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)

Apoptosis is usually associated with genomic DNA fragmentation which can be detected in situ by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) assay. We describe a combined TUNEL and double immunofluorescent labeling technique to determine the fate of inflammatory infiltrates and resident glial cells in the central nervous system following the onset of an autoimmune demyelinating disease such as experimental allergic encephalomyelitis (EAE) in rats. Anti-digoxigenin (anti-DIG) antibody conjugated with 7-amino-4-methylcoumarin-3-acetic acid (AMCA) emitting blue fluorescence was used to detect apoptotic cell DNA, which was already labeled by modified TUNEL using alkali-stable DIG-11-dUTP. Anti-mouse IgG secondary antibody conjugated with Texas Red emitting red fluorescence was used to detect anti-rat CD11b primary antibody (clone OX-42) directed to the surface antigen of mononuclear phagocytes including microglia. Using this technique, we detected apoptotic mononuclear phagocytes (co-labeled with blue and red fluorescences) in the spinal cord sections of rats with EAE.
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PMID:Combined TUNEL and double immunofluorescent labeling for detection of apoptotic mononuclear phagocytes in autoimmune demyelinating disease. 1090 97

We recently used a modification of gene therapy (naked DNA vaccination) to induce immunological memory against self-pro-inflammatory chemokines such as macrophage inflammatory protein-1 alpha or monocyte chemoattractant protein-1, and against the pro-inflammatory cytokine tumor necrosis factor-alpha. First, DNA constructs encoding each of the different pro-inflammatory mediators together with a repeated immunostimulatory sequence were prepared. Then, experiment animals were subjected to a repeated administration of each construct. Under these conditions, tolerance to the product of each insert was broken, and immunological memory established. Upon induction of experimental autoimmune encephalomyelitis, a T cell-mediated autoimmune disease of the central nervous system that serves as a model for multiple sclerosis or adjuvant induced arthritis, this memory was "turned on" to provide DNA-vaccinated animals a high state of disease resistance. Antibodies to the product of each inserted gene were isolated form these animals. Each antibody was found capable of neutralizing in vitro the chemoattractive properties of each relevant chemokine, thereby transferring disease resistance. Interestingly, the level of their production was dependent on disease severity, that is, each titer was accelerated in accordance with disease progression. Thus, by using a simple gene therapy technique the immune system could be "re-educated" to restrain its own harmful activities.
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PMID:Gene therapy for T cell-mediated autoimmunity: teaching the immune system how to restrain its own harmful activities by targeted DNA vaccines. 1090 20

Gene therapy offers advantages for the immunotherapeutic delivery of cytokines or their inhibitors. After gene transfer, these mediators are produced at relatively constant, non-toxic levels and sometimes in a tissue-specific manner, obviating limitations of protein administration. Therapy with viral or nonviral vectors is effective in several animal models of autoimmunity including Type 1 diabetes mellitus (DM), experimental allergic encephalomyelitis (EAE), systemic lupus erythematosus (SLE), colitis, thyroiditis and various forms of arthritis. Genes encoding transforming growth factor beta, interleukin-4 (IL-4) and IL-10 are most frequently protective. Autoimmune/ inflammatory diseases are associated with excessive production of inflammatory cytokines such as IL-1, IL-12, tumor necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma). Vectors encoding inhibitors of these cytokines, such as IL-1 receptor antagonist, soluble IL-1 receptors, IL-12p40, soluble TNFalpha receptors or IFNgamma-receptor/IgG-Fc fusion proteins are protective in models of either arthritis, Type 1 DM, SLE or EAE. We use intramuscular injection of naked plasmid DNA for cytokine or anticytokine therapy. Muscle tissue is accessible, expression is usually more persistent than elsewhere, transfection efficiency can be increased by low-voltage in vivo electroporation, vector administration is simple and the method is inexpensive. Plasmids do not induce neutralizing immunity allowing repeated administration, and are suitable for the treatment of chronic immunological diseases.
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PMID:Gene therapy of autoimmune diseases with vectors encoding regulatory cytokines or inflammatory cytokine inhibitors. 1095 13

Inflammatory demyelinating diseases are a common cause of neurologic disability in young adults, and usually the cause is unknown. We describe a case of acute disseminated encephalomyelitis (ADEM) associated with Chlamydia pneumoniae infection. An 18-year-old previously healthy women, with a one-week history of coryzal illness, was admitted because of progressive headache, dizziness, and a left-sided hemiparesis. MR imaging of the brain and brainstem showed typical signs of ADEM. The diagnosis was established by PCR Chlamydia pneumoniae DNA positivity in a tracheal swab and by increasing titres of Chlamydia IgM antibody. The patient was treated with doxycycline and steroids and recovered completely. Apart from therapeutic implications, this case may contribute to our understanding of demyelinating diseases of the central nervous system.
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PMID:Chlamydia pneumoniae-associated ADEM. 1097 4

This study used naked DNA vaccination to induce breakdown of tolerance to self and thus elicit immunological memory to native, membrane-bound Fas ligand (FasL). Upon induction of experimental autoimmune encephalomyelitis (EAE), this memory was turned on to provide protective immunity. FasL-specific autoantibodies isolated from protected animals differentially downregulated the in vitro production of TNF-alpha, but not IFN-gamma, by cultured T cells. These autoantibodies were highly protective when they were administered to rats at the onset of EAE. In contrast, administration of these FasL-specific Ab's to EAE rats after the peak of the acute phase of disease prevented spontaneous recovery from disease. This extended illness is partially explained by inhibition of mononuclear cell apoptosis at the target organ, which resulted in increased accumulation of T cells and macrophages at the site of inflammation. Hence, FasL exerts two distinct, stage-specific regulatory functions in the control of this T-cell mediated autoimmune disease of the central nervous system.
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PMID:A targeted DNA vaccine encoding fas ligand defines its dual role in the regulation of experimental autoimmune encephalomyelitis. 1097 20

Organ-specific autoimmune diseases and their animal models are characterized by the finding that the development of the diseases is closely associated with, or induced by, T cells reactive to organ-specific antigens. Therefore, the identification of T cell receptors (TCR) used by disease-inducing T cells within a short period of time is a key factor for designing TCR-based immunotherapy. The findings introduced in this article show that TCR associated with the development of multiple sclerosis and experimental autoimmune diseases including encephalomyelitis (EAE), neuritis (EAN) and carditis (EAC) are identifiable by complementarity-determining region 3 (CDR3) spectratyping analysis and subsequent sequencing of the CDR3 region of spectratype-derived TCR clones. It is also demonstrated that immunotherapy targeting disease-associated TCR using monoclonal antibodies and DNA vaccines significantly reduced the histological severity, and completely suppressed the inflammation in some animals. Since depletion or suppression of one of several types of effector cells does not significantly improve the severity of the disease, combined TCR-based immunotherapy should be considered as a primary therapy for T cell-mediated autoimmune diseases. TCR-based immunotherapy after rapid identification of autoimmune disease-associated TCR by CDR3 spectratyping can be applicable, not only to animal, but also to human autoimmune diseases whose pathomechanism is poorly understood.
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PMID:Characterization of T cell receptor (TCR) of organ-specific autoimmune disease-inducing T cells and TCR-based immunotherapy with DNA vaccines. 1102 29

Gene therapy traditionally has been associated with "gene replacement." where exogenous recombinant DNA is introduced ex vivo into somatic cells that are then introduced back into the patient as a way to correct an inherited genetic defect. However, several novel gene therapy strategies for treating autoimmune diseases recently have emerged. Strategies involving the use of several types of DNA vaccines, the application of various viral vectors, and the use of diverse cellular vectors have shown promise in inhibiting autoimmune-mediated inflammation and repairing tissue damaged as a result of autoimmune attack. In the current review, we examine and discuss the development and proposed use of emerging gene therapy strategies for the treatment of autoimmune disease with specific emphasis on experimental autoimmune encephalomyelitis (EAE), an animal model widely used in multiple sclerosis (MS) research.
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PMID:Gene therapy in experimental autoimmune encephalomyelitis. 1105 Dec 74

Estrogen has been reported to have immunosuppressive functions, and to inhibit the progression of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Since estrogen shows its biological effects via estrogen receptors (ER), we investigate the possible role of ER genes (ERG) in the pathogenesis of MS. PvuII and XbaI polymorphisms in ERG were detected by PCR-RFLP from the DNA of 79 conventional MS patients and 73 healthy controls. The [P] allele in the profiles in PvuII was significantly more prevalent in MS patients than in the controls (P<0.0005). In the study of XbaI polymorphism, the onset age of MS patients with the Xx genotype was earlier than that of the xx genotype group (mean age+/-S.D.; 22.60+/-8.04, and 27.49+/-9.14, respectively) (P<0.05) by ANOVA followed by Fisher's PLSD. Although the Xx genotype group tended to earlier onset age than the XX genotype group (29.60+/-11.10), this difference did not reach. On the basis of these results, PvuII polymorphism might be associated with susceptibility to MS, and XbaI polymorphism with onset age of MS. ERG polymorphism should be further studied in other populations to improve strategies for treatment of MS.
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PMID:Estrogen receptor gene polymorphism in Japanese patients with multiple sclerosis. 1105 88

Vaccination with naked DNA represents a therapeutic strategy currently under consideration in multiple sclerosis (MS). In this study, we tested the potential therapeutic effect of vaccination with a naked DNA construct encoding proteolipid protein (pRc/CMV-PLP) upon the outcome of subsequent sensitization for experimental autoimmune encephalomyelitis (EAE) actively-induced in SJL mice with PLP139-151 peptide in adjuvant. Intramuscular vaccination with the naked DNA pRc/CMV-PLP construct led to PLP expression in local muscle tissue that persisted for about 8 weeks. Early sensitization for EAE (4 weeks after DNA vaccination) caused recipient mice to develop a severe, exacerbated form of disease (in comparison to control mice), while late sensitization (>10 weeks) resulted in a milder, ameliorated form. In the groups sensitized <10 weeks post-DNA vaccination with pRc/CMV-PLP induction of a Th1-type cytokine response was noted. In contrast, sensitization >10 weeks post-DNA vaccination led to peripheral tolerance as evidenced by a decrease in T cell proliferation and cytotoxic T cell response, no Th2 response, and no increase in apoptosis. These data are novel in that they demonstrate a differential effect of DNA vaccination and have important implications for its use as a mechanism to enhance or modulate immune reactivity.
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PMID:Naked DNA vaccination differentially modulates autoimmune responses in experimental autoimmune encephalomyelitis. 1106 19

Lyme borreliosis, multisystem disease, when involve neurologic system is named neuroborrelosis. Symptomatology of neuroborreliosis is rich and various. Difficulties in recognition are connected usually with long period from tick bite to late neurological signs. Any headache and psychiatric disorder in the course of Lyme disease could be an early manifestation of invasion of the CNS by the spirochaetes. Each part of neurologic system could be involved. The most common clinical picture of neuroborreliosis is meningitis with cranial or peripheral neuropathies connected with radiculalgia, less common are encephalitis and myelitis, neuropathies and polyneuropathies, encephalopathies. Encephalomyelitis is the most serious form of neuroborreliosis. From the pathophysiologic point of view all cranial and peripheral neuropathies are forms of mononeuritis multiplex. Vasculitis and autoimmunology processes are present. Encephalopathy is due to neuroimmunomodulators, like lymphokines and by toxico-metabolic effect could be connected with each form of systemic borreliosis. Spheroplast L-form of borrelia could be responsible for difficulties with their eradication. Diagnosis of neuroborreliosis is based on culturing of B. burgdorferi from CSF, detection of specific antispirochaetal antibodies produced in subarachnoid space, detection of activated lymphocytes, other antigens detection in CSF (also after dissociation of complexes) or borrelial DNA sequences.
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PMID:[Neurologic syndromes in Lyme disease]. 1108 32


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