Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mice of the inbred strains SJL (H-2s) and AKR (H-2k) are "non-responders" and "low-responders," respectively, in terms of their capacity to develop antibody responses of the IgE class when immunized with conventional proteins and hapten-protein conjugates under conditions optimal for eliciting IgE responses in "high-responder" mice, such as BALB/c (H-2d), to these same antigens. For example, BALB/c mice preimmunized with ASC and then challenged 7 days later with DNP-ASC develop peak augmented primary IgE anti-DNP antibody responses of 320 PCA units, whereas SJL and AKR mice develop responses which are 16-fold and 4-fold lower, respectively. However, pretreatment of the latter two strains with appropriate doses of either x-irradiation (150 R), cyclophosphamide (100 mg/kg) or ALS (150 mul) before carrier-preimmunization strikingly enhances the magnitude of IgE antibody responses in such mice to levels as high as 64-fold above those of untreated control mice of the same strains. Evidence obtained in these experiments indicates that the capacity of such maneuvers to to convert poor IgE responders to high responder status reflects elimination of nonantigen-specific suppressor T lymphocytes which are naturally present and normally function to suppress or "dampen" the IgE antibody response in a relatively selective manner. It appears that these cells modulate IgE responses by acting at least at two distinct points: 1) The most effective activity seems to be at the level of induction of carrier-specific helper T cells; 2) A second locus of inhibitory activity is more distal in the response, either impeding helper T cell-B cell cooperative interactions or suppressing B cell differentiation and/or function directly. Taken collectively, these observations demonstrate that the state of poor responsiveness of the SJL and AKR strains for the IgE antibody class is not a reflection of a genetic inability to develop IgE responses but rather a manifestation of a genetic capability to actively inhibit IgE antibody synthesis.
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PMID:Hapten-specific IgE antibody responses in mice. VII. Conversion of IgE "non-responder" strains to IgE "responders" by elimination of suppressor T cell activity. 29 62

Spleen cells taken from mice soon after infection with Trypanosoma brucei S 42 enhance the primary in vitro antibody response of normal spleen cells to sheep red blood cells (SRBC), but do not affect their response to DNP-Ficoll. Spleen cells harvested later in the infection (day 6 onwards) suppress the antibody response of normal spleen cells to both SRBC and DNP-Ficoll. The enhancing and suppressive effects of "infected" spleen cells are sensitive to treatment with anti-Thy 1.2 anti-serum and complement, and can be mediated by nylon wool-purified populations of T cells. The enhancing T cell is sensitive to ALS, not lost within 4 weeks of adult thymectomy, and bears the Ly-1+, 23- phenotype. The suppressor T cell is insensitive to ALS, lost within 20 weeks of adult thymectomy, and bears the Ly-1+, 23+ phenotype. The significance of the activation of distinct helper and suppressor T cells is discussed in relation to the pathogenesis of trypanosomiasis.
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PMID:Activation of distinct helper and suppressor T cells in experimental trypanosomiasis. 35 49

As part of our effort to study the role of reactive species in amyotrophic lateral sclerosis (ALS), the goal of this work is to explore the correlation between nitration and oxidation of proteins and mutation of Cu, Zn-superoxide dismutase (SOD1) in ALS. Transgenic mice overexpressing the mutant Cu, Zn-superoxide dismutase (mSOD1) gene from humans with familial ALS, wild-type mice overexpressing the normal human SOD1 gene and normal mice without gene overexpression were used. Brain sections from different regions of three groups of mice were double immunohistochemically stained with anti-neurofilament plus anti-nitrotyrosine or treated with 2,4-dinitrophenylhydrazine to label protein carbonyls, then double stained with anti-neurofilament plus anti-2,4-dinitrophenyl (anti-DNP). Neurons containing nitrated and oxidized proteins were visualized only in mSOD1 mice in the motor cortex, the cerebellar cortex and nucleus of hypoglossal nerves (regions related with movement). This correlates mutation of SOD1 to nitration and oxidation of neurons in the movement regions. By counting double-stained neurons, we demonstrated that the number of nitrotyrosine- and DNP-positive neurons was significantly higher in the brain sections of both motor and sensory cortex in mSOD1 mice than in the corresponding regions of control mice (P=0.005 to <0.001), further correlating nitration and oxidation of proteins to SOD1 mutation. Neurons underwent significantly more nitration and oxidation in the motor cortex than in the sensory cortex in mSOD1 mice (P=0.002 and 0.02 respectively), indicating enhanced susceptibility of the motor cortex to nitration and oxidation of proteins and thereby targeting oxidation and nitration of proteins in neurons of the motor cortex in ALS. Significantly elevated protein nitration and nitric oxide synthesis were also demonstrated biochemically in the brain tissues and in cerebrospinal fluid of mutant SOD1 mice. Our in vivo evidence correlates mutation of the SOD1 gene to increased nitric oxide, nitration and oxidation of proteins in ALS.
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PMID:Mutation of superoxide dismutase elevates reactive species: comparison of nitration and oxidation of proteins in different brain regions of transgenic mice with amyotrophic lateral sclerosis. 1736 52