Trophic effects of sympathetic ganglia on normal and dystrophic chicken skeletal muscles in tissue culture.
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Biomedical subjects
Publications and source records attributed to H Tsukagoshi.
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Biopsied muscle from 7 patients with Duchenne muscular dystrophy and from 5 normal controls was studied. Sections of 1-1.5 microns thickness treated with lanthanum were studied under a Hitachi H700 electron microscope at an accelerating voltage of 200 kV. The T-system in control muscle showed the network formation running transversely against muscle fiber at the level of the A-I junction, and occasional longitudinal connection between adjacent transverse tubules whereas that in Duchenne muscular dystrophy showed irregularity in course and position, an increase in the number of longitudinal tubules, dilatation of diameter, tangle formation and stratification. Degeneration, developmental defects, and abnormal regeneration may be considered as possible causes of these changes. Larger and relatively electron-dense areas connected with neighboring tubules which were found in this study are probably sarcoplasmic reticulum invaded by lanthanum. The changes in the T-system and anastomoses between the T-system and sarcoplasmic reticulum were more clearly detected by observation of 1-1.5 microns thick sections with the high-voltage electron microscope than with the conventional electron microscope.
Morphometric studies by histological and teased-fiber methods on myelinated fibers of the C6 and C8 ventral roots were made in cases of myotrophic lateral sclerosis (ALS) and in age-matched controls. In 11 controls myelinated fibers were divided into two groups: large and small fibers. The fiber density was calculated and the actual number of fibers was counted in both groups. The number of large fibers was significantly decreased in 14 of 17 cases with ALS, and correlated with the muscle strength of the ipsilateral upper limb as determined by manual muscle testing before death. The absolute number of small fibers of the C6 ventral root was increased in 3 of 5 cases of ALS. In these cases, there was a group of small myelinated fibers showing very thin myelin lamellae compared to axon circumference, and these were considered as regenerating myelinated fibers. On teased-fiber study, the frequency of fibers with axonal degeneration was 23.8% in ALS in contrast to 0.6% in controls (P less than 0.001). In addition, 5.5% of fibers showed segmental demyelination, and remyelination after segmental demyelination was found in 16.4% of fibers in ALS. These figures were also significantly larger (P less than 0.01) than controls (2.4% and 10.1%, respectively). These results suggest that the essential pathological change in the ventral spinal root in ALS is axonal degeneration of large myelinated fibers, and that Schwann cell involvement may also occur.
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The number of motor cells was significantly reduced in the C8 segment of the cervical spinal cord in all 12 cases of amyotrophic lateral sclerosis (ALS), in the C6 and/or C8 segments in 1 case of adult onset spinal muscular atrophy, 2 cases of Werdnig-Hoffmann (W-H) disease, 3 of 4 cases of chronic polyneuropathy and in 1 case of poliomyelitis and 1 of ossification of the posterior longitudinal ligament in the cervical spine (OPLL). The numbers of motor cells were normal in the C6 or C8 segment in 6 cases of muscular dystrophy, except in one case of congenital muscular dystrophy, who showed reduced numbers of the motor cells. Examination of the distribution of motor cells per 500 micrometers thickness in serial sections revealed that reduction in numbers of the motor cells was diffuse and symmetrical in half the cases of ALS and W-H disease and in the cases of chronic polyneuropathy and congenital dystrophy; diffuse but asymmetrical in the other ALS and W-H disease cases and in a case of adult spinal muscular atrophy, and localized and asymmetrical in the cases of poliomyelitis and OPLL. In muscular dystrophy the distribution of motor cells showed segmental variations similar to controls.
Muscle biopsies in 4 cases of Duchenne muscular dystrophy and two normal controls were examined by electron microscopy using lanthanum as a tracer for assessment of the T-system. Lanthanum was localized in the extracellular spaces, the basement membranes, intercellular spaces between muscle fibers and satellite cells, subsarcolemmal vesicles (caveola), motor end-plate, and the T-system in the controls. The T-system was sometimes connected with the caveolae, and was located at right angles to the myofibrils in the controls. In Duchenne muscular dystrophy, the T-system showed irregularities of position, tangle formations and dilatation of the diameters when observed using lanthanum as a tracer, even in muscle fibers which under light- and electron-microscopic examinations did not show any changes. Structure of the triad was destroyed and lanthanun was localized in the sarcoplasmic reticulum (SR). The changes of the T-system and triad seemed to play an important role in the high level of creatine phosphokinase (CPK) in the serum of Duchenne muscular dystrophy patients who do not show any clinical symptoms. Because of the destruction of the triad, CPK will easily flow out to the exterior of muscle fibers via the T-system.