Rats and guinea pigs were injected with 2,4-dichlorophenoxyacetate (2,4-D) in amounts sufficient to keep them myotonic for over 12 hr daily. The biceps brachii muscles were studied by histochemistry, epoxy resin histology, and electron microscopy after one to five days. Changes observed include proliferation of the longitudinal component of the sarcoplasmic reticulum, production of new myofilaments on the periphery of cells and in nuclei, activation of satellite cells, accumulation of lipid droplets, myofibrillar damage with Z-disc streaming, necrosis, and regeneration. The action mehanisms of 2,4-D are not well understood. Some of the phenomena observed could be classified as proliferative and may be analogous to the auxin action of 2,4-D in plants. The production of intranuclear filaments is probably related to the diffusion of newly formed cytoplasmic proteins into nuclei.

2,4-Dichlorophenoxyacetic Acid↗

PubMedDate not supplied

Cylindrical spirals in human skeletal muscle.

Muscle biopsies from two patients revealed that numerous type 2 fibers contained large abnormal areas filled with cylindrical spirals. The cytochemical profile of these cylindrical spirals was sufficiently characteristic that they could be distinguished from tubular aggregates. Their electron microscopic appearance was unmistakable. Their origin and significance are uncertain. The diverse nature of the patients' conditions (cramps and malignancy, and an unusual form of spinocerebellar degeneration) indicate that these abnormal structures are not disease specific.

Biopsy↗

PubMedDate not supplied

An experimental morphometric study of neutral lipid accumulation in skeletal muscles.

The neutral lipid content of skeletal muscle fibers was determined by computing the lipid accumulation index (LAI) on transverse cryostat sections stained with Oil Red O. The LAI was defined as: (total area of neutral lipid droplets in a fiber) x 100/(total cross-sectional area of a fiber). The biceps, diaphragm, and soleus muscles were studied in 3 groups of guinea pigs: normal animals, animals fasted for 48 hours, and animals subjected to muscle denervation and then fasted for 48 hours. In normal animals, the highest mean LAI was found in the diaphragm (4.93) in comparison with lower values in the biceps (2.25) and soleus (2.09). After fasting, these values were markedly increased; there was also a concomitant increase in plasma free fatty acid (FFA) concentration. Prior denervation further increased the LAI in biceps and soleus but reduced it in the diaphragm. Type 2A fibers tended to show high lipid accumulation when the plasma FFA concentration was high. Type 2B fibers never accumulated much lipid under any circumstances. Type 1 fibers varied in their response in the different muscles.

Animals↗

PubMedDate not supplied

Prevention of skeletal muscle fiber necrosis in hamster dystrophy.

Necrosis and widespread central nucleation of skeletal muscle cells, which are the main features of skeletal muscle pathology in genetically dystrophic hamsters (UMX-7.1 strain), were not present in muscles of 45- to 65-day-old animals which had been surgically denervated at 15 to 18 days of age. Necrosis and widespread central nucleation were also absent in hind leg muscles at 30 to 60 days of age after transection of the high thoracic spinal cord at 15 to 18 days. Normal excitation or contraction of the skeletal muscle fibers in early age appears necessary for the microscopic pathological expression of the dystrophic gene in skeletal muscles in the UMX-7.1 strain hamsters. These experiments constitute a rare and clear example of consistent prevention of skeletal muscle cell destruction in vivo in an inherited myopathy.

Animals↗

PubMedDate not supplied

The neurotoxins 2,5-hexanedione and acrylamide promote aggregation of intermediate filaments in cultured fibroblasts.

Axonal swellings associated with large aggregates of neurofilaments are characteristic of neuropathies caused by chemical neurotoxins (n-hexane, methyl n-butyl ketone, and acrylamide) or giant axonal neuropathy (GAN--an autosomal recessive genetic disease). In GAN, filamentous aggregates have been shown also to occur in other cell types including cultured skin fibroblasts. Therefore, we studied the effects of 2,5-hexanedione (the neurotoxic metabolite of n-hexane and methyl n-butyl ketone) and acrylamide on normal human skin fibroblasts in tissue culture. We show that both neurotoxins induce aggregation of intermediate filaments of the vimentin type in the cultured fibroblasts without disrupting microtubules.

Acrylamide↗