SUMMARY Morphological findings in sural nerves were related to nerve conduction in 12 patients with diabetic neuropathy, five with mainly sensory involvement, four with severe, symme,trical sensory-motor polyneuropathy, and three with multiple mononeuropathy. All had loss of large and small myelinated and of unmyelinated fibres, even early in the disease; segmental remyelination was the most prominent myelin alteration in teased fibres, segmental demyelination was found in only a few fibres. Axonal degeneration and Schwann cell damage seem to proceed independently of each other. The relation between recorded conduction velocity and that expected from the diameter of the largest fibres indicated that slowing of 20 to 30% was due to causes other than fibre loss; a grossly diminished conduction velocity was caused mainly by fibre loss. Electrophysiological findings in the sural nerve were largely representative of findings in other nerves, though abnormalities were less marked in the median nerve. In half the endoneurial vessels from diabetic neuropathy the perivascular space was thickened or contained more layers of basal laminae than normal. The same abnormalities were found in one-quarter of the endoneurial vessels from other acquired neuropathies.
This electron microscopic study dcals with thc structure of thc Z disc of frog's skeletal musclc, with special rcgard to thc I filamcnts--whcthcr thcy pass through thc Z disc or terminate at it. In most longitudinal sections thc I filaments tcrminatc as rod-likc projections on cithcr sidc of the Z disc, one I filamcnt on onc side lying between two I filaments on thc opposite side. This indicatcs that the I filamcnts arc not continuous through the Z disc. Thc rod-like projections arc oftcn sccn to consist of filaments (dcnotcd as Z filaments) which mcct at an anglc. In cross-scctions through thc Z region the I filamcnts and Z filamcnts form tctragonal patterns. Thc I filaments are situatcd in the corners of thc squarcs; the obliquc Z filaments form the sides of squares. Thc tctragonal pattern formed by the Z filamcnts is rotated 45 degrees with respcct to thc tctragons formed by thc I filaments on both sides of Z. This structural arrangement is intcrprctcd to indicate that cach I filamcnt on onc sidc of the Z disc faces thc ccntcr of the space bctwccn four I filaments on the oppositc sidc of Z and that the intcrconnection is formed by four Z filaments.
Passive stretch, isometric contraction, and shortening were studied in electron micrographs of striated, non-glycerinated frog muscle fibers. The artifacts due to the different steps of preparation were evaluated by comparing sarcomere length and fiber diameter before, during, and after fixation and after sectioning. Tcnsion and length were recorded in the resting and contractcd fiber before and during fixation. The I filaments could be traced to entcr the A band between the A filaments on both sides of thc I band, creating a zone of overlap which decreased linearly with stretch and increased with shortening. This is consistent with a sliding filament model. The decrease in the length of the A and I filaments during isometric contraction and the finding that fibers stretched to a sarcomere length of 3.7 # still developed 30 per cent of the maximum tetanic tension could not be explained in terms of the sliding filament model. Shortening of the sarcomeres near the myotendinous junctions which still have overlap could account for only one-sixth of this tension, indicating that even those sarcomeres stretched to such a degree that there is a gap between A and I filaments are activated during isometric contraction (increase in stiffness). Shortening, too, was associated with changes in filament length. The diameter of A filaments remained unaltered with stretch and with isometric contraction. Shortening of 50 per cent was associated with a 13 per cent increase in A filament diameter. The area occupied by the fibrils and by the interfibrillar space increased with shortening, indicating a 20 per cent reduction in the volume of the fibrils when shortening amounted to 40 per cent.
By electron microscopy, the ultrastructure of the M line was investigated in fibers from frog nonglycerinated semitendinosus muscles at body length and at different degrees of shortening and stretch. The M line appeared as a line of high electron opacity in the middle of the A band. Its framework consists of: (i) three (four or five) arrays of transverse M bridges, 200 A apart, connecting each A filament with its six neighbors; (ii) M filaments, parallel to the A filaments, passing through the M line and linking each set of M bridges together. In the shortened fiber the M line remained distinct. At high degrees of stretch, the M line became fainter or indiscernible. This appearance reflects a misalignment of the M components caused by a staggering of the A filaments. The M line reappeared after release of fibers stretched 70-80% above equilibrium length. On the basis of the structural analysis, the possible function of the M line is compared with that of the Z line, and a model is suggested for the M line.
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