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)

A 17-residue peptide (Peptide Y) was isolated from the COOH-terminal end of the basic protein of bovine myelin by peptic digestion. This peptide induced experimental allergic encephalomyelitis in the rhesus monkey. Treatment of Peptide Y with cyanogen bromide released three amino acids from the COOH-terminal end and resulted in a tetradecapeptide (Peptide M) which was also encephalitogenic in the rhesus monkey. The sequence of Peptide M is: Phe-Lys-LEU-Gly-Gly-Arg-Asp-Ser-Arg-Ser-Gly-Ser-Pro-Met. Thus a major disease-inducing site active in the rhesus monkey is contained within a 14-residue peptide localized near the COOH-terminal end of the protein. This peptide differs markedly in location and sequence from the 9-residue peptide shown to contain the encephalitogenic determinant for the guinea pig.
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PMID:Allergic encephalomyelitis. Isolation of an encephalitogenic peptide active in the monkey. 4 30

Myelin basic proteins and peptides derived from them by limited cleavage with pepsin were tested for their ability to induce experimental allergic encephalomyelitis (EAE) in Lewis rats. The encephalitogenicity of the weakly active bovine protein was found to be associated with both halves of the molecule, peptides (1-88) and (89-169). Of the four smaller derivates of peptide (1-88), peptides (1-36), (43-88), (1-42), and (37-88), only the last two were active. This demonstrated that the overlap region consisting of residues 37-42 (sequence Asp-Ser-Leu-Gly-Arg-Phe) constitutes an encephalitogenic determinant. Of the two smaller derivatives of peptide (89-169), peptides (111-169) and (89-152), only the last was active. This indicated that the second encephalitogenic determinant begins between residues 88 and 111 and ends before residue 153. This region contains the sequence Leu-Ser-Leu-Ser-Arg-Phe (residues 108-113), which is strikingly similar to that of the first encephalitogenic determinant. Studies involving the extremely encephalitogenic guinea pig protein demonstrated that virtually all of the activity was recovered in the peptides corresponding to bovine peptides (37-88) and (43-88). These peptides, but not those comprising the remainder of the protein, were active in inhibiting the passive transfer of EAE with lymph node cells from donors immunized with guinea pig spinal cord.
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PMID:The location of regions in guinea pig and bovine myelin basic proteins which induce experimental allergic encephalomyelitis in Lewis rats. 4 54

Two peptic fragments (residues 37-88 and 43-88) of guinea pig myelin basic protein which are capable of inducing experimental allergic encephalomyelitis in Lewis rats were cleaved to shorter fragments with alpha-protease (Crotalus atrox proteinase, EC 3.4.24.1) and thermolysin (EC 3.4.24.4). The fragments were isolated, purified, and identified by amino acid composition and NH2- and COOH-terminal residues. The time courses of the reactions, monitored by thin layer electrophoresis of the digests, showed that alpha-protease cleaves peptide (43-88) initially at the Pro(71)-Gln(72) bond, and that the product peptides are subsequently attacked at the Arg(63) -Thr(64), Ser(74)-Gln(75), Arg(78)-Ser(79), and Ser(76)-Gln(80) bonds. No significant cleavages occurred at the -Leu, -Val, and -Ala bonds. These results are in striking contrast to those obtained previously by others workers with other peptide substrates, where selective cleavage at hydrophobic residues occurred. Thermolysin was found to attack peptide (37-88) at the Phe(42)-Phe(43) bond very rapidly; the product peptides were subsequently attacked at the His(60)-Ala(61), Ser(38)-Ile(39)-Tyr(67)-Gly(68), and Pro(84)-Val(85) bonds. These cleavages are compatible with the known specificity of this enzyme. Several of the fragments prepared with these two enzymes, peptides (43-71), (61-88), (75-88), and (72-84) have been used in other studies to locate the encephalitogenic site in the parent peptic peptide.
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PMID:Treatment of an encephalitogenic peptide from guinea pig myelin basic protein with alpha-protease and thermolysin. Isolation of fragments and determination of cleavage sites. 6 52

Two amino acid sequences from the same regions of guinea pig and bovine myelin basic protein which induce experimental allergic encephalomyelitis in Lewis rats were synthesized. The sequences of these two regions may be defined by residues 69 to 84 of the bovine basic protein. The encephalitogenic sequence from guinea pig basic protein (peptide S49), H-Gly-Ser-Leu-Pro-Gln-Lys-Ala-Gin-Arg-Pro-Gin-Asp-Glu-Asn-OH, is a much more potent encephalitogen than that of H-Gly-Ser-Leu-Pro-Gln-Lys-Ala-Gln-Gly-His-Arg-Pro-Gln-Asp-Glu-Asn-OH (peptide S8) found in the bovine protein. The primary structures of the two determinants are similar; however, a Gly-His deletion from the guinea pig sequence is noted. Study of the encephalitogenicity of peptide S49, peptide S8, and the parent proteins suggests that the difference in the encephalitogenic potency of the parent proteins in Lewis rats is due to a natural modification in the primary structure of their respective encephalitogenic determinants.
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PMID:Experimental allergic encephalomyelitis in Lewis rats: chemical synthesis of disease-inducing determinant. 6 39

After in vitro incubation of brain slices from guinea pigs in the intermediate (10 days postinduction) stage of experimental allergic encephalomyelitis (EAE), incorporation of [14C]leucine into protein was increased in a glial-enriched fraction. By the late (17-18 days postinduction) stage of the disease, when EAE symptoms were manifest, both the neuronal- and glial-enriched fractions showed increased specific activity of their total protein. SDS polyacrylamide gel electrophoresis showed that the increased leucine incorporation occurred in those proteins which labeled in a control material. After intraperitoneal injection of [3H]leucine the incorporated radioactivity was slightly increased in unfractionated brains from EAE animals. The neuronal-glial ratios for protein-bound radioactivity indicated that the increased incorporation resided mainly in the glial population.
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PMID:Amino acid incorporation into neurons and glia of guinea pigs with experimental allergic encephalomyelitis. 111 9

The in vitro protein synthetic capactiy of brain slices from guinea-pigs in the late stage (17-18 days post-induction) of experimental allergic encephalomyelitis was increased over that of Freund's adjuvant injected controls, as determined by the rate of (14C)-leucine incorporation into both tris-soluble and tris-insoluble proteins. All subcellular fractions prepared from incubated slices showed increased incorporation, with a crude nuclear fraction having the largest increase. Isolated brain mitochondria from EAE animals incorporated more amino acid into protein during the late stage of the disease, while isolated microsomes and "pH5 enzymes" show decreased amino acid incorporation compared with controls in the late stage of EAE. Polyacrylamide gel electrophoresis of acidic, soluble proteins isolated from (3H)-leucine labeled nuclear or synaptosomal fractions revealed that increases of incorporation were generalized, and not restricted to a few proteins.
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PMID:Amino acid incorporation into brain subcellular fractions in experimental allergic encephalomyelitis. 114

Methionine-enkephalin (Met-Enk) and leucine-enkephalin (Leu-Enk) belong to family of opioid peptides. In vivo studies on immunomodulating activity of enkephalins performed in the rat revealed the following: (a) both neuropentapeptides showed a dual, dose-dependent effect, i.e., high doses suppressed while low doses potentiated immune responses; (b) Met-Enk is more potent immunomodulator than Leu-Enk; (c) high doses of Met-Enk suppressed immune inflammatory reactions, such as systemic anaphylactic shock, Arthus and delayed hypersensitivity skin reactions to protein antigen, allograft rejection, adjuvant arthritis, and experimental allergic encephalomyelitis. Met-Enk is more efficient when applied intracerebroventricularly. A preliminary clinical trial showed that intrathecally given Met-Enk exerted a beneficial effect on 13 patients with chronic severe progressive multiple sclerosis.
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PMID:Enkephalins and immune inflammatory reactions. 166 93

In vivo therapy with monoclonal antibody (mAb) GK1.5, which recognizes a glycoprotein antigen designated L3T4 on murine helper T lymphocytes, either prevented or suppressed the development of murine lupus, autoimmune encephalomyelitis, and collagen arthritis. The L3T4 antigen in the mouse is analogous to the human Leu-3/T4 antigen expressed on helper T lymphocytes, because they both participate in the T cell response to class II major histocompatibility complex (MHC) antigens. Class II MHC genes and I-A antigens mediate murine experimental autoimmune myasthenia gravis (EAMG) induced by acetylcholine receptor (AChR) autoimmunity. We studied the efficacy of mAb GK1.5 as an immunotherapeutic agent for murine EAMG. Therapy with mAb GK1.5 not only suppressed established autoimmunity to AChR but also prevented loss of muscle AChR in mice with EAMG. Moreover, permanent remission of clinical muscle weakness was induced if mAb GK1.5 therapy was initiated after the onset of clinical disease. Because the function of the Leu-3/T4 determinant on human helper T lymphocytes is analogous to the murine L3T4 determinant, use of antibody to the Leu-3/T4 determinant as an immunotherapeutic agent may provide a way to control the progression of human MG.
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PMID:Immunotherapy for myasthenia gravis: a murine model. 241 35

In order to determine if axonal transport changes in chronic experimental allergic encephalomyelitis (EAE) were due to blockade or increased discharge of fast transported proteins from the inner retina, we examined the presence of pulse labeled proteins in autoradiograms of the optic nerve head, retinal ganglion cell and nerve fiber layers of juvenile strain-13 guinea pigs with chronic EAE and normal controls. Quantitative analysis of silver grains, performed six and twenty-four hours following the intravitreal injection of tritiated leucine, showed a decrease in inner retinal radioactivity in those with EAE, whereas no difference was detected between the two groups after three days. Grain counts within the optic nerve heads of guinea pigs with EAE were reduced at all time intervals studied. These results are consistent with an increase in discharge of fast transported proteins from retinal ganglion cells into optic nerve axons and support our previous observations of increased radioactivity at the foci of optic nerve demyelination.
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PMID:Quantitative analysis of labelled inner retinal proteins in experimental optic neuritis. 270 41

In order to determine if changes in axonal transport were different in adult animals with acute experimental allergic encephalomyelitis (EAE), in comparison to juvenile animals with chronic EAE, the effects of this acute demyelinating disorder on axonal transport were examined in the optic nerves of adult strain-13 guinea pigs. Utilizing autoradiographic analysis of silver grain counts, both the fast and slow components of orthograde transport were studied at intervals of thirty minutes, three hours, one day and three days after tritiated leucine injection into the vitreous cavity. In order to determine the contribution of fiber loss in acute EAE, optic nerve fiber density was analyzed from electron micrographs of normal and demyelinated nerves. Animals with acute EAE had a decrease in radioactivity at the lamina retinalis and lamina choroidalis after thirty minutes and three hours, and at the lamina scleralis and foci of demyelination after one and three days. A 16% loss of fibers did not account for as much as a 74% reduction in radioactivity with acute EAE. The global reductions in axonal transport observed in acute EAE animals may contribute to their progressive deterioration and eventual demise by lack of delivery of tubulo-vesicular materials for synaptic transmission, axolemmal proteins for electrogenesis and neurofilamentary components of the cytoskeleton. Moreover, they are unlike the increase of fast axonal transport associated with recovery of physiologic function characteristic of animals with the chronic form of the disease.
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PMID:Axonal transport reductions in acute experimental allergic encephalomyelitis: qualitative analysis of the optic nerve. 270 42


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