Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypersensitivity to the lethal effects of DNA-damaging agents is usually demonstrated using the classical colony-forming ability assay with cultured fibroblast lines. Based on the ability of viable cells in lymphoblastoid lines (Epstein-Barr virus-transformed B lymphocytes) to exclude the vital dye trypan blue, we have developed a more rapid survival assay which has been useful in detecting hypersensitivity to ionizing radiation in certain diseases characterized by primary degeneration of excitable tissue. We now present a complete description of this post-X-ray survival assay. We also demonstrate the suitability of both our assay and our method of data analysis for detecting hypersensitivity to ionizing radiation. This demonstration is based on a detailed analysis of assay results with lymphoblastoid lines from 28 normal donors, 3 ataxia telangiectasia (AT) patients, 2 obligate AT heterozygotes, 7 patients with diseases characterized by cellular hypersensitivity to ultraviolet radiation (UV), and 10 Duchenne muscular dystrophy (DMD) patients.
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PMID:A sensitive assay for detecting hypersensitivity to ionizing radiation in lymphoblastoid lines from patients with Duchenne muscular dystrophy and primary neuronal degenerations. 633 87

Using lymphoblastoid cell cultures the response to gamma (gamma)-radiation, was examined in 6 Duchenne muscular dystrophy (DMD) patients; 2 clinically normal males as negative controls, and 2 patients with ataxia telangiectasia (AT) showing sensitivity to ionising radiation as positive controls. In a series of experiments, cell recovery and growth at day 2 post radiation, was determined after 5 separate gamma-irradiation dose levels: 50, 100, 150, 200 and 300 rads. The DMD cell strains showed a radiation dose response that was significantly greater than in cells from 2 normal males, while both DMD and normal cells were significantly less responsive than were AT-sensitive cell strains.
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PMID:Response to ionising radiation in Duchenne muscular dystrophy. 664 28

The mean telomere length (TL) of somatic cells indicates their replicative age. In comparison with normal leukocytes (-0.03 kbp/y, 6.2 kbp at 80 y), we found advanced TL shortening in premature aging due to ataxia-telangiectasia or the Nijmegen chromosomal breakage syndrome. Duchenne muscular dystrophy (DMD) has been related to replicative senescence of satellite cells (SCs) caused by increased fiber turnover. Therefore, we determined TLs in DMD muscle. Because the regenerated fiber nuclei are produced by SCs. telomeres of both fiber and SC nuclei should be shortened. In DMD the SC number is increased. We determined that up to the age of 7 y the sum of fiber and SC nuclei should be large enough (73%) for the detection of TL shortening. Normal muscle fibers have negligible turnover rates, and, as expected, we did not find age-related TL shortening (10-83 y, n = 24, 8.3 +/- 0.5 kbp). Surprisingly, there was only slight TL shortening in patient muscles (DMD, 0.3-4.8 y, n = 4, 8.3 +/- 0.7 kbp; 5-7 y, n = 7, 7.9 +/- 0.4 kbp; limb-girdle muscular dystrophy 2C, 13 y, 7.6 kbp; Becker muscular dystrophy, 7 y, 8.5 kbp). Similarly, the peak positions of the telomere blots varied only slightly (DMD, 10.0 +/- 0.9 kbp; normal: 10.7 +/- 0.9 kbp). In accordance with our TL findings we derived less than 4 annual doublings per SC from published histologic data on DMD.
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PMID:Examination of telomere lengths in muscle tissue casts doubt on replicative aging as cause of progression in Duchenne muscular dystrophy. 926 27

Molecules that induce ribosomal read-through of nonsense mutations in mRNA and allow production of a full-length functional protein hold great therapeutic potential for the treatment of many genetic disorders. Two such read-through compounds, RTC13 and RTC14, were recently identified by a luciferase-independent high-throughput screening assay and were shown to have potential therapeutic functions in the treatment of nonsense mutations in the ATM and the dystrophin genes. We have now tested the ability of RTC13 and RTC14 to restore dystrophin expression into skeletal muscles of the mdx mouse model for Duchenne muscular dystrophy (DMD). Direct intramuscular injection of compound RTC14 did not result in significant read-through activity in vivo and demonstrated the levels of dystrophin protein similar to those detected using gentamicin. In contrast, significant higher amounts of dystrophin were detected after intramuscular injection of RTC13. When administered systemically, RTC13 was shown to partially restore dystrophin protein in different muscle groups, including diaphragm and heart, and improved muscle function. An increase in muscle strength was detected in all treated animals and was accompanied by a significant decrease in creatine kinase levels. These studies establish the therapeutic potential of RTC13 in vivo and advance this newly identified compound into preclinical application for DMD.
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PMID:Read-through compound 13 restores dystrophin expression and improves muscle function in the mdx mouse model for Duchenne muscular dystrophy. 2269 82