Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.17 (lysozyme)
 21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Here, we report on an elderly woman with sarcoidosis and Hashimoto's disease who later developed myasthenia gravis. She was 68-year-old with a long history of Hashimoto's disease who had a clinical diagnosis of sarcoidosis with uveritis at the age of 66 years. On laboratory examination, angiotensin-converting enzyme, lysozyme and gamma-globulin were elevated and there was bilateral hilar lymphoadenopathy. She was admitted to our hospital because of left blepharoptosis and mild fatigability in the proximal muscles at the age of 68 years. Myasthenia gravis, type IIa, was confirmed by elevated titer of anti-acetylcholine receptor antibody in serum (0.8 nmol/l, normal < 0.6), positive edrophonium test and decremental EMG response. Oral prednisolone therapy was effective. Her muscle biopsy revealed HLA ABC-positive fibers in all fascicles, and HLA-DR positive fibers in the perifascicular areas. Myasthenia gravis complicated by sarcoidosis and Hashimoto's thyroiditis is extremely rare, suggesting that the common underlying immunological abnormalities for the three disorders such as a certain defective cellular immunity are responsible for the pathomechanism to induce the patient condition.
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PMID:[A case of myasthenia gravis following sarcoidosis and Hashimoto's thyroiditis]. 1121 99

The crystal structure of the Fab fragment of the rat monoclonal antibody 198, with protective activity for the main immunogenic region of the human muscle acetylcholine receptor against the destructive action of myasthenic antibodies, has been determined and refined to 2.8 A resolution by X-ray crystallographic methods. The mouse anti-lysozyme Fab D1.3 was used as a search model in molecular replacement with the AMORE software. The complementarity determining regions (CDR)-L2, CDR-H1 and CDR-H2 belong to canonical groups. Loops CDR-L3, CDR-H2 and CDR-H3, which seem to make a major contribution to binding, were analyzed and residues of potential importance for antigen-binding are examined. The antigen-binding site was found to be a long crescent-shaped crevice. The structure should serve as a model in the rational design of very high affinity humanized mutants of Fab198, appropriate for therapeutic approaches in the model autoimmune disease myasthenia gravis.
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PMID:Crystal structure of Fab198, an efficient protector of the acetylcholine receptor against myasthenogenic antibodies. 1143 34

Selection in vivo of potent mAbs to human CD4 useful for immunotherapy, e.g., for the induction of immunological tolerance, is restricted for ethical reasons. We therefore used multiple transgenic mice that lack murine CD4, but express human CD4 specifically on Th cells, and HLA-DR3 as its natural counterligand (CD4/DR3 mice). The injection of CD4/DR3 mice with anti-human CD4 (mAb Max.16H5) before immunization with tetanus toxoid (TT, day 0) totally blocked the formation of specific Abs. This state of unresponsiveness persisted a subsequent boost again performed in the presence of anti-human CD4. When these mice were left untreated for at least 40 days, and were then re-exposed with TT, but in the absence of anti-human CD4, they consistently failed to induce specific Abs (long-term unresponsiveness). Exposure to second party Ags (hen egg lysozyme, human acetylcholine receptor) induced specific Abs comparable with control mice, demonstrating that the anti-CD4-induced unresponsiveness was Ag specific (immunological tolerance). Importantly, the concurrent injection of TT and anti-human CD4 at day 0, followed by another two anti-CD4 treatments, also led to tolerant animals, indicating that tolerance was inducible at the same day as the Ag exposure is provided. We finally demonstrate a limited ability of spleen cells to respond to TT in vitro, indicating that T cells are essentially involved in the maintenance of TT-specific tolerance. These data show for the first time that the human CD4 coreceptor mediates tolerance-inducing signals when triggered by an appropriate ligand in vivo.
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PMID:Anti-human CD4 induces peripheral tolerance in a human CD4+, murine CD4-, HLA-DR+ advanced transgenic mouse model. 1221 8