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

We report the preliminary results of an ongoing study of multiple sclerosis (MS) in childhood. The investigations include an analysis of the clinical picture and course. Multiple sclerosis in early childhood may present atypically, with a symptomatology suggesting diffuse encephalomyelitis, meningeal reaction, brain oedema, seizures, impaired consciousness and in some cases take a lethal course. Imaging studies including MRI and MR-spectroscopy, CSF-analysis, electrophysiology (VEP, BAEP, SER), and virological and immunological investigations are performed. So far 15 children have been studied. Their age at the onset of the disease ranged from 3 to 15 years. Abnormal CSF-findings with pleocytosis and oligoclonal IgG bands were present in 11 and 10 out of 15 patients respectively. MRI revealed numerous white matter lesions in the brain stem and cerebral hemispheres. VEP, BAEP and SER's were abnormal in most children. Proton magnetic resonance spectra from plaques exhibited a 50-80% decrease in N-acetyl aspartate, which is a potential marker of vital neuronal tissue, a decrease of the creatine pool and an increase of choline-containing compounds. Lactate was not increased. Our observations of MS in early childhood cast doubt on some of the previous notions concerning a latency period of several years between the exposure to a still unknown agent and the manifestation of MS. In view of atypical features in the initial phase, it would seem desirable to record cases of encephalomyelitis of undetermined origin as potential cases of MS and to register the further course for verification or exclusion.
 ...
PMID:Multiple sclerosis in childhood: report of 15 cases. 833 16

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.
 ...
PMID:Structural refinement and analysis of Mengo virus. 215 78

The association of reactive oxygen species to altered permeability of the blood-brain barrier in acute experimental encephalomyelitis was investigated by ultrastructural cytochemical localization of hydrogen peroxide (H2O2) to sites in the optic nerve previously identified by extravasation of intravascular horseradish peroxidase. Using a modified cerium method, we found electron-dense cerium-derived H2O2 reaction product was localized to the perivascular space at the lamina retinalis, lamina choroidalis, and lamina scleralis. In the optic nerve head, electron-dense reaction product was observed in the presence of intravascular leukocytes, although adjacent perivascular and interstitial inflammatory cells at this site were scant. In the myelinated retrobulbar optic nerve, cerium-derived H2O2 reaction product was seen in the intravascular space of blood vessels and surrounding perivascular and interstitial foci of inflammatory cells. Reaction product was also observed in the extracellular space adjacent to the plasmalemma of axons and glial cells in the optic nerve head and retrobulbar nerve. The perivascular and intravascular distribution of cerium-derived reaction product suggests that H2O2 may play a role in the pathogenesis of altered vascular permeability in experimental optic neuritis and supports our previous observations of suppression of blood-brain barrier permeability by detoxification of H2O2 with the exogenous administration of antioxidant enzymes.
 ...
PMID:Hydrogen peroxide localization in experimental optic neuritis. 224 46

Detoxification of hydrogen peroxide by the antioxidant enzyme catalase suppressed the neurologic manifestations of acute experimental allergic encephalomyelitis (EAE) and prevented death of treated adult strain-13 guinea pigs. The oxygen radical scavenger superoxide dismutase (SOD) delayed the onset of paralysis by one day, but did not prevent death from encephalomyelitis common to most of this group and all untreated animals. Histopathologic analysis of the optic nerves confirmed a statistically significant reduction in demyelination with catalase treatment, but not with SOD. Hydrogen peroxide, and/or its conversion products, discharged by phagocytic mononuclear cells, may play a role in the pathogenesis of demyelination in experimental optic neuritis.
 ...
PMID:Antioxidant enzyme suppression of demyelination in experimental optic neuritis. 273 52

We studied the effect of antioxidant enzymes on the loss of integrity of the blood-brain barrier in the optic nerves of strain-13 guinea pigs with chronic experimental allergic encephalomyelitis, a demyelinating disorder with neurologic and histopathologic characteristics similar to multiple sclerosis. Animals with experimental allergic encephalomyelitis received daily intraperitoneal injections of either preservative-free saline (group 1), catalase (group 2), or glutathione peroxidase (group 3) for 2.2 months after the onset of appendicular paralysis. Following intravascular administration, extravascular leakage of horseradish peroxidase was histopathologically graded as mild, moderate, or severe within the optic nerve head and myelinated retrolaminar nerve. Severe extravasation of horseradish peroxidase was exclusive to group 1, in addition to moderate and mild leakage. In groups 2 and 3, leakage of horseradish peroxidase was infrequent, and when detected, it was graded as mild. Detoxification of hydrogen peroxide with catalase and glutathione peroxidase substantially reduced horseradish peroxidase leakage in experimental optic neuritis, suggesting a role for hydrogen peroxide and its reactive by-products in the pathogenesis of increased vascular permeability of the blood-brain barrier in experimental allergic encephalomyelitis.
 ...
PMID:Antioxidant enzymes reduce loss of blood-brain barrier integrity in experimental optic neuritis. 278 67

Chronic recurrent experimental allergic encephalomyelitis was induced in a strain 13 guinea pig by inoculation of isologous spinal cord homogenate. The spinal cord was obtained after perfusion with 4% paraformaldehyde and examined with nuclear magnetic resonance (NMR) imaging. Proton NMR spin echo images (repetition time: 3 s; echo times: 20 and 60 ms) were obtained from intact, isolated spinal cord in a 4.7 Tesla, 50 mm bore magnet. The slice thickness of the images was 380 microns and the inplane resolution was 40 X 40 microns. The images showed superficial areas of low signal intensity in the lateroventral regions of the white matter, in some instances with a seam of higher signal intensity. Neuropathologically, these abnormalities corresponded exactly to areas of demyelination. Control images did not show these abnormalities. The present high resolution imaging allowed a correlation between demyelination and abnormal NMR signals in a small laboratory animal with an inflammatory demyelinating disease.
 ...
PMID:High resolution nuclear magnetic resonance imaging of the spinal cord in experimental demyelinating disease. 320 26

The purpose of this paper was to investigate the role of deferoxamine (DFO) scavenging of hydroxyl radical (.OH) on disruption of the blood-brain barrier (BBB) and demyelination in experimental optic neuritis. Eighteen strain-13 guinea pigs were sensitized for experimental allergic encephalomyelitis. Nine animals received 100 mg/kg of hydroxyethyl starch-conjugated (HES) DFO by daily intraperitoneal injection commencing the day of antigenic sensitization. Nine paired litter mates received daily IP injections of HES. Serial fat-suppressed magnetic resonance imaging of the optic nerves was obtained with a T2 weighting (T2w) to evaluate demyelination and after intravascular administration of Gd-DTPA to evaluate BBB disruption. The intensity of Gd-DTPA enhancement and T2w signal of the optic nerves was quantitated 3, 7, 10 and 14 days after antigenic sensitization. Animals were then sacrificed and the optic nerves processed for light and transmission electron microscopy with ultracytochemical localization of endogenous hydrogen peroxide (H2O2) and immunogold colocalization of extravasated serum albumin. The area of the optic nerve head, intensity of toluidine blue staining, and the cellular infiltrate were digitized and quantitated. Administration of HES-DFO significantly reduced the intensity of Gd-DTPA enhancement in the optic nerves of HES-DFO-treated animals compared to paired control HES animals (p = 0.0236), with the mean difference between control and treated animals of 19.39. The difference in T2w signal was not significant (p = 0.39), with a mean difference between control and treated animals of -5.51. The intensity of toluidine blue staining of optic nerve specimens was slightly less with HES-DFO compared to untreated animals (mean pair difference 2.48), and the inflammatory infiltrate was reduced with HES-DFO compared to untreated animals (mean pair difference = 61.57); these differences were not statistically significant. In the optic nerve specimens of both groups cerium perhydroxide-derived H2O2 reaction product was evident in a predominantly perivascular and perineural distribution. Immunogold-labeled serum albumin showed extravasation at foci of perivascular inflammation in both the presence and absence of H2O2-derived reaction product. Conjugated DFO reduces disruption of the BBB, as measured by Gd-DTPA enhancement, suggesting the .OH radical generated from perivascular H2O2 may play a role in alterations of vascular permeability in experimental optic neuritis.
 ...
PMID:Conjugated deferoxamine reduces blood-brain barrier disruption in experimental optic neuritis. 753 78

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.
 ...
PMID:Longitudinal in vivo magnetic resonance imaging studies in experimental allergic encephalomyelitis: effect of a neurotrophic treatment on cortical lesion development. 913 Jul 95

Peroxynitrite is formed by the reaction of nitric oxide (NO) and superoxide. Since widespread peroxynitrite activity was observed during experimental allergic encephalomyelitis (EAE), the effect of this strong lipid-peroxidizing agent on myelin integrity was examined. Incubation of myelin suspensions with the peroxynitrite donor 3-morpholinosydnonimine (SIN-1) resulted in the formation of the lipid peroxidation product, malondialdehyde (MDA). MDA formation was inhibited in the presence of butylated hydroxytoluene, which interrupts the progression of the lipid peroxidation chain reaction. Superoxide dismutase inhibited the effect of SIN-1, which indicates a role for superoxide, and contradicts a role for its dismutation product, hydrogen peroxide. The latter was confirmed by the failure of the catalase to inhibit MDA formation. Neither NO nor superoxide alone induced significant MDA formation in myelin, indicating that peroxynitrite formation is required for myelin-lipid peroxidation. Interestingly, NO actually inhibited lipid peroxidation in myelin, as demonstrated using simple NO donors. On the other hand, the simultaneous production of superoxide, as achieved with the NO-donor SIN-1, negated the inhibitory effect of NO. Finally, the production of isoprostanes, novel products generated during lipid peroxidation, was examined. Peroxynitrite-induced peroxidation of myelin resulted in isoprostane formation. Furthermore, increased levels of F2-isoprostanes and neuroprostanes were observed in spinal cords of mice during early progressive stages of autoimmune encephalomyelitis.
 ...
PMID:Contrasting roles for nitric oxide and peroxynitrite in the peroxidation of myelin lipids. 1022 10


1 2 3 Next >>