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)

The effects of neuroantigen-specific tolerance on the induction and effector stages of relapsing experimental autoimmune encephalomyelitis (R-EAE) were examined. The incidence of clinical and histologic signs of active MSCH-induced R-EAE, and accompanying neuroantigen-specific DTH responses, were dramatically reduced in SJL/J mice tolerized via the i.v. injection of syngeneic splenocytes coupled with MSCH, PLP, or encephalitogenic PLP peptides 7-14 days before priming. MBP-specific tolerance was not effective in preventing active R-EAE. In contrast to MSCH-induced active R-EAE, treatment of recipient mice with splenocytes coupled with MBP and the encephalitogenic MBP 84-104 peptide, but not with PLP, suppressed of clinical signs of adoptive R-EAE mediated by MBP-specific effector T cells in a dose-dependent manner. Neuroantigen-coupled splenocytes were also efficient in treating established disease as tolerization of SJL/J mice after the first incidence of clinical disease significantly reduced the incidence and severity of subsequent paralytic relapses. Antigen-specific tolerance thus provides a powerful approach for the prevention and/or treatment of autoimmune disease.
Ann N Y Acad Sci 1991 Dec 30
PMID:Specific immunoregulation of the induction and effector stages of relapsing EAE via neuroantigen-specific tolerance induction. 172 64

The homing and adhesion of circulating cells to target tissue vasculature precedes their subsequent invasion of inflamed tissue. Polymorphonuclear cells (PMNs), key players in most inflammatory events, are among the first cells to arrive. The present work, performed on CNS lesions from mice with experimental autoimmune encephalomyelitis, provides morphologic evidence for interactions between PMNs and unique, frondlike extensions from endothelial cells (EC) during early attachment. Platelets also were seen attached to these endothelial fronds. The structures projected into vessel lumina from the vicinity of tight junctions and were often branched and complex, the latter characteristics suggesting a possible role in cellular 'trapping'. Polymorphonuclear cells appeared to traverse the CNS vasculature between EC where the blood-brain barrier was severely compromised with junctional complexes reduced to simple contact points. The cells from which the fronds derived were often plump and possessed cytoplasm rich in organelles, perhaps indicative of activation. The present report contrasts with previous observations on lymphocytes in the same system where lymphocytic pseudopodia formed intimate contacts before their burrowing directly through the endothelium and where EC fronds were not involved.
Am J Pathol 1991 Dec
PMID:Central nervous system endothelial cell-polymorphonuclear cell interactions during autoimmune demyelination. 175 May 10

The immunomodulatory action of corticosteroids and the ability of central noradrenergic systems to activate the hypothalamic-pituitary-adrenal (HPA) axis led us to investigate the relationship between neuroendocrine status and the clinical course of encephalomyelitis (EAE) following adrenalectomy and depletion of noradrenaline (NA) centrally or peripherally. A significant inverse correlation was found between hypothalamic NA and serum corticosterone (CS) at peak clinical signs of EAE in all the sham groups or when NA was depleted only in the peripheral nervous system. A positive correlation was found between serum CS and disease severity, and in all experimental groups with intact peripheral and/or central noradrenergic pathways a uniformly increased splenic NA content was also observed at peak disease. Administration of 6-OHDA i.p. to neonatal or adult Lewis rats produced a significant depletion of splenic NA alone which resulted in increased disease severity, despite the fact that circulating CS was elevated. Thus the rise in the NA content of lymphoid tissue at peak clinical signs contributes to recovery. A single i.c.v. injection of 6-OHDA into the hypothalamic region resulted in an 80% reduction in NA content, which subsequently modified the clinical severity of EAE. Serum CS levels rose preclinically in the treated group and remained high despite milder clinical disease than that seen in the sham group. The overriding immunoregulatory influence of glucocorticoids is demonstrated by the rapid onset of clinical EAE and morbidity in adrenalectomized animals. However, the strong inverse correlation found between hypothalamic NA and circulating CS indicates that regulation of the HPA axis may ultimately be controlled by central sympathetic pathways.
Brain Behav Immun 1991 Dec
PMID:Hypothalamic noradrenergic pathways exert an influence on neuroendocrine and clinical status in experimental autoimmune encephalomyelitis. 177 27

We describe a case of continuous motor unit potential (MUP) activity of central origin (unlike stiff man syndrome and progressive encephalomyelitis) characterized clinically by rigidity, painful muscle spasms, abnormal postures and spinal myoclonus. The topography of the manifestations, the subacute and benign course, the presence of stable sequels 2 years after onset and a searching process of differential diagnosis lead us to attribute the condition to an inflammation of the cord, which makes the case of particular clinical interest.
Ital J Neurol Sci 1991 Dec
PMID:Rigidity and painful muscle spasms in a patient with probable myelitis. 178 38

Experimental allergic encephalomyelitis is characterized by invasion of lymphocytes and macrophages into the central nervous system resulting in inflammation, edema, and demyelination. Sera from Lewis rats from 7-95 days after immunization with purified guinea pig CNS myelin were examined with respect to their ability to opsonize myelin. This was correlated with the appearance of antibody components and the relative amounts of antibody to myelin basic protein (MBP) and proteolipid protein (PLP). Sera from rats 10-95 days after immunization preincubated with purified myelin induced phagocytosis of myelin by cultured macrophages with the resulting production of cholesterol ester. This opsonization activity as measured by the percentage of cholesterol esterified reached a peak at 26-27 days after immunization but remained significantly elevated up to 95 days post-immunization compared to the activity of serum from the Freund's adjuvant-injected controls. Immunoblots of the sera revealed a gradual increase in antibody activity against myelin components. ELISA assays for MBP and PLP antibody showed a similar pattern. Antibody to galactocerebroside (GC) was not detected by immunostains nor by the ELISA assay. Areas of demyelination were observed histologically by luxol-fast blue stained spinal cords up to 60 days post-immunization. These results indicate that antibodies to myelin protein when given access to myelin through or within the blood brain barrier could initiate or enhance the phagocytic response by peripheral or resident macrophages.
J Neurosci Res 1991 Dec
PMID:Induction of anti-myelin antibodies in EAE and their possible role in demyelination. 178 38

The effectiveness and the mechanism of T cell vaccination were studied in two experimental models of autoimmune disease. The attempt to modulate autoimmune disease via idiotypic regulation of autoreactive antigen-specific T cells was first shown in the rat experimental autoimmune encephalomyelitis (EAE) model where inactivated EAE-inducing T cells could both immunize and protect rats from EAE. We previously reported that low dose T cell vaccination against EAE in Lewis rats was immunologically specific, long lasting and extremely efficient in preventing adoptive transfer of the disease. In experimental autoimmune uveitis (EAU) T cell vaccination was also found to be effective. In both cases, antigen or mitogen activation of the T cells prior to inoculation was required. In the EAE model, T cell vaccination appeared to be associated with two sets of T lymphocytes (CD4+ CD8- helper and CD4- CD8+ cytotoxic/suppressor cells) which were cloned and found to be specifically reactive to the vaccine cells. These anti-idiotypic T cell clones were able to antagonistically modulate the in vitro proliferation of encephalitogenic Z1a cells. In vivo, transfer of the lymph node cells (from which the anti-idiotypic clones were derived) from vaccinated animals to naive syngeneic recipients conferred resistance to EAE. In the EAU model, we also found a consistent immunological response raised against different activated T cells (four T cell lines with irrelevant specificities and mitogen-activated lymphoid cells) in addition to the anti-idiotypic cells. This response, apparently directed to T cell activation markers, might combine with the anti-idiotypic response to regulate autoimmunity.
Ann N Y Acad Sci 1991 Dec 30
PMID:T cell vaccination in autoimmune diseases. 179 4

This study explores the usage of T cell antigen receptor (TCR) beta chain elements in Lewis rats with experimentally induced allergic encephalomyelitis (EAE). TCRs from 15 different T cell clones and hybridomas derived from animals immunized with myelin basic protein (MBP), and all having specificity for the 21-mer encephalitogenic fragment MBP 68-88, utilized V beta 8.2. In addition, there was a marked conservation of the first two amino acid residues of the junctional complementarity determining region 3 (CDR3) associated with the V beta 8.2 receptors. 12 of 15 contained an aspartic acid followed by serine regardless of the associated J beta element. At the nucleotide level, this conservation of AspSer residues was accomplished with few or no nongermline-encoded nucleotide (N) additions. A similar pattern of AspSer usage and N region nucleotide additions was observed in a number of V beta 8.2 isolates derived from MBP-immunized lymph nodes. In contrast, V beta 8.2 polymerase chain reaction amplified isolates from Lewis T cells activated with concanavalin A or from lymph nodes of complete Freund's adjuvant-immunized animals showed no AspSer utilization (0/31) in the CDR3, and four to nine N region nucleotide additions. We conclude from this finding that AspSer residues in the CDR3, limited N region nucleotide additions, along with V beta 8.2 sequences, contribute to TCR specificity for MBP 68-88. This raises the possibility that encephalitogenic, disease-causing T cells either represent a population that derives from late fetal life or alternatively, that they are rare cells with this particular TCR phenotype contributed to the T cell pool throughout adulthood and are selected by antigen. In either case, the CDR3 AspSer sequences as well as V beta 8.2 sequences are candidates for the receptor target structures recognized by regulator T cells in recovery from and resistance to active EAE. In this respect, a preliminary analysis of TCR utilization in three T cell clones specific for MBP 68-88 isolated from animals recovered from active EAE indicates that while all three use V beta 8.2, only one contains AspSer in the CDR3.
J Exp Med 1991 Dec 01
PMID:Analysis of T cell receptor beta chains in Lewis rats with experimental allergic encephalomyelitis: conserved complementarity determining region 3. 183 12

Intracerebral inoculation of susceptible mice with Theiler's murine encephalomyelitis virus induces a demyelinating disease that is similar to human multiple sclerosis. This murine model for human multiple sclerosis is apparently immune-mediated and the genes involved in the immune response influence the outcome of disease susceptibility as observed with human multiple sclerosis. These genes include the MHC and TCR genes. However, the functional relationships among these genes on the disease susceptibility has not yet been studied. In this study, we demonstrate that the effect of the H-2s genotype from susceptible SJL/J mice overrides the resistant effect of the BALB/c TCR beta-chain gene in CXJ recombinant-inbred and BALB.S congenic mice. These results strongly suggest the presence of a hierarchy of genes involved in the immune response in Theiler's murine encephalomyelitis virus-induced demyelinating disease.
J Immunol 1991 Dec 15
PMID:Hierarchy of effects of the MHC and T cell receptor beta-chain genes in susceptibility to Theiler's murine encephalomyelitis virus-induced demyelinating disease. 183 84

The effect of neurotropin, an extract isolated from the inflamed skin of rabbits inoculated with Vaccinia virus was examined on acute experimental allergic encephalomyelitis (EAE) in Lewis rats. A dose of 40 mg per kg body weight of neurotropin was administered intraperitoneally for 7 days post-inoculation. The severity of clinical signs of acute EAE was decreased by the administration of neurotropin. Histopathologic evaluation showed that lesion severity of EAE in neurotropin-treated rats was less than that seen in untreated rats. Blood lymphocyte subset analysis revealed that in comparison to untreated EAE rats, in neurotropin-treated rats, the percentage of OX6+ (Ia antigen) cells was lower and the W3/25+ (helper T cell): OX8+ (suppressor/cytotoxic T cell) cell ratio was greater during the period of peak inflammation. Immunohistochemical examination of neurotropin-treated rats demonstrated that OX6+ and W3/25+ cells within EAE lesions were fewer and that OX8+ cells in lesions occurred in greater numbers than those in untreated rats. These findings suggest that the OX8+ cells in the inflammatory lesions may have been induced by neurotropin treatment and that the suppressive effects on the disease may have been causally related to their presence.
J Neuroimmunol 1991 Dec
PMID:Suppression of acute experimental allergic encephalomyelitis by neurotropin: clinical, histopathologic, immunologic and immunohistochemical studies. 195 67

Experimental allergic neuritis (EAN) was studied in the SJL/J mouse and compared to EAN in the Lewis rat. The Lewis rat developed hind limb weakness and weight loss while the SJL/J mouse had no discernible clinical abnormalities. The SJL/J mouse, however, suffered subclinical damage to peripheral nerve (PN) myelin. Both species reproducibly developed electrophysiologic dysfunction of PN and histopathology confined to the peripheral nervous system (PNS). Understanding of autoimmune demyelination in the central nervous system was greatly enhanced by the development of experimental allergic encephalomyelitis in the SJL/J mouse. We believe that EAN in the SJL/J mouse could lead to a similar increase in our understanding of autoimmune demyelination in the PNS.
J Neuroimmunol 1991 Dec
PMID:Experimental allergic neuritis in the SJL/J mouse: dysfunction of peripheral nerve without clinical signs. 195 68


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