cross-react with proteins expressed in neurons of the central and peripheral nervous system and are associated with paraneoplastic encephalomyelitis and sensory neuropathy (PEM/SN). We isolated anti-HuD Fab fragments from an antibody phage display library that was constructed from mRNA of a metastatic lymph node from a patient with SCLC and Pem/SN. Fab GLN495 recognized HuD and other related proteins (HuC and Hel-N1, or Hu antigens) in immunoblots of these recombinant proteins and in immunohistochemical and Western blot analysis of SCLC and neurons. Fab GLN495 inhibited up to 75% of the anti-Hu antibodies of the patient from which it was derived, suggesting that recognizes a dominant epitope in the polyclonal anti-Hu antibody response. Fab GLN495 also competed with anti-Hu sera from most but not all patients with PEM/SN, indicating that the same epitope is recognized by a large subgroup of patients. Human monoclonal anti-HuD antibodies may be useful in diagnosis of HuD expressing tumors and in clarifying the autoimmune etiology of PEM/SN. This study, the first to demonstrate that tumor specific recombinant antibodies can be isolated from metastatic lymph node tissue, shows that this approach may be generally applicable to isolate human antibodies against tumor specific antigens.
 ...
PMID:Selection of recombinant anti-HuD Fab fragments from a phage display antibody library of a lung cancer patient with paraneoplastic encephalomyelitis. 958 17

Neuroradiologic, neuropathologic and immunohistochemical features are reported in a young man with a impairment of the central nervous system mimicking an acute diffuse encephalomyelitis. A white male, 17 years old, healthy till 4 months before, when developed a right hemiparesis and after 2 months a bilateral hemiparesis with a progressive impairment of several cranial nerves. Magnetic resonance imaging showed multiple lesions without a mass effect that suggested myelin loss. He remained unconscious for almost one month before dying of pneumonia. The neuropathologic examination showed a heavy brain (1505 g) with herniations and a large right midbrain. There were several soft and pink areas mainly at the right midbrain, left cerebellum and in the white matter of the left cerebral hemisphere. The histopathologic sections showed diffuse blastomatous proliferation without total replacement or destruction of the original tissue. The tumor cells had astrocytic, oligodendrocytic and spongioblastic phenotypes, some of them with a GFAP-positive reactivity. There were focal anaplastic changes. The diagnosis of "gliomatosis cerebri" was only possible by the autopsy.
 ...
PMID:"Gliomatosis cerebri" simulating an acute diffuse encephalomyelitis. Case report. 962 70

In experimental allergic encephalomyelitis (EAE) myelin basic protein (MBP) specific T cells differ in their encephalitogenic potential. To investigate the functional diversity of human MBP specific T cell lines, we analysed their cytotoxic activity against human astrocytes and monocytes. Five out of 14 MBP specific T cell lines killed astrocytes in the presence of MBP. Nevertheless, all lines lysed blood derived monocytes. T cell lines that lysed astrocytes efficiently in the presence of MBP, recognized peptide aa 80-99/86-105 in context with HLA-DRB5 * 0101, peptide aa 50-69/61-83 in context with HLA-DRB1 * 1501 and peptides aa 139-153, and aa 148-162 in context with HLA-DRB1 * 0101. There was no correlation of MBP-mediated lysis of astrocytes with TCR-Vbeta usage, HLA-restriction and the production of tumor-necrosis-factor-alpha (TNF-alpha), lymphotoxin (LT) and interferon-gamma (IFN-gamma). Different lysis of astrocytes, however, revealed a functional heterogeneity of MBP specific T cells, which was not observed by using monocytes as targets.
 ...
PMID:Human myelin basic protein specific T cell lines display differential cytotoxicity against astrocytes, but are consistently cytotoxic against monocytes. 968 30

The OX-40 receptor (OX-40R) is a transmembrane protein found on the surface of activated CD4(+) T cells. When engaged by an agonist such as anti-OX-40 antibody or the OX-40 ligand (OX-40L) during antigen presentation to T cell lines, the OX-40R generates a costimulatory signal that is as potent as CD28 costimulation. Engagement of OX-40R enhances effector and memory-effector T cell function by up-regulating IL-2 production and increasing the life-span of effector T cells. We hypothesize that the signal generated by the OX-40R inhibits activation-induced T cell death (AICD) and thereby increases the number of cells differentiating from the effector to memory T cell stage. In experimental autoimmune encephalomyelitis (EAE) OX-40R+ T cells are found only within the inflammatory site [central nervous system (CNS)]. Sorting OX-40R+ T cells from the CNS of animals with EAE revealed that they are autoantigen-specific T cells. Therefore, OX-40R-specific therapies were devised to eliminate or inhibit autoreactive T cells, while sparing the remainder of the T cell repertoire. In contrast, in vivo costimulation through the OX-40R in animals with cancer generated enhanced tumor-specific immunity leading to improved tumor-free survival. Thus, manipulation of the OX-40R during inflammatory responses can alter effector CD4(+) T cell function by enhancing or limiting T cell activation and survival.
 ...
PMID:OX-40: life beyond the effector T cell stage. 982 80

Some patients with small cell lung cancer (SCLC) or neuroblastoma develop an immune response against HuD, a human homologue of the Drosophila protein, elav, which is expressed in the nucleus and to a lesser degree the cytoplasm of neurons and tumor cells. This immune response is characterized by antibodies (anti-Hu) that at high titers are associated with a disease called paraneoplastic encephalomyelitis/sensory neuronopathy, in which infiltrates of T cells are found in the tumor and nervous system. Although all SCLCs express HuD, anti-Hu antibodies are identified in only 17% of patients with SCLC, usually at low titers, and are associated with indolent tumor growth. To determine whether the anti-Hu immune response causes indolent tumor growth, we developed an animal model using HuD DNA immunization. We found that a plasmid coding for a secreted form of HuD induced a strong and specific anti-Hu response. Immunized animals were challenged by s.c. implantation of a neuroblastoma cell line that constitutively expresses HuD. When compared with controls, mice immunized with the secreted HuD showed significant tumor growth inhibition (51% reduction volume; P = 0.0012), and 14% of them had complete tumor rejection. Tumors from these animals showed three times more CD3+ lymphocytic infiltrates than those from control mice and had a higher CD8+:CD4+ ratio. None of the animals developed neurological deficits or neuropathological evidence of nervous system pathology. In this mouse model of neuroblastoma, DNA immunization with HuD resulted in tumor growth inhibition but did not induce neurological disease. This model closely mimics the clinical course of more indolent tumor growth seen in patients with the anti-Hu immune response.
 ...
PMID:DNA vaccination with HuD inhibits growth of a neuroblastoma in mice. 982 48

Cyclooxygenases (COX) mediate a wide variety of derangements observed during diseases of the brain. Their overexpression is involved in the mediation of inflammation, immunomodulation, blood flow, apoptosis and fever. Here, we have analyzed the localization of COX-1 and COX-2 in rat experimental autoimmune encephalomyelitis (EAE), C6 glioblastoma and 9L gliosarcoma by immunohistochemistry. In healthy brain, COX-1 was expressed in single macrophages/microglial cells. Neurons and few endothelial cells expressed COX-2. In EAE, we observed an increase in COX-1+ macrophages/microglial cells and COX-2+ endothelial cells that was closely linked to disease progression. Both COX-1+ macrophages/microglial cells and COX-2+ endothelial cells were abundant in areas of cellular infiltration. In C6 and 9L tumors, high numbers of COX-1+ macrophages/microglial cells and COX-2+ endothelial cells were found both in the tumor parenchyma and in areas of infiltrative tumor growth. Double labeling experiments confirmed expression of COX-2 in vWF+ (endothelial) cells and COX-1 in ED1+ (macophages), OX6+ (MHC class II) and in W3/13+ (lymphoblasts) cells. These data provide further evidence that expression of COX-1 in macrophages/microglial cells and COX-2 in endothelial cells might represent important regulatory mechanisms in inflammatory processes associated with autoimmunity and neoplasia of the rat brain.
 ...
PMID:Cyclooxygenases-1 and -2 are differentially localized to microglia and endothelium in rat EAE and glioma. 1022 32

DEF-3(g16/NY-LU-12) encodes a novel RNA binding protein isolated by positional cloning from an SCLC homozygous deletion region in 3p21.3 and, in parallel, as a differentially expressed gene during myelopoiesis from FDCPmix-A4 cells. DEF-3(g16/NY-LU-12) is ubiquitously expressed during mouse embryogenesis and in adult organs while human hematopoietic tissues showed differential expression. The mouse and human proteins are highly conserved containing two RNA recognition motifs (RRMs) and other domains associated with RNA binding and protein-protein interactions. A database search identified related proteins in human, rat, C. elegans and S. pombe including the 3p21.3 co-deleted gene, LUCA15. Recombinant proteins containing the RRMs of DEF-3(g16/NY-LU-12) and LUCA15 specifically bound poly(G) RNA homopolymers in vitro. These RRMs also show similarity to those of the Hu protein family. Since anti-Hu RRM domain antibodies are associated with an anti-tumor effect and paraneoplastic encephalomyelitis, we tested sera from Hu syndrome patients with the RRMs of DEF-3(g16/NY-LU-12) and LUCA15. These were non-reactive. Thus, DEF-3(g16/NY-LU-12) and LUCA15 represent members of a novel family of RNA binding proteins with similar expression patterns and in vitro RNA binding characteristics. They are co-deleted in some lung cancers and immunologically distinct from the Hu proteins.
 ...
PMID:DEF-3(g16/NY-LU-12), an RNA binding protein from the 3p21.3 homozygous deletion region in SCLC. 1035 2

CP-10 (chemotactic protein of m.w. 10,000) is a member of the S100 superfamily of Ca2+ binding peptides, which has potent chemotactic activity for murine and human myeloid cells. Here we report on the generation of monoclonal antibodies against CP-10 and accumulation of CP-10+ cells during experimental autoimmune encephalomyelitis (EAE), neuritis (EAN), uveitis (EAU) and in experimentally transplanted C6 gliomas. During acute inflammation, CP-10 is mainly expressed by large ED1+ monocytic perivascular cells that accumulate at days 11-14. CP-10+ cells are predominantly located in areas of cellular infiltration but are as well found in the meninges and infiltrating the brain parenchyma. In transplanted gliomas, CP-10+ cells are located exclusively within the tumor parenchyma. Using double labeling experiments, other cells participating in the inflammatory reaction were found to express CP-10, like few lymphoblastic W3/13+ cells in the vicinity of the inflammatory infiltrate.
 ...
PMID:CP-10, a chemotactic peptide, is expressed in lesions of experimental autoimmune encephalomyelitis, neuritis, uveitis and in C6 gliomas. 1037 79

The OX-40 receptor (OX-40R), a member of the TNFR family, is primarily expressed on activated CD4+ T lymphocytes. Engagement of the OX-40R, with either OX-40 ligand (OX-40L) or an Ab agonist, delivers a strong costimulatory signal to effector T cells. OX-40R+ T cells isolated from inflammatory lesions in the CNS of animals with experimental autoimmune encephalomyelitis are the cells that respond to autoantigen (myelin basic protein) in vivo. We identified OX-40R+ T cells within primary tumors and tumor-invaded lymph nodes of patients with cancer and hypothesized that they are the tumor-Ag-specific T cells. Therefore, we investigated whether engagement of the OX-40R in vivo during tumor priming would enhance a tumor-specific T cell response. Injection of OX-40L:Ig or anti-OX-40R in vivo during tumor priming resulted in a significant improvement in the percentage of tumor-free survivors (20-55%) in four different murine tumors derived from four separate tissues. This anti-OX-40R effect was dose dependent and accentuated tumor-specific T cell memory. The data suggest that engagement of the OX-40R in vivo augments tumor-specific priming by stimulating/expanding the natural repertoire of the host's tumor-specific CD4+ T cells. The identification of OX-40R+ T cells clustered around human tumor cells in vivo suggests that engagement of the OX-40R may be a practical approach for expanding tumor-reactive T cells and thereby a method to improve tumor immunotherapy in patients with cancer.
 ...
PMID:Engagement of the OX-40 receptor in vivo enhances antitumor immunity. 1065 70


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>