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

There is a large number of interactions at molecular and cellular levels between the nervous system and the immune system. It has been demonstrated that the opioid neuropentapeptide methionine-enkephalin (Met-Enk) is involved in humoral and cell-mediated immune reactions. Met-Enk injected peripherally produces a dual and dose-dependent immunomodulatory effect: high doses suppress, whereas low doses potentiate the immune reactivity. The present mini-review concerns the immunological activity of Met-Enk after its administration into the lateral ventricles of the rat brain, and describes the extraordinary capacity of centrally applied Met-Enk to regulate/modulate the immune function. This survey is composed of sections dealing with (a) the role of opioid peptides in the central nervous system (CNS); (b) the activity of opioid peptides in the immune system; (c) the application of Met-Enk into the cerebral cavity; (d) the influence of centrally administered Met-Enk on nonspecific local inflammatory reaction; (e) the effect of Met-Enk injected intracerebroventricularly (i.c.v.) on specific delayed hypersensitivity skin reaction, experimental allergic encephalomyelitis, anaphylactic shock, plaque-forming cell response, and hemagglutinin production; (f) the central antagonizing action of quaternary naltrexone, an opioid antagonist that does not cross the brain-blood barrier, on Met-Enk-induced immunomodulation; (g) the alteration of immune responsiveness by i.c.v. injection of enkephalinase-degrading enzymes; (h) the participation of the brain-blood/blood-brain barrier in the CNS-immune system interaction; and (i) the role of opioid receptors in immunological activity of Met-Enk. A hypothesis has been advanced for the reaction of Met-Enk and opioid receptor sitting on the cell membrane. This concept suggests that the constellation of chemical residues of enkephalin and receptor in the microenvironment determines the binding between the opioid partners. The plurality of conformational structures of enkephalins and receptors makes possible their involvement in a variety of processes which occur in different physiological systems, including the nervous system and the immune system, and intercommunications between the two systems.
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PMID:Enkephalins, brain and immunity: modulation of immune responses by methionine-enkephalin injected into the cerebral cavity. 130 37

The dominant immune response to rat myelin basic protein in H-2u mice is directed against the acetylated, N-terminal peptide Ac1-11 (AcASQKR-PSQRHG). This peptide causes encephalomyelitis on injection into mice of the H-2u haplotype. Only two residues of the peptide are required for ligation of the TCR from an Ac1-11-specific T cell hybridoma. Proline at position 6 could not be substituted by any other L-amino acid, whereas glutamine at position 3 could be replaced by phenylalanine, histidine, methionine, or tyrosine. Cross-reactive recognition of these residues appears to be specific, because increasing the affinity of each analogue for its MHC restriction element, by replacing lysine with tyrosine at position 4, did not alter the pattern of cross-reactivity. For the majority of substitutions at this position, a lack of stimulation could not be explained by failure to bind to I-Au. However, competition binding studies showed that introduction of proline at position 3 reduced the efficacy of binding to I-Au. Cross-reactive analogues of Ac1-11 were injected into H-2u mice to test the extent to which cross-reactive T cell activation might lead to autoimmune disease in this model. An analogue containing methionine at position 3 caused clinical experimental autoimmune encephalomyelitis in a small percentage of H-2u mice.
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PMID:Cross-reactive antigen recognition by an encephalitogenic T cell receptor. Implications for T cell biology and autoimmunity. 138 32

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

Our previous investigations have shown that the opioid peptide methionine-enkephalin (Met-Enk) modulates in vivo a variety of humoral and cell-mediated immune performances. In this study, rats bearing polyethylene cannulae permanently inserted into the lateral ventricles of the brain were used. Experimental allergic encephalomyelitis (EAE) was induced with guinea pig spinal cord in complete Freund's adjuvant injected into the left hind foot pad. The following groups of cannulated rats were tested: nontreated with Met-Enk or saline, intracerebroventricularly (i.c.v.) injected with saline, and i.c.v. treated with low (1 microgram/kg) dose of Met-Enk and high (1 mg/kg) dose of Met-Enk. Intact noncannulated rats sensitized for EAE served as an additional control. The results showed that i.c.v. treatment with 1 microgram/kg of Met-Enk significantly increased the incidence and severity of EAE. In contrast, injections of 1 mg/kg of Met-Enk produced a moderate decline of clinical EAE, but marked diminution of inflammatory lesions in the brain. Interestingly, histopathology of EAE was more pronounced in control rats treated i.c.v. with saline. On the other hand, control cannulated rats noninjected with saline exhibited a striking decrease of neurological and histopathological signs of the disease, thus indicating a suppressive effect of stress (surgical procedure) on EAE. In conclusion, the present study showing the central effect of Met-Enk on EAE when peptide was applied in the cerebral cavity, and earlier studies which revealed the peripheral effect on EAE when Met-Enk was administered intraperitoneally, suggests that Met-Enk exerts its immunomodulatory action both centrally and peripherally.
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PMID:Changes of experimental allergic encephalomyelitis by methionine-enkephalin injected into lateral ventricles of the rat brain. 177 41

The structure of Mengo encephalomyelitis virus was refined at 3 A resolution with a final R-factor of 0.221 and a root-mean-square deviation from idealized bond lengths of 0.019 A for 10 A to 3 A data with F greater than or equal to 3 sigma(F). The Hendrickson-Konnert refinement was restrained by the phases derived from the molecular replacement averaging procedure and constrained by the icosahedral symmetry of the virus. The virus consists of 60 protomers each having three major subunits, VP1, VP2 and VP3, along with one smaller internal protein, VP4. The three major subunits form similar eight-stranded beta-barrel structures. Alterations in the original sequence were found at position 45 in VP1 (Arg to Ala) and at position 58 in VP3 (Met to Val). The residues in loops I and II of VP1 (82 to 102), the "FMDV loop" in VP1 (205 to 213), the flexible loop of VP3 in the putative receptor attachment site (175 to 185) as well as the terminal regions 260 to 268 in VP1, 253 to 256 in VP2 and 13 to 15 in VP4 were built or modified in regions of weak density. The variation in temperature factors at the end of the refinement is over a wide range (from 2 to 80 A2), with the disordered outer and inner regions showing high mobility. Four cis proline residues, 105 in VP1, 85 and 152 in VP2 and 59 in VP3, have been identified. The disulfide bridge Cys86 to Cys88 in VP3 has been characterized. One phosphate ion and 233 water positions were included in the refinement. It is suggested that this phosphate is associated with the receptor attachment site. There are two major hydrogen-bonding networks involving solvent atoms; one involving only the subunits of a protomer, and the other connecting the protomers in a pentamer. The distribution of atom types around the icosahedral symmetry axes shows that the 5-fold channel is more hydrophobic than that along the 3-fold axis and that there are more charged residues around the 2-fold axis. The analysis of contacts between the different subunits supports the assignment of the protomeric unit. The five protomers that form the pentameric unit are held together by interactions involving the smaller VP4 protein and the amino termini of VP1 and VP3. The pentamers are associated by means of the amino-terminal region of the VP2 subunits, the beta F strand of the VP3 subunits, the C terminus of the VP4 subunits and the electrostatic helical (alpha A) interactions of VP2 subunits across the icosahedral 2-fold axes. The superposition of the corresponding subunits of Mengo virus, human rhinovirus 14 and southern bean mosaic virus has provided an improved sequence alignment. The largest structural similarity is between the VP3 subunits of Mengo virus and rhinovirus, while the least similarity is between the VP1 subunits. The various specialized insertions in the different subunits can be associated with specific functional requirements.
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PMID:Structural refinement and analysis of Mengo virus. 215 78

Experimental allergic encephalomyelitis could be induced in rabbits by injection in Freund's complete adjuvant of either peptide 1-44 or peptide 45-87 of rabbit myelin basic protein. In order to localize the encephalitogenic determinant present in peptide 1-44, several smaller derivative peptides were prepared and examined. Peptic peptide 15-44 and thrombic peptide 1-31 were as active as peptide 1-44, whereas peptic peptides 1-14 and 18-38 and BrCN peptide 22-44 were virtually inactive. Weak activity was shown by BrCN peptide 1-21. These results provide evidence that a major encephalitogenic determinant present in peptide 1-44 lies within sequence 15-31. The encephalitogenic activity of peptide 15-44 was essentially destroyed by oxidation of methionine-21 to methionine sulfoxide; methylation of Met-21, on the other hand, appeared to be relatively ineffective in eliminating the encephalitogenicity of peptide 1-44.
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PMID:Experimental allergic encephalomyelitis in rabbits. A major encephalitogenic determinant within residues 1-44 of myelin basic protein. 242 3

To evaluate the immunomodulating activity of methionine-enkephalin (Met-Enk) and leucine-enkephalin (Leu-Enk) in the development of experimental allergic encephalomyelitis (EAE), two strains of rats, one highly susceptible to EAE (Lewis rats) and the other relatively resistant to the disease (Wistar rats) were used. The animals were given daily injections of either a high dose (5 mg/kg b.w.) or a low dose (0.2 mg/kg b.w.) of these opioid peptides, after receiving guinea pig spinal cord in combination with immunological adjuvants. A major conclusion from this study is that Met-Enk is a potent immunomodulator/regulator of the autoimmune disease, whereas Leu-Enk does not affect EAE. The high dose of 5 mg/kg b.w. of Met-Enk completely or significantly inhibited neurological signs and markedly diminished occurrence and intensity of histological lesions in the brain, and cervical, thoracic, and lumbar spinal cord. The loss of body weight, which accompanies EAE, was also prevented by a high dose of Met-Enk. In contrast, the low dose of 0.2 mg/kg b.w. of Met-Enk potentiated neurological and histopathological features of the disease. Nonimmunized rats injected with enkephalins for a period of 17 consecutive days showed neither neurological nor histological signs of EAE, nor signs of intoxication due to the application of enkephalins. Thus, these data establish a link between methionine-enkephalin and EAE, and suggest that this opioid pentapeptide might be important in the pathogenesis and prevention of the inflammatory autoimmune disease.
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PMID:Enkephalins and autoimmunity: differential effect of methionine-enkephalin on experimental allergic encephalomyelitis in Wistar and Lewis rats. 350 Mar 26

Proton magnetic resonance imaging enables non-invasive monitoring of lesion formation in multiple sclerosis and has an important role in assessing the potential effects of therapy. T2-weighted and short tau inversion recovery magnetic resonance imaging were used to assess the effect of a neurotrophic adrenocorticotrophic hormone analogue [H-Met(O(2))-Glu-His-Phe-D-Lys-Phe-OH] on the volume of lesions in the brains of rats suffering from chronic experimental allergic encephalomyelitis, an animal equivalent of multiple sclerosis. Lesion volume was monitored during a five-month period. Magnetic resonance imaging indicated that treatment with the adrenocorticotrophic hormone analogue significantly reduced the lesion volume by 84 and 85% 10 and 20 weeks after lesion induction, respectively. Furthermore, peptide treatment significantly reduced chronic experimental allergic encephalomyelitis-related neurological symptoms during the chronic phase of the disease (week 3 until week 20 after lesion induction). Both functional and morphological recovery were considerably advanced by peptide treatment. Twenty weeks after lesion induction rats with chronic experimental allergic encephalomyelitis were killed for histological analysis, to correlate magnetic resonance imaging findings with morphological changes. The regions of abnormally high signal intensities on T2-weighted magnetic resonance images coincided with areas of demyelination and concomitant widespread inflammatory infiltration, oedema formation and enlarged ventricles. The improved neurological status and the 84% reduction in the lesion volume in the cerebrum of rats chronic experimental allergic encephalomyelitis point to the potential value of trophic peptides in the development of strategies for limiting the damage caused by central demyelinating lesions in syndromes such as multiple sclerosis.
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PMID:Longitudinal in vivo magnetic resonance imaging studies in experimental allergic encephalomyelitis: effect of a neurotrophic treatment on cortical lesion development. 913 Jul 95

Chronic experimental allergic encephalomyelitis (CEAE) is an established experimental model for multiple sclerosis (MS). The demyelinating lesions in the white matter of the central nervous system observed in CEAE and in MS are accompanied by various neurophysiological alterations. Among the best defined electrophysiological abnormalities are the changes in event-related potentials, in particular evoked potentials involving the spinal cord, i.e. motor and sensory evoked potentials. Less familiar are the changes observed in the electroencephalogram of CEAE-affected animals, which are also encountered in the human equivalent, MS. In the present experiment we evaluated the therapeutic value of a neurotrophic peptide treatment [H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH, an ACTH4-9 analogue] and its effect on the delayed flash visual evoked potentials (VEP) and power spectra of the electroencephalogram, during a 17-week follow-up of CEAE. CEAE animals treated with the neurotrophic peptide were protected against the development of neurological symptoms during the course of the demyelinating syndrome. VEPs of animals suffering from CEAE showed a delay of the latencies of the late components which was significantly counteracted by peptide treatment. The peak-to-peak amplitude of the VEP afterdischarge recorded from CEAE animals was significantly increased during the course of CEAE and correlated closely with the progression of the myelinopathy. Furthermore, CEAE animals showed an increase of electroencephalogram (EEG) beta activity of up to 500% as compared with the age-matched control group. This increase in beta power mainly consisted of a prevailing 20-21 Hz peak, a frequency that normally is not dominant in control EEG recordings of the rat during passive wakefulness. All these electrophysiological phenomena were absent in ACTH4-9 analogue-treated animals. The present findings underscore the potential importance of a neurotrophic peptide treatment in the pharmacotherapy of central demyelinating syndromes, and possibly of MS.
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PMID:Neurotrophic ACTH4-9 analogue therapy normalizes electroencephalographic alterations in chronic experimental allergic encephalomyelitis. 987 50


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