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)

Globoid cell leukodystrophy (GLD) is a severe genetic demyelinating disorder with an increased number of Ia (immune response antigen) positive brain microglia/macrophages. To assess the role of aberrant Ia expression in the central nervous system (CNS), twitcher mice, which represent the murine model for GLD, were mated with Ia- transgenic mice. Compared with the Ia+ controls, Ia- twitcher mice showed a profound reduction in the severity of demyelinating lesions correlated with significantly fewer microglia/macrophages. Most importantly, Ia- twitcher mice showed significantly reduced twitching compared with ia+ twitcher mice. In contrast with experimental allergic encephalomyelitis (EAE), there was no significant amount of inflammatory T cell infiltrates, implying that T cells may not play a predominant role in this disease. These findings may have broad therapeutic implications for Alzheimer's disease, Parkinson's disease, and Huntington's disease, which display enhanced Ia expression in the CNS without obvious T cell infiltrates.
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PMID:Absence of MHC class II molecules reduces CNS demyelination, microglial/macrophage infiltration, and twitching in murine globoid cell leukodystrophy. 806 13

Twitcher mice have an autosomal recessive mutation in the gene for the lysosomal enzyme galactosylceramidase, which is the same gene that is affected in human globoid cell leukodystrophy (Krabbe's disease). The failure to digest galactosylceramide and psychosine leads to initial pathological changes in oligodendrocytes. Secondary pathological changes that include infiltrating macrophages and other inflammatory responses have been postulated to promote the disease course. TNFalpha levels are elevated in twitcher mice compared to control animals, and studies on another demyelinating disease, experimental allergic encephalomyelitis, indicate that TNF promotes pathogenesis via TNF-receptor 1 (TNF-R1). In the present study, twitcher/TNF-R1 deficient mice were generated, and the clinical and pathological course was compared between these mice and regular twitcher mice. There was no statistical evidence for any differences between these two groups of mice for all clinical (life span, weight loss, onset day of twitching) and pathological (demyelination, astrocyte gliosis, macrophage infiltration) measures that were examined. If mice were administered an intraperitoneal injection of LPS, then twitcher/TNF-R1 deficient mice had a longer [corrected] life span and a decreased [corrected] disruption to the blood-brain barrier compared to regular twitcher mice. These results showed that TNF-R1 is not sufficiently activated to affect the pathological and/or clinical signs during the natural course of this disease. However, when there is a secondary insult, TNF-R1 activation does lead to a significant acceleration of the development of clinical and pathological signs.
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PMID:TNF-receptor 1 deficiency fails to alter the clinical and pathological course in mice with globoid cell leukodystrophy (twitcher mice) but affords protection following LPS challenge. 1102 49

A previously healthy 3-year-old female presented with rapidly progressive neurologic deterioration. She was initially diagnosed with acute disseminated encephalomyelitis but was subsequently found to have late-onset Krabbe's disease.
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PMID:Late-onset Krabbe's disease mimicking acute disseminated encephalomyelitis. 1613 37

The purpose of this paper is to facilitate the comparison of magnetic resonance (MR) spectra acquired from unknown brain lesions with published spectra in order to help identify unknown lesions in clinical settings. The paper includes lists of references for published MR spectra of various brain diseases, including pyogenic abscesses, encephalitis (herpes simplex, Rasmussen's and subacute sclerosing panencephalitis), neurocysticercosis, tuberculoma, cysts (arachnoid, epidermoid and hydatid), acute disseminated encephalomyelitis (ADEM), adrenoleukodystrophy (ALD), Alexander disease, Canavan's disease, Krabbe disease (globoid cell leukodystrophy), Leigh's disease, megalencephalic leukoencephalopathy with cysts, metachromatic leukodystrophy (MLD), Pelizaeus-Merzbacher disease, Zellweger syndrome, HIV-associated lesions [cryptococcus, lymphoma, toxoplasmosis and progressive multifocal leukoencephalopathy (PML)], hydrocephalus and tuberous sclerosis. Each list includes information on the echo time(s) (TE) of the published spectra, whether a control spectrum is shown, whether the corresponding image and voxel position are shown and the patient ages if known. The references are listed in the approximate order of usefulness, based on spectral quality, number of spectra, range of echo times and whether the voxel positions are shown. Spectra of Zellweger syndrome, cryptococcal infection, toxoplasmosis and lymphoma are included, along with a spectrum showing propanediol (propylene glycol).
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PMID:Identification of diffuse and focal brain lesions by clinical magnetic resonance spectroscopy. 1676 70

Natural killer (NK) cells are antitumour/anti-viral effectors and play important roles in shaping the immune system, but their role in neurodegenerative diseases is not clear. Here, we investigated the fate of these cells in two neurodegenerative diseases. In the first model, the activity of NK cells was examined in mice with experimental autoimmune encephalomyelitis (EAE) treated with glatiramer acetate (GA or Copaxone), a drug used to treat EAE in animals and multiple sclerosis in human. The second disease model is twitcher (Galc(twi)/Galc(twi)) mice, which represents an authentic model of human Krabbe's disease. Administration of GA ameliorated EAE in SJL mice corroborated with isolating NK cells that expressed higher killing than cells isolated from vehicle-dosed animals against immature or mature dendritic cells (DCs). However, this drug showed no effect on the numbers of NK cells or the expression of CD69 molecule. On the other hand, NK cells either disappeared from the spleens or were present in low numbers in the white pulp areas of Galc(twi)/Galc(twi) mice, which have increased D-galactosyl-beta1-1'-sphingosine (GalSph) levels. Analysis by confocal microscopy shows that NK cells found in the spleens of Galc(twi)/Galc(twi) mice were apoptotic. Incubating NK cells in vitro with GalSph induced the apoptosis in these cells, confirming the results of twitcher mice. Our results provide the first evidence showing that amelioration of EAE in mice is corroborated with NK cell lysis of antigen-presenting DCs, whereas NK cell distribution into the spleen is altered in a devastating lipid disorder corroborated with induction of their apoptosis.
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PMID:Splenic natural killer cell activity in two models of experimental neurodegenerative diseases. 1939 84