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M Ontell

Publications and source records attributed to M Ontell.

54 records · Page 3Linked to original sources
PubMed1984

Organogenesis of the mouse extensor digitorum logus muscle: a quantitative study.

A quantitative analysis of the pattern of development and growth of the fetal extensor digitorum longus muscle of the 129 ReJ mouse was carried out in spaced, serial ultrathin sections with computer-assisted morphometry. Muscle from 12-, 14-, 16-, and 18-day in utero mice and from newborn and 5-day postnatal mice was analyzed to determine age-related changes in such factors as the maximal girth and length of the muscle, the number of myotubes, the "cluster" frequency, and the diameters and lengths of the myotubes and muscle units. A distinct temporal pattern of development was established. It was quantitatively determined that a delay less than or equal to 2 days occurs between the formation of primary myotubes (present at 12 days in utero) and secondary myotubes (present at 16 days in utero). By 16 days in utero, groups of myotubes, consisting of one primary myotube and a variable number of secondary myotubes, form "clusters" surrounded by a common basal lamina. Morphometric analyses of diameter distributions establish that most, if not all, secondary-generation myotubes are formed in association with larger, more mature myotubes. Quantitative data support the hypothesis (Ontell and Kozeka, 1984) that cluster formation and cluster dispersion occur simultaneously, beginning sometime between 16 and 18 days in utero. By 18 days in utero, the adult number of myofibers is present in the developing muscle mass. Analyses of lengths and diameters of the same fibers establish that the pattern of growth of the last-formed myotubes of the developing muscle mass is different from that of myotubes formed earlier in development.

Animals↗
PubMed1984

Myosatellite cells, growth, and regeneration in murine dystrophic muscle: a quantitative study.

Patterns of growth and regeneration in 2-, 4-, 8-, and 17-week-old murine dystrophic (129 ReJ dy/dy) extensor digitorum longus muscles have been determined. Necrosis and myofiber loss, hypertrophy, and regeneration result in a reduced population of myofibers whose diameter distribution is more extensive than that found in the extensor digitorum longus muscles of age-matched normal mice. At the onset of dystrophic symptoms (2 weeks postnatal), the ratio of myosatellite cell nuclei to the total sublaminal nuclear population (myonuclei + myosatellite cells) is similar to that found in 2-week-old control muscles. The frequency of finding myosatellite cells decreases with age in both control and dystrophic muscles. Myosatellite cells account for 11%, 6%, 5%, and 3% of the total sublaminal nuclear population in control muscle and 12%, 8%, 6%, and 5% of the total sublaminal nuclear population in dystrophic muscle at 2, 4, 8, and 17 weeks, respectively. No preferential association of myosatellite cells with myofibers of a particular diameter is found in control muscle or in the two youngest dystrophic groups. At 8 and 17 weeks, myosatellite cells are less frequently encountered on small-diameter, regenerating myofibers of dystrophic muscle, and they are preferentially associated with large diameter, hypertrophied myofibers. The labeling index of myosatellite cells decreases with age in both normal and dystrophic muscle. At all ages the myosatellite cell labeling index is higher in dystrophic muscle (23%, 7%, 5%, and 2% at 2, 4, 8, and 17 weeks, respectively) than in normal muscle (5%, less than 1% at 2 and 4 weeks, respectively), with no labeled myosatellite cells being found in 8- and 17-week-old normal muscles. It is suggested that the magnitude of the regenerative response of dystrophic murine muscle decreases with age and that this factor may be responsible for the inability of the regenerative response of dystrophic muscle to keep pace with the rapid muscle deterioration.

Animals↗
PubMed1984

Branched myofibers in long-term whole muscle transplants: a quantitative study.

Orthotopic transplants of whole extensor digitorum longus muscles were performed on six 4-6-week-old 129 ReJ mice. One hundred days posttransplantation, the animals were killed and the regenerated muscles were processed for electron microscopy. The grafts contained polygonal-shaped myofibers with persistent central nuclei, organized into discrete muscle fascicles. No central area of fatty infiltration or fibrosis was observed. The mean number of myofibers in a regenerating transplanted muscle, as determined from an ultrathin section taken from the graft's widest girth, was 631 (SEM = +/- 59), a reduction of approximately 32% from that found in age-matched control muscle (Ontell et al., 1983). By following the myofibers in spaced, serial ultrathin sections along their length, it was found that the branched, regenerating myofibers found in immature grafts of normal muscle (Ontell et al., 1982) persisted in stabilized, long-term transplanted muscle. The frequency of branching was determined by following each fiber found at the widest girths of four of the grafts in spaced, serial ultrathin sections (15-micron intervals) for approximately 2% of the total length of the grafts. Over this distance, 6.6% of the fibers were involved in the branching phenomenon. The persistence of branched fibers in long-term grafts and the frequency with which the branching phenomenon was found to occur may have physiological consequences and should be investigated.

Animals↗
PubMed1984

A new approach to intramuscular placement of horseradish peroxidase.

A new method of intramuscular placement of a semisolid paste of horseradish peroxidase (HRP) using a root canal file is described. This method has been demonstrated to produce consistent and reproducible numbers of labeled motoneurons in the mouse extensor digitorum longus muscle (EDL). While the number of labeled cells is similar to that found with optimal intramuscular injection of liquid HRP, this new technique provides more reproducible results by eliminating the reflux often associated with intramuscular injection of liquid HRP.

Animals↗
PubMed1982

Secondary myogenesis of normal muscle produces abnormal myotubes.

The extensor digitorum longus muscles of 2-, 4-, and 12-week-old 129-ReJ mice were subjected to homotopic, whole-muscle transplantation. Subsequent to myofiber necrosis and phagocytosis, a new population of myotubes was produced. The three-dimensional cytoarchitecture of these newly formed myotubes was determined in spaced, serial, ultrathin sections. Myotubes, which for long distances along their length appeared to be separate and discrete, were found to branch and recombine, forming a complex syncytium.

Aging↗
PubMed1981

The three-dimensional cytoarchitecture and pattern of motor innervation of branched striated myotubes.

Three-dimensional reconstructions of "regenerating" myotubes in the "degeneration-regeneration" regions and in the "regenerative" foci of the extensor digitorum longus muscle of the C57BL6J/dy2J myopathic mutant mouse were made from spaced serial ultrathin section. Complex branching and recombination occurred, involving myotubes which for extensive regions along their length appeared to be independent. No accumulation of specialized organelles occurred at the branching site. Continuous branches displayed multiple discrete motor endplates.

Animals↗
PubMed1981

The lack of a "pleiotypic response' in hepatocyte proliferation induced in the rat by 3,5,3'-triiodothyronine.

Early morphological and biochemical alterations in proliferatively stimulated liver tissue obtained from 3,5,3'-triiodo-L-thyronine-treated rats were compared to those occurring in the liver remnant of 70% hepatectomized animals, and to controls. Subjecting photographic enlargements of histological slides prepared from these liver tissues to computer-assisted analyses, hepatocyte nuclear and nucleolar volumes were shown to be virtually identical in control and hormone-treated preparations through the first 24 hours after treatment, but significantly different from tissues obtained from partially hepatectomized animals, In vitro estimations of hepatic nuclear RNA polymerase activities early after treatment were also shown to be similar when comparing the hormone- and the saline-treated rats. Estimated by either 3H-orotic acid or 3H-leucine incorporation, the early accumulation of hepatic RNA and liver and serum proteins, significantly enhanced by 70% hepatectomy, were found similar in triiodothyronine-injected and control animals at least through the first 6 h after treatment; hormone administration appeared to cause slight enhancements in these parameters at later prereplicative times. While pharmacological doses (200 micrograms/100g) of the thyroid hormone induce a strong proliferative response in rat liver tissue, only minor prereplicative alterations appear to be elicited in the hepatocytes. This hepatic model offers an important potential tool to investigations aimed at understanding proliferative controls in mammalian liver cells.

Animals↗
PubMed1980

Necrotic extrafusal muscle fibers of the dystrophic mutant mouse: the ultrastructure of the myoneural junction.

At 28 days postpartum, the extensor digitorum longus muscle of the dy2J mutant mouse contains a population of myofibers which exhibit coagulation necrosis for approximately 90% of their length. Using the electron microscope, motor endplates were found on more than half of the necrotic fibers studied, occurring in mildly, moderately, and severely necrotic regions of these fibers. The ultrastructural features of the axonal terminals did not vary with the condition of the fiber segment at which the endplate occurred. No morphological criteria could be established for distinguishing between the axonal terminals of necrotic fibers and those of "healthy" fibers in the dystrophic animal. The principle morphological changes at motor endplates of necrotic fibers involved not the axonal terminal, but the muscle fiber itself. This study demonstrates that the necrotic myofibers, which are present at the onset of the first clinical symptoms of murine dystrophy, are innervated. Therefore, necrosis is not precipitated by structural denervation. Furthermore, observations of motor endplates on mildly, moderately, and severely necrotic regions of the myofibers indicate that regional changes along the necrotic fiber's length are not a function of distance from the motor endplate.

Animals↗
PubMed1979

Involvement of transverse tubules in induced myotonia.

A single oral dose of clofibrate (30 mg/100 gm body weight) given to 250-300 gm male rats produced myotonic discharges from both the gastrocnemius and soleus muscles 2 hours after feeding. Rats fed the same dosage for 14 consecutive days exhibited electromyographic discharges consistent with profound myotonia. Fibers removed from the superficial region of the gastrocnemius muscle served as the source of fast twitch fibers for histological studies. Slow twitch fibers were observed in the soleus muscle. After a single clofibrate feeding localized T-tubule dilation was observed in a small percentage of myofibers in both muscles. In rats fed clofibrate for 14 days, approximately 30% of the fibers of the gastrocnemius and soleus muscles had dilated T-tubules. The motochondria of the soleus muscles of these rats were characterized by dilated intercristal matrixes containing electron densities. No mitochondrial changes were observed in the fibers of the gastrocnemius muscles taken from the same rats.

Action Potentials↗
PubMed1977

Neonatal muscle: an electron microscopic study.

A spaced serial section, electron microscopic study of the extensor digitorum longus of the 2-day-old rat was undertaken to determine whether all cells wedged between the basement membrane and the sarcolemma of a muscle fiber, regardless of their morphology, were true myosatellite cells. The muscle was relatively immature, containing groups of cells enclosed in a common basement membrane (clusters) and exhibiting primitive myoneural junctions. Cells of the muscle line included in the clusters were primary fibers, satellite fibers, myotubes in different stages of development and myosatellite cells. In single ultrathin sections, some early myotubes lacked myofilaments and were difficult to distinguish from myosatellite cells. Spaced serial sections revealed that all myosatellite cells have heterochromatic nuclei and a high nuclear/cytoplasmic ratio, and that all pale staining nuclei were found in cells with a lower nuclear/cytoplasmic ratio, containing variable quantities of myofilaments. In addition to the cells of the muscle line, mast cells, fibroblast-like cells and other "unclassified" cells were entirely or partially enclosed within the cluster's basement membrane. This study demonstrated that location alone or location and the morphological appearance of cells in a single ultrathin section failed to provide sufficient criteria to properly classify all of the cells found in neonatal muscles clusters.

Animals↗
PubMed1975

Evidence for myoblastic potential of satellite cells in denervated muscle.

The failure of denervated muscle to undergo effective regeneration, despite reported increases in the number of muscle satellite cells, warranted an investigation of the viability and myoblastic capacity of these cells present in denervated muscle. Four types of satellite cells present in muscle denervated for three weeks are described, based on their ultrastructure and relationship to their principal fiber. The increased number of ribosomes, including helically arranged polysomes; the number of Golgi complexes; the presence of microtubules; the branching subsarcolemmal tubular system; and the appearance of regularly arranged 96 A microfilaments with diffuse electron dense areas are structural features of satellite cells that are similar to those of developing myoblasts in growing and regenerating muscle. The electron microscopic observations suggest that "activated" satellite cells do have myoblastic potential. Possible explanations for the ultimate failure of denervated muscle to regenerate include: 1) the inability of the muscle to produce satellite cells rapidly enough to keep pace with muscle degeneration; 2) a cytotoxic effect produced by the degenerating muscle fiber on the satellite cell; and 3) the inability of satellite cells to form stable, mature multinucleated fibers in the absence of the trophic effect of the nerve.

Animals↗
PubMedDate not supplied

Muscle fiber necrosis in murine dystrophy.

A sampling technique based on spaced serial ultrathin sections was used to examine the ultrastructure and cytoarchitecture of myofibers, which were necrotic throughout their length, in the dystrophic mutant mouse (C57Bl6J/dy2J). Regional variations along the length of the myofibers were described. The necrotic fibers extended the full length of the muscle fascicle and did not branch. In necrotic fibers which were free of invasive cells, the only nuclei found under the basal lamina were peripherally placed, euchromatic myonuclei, or nuclear membrane remnants. In these fibers, the nuclear population was approximately 14% of the nuclear population of "healthy" fibers from the same animals. No myosatellite cells were observed to be associated with these necrotic fibers. In necrotic fibers, which had undergone foreign cell invasion, the existence of a pleomorphic population of mononucleated invasive cells, many of which had not begun to express phagocytic characteristics, caused considerable confusion, because their appearance tended to mimic that of myonuclei or satellite cells. No heterochromatic nuclei or true myosatellite cells were found associated with necrotic fibers displaying macrophage invasion.

Animals↗
PubMedDate not supplied

The size of the myofibers in mature grafts of the mouse extensor digitorum longus muscle.

The histochemical profile of stabilized orthotopically grafted mouse extensor digitorum longus muscles (EDL) and fiber type diameter distribution in the graft was compared with control muscles. Histochemical fiber typing, based on myofibrillar ATPase reactions, indicated that type 1 fiber accounted for less than 1%, type 2a fibers for 30%, and type 2b fibers for 69% of the total fiber population of the graft. In control muscles of 56-day-old and 156-day-old mice, type 1 fibers accounted for less than 1%, type 2a fibers for 36%, and type 2b fibers for 63% of the total fiber population of normal muscles. The regenerating myofibers in stabilized grafts failed to achieve the normal fiber diameter. The type 2b fibers exhibited greater growth inhibition than did type 2a fibers.

Animals↗
PubMedDate not supplied

Enhancement of adult muscle regeneration by primary myoblast transplantation.

Extensor digitorum longus muscles (EDL) of SCID mice were induced to undergo degeneration-regeneration subsequent to orthotopic, whole-muscle transplantation. Two days after transplantation some of these muscles received injections of primary myoblasts derived from EDL muscles of transgenic mice, which express nuclear localizing beta-galactosidase under the control of the myosin light-chain 3F promoter and enhancer. Nine weeks after transplantation, regenerated muscles that received exogenous myoblasts were compared to similarly transplanted muscles that received no further treatment and to unoperated EDL muscles in order to determine the effect of myoblast transfer on muscle regeneration. Many myofibers containing donor derived myonuclei could be identified in the regenerated muscles that had received exogenous myoblasts. The mass of the muscles subjected to transplantation only was significantly less (31% less) than that of unoperated muscles. The addition of exogenous myoblasts to the regenerating EDL resulted in a muscle mass similar to that of unoperated muscles. The absolute twitch and tetanic tensions and specific twitch and tetanic tensions of transplant-only muscles were 28%, 36%, 32%, and 41%, respectively, of those of unoperated muscles. Myoblast transfer increased the absolute twitch and tetanic tensions of the regenerated muscles by 65% and 74%, respectively, and their specific twitch and tetanic tensions were increased by 41% and 48%, respectively. These data suggest a possible role for the addition of exogenous, primary myoblasts in the treatment of traumatized and/or diseased muscles that are characterized by myofiber loss.

Animals↗
PubMedDate not supplied

[Morphogenesis of transverse straited muscles].

During the past 50 years there have been significant advances in our understanding of striated muscle development, both from tissue culture studies and from observations of myogenesis in the developing foetus. Experiments, using the distinctive nucleolar marker of quail nuclei, have led to reexamination of the source of the body's muscle masses. Advances have been made in our understanding of the events which occur and mechanisms involved in the formation of multinucleated myofibers from mononucleated myoblasts. Recently, the development of entire muscle organs has been studied. The present review attempts to synthesize the results of both in vivo and in vitro studies of myogenesis, comparing both their similarities and their differences. Attention has been focused on recent advances in our understanding of the source of muscles in the intact foetus, the formation of extrafusal and intrafusal fibers, and the development of the afferent and efferent neuromuscular relationships.

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