Familial centronuclear myopathy

Sher, Joanna; Rimalovski, Alexander B.; Athanassiades, Thomas J.; Aronson, Stanley M

doi:10.1212/wnl.17.8.727

Cited by 120 publications

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“…9 b, X 73,500. Membranous whorls in mitochondria have been found in spinal ganglion neuroblasts (18) and in cases of familial myopathy (19,20) . Pannese (18) has suggested that the whorls may be related to the The excellent technical assistance of Mrs .…”

Section: Resultsmentioning

confidence: 99%

Degenerative Changes in the Mitochondria of Flight Muscle From Aging Blowflies

Sacktor

Shimada

1972

The Journal of Cell Biology

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Mitochondria from flight muscle of aging blowflies, Phormia regina, were examined morphologically and biochemically with the electron microscope . An age-dependent degeneration of the mitochondria that is characterized, in part, by the reorganization of the inner membrane into myelin-like whorls has been found . The concentric rings increase in size and number, eventually replacing the normal cristal conformation . Glycogen rosettes are frequently seen in the center of the whorl and may represent the intrusion into the mitochondria of the glycogen in the cytoplasmic matrix of the muscle . The degenerating mitochondria are not associated with lysosomal activity, as indicated by the absence of acid phosphatase . An intense acid phosphatase activity is noted, however, in the dyad, comprising elements of the T system and sarcoplasmic reticulum . Cytochrome oxidase is active in the ultrastructurally intact portion of the mitochondrion but activity is not evident in that part of the mitochondrion that has undergone morphological change . Thus, the ultrastructural degradation of the mitochondria is correlated with a decrease in biochemical function . This suggests a correspondence between a decrease in the bioenergetic capacity of the flight muscle and a decline in the ability of the aged insect to fly .In pioneering experiments, Williams et al . (1) reported that the flight ability of flies declines markedly with age . The mechanism of this deterioration with senescence remains essentially unknown . Our previous studies on the control of intermediary metabolism in flight muscle (2-4) prompted us to examine whether the bioenergetic processes in this horrendously active tissue undergo changes during aging . Notable differences in the ultrastructure and biochemical activity of the muscle from young and old blowflies, Phormia regina, have now been found . In this paper, degenerative alterations in mitochondria with age, as determined by electron microscopy, are reported. METHODSBlowflies were maintained in laboratory culture as reported previously (5) . The flight muscles from female flies, 7-46 days old, were used . Mitochondria were isolated as described earlier (6) ; the isolation medium consisted of 0.15 M KCI, 0 .01 M Tris chloride, 1 mm ethylenediaminetetraacetate (EDTA), and 0 .5% bovine serum albumin, adjusted to pH 7 .4 .Unless noted otherwise, flies were bisected by a medical cut with a razor blade in ice-cold fixative containing 2 .5% glutaraldehyde, 0 .05 M cacodylate buffer, pH 7.4, and 0 .18 M sucrose (7) . Samples of muscle, less than 1 mm 3, were kept in fixative, at 0-4°C, for 3 hr and washed overnight in the cold with 0 .05 M cacodylate in 0 .3 M sucrose . The tissue was transferred to cold 1 % osmium tetroxide in 0 .1 M phosphate buffer, pH 7 .4, for 2 hr, dehydrated in an ethanol series, and embedded via propylene oxide in Epon 812 . Sections were cut with a diamond knife on an LKB Ultrotome III and mounted on 300-mesh copper grids. The specimens were stained with saturated uranyl acetate and l...

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Section: Resultsmentioning

confidence: 99%

Degenerative Changes in the Mitochondria of Flight Muscle From Aging Blowflies

Sacktor

Shimada

1972

The Journal of Cell Biology

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“…Many of these fibers are similar to fetal myotubes that are hypotrophic with a centrally placed nucleus and perinuclear halo devoid of myofibrils 30,31 . In longitudinal sections the centralized nuclei are seen in rows and oriented longitudinally to the greater axis of the fiber 5,30 . In our series of patients the percentage of nuclear centralization varied from 25% to 95%.…”

Section: Discussion Discussion Discussion Discussion Discussionmentioning

confidence: 90%

“…In our series of patients the percentage of nuclear centralization varied from 25% to 95%. This percentage may vary according to the muscle group examined, the type of sections (transversal or longitudinal) and the period in which the muscle biopsy is performed in a same patients 12,14,20,26,30 .…”

Section: Discussion Discussion Discussion Discussion Discussionmentioning

confidence: 99%

“…Increase in the endomysial connective tissue is mild to moderate 16,30,31 . Only one patient of our series had a severe increase and in the other patients it was absent or insignificant.…”

Section: Discussion Discussion Discussion Discussion Discussionmentioning

confidence: 99%

“…It presents with diffuse involvement of skeletal muscles, including those innervated by the cranial nerves, with onset in early childhood and a slowly progressive evolution. The basic histological abnormality is the high percentage of centrally placed nuclei associated, in most cases, with a perinuclear halo without myofibrils and a high oxidative activity 30,31 . Other…”

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Centronuclear myopathy: histopathological aspects in ten patients with chilfhood onset

Zanoteli¹,

Oliveira

Kiyomoto³

et al. 1998

Arq. Neuro-Psiquiatr.

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-Centronuclear myopathy is a rare congenital myopathy. According to the period of onset of signs and symptoms and the degree of muscular involvement three clinical forms are distinguished: severe neonatal; childhood onset; and adult onset. We describe herein the muscle biopsy findings of ten patients with the childhood onset form of the disease including three cases with ultrastructural study. The biopsies disclosed increased nuclear centralization that varied from 25 to 90% of the fibers, type 1 predominance, great variability in fiber diameters, involvement in the internal fiber's architecture, and focal areas of myofilament disorganization. The main histopathologic differential diagnoses included type I fiber predominance, congenital fiber type disproportion, and myotonic dystrophy. The histologic abnormalities in centronuclear myopathy may be due to an arrest of maturation on the fetal myotubular stage. The cause of this arrest remains elusive.KEY WORDS: centronuclear myopathy, myotubular myopathy, histochemical, ultrastructure. Miopatia centronuclear: aspectos histopatológicos em dez pacientes com a forma clínica de início na infânciaRESUMO -A miopatia centronuclear (MCN) é uma forma rara de miopatia congênita. De acordo com a época do início dos sinais e sintomas e com o grau de envolvimento muscular são distinguidas três formas clínicas: forma neonatal severa; forma de início na infância; e de início na vida adulta. São apresentados neste estudo os achados histopatológicos de dez pacientes portadores da forma de início na infância da MCN. Os fragmentos musculares foram processados através de colorações de rotina e histoquímica, e em três casos foi realizado estudo ultraestrutural. Dentre os resultados obtidos, destacou-se o aumento da centralização nuclear na fibra muscular, que variou de 25 a 90%. Adicionalmente, foram observadas predominância de fibras do tipo I, variabilidade entre o diâmetro das fibras musculares, alterações da arquitetura interna das fibras musculares e presença de áreas focais de desorganização dos miofilamentos. Devido a estes aspectos, os principais diagnósticos diferenciais considerados foram as miopatias por predominância de fibras e por desproporção de fibras, e a distrofia miotônica. As anormalidades histológicas observadas na MCN podem ser devidas a uma parada no processo maturacional do músculo esquelético na fase miotubular fetal. A causa deste defeito ainda permanece sem explicação completa. PALAVRAS-CHAVE: miopatia centronuclear, miopatia miotubular, histoquímica, ultra-estrutura.Centronuclear myopathy (CNM) is a rare disease, classified in the congenital myopathy group, described in 1966 by Spiro, Shy and Gonatas 31 . It presents with diffuse involvement of skeletal muscles, including those innervated by the cranial nerves, with onset in early childhood and a slowly progressive evolution. The basic histological abnormality is the high percentage of centrally placed nuclei associated, in most cases, with a perinuclear halo without myofibrils and a high oxidative ...

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