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Biomedical subjects

S A Shafiq

Publications and source records attributed to S A Shafiq.

At least 37 records · Page 2Linked to original sources

Characterization of a monoclonal antibody to myosin specific for mammalian and human type II muscle fibers.

We have characterized a monoclonal antibody (McAb), ALD-19, generated against slow myosin from chicken anterior latissimus dorsi (ALD) muscle for use in studies of human and animal muscle fiber types. This McAb bound selectively to the 200 kDa myosin heavy chain band in immunoblots against chicken, rat and human myosins and showed selective staining of A bands in the myofibrils. The reactivity of ALD-19 with various myosin types was quantitated by radioimmunoassays. Fiber type analysis revealed unexpected specificity of McAb ALD-19 for type II mammalian muscle fibers. This antibody should, therefore be useful for identification and quantification of normal type II fibers in human muscle biopsy specimens.

Animals↗

Heterogeneity of type 1 skeletal muscle fibers revealed by monoclonal antibody to slow myosin.

Monoclonal antibodies (McAbs) were generated against slow myosin from the chicken anterior latissimus dorsi (ALD) muscle and their reactivity was checked against fast (pectoralis), slow (ALD), cardiac (ventricular), and smooth (gizzard) myosins by radioimmunoassay (RIA), immunoautoradiography (immunoblots), and indirect immunofluorescence techniques. In RIAs, the McAb (ALD-58) described in this article reacted specifically with slow myosin, with only a weak cross-reactivity to cardiac myosin. In immunoblots against whole muscle homogenates and purified myosins, it bound selectively to the 200 Kd myosin heavy chain band. The ALD-58 antibody stained the fibers of the ALD muscle uniformly but gave three grades of reactions (strong, weak, and negative), with histochemically identified type 1 fibers of sartorius and gastrocnemius muscles demonstrating the immunological heterogeneity of myosins in type 1 skeletal muscle fibers.

Animals↗

I-cell disease (mucolipidosis II). Differential expression in satellite cells and mature muscle fibers.

A well documented case of I-cell disease is presented. Light- and electron-microscopic studies of muscle revealed marked accumulation of characteristic I-cell inclusions in satellite cells and only scattered autophagic vacuoles in muscle fibers. Correlation with previous tissue culture studies indicated an amelioration of structural abnormalities with differentiation from satellite cell to mature muscle fiber. Histochemically, the muscle demonstrated paucity of type I fibers without evidence of denervation thus suggesting a developmental disturbance in motor unit organization. Selective type I fiber dysfunction and reduced satellite cell regenerative capacity may be related factors in the neuromuscular disability of patients with I-cell disease.

Child, Preschool↗

Developmental changes in the plasma membrane of gizzard smooth muscle of the chicken. A freeze-fracture study.

Plasma membranes of chicken gizzard at embryonic, early post-hatching and adult stages were examined by the freeze-fracture technique and developmental changes in surface caveolae, intramembranous particles and gap junctions were found. The number of caveolae increased linearly during 11 to 21 days embryonic stages, from 1 to 7/micrometers2 of membrane surface, and their arrangement into subparallel bands took place in the early post-hatching period. The average density of caveolae at this time was 14/micrometers2, which increased in the adult to about 37/micrometers2. The intramembranous particles in embryonic muscle membranes were uniformly distributed with a P-face density of about 1000 particles/micrometers2; at 5 days post-hatching and at adult stages this particle density in the caveolar band regions increased to about 1700/micrometers2 and 2000/micrometers2, respectively. The gap junctions in contained embryonic gizzard consisted of only 12-14 particles, in the 5-days old chick they contained up to 200 particles, whereas in the adult up to 1000 particles were seen. The gizzard muscle shows the most striking developmental changes during the early post-hatching period and offers a good system for studies of membrane differentiation.

Animals↗

Freeze-fracture analysis of the effects of age and 2,4-dinitrophenol on the morphology of flight muscle mitochondria of Musca domestica L.

Morphometric comparison of freeze-fractured mitochondria in flight muscles of adult (37-day-old) and old (68-day-old) houseflies revealed a 28% decrease of cristae in the old flies. The major membrane change with age was an increase in the 90-120-A particles in the inner membrane external face concomitant with a loss of particle clusters associated with the openings of the cristae on to the inner membrane. In vitro treatment of flight muscle with 2,4-dinitrophenol, and uncoupler of mitochondrial respiration, did not produce this change but resulted in the formation of smooth particle-free vesicular swellings in the mitochondria. Such swelling were infrequent in the old muscle. The cause for the aging change is not clear, but a reduction in the ability of the intramembranous particles to aggregate, either through modification of altered synthesis, is indicated.

2,4-Dinitrophenol↗

Successful treatment of murine muscular dystrophy with the proteinase inhibitor leupeptin.

Mice with genetic muscular dystrophy were treated with intraperitoneal injections of the proteinase inhibitor leupeptin, beginning before the onset of weakness. A significant number of the treated animals failed to develop histological evidence of dystrophy, compared with controls. Leupeptin treatment prevented (or delayed) the onset of muscular dystrophy in this experiment.

Animals↗

A freeze-fracture study of the anterior and posterior latissimus dorsi muscle of the chicken.

The sarcolemma, sarcoplasmic reticulum (SR), and T system of the anterior (tonic) and posterior (fast twitch) latissimus dorsi muscles of the chicken have been examined by the freeze-fracture technique, and quantitative data on the P and E fracture faces have been obtained. The fractured plasma membranes reveal (a) profiles of surface caveolae, (b) randomly distributed intramembranous particles ranging in size from 40-100 A in diameter, and (c) orthogonal assemblies composed of groups of 60 A particles in close association, and differences with respect to all three structures are present between the tonic (ALD) and fast twitch (PLD) muscles. In the ALD muscle, the surface caveolae are more uniformly distributed and have smaller openings than in the PLD muscle; the former muscle also has a two-fold higher caveolae density than the latter muscle. The intramembranous particles are more numerous in the ALD than in the PLD muscle in both fracture faces, but the orthogonal assemblies are fewer. The functional significance of these differences in the two fiber types are discussed. The fractured membranes of the SR have intramembranous particles (IMPs) approximately 80 A in diameter, with a two-fold higher packing density in the PLD than in the ALD muscle. This difference is present in both the longitudinal and cisternal components of the SR. In addition, there are collar-like expansions (CLE's) in the SR of the ALD muscle which are particularly poor in intramembranous particles. These particles are considered to represent Ca2+ transport ATP-ase, and the reduced density of IMP's could be a significant factor in the low calcium uptake and and slow relaxation characteristics of the ALD muscle.

Animals↗

A freeze-fracture study of fiber types in normal human muscle.

The sarcoplasmic reticulum (SR) and plasma membranes of Type 1 and Type 2 fibers of normal human muscle were examined by the freeze-fracture technique. Total particle counts in the SR appeared much lower than in other mammals and a packing density of about 1200 particles/micrometer 2 was found in both longitudinal and cisternal components of SR. There was no difference in particle density of Type 1 and Type 2 fibers. In freeze-fracture replicas of plasma membranes several fiber type differences were seen. The surface caveolae were uniformly distributed in Type 1 fibers whereas in Type 2 they were clustered preferentially at the I-band levels. Total density of intramembranous particles was greater in Type 1 fibers (347 +/- 68/micrometer 2 in P-face, 58 +/- 11/micrometer 2 in E face) than in Type 2 fibers (207 +/- 30/micrometer 2 in P-face, 80 +/- 9/micrometer 2 in E-face). There was a striking difference in respect to rectilinear arrays which were virtually absent in Type 1 fibers (0--2/micrometer 2) and numberous (up to 50--70/micrometer 2) in Type 2 fibers.

Adolescent↗

Quantitative morphological analysis of age-related changes in flight muscle of Musca domestica L.

Electron micrographs of dorsal indirect flight muscle of 37 (adult) and 68 (old) day old female houseflies were analyzed by morphometric techniques. In the muscle of the old female housefly there is no significant atrophy and the fine structure is well preserved. There is a small loss in both the myofibril and mitochondrial volumes, an increase in average myofibril size, and a 28% decrease in myofibril number. The thin/thick filament ratio and sarcomere structure are not altered. There is little decrease of particulate glycogen. The fractional volume occupied by SR at the dyads is increased. The most marked change is in the density of mitochondrial cristae which declines by 55% in old muscle and could account for the functional loss. Cristal anomalies and SR changes indicate that the membranes may be the specific target of deleterious aging effects.

Aging↗

Acute myopathy with selective lysis of myosin filaments.

An acute reversible myopathy characterized by extensive lysis of myosin occurred in a patient who suffered from severe shock, hypoxia, and acidosis. This new clinical pathologic entity illustrates an unusual structural change in muscle associated with these catastrophic clinical circumstances.

Acute Disease↗

Muscular dystrophy: inhibition of degeneration in vivo with protease inhibitors.

The protease inhibitors leupeptin and pepstatin were used in vivo in genetically dystrophic chickens to determine their effects on the histological and biochemical changes observed in this disease. These compounds appear to delay the degeneration of muscle tissue which is characteristic of this disorder and thus may have potential therapeutic value in the treatment of muscular dystrophy.

Animals↗