TY - JOUR
T1 - DNA single-strand breaks are increased in muscle diseases with rimmed vacuoles
AU - Tateyama, Maki
AU - Tobita, Muneshige
AU - Takeda, Atsushi
AU - Chida, Keiji
AU - Onodera, Yoshiaki
AU - Kikuchi, Akio
AU - Aoyagi, Naoko
AU - Itoyama, Yasuto
N1 - Funding Information:
Acknowledgements We wish to thank Dr. Kazuo Kobayashi for suggestions about histological findings, Dr. Junichi Onodera for his kind gift of thymus samples, and Dr. Hareaki Seki, Dr. Akihisa Saito and the staff at the Department of Neurology, Tohoku University School of Medicine for providing us with clinical records, and Mr. Brent Bell for reading the manuscript. This study was supported in part by the Sasakawa Health Science Foundation.
PY - 2000/10
Y1 - 2000/10
N2 - Some pathological similarities between Alzheimer's disease and muscle diseases with rimmed vacuoles (RV) have been pointed out. For example, several pathological hallmark proteins have been reported to be immunopositive in the lesions of both diseases. Since apoptotic processes or primary DNA damage are suggested to play a role in the pathomechanism of Alzheimer's disease, we examined DNA double-strand breaks (DSB) and single-strand breaks (SSB) in the muscle biopsy specimens of several diseases, including muscle diseases with RV. Although no DSB-positive myonuclei were detected in any muscles examined, the number of SSB-positive myonuclei markedly increased in the muscles from cases with polymyositis and muscle diseases with RV. In polymyositis, SSB-positive myonuclei were observed in regenerating fibers and muscle fibers in the vicinity of inflammatory infiltrates, suggesting that the increase of SSB is due to muscle fiber regeneration following necrosis and inflammation. In muscle diseases with RV, however, SSB-positive myonuclei were observed in small angulated fibers and in morphologically normal fibers, regardless of necrosis, regeneration or inflammation. These findings suggest that muscle diseases with RV may share a common pathological process involving DNA damage.
AB - Some pathological similarities between Alzheimer's disease and muscle diseases with rimmed vacuoles (RV) have been pointed out. For example, several pathological hallmark proteins have been reported to be immunopositive in the lesions of both diseases. Since apoptotic processes or primary DNA damage are suggested to play a role in the pathomechanism of Alzheimer's disease, we examined DNA double-strand breaks (DSB) and single-strand breaks (SSB) in the muscle biopsy specimens of several diseases, including muscle diseases with RV. Although no DSB-positive myonuclei were detected in any muscles examined, the number of SSB-positive myonuclei markedly increased in the muscles from cases with polymyositis and muscle diseases with RV. In polymyositis, SSB-positive myonuclei were observed in regenerating fibers and muscle fibers in the vicinity of inflammatory infiltrates, suggesting that the increase of SSB is due to muscle fiber regeneration following necrosis and inflammation. In muscle diseases with RV, however, SSB-positive myonuclei were observed in small angulated fibers and in morphologically normal fibers, regardless of necrosis, regeneration or inflammation. These findings suggest that muscle diseases with RV may share a common pathological process involving DNA damage.
KW - DNA double-strand breaks
KW - DNA single-strand breaks
KW - In situ nick translation
KW - Rimmed vacuole
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U2 - 10.1007/s004010000192
DO - 10.1007/s004010000192
M3 - Article
C2 - 10985697
AN - SCOPUS:0033927292
VL - 100
SP - 390
EP - 394
JO - Acta Neuropathologica
JF - Acta Neuropathologica
SN - 0001-6322
IS - 4
ER -