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)

The effect on encephalitogenicity of using a serinyl substitution for the glutaminyl group in the peptide ser arg phe ser trp gly ala glu gly gln arg is reported. We conclude from these results that the function of the glutaminyl residue is assisting this peptide to produce allergic encephalomyelitis in guinea pigs is as a hydrogen donor-receptor.
 ...
PMID:Further definition of the encephalitogenic region for guinea pigs. 6 93

A 1983 human Mississippi isolate of eastern equine encephalomyelitis virus (EEEV), recently identified as an antigenic subtype of the North American variety, was genetically characterized using oligonucleotide fingerprinting and sequencing of viral RNA. This strain was found to be very closely related to other North American EEEV isolates from the same time period. Phylogenetic analysis suggested that this subtype belongs to a single EEEV lineage in North America. Two amino acid substitutions in the E2 envelope glycoprotein, not seen in either other isolates sequenced, probably contributed to the antigenic difference with respect to other EEEV strains. These substitutions include threonine for lysine at position 71, resulting in the addition of a potential N-linked glycosylation site, and lysine for glutamic acid at position 147.
 ...
PMID:Genetic characterization of an antigenic subtype of eastern equine encephalomyelitis virus. 128 Sep 45

Copolymer 1 (Cop 1) is a synthetic basic random copolymer of amino acids that has been shown to be effective in suppression of experimental allergic encephalomyelitis and has been proposed as a candidate drug for multiple sclerosis. Cop 1 is immunologically cross reactive with myelin basic protein (BP) and was shown to inhibit murine BP-specific T-cell lines of various H-2 restrictions. In the present study these findings were extended to include human T-cell lines. Cop 1 competitively inhibited the proliferative responses and interleukin 2 secretion of six BP-specific T-cell lines and 13 clones with several DR restrictions and epitope specificities. Conversely, BP inhibited--albeit to a lesser extent--the response of all the Cop 1-specific T-cell lines and clones, irrespective of their DR restrictions. Another random copolymer of tyrosine, glutamic acid, and alanine, denoted TGA, had no effect on these lines. Neither Cop 1 nor BP inhibited the response of lines and clones specific for purified protein derivative. Cop 1 and BP exerted their cross-inhibitory effects only in the presence of antigen-presenting cells. These results suggest that Cop 1 can compete with BP for the binding to human major histocompatibility complex molecules. In view of recent studies implicating BP reactivity in multiple sclerosis, these findings suggest a possible mechanism for the beneficial effect of Cop 1 in this disease.
 ...
PMID:Synthetic copolymer 1 inhibits human T-cell lines specific for myelin basic protein. 137 Mar 47

Cop 1 is a synthetic basic random copolymer of L-alanine, L-glutamic acid, L-lysine, and L-tyrosine in a residue molar ratio of 6.0:1.9:4.7:1.0 and with a molecular weight of 21,000 which proved to be effective in specific suppression of experimental allergic encephalomyelitis and has been proposed as a candidate drug against multiple sclerosis. In the present study we further investigated the mechanism of Cop 1 suppressive activity and tested whether Cop 1 could inhibit the specific T-cell response to myelin basic protein (BP). Eight BP-specific T-cell lines and clones with various H-2 restrictions and antigenic specificities were used. The responses of all these lines and clones to BP, as followed by both cell proliferation and interleukin 2 secretion assays, were affected by Cop 1. For one line, a direct cross proliferation with Cop 1 was observed, whereas in the other seven lines and clones, Cop 1 specifically inhibited the responses to BP in a competitive dose-dependent manner. The inhibition of the response to BP is specific to Cop 1, as D-Cop 1 and another random acidic polymer, poly(Tyr,Glu,Ala) (TGA), both of which were previously demonstrated to be ineffective in suppression of experimental allergic encephalomyelitis, did not inhibit the response to BP. Furthermore, Cop 1 specifically inhibited only the response of the T-cell lines and clones to BP. It did not inhibit their response to the mitogen Con A, nor did it inhibit the responses of the purified protein derivative-specific T-cell line and clone. These results suggest that Cop 1 may be effective in suppression of experimental allergic encephalomyelitis, not only because of the selective stimulation of suppressor T cells, as we have previously demonstrated, but also by specific inhibition of BP-specific effector T cells.
 ...
PMID:Specific inhibition of the T-cell response to myelin basic protein by the synthetic copolymer Cop 1. 246 52

Cop 1 is a random polymer (molecular weight, 14,000 to 23,000) simulating myelin basic protein. It is synthesized by polymerizing L-alanine, L-glutamic acid, L-lysine, and L-tyrosine. It suppresses but does not induce experimental allergic encephalomyelitis, an animal model of multiple sclerosis. It is not toxic in animals. In a double-blind, randomized, placebo-controlled pilot trial, we studied 50 patients with the exacerbating-remitting form of multiple sclerosis, who self-injected either 20 mg of Cop 1 dissolved in 1 ml of saline or saline alone daily for two years. Six of 23 patients in the placebo group (26 percent) and 14 of 25 patients in the Cop 1 group (56 percent) had no exacerbations (P = 0.045). There were 62 exacerbations in the placebo group and 16 in the Cop 1 group, yielding two-year averages of 2.7 and 0.6 per patient, respectively. Among patients who were less disabled on entry (Kurtzke disability score, 0 to 2), there were 2.7 exacerbations in the placebo group and 0.3 in the Cop 1 group over two years. Among patients who were more affected (Kurtzke disability score, 3 to 6), there was an average of 2.7 exacerbations in the placebo group and 1.0 in the Cop 1 group. Over two years, less disabled patients taking Cop 1 improved an average of 0.5 Kurtzke units; those taking placebo worsened an average of 1.2 Kurtzke units. More disabled patients worsened by 0.3 (Cop 1 group) and 0.4 (placebo group) unit. Irritation at injection sites and rare, transient vasomotor responses were observed as side effects. These results suggest that Cop 1 may be beneficial in patients with the exacerbating-remitting form of multiple sclerosis, but we emphasize that the study is a preliminary one and our data require confirmation by a more extensive clinical trial.
 ...
PMID:A pilot trial of Cop 1 in exacerbating-remitting multiple sclerosis. 330 5

The effect of methotrexate and of silyl-methotrexate were compared in the treatment of experimental allergic encephalomyelitis (EAE) mediated by T-line lymphocytes. It was demonstrated that, during the first three days after cell transfer, no difference between methotrexate and its silyl derivative could be seen. At a time when the cytotoxic lymphoblasts must have penetrated the blood brain barrier, only silyl methotrexate was able to prevent severe paralysis and death of the animals. It is suggested that the effect of N,N,O,O-Tetrakis (t-butyldimethylsilyl)-methotrexate, (N-4-N-(2,3-bis-t-butyldimethylsilyl-amino-6-pteridinyl-methyl)- methylamino-benzoyl-glutamic acid-bis-(t-butyldimethylsilyl)-ester), depends on the increased lipid solubility and permeability of the blood brain barrier of silylated drugs.
 ...
PMID:The effect of silyl substituted methotrexate in the treatment of experimental allergic encephalomyelitis in rats mediated by T-line cells. 349 44

This study was undertaken to test the hypothesis that preferential responder strain-specific Ia expression can be detected in delayed hypersensitivity (DH) skin reactions. Seven adult (strain 2 X strain 13)F1 and two strain 13 guinea pigs were sensitized with poly-L glutamic acid-lysine (GL), poly-L glutamic acid-tyrosine (GT), and bovine insulin in complete Freund's adjuvant, and were skin tested with GL, GT, PPD, bovine insulin, porcine insulin (which has the same B chain as bovine insulin), and saline. Strain 2 guinea pigs react with bovine insulin A chain, GL, and PPD but not with GT or the bovine insulin B chain, whereas strain 13 guinea pigs react with bovine insulin B chain, GT, and PPD but not with GL or bovine insulin A chain. The (2 X 13)F1 animals had positive DH responses to GT, GL, PPD, and bovine insulin. At 24 hr, areas of induration were measured and the test sites and draining lymph nodes were biopsied. Cryostat sections were stained with monoclonal antibodies to strain 2 Ia, strain 13 Ia, and Ia framework determinants with immunoperoxidase. Stained dermal and subdermal inflammatory cells and vessels were counted on coded slides. In GT tests, there was more staining of dermal and subdermal cells and vessels for strain 13 Ia than strain 2 Ia (p less than 0.02). In bovine insulin tests there was more staining of dermal cells and vessels for strain 13 than strain 2 Ia (p less than 0.05). In GL tests there was more staining on dermal vessels and subdermal cells and vessels of strain 2 Ia than strain 13 Ia (p less than 0.05). There was much greater staining of strain 2 Ia of dermal cells and vessels in GL tests compared with strain 2 Ia staining in GT and bovine insulin tests (p less than 0.02, cells; p less than 0.01, vessels). No significant differences between strain 2 and strain 13 Ia expression were found in PPD, porcine insulin tests, saline controls, or in lymph nodes that drained sensitization sites from animals in which GL and GT had been injected on different sides. Anti-Ia framework expression generally correlated with the greater parental strain Ia in each reaction. These findings and previous observations in experimental allergic encephalomyelitis suggest that responder type Ia may be selectively found in vivo on mononuclear and endothelial cells in sites of T cell-mediated hypersensitivity reactions.
 ...
PMID:Responder strain-specific enhancement of endothelial and mononuclear cell Ia in delayed hypersensitivity reactions in (strain 2 X strain 13)F1 guinea pigs. 353 27

A synthetic polypeptide, copolymer I (COP I), composed of alanine, glutamic acid, lysine, and tyrosine, has been demonstrated to be nonencephalitogenic and nontoxic in laboratory animals, yet it is capable of suppressing experimental allergic encephalomyelitis. A preliminary open trial examined the ability of COP I to alter the course of disease in 12 patients with chronic progressive and 4 with exacerbating-remitting multiple sclerosis (MS). After therapy for as long as two years or more, no undesirable side reaction was noted in any patient. Three patients with chronic progressive MS and 2 with exacerbating-remitting disease are better. These results, which may represent simply a placebo effect or may be a significant response, are now being examined in randomized, placebo-controlled, double-blind pilot trials.
 ...
PMID:Multiple sclerosis: trial of a synthetic polypeptide. 709 85

Copolymer 1 (Cop 1) is a random synthetic amino acid copolymer of L-alanine, L-glutamic acid, L-lysine, and L-tyrosine, effective both in suppression of experimental allergic encephalomyelitis and in the treatment of relapsing forms of multiple sclerosis. Cop 1 binds promiscuously and very efficiently to living APCs of various HLA haplotypes. In the present study, a substantial part of the whole mixture of random polypeptides that compose Cop 1 was shown to bind to purified human HLA-DR1, DR2, and DR4 with high affinity in a temperature- and time (and, in the case of DR4, pH)-dependent manner, and was competitively inhibited by DR-restricted peptides, but not by peptide derivatives that bind with low affinity. Bacterial superantigens inhibited Cop 1 binding only at very high concentrations. The formation of the Cop 1-DR1 complex was also shown by SDS-PAGE. These findings represent the first direct evidence for interactions of Cop 1 with purified DR molecules, and suggest that its effectiveness in experimental allergic encephalomyelitis and multiple sclerosis may be directly related to its binding in the groove of HLA-DR proteins.
 ...
PMID:Promiscuous binding of synthetic copolymer 1 to purified HLA-DR molecules. 957 43

Copolymer 1 [poly(Y,E,A,K)] is a random synthetic amino acid copolymer of L-tyrosine, L-glutamic acid, L-alanine, and L-lysine that is effective both in suppression of experimental allergic encephalomyelitis and in the treatment of relapsing forms of multiple sclerosis. Copolymer 1 binds promiscuously and very efficiently to purified HLA-DR molecules within the peptide-binding groove. In the present study, YEAK and YEAK-related copolymers and type II collagen (CII) peptide 261-273, a candidate autoantigen in rheumatoid arthritis (RA), competed for binding to RA-associated HLA-DR molecules encoded by DRB1*0101 and DRB1*0401. Moreover, these copolymers (particularly YEAK, YAK, and YEK) inhibited the response of DR1- and DR4-restricted T cell clones to the CII epitope 261-273 by >50%. This direct evidence both for competitive interactions of these copolymers and CII peptide with RA-associated HLA-DR molecules and for inhibition of CII-specific T cell responses suggests that these compounds should be evaluated in animal models for rheumatoid arthritis.
 ...
PMID:Synthetic amino acid copolymers that bind to HLA-DR proteins and inhibit type II collagen-reactive T cell clones. 977 May 19


1 2 Next >>