Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein transduction domains (PTDs), both naturally occurring and synthetic, have been increasingly employed to deliver biologically active agents to a variety of cell types in vitro and in vivo. In addition to the previously characterized arginine-rich PTDs, including Tat (transactivator of transcription), Antp (Antennapedia) and PTD-5, we have demonstrated that lysine and ornithine, as well as arginine, homopolymers are able to mediate transduction of a wide variety of agents. To screen for optimal PTDs, we have used as a therapeutic cargo a peptide derived from IKK {IkappaB [inhibitor of NF-kappaB (nuclear factor kappaB)] kinase} beta, able to bind to the IKK regulatory subunit [NEMO (NF-kappaB essential modulator)], preventing formation of an active kinase complex. This peptide, termed NBD, is able to block activation of NF-kappaB, but not basal activity. We demonstrate that PTD-mediated delivery of NBD using certain PTDs, in particular 8K (octalysine), is therapeutic following systemic delivery in murine models of inflammatory bowel disease, diabetes and muscular dystrophy. In addition, we have developed a peptide phage display library screening method for novel transduction peptides able to facilitate tissue-specific internalization of marker protein complexes. Using this approach, we have identified transduction peptides that are able to facilitate internalization of large protein complexes into tumours, airway epithelia, synovial fibroblasts, cardiac tissue and HEK-293 (human embryonic kidney) cells in culture and/or in vivo.
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PMID:Protein transduction: identification, characterization and optimization. 1763 54

This study aimed to analyze the correlation between the phenotype and genotype of Chinese patients with early-onset lamin A (LMNA)-related muscular dystrophy (MD). The clinical and myopathological data of 21 Chinese pediatric patients with early-onset LMNA-related MD were collected and analyzed. LMNA gene mutation analysis was performed by direct sequencing of genomic DNA. Sublocalization of wild-type and mutant proteins were observed by immunofluorescence using cultured fibroblasts and human embryonic kidney 293 (HEK 293) cell. Seven patients were diagnosed with Emery-Dreifuss muscular dystrophy (EDMD) and 14 were diagnosed with LMNA-associated congenital muscular dystrophy (L-CMD). Four biopsy specimens from the L-CMD cases exhibited inflammatory changes. Abnormal nuclear morphology was observed with both transmission electron microscopy and lamin A/C staining. We identified 10 novel and nine known LMNA gene mutations in the 21 patients. Some mutations (c.91G>A, c.94_96delAAG, c.116A>G, c.745C>T, c.746G>A, and c.1580G>C) were well correlated with EDMD or L-CMD. LMNA-related MD has a common symptom triad of muscle weakness, joint contractures, and cardiac involvement, but the severity of symptoms and disease progression differ greatly. Inflammatory change in biopsied muscle is a characteristic of early-stage L-CMD. Phenotype-genotype analysis determines that some mutations are well correlated with LMNA-related MD.
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PMID:Phenotype-Genotype Analysis of Chinese Patients with Early-Onset LMNA-Related Muscular Dystrophy. 2609 24