William W. Hofmann

Experimental allergic neuritis in the Lewis rat.

Purified myelin from the peripheral nervous system of guinea pig, frog (Rana catesbeiana), rat, rabbit, beef, and human in Freunds adjuvant were injected into the Lewis rat. Groups of rats receiving injections of myelin from different species were examined for signs of dysfunction and lesions in the PNS and CNS. Injection of frog PNS myelin into the Lewis rat did not produce any clinical signs or lesions typical of experimental allergic neuritis (EAN) or experimental allergic encephalomyelitis (EAE). Injection of myelin from the PNS of rat, rabbit, beef, and human elicited clinical signs and lesions characteristic of EAN, while guinea pig myelin injection caused superimposed conditions of EAE and EAN. The myelin proteins from the various species were separated by polyacrylamide gel electrophoresis, the gels were scanned and the individual proteins measured. There did not appear to be a correlation between the amount of P2 protein contained in the different myelin species and the severity of the EAN symptoms and lesions produced. Although the Lewis rat is far more susceptible to EAE caused by guinea pig CNS myelin than by any other species, EAN can be easily induced in this animal by injection of PNS myelin from a number of species.

Mechanisms of muscular hypertrophy

The effects of synergist tenotomy have been studied on rat soleus muscles after denervation and after interference with sciatic axoplasmic flow with colchicine. The results suggest that neural, as well as muscular, factors cause compensatory hypertrophy (CH) of soleus. The myogenic factor may be mild depolarization of the muscle membranes by passive stretch, as a result of which Ca++ ions enter and stimulate metabolism.

Postjunctional changes induced by partial interruption of axoplasmic flow in motor nerves

Abstract When the nerve to a fast muscle in a rat is exposed to colchicine there is a partial block of axoplasmic flow which results in slowing of the muscles twitch relaxation. This biomechanical change is thought to represent a transsynaptic metabolic effect caused by loss of some presynaptic trophic substance. The colchicine blockade is temporary, and, though the muscle briefly stops growing, it recovers and gains weight normally. Even while the contraction is temporarily slowed the muscle behaves differently from a denervated or a dystrophic one.

Observations on the efficiency of dystrophic muscle in vitro.

A study of muscles of the dystrophic mouse has failed to substantiate earlier claims that these muscles were especially resistant to fatigue in vitro or that fast muscles are preferentially damaged. It has been found that the fast muscle selected for previous studies is very often unable to withstand isolation in an organ bath if it is working, and both the difficulty in removing the normal gastrocnemius muscle intact and the need to trim it surgically contribute independently toward its deterioration in vitro. The smaller dystrophic gastrocnemius muscle is less liable to excision damage, is able to satisfy its resting metabolic needs in nutrient solution, and requires no damaging dissection, but is nevertheless unable to recover normally from fatigue. Using EDL and soleus muscles which are small enough to withstand isolation in vitro, no differences are found between fatigue patterns of normal and dystrophic specimens. Responses to rest, KCl, and 2 mM caffeine are also quite similar, and the only distinguishing biomechanical characteristic we have found in dystrophic mouse muscle is a weaker contraction and a longer total twitch time.

Musculotrophic effects of insulin receptors before and after denervation.

Insulin binding and metabolic effects have been used to assess properties of the insulin receptor of rodent skeletal muscles before and after denervation. It has been found that the amount of insulin-displaceable insulin binding on both type I (soleus) and type II (extensor digitorum longus) muscles rises slowly for up to 3 weeks after denervation, following a brief period of reduced binding. As estimated from weight loss and unstimulated deoxyglucose uptake, the extra binding sites are not functional. Stimulation in vitro with shocks or excess potassium can temporarily cause a relative increase in sugar uptake in both types of muscle, but an excess of insulin rapidly loses its effect in the soleus muscle. The effects of stimulation are taken to mean either conformational changes in the receptor or enhancement of some postbinding step, or both. It is suggested that the slow increase of binding sites for insulin after denervation may reflect loss of a neural substance normally effective in activating receptor degradation.

Inhibition of autoreactive antibody effects with antibody feedings: a pilot study

This study seeks to determine if tolerance to autoreactive antibody can be achieved by exposing gut-associated lymphocytic tissue (GALT) to the protein. The method involved immunizing rats with AchR after feeding anti-AchR purified from myasthenic plasma or non-specific, pooled human immunoglobulins. Both feedings improved the neuromuscular block of EAMG, the commercial preparation requiring a tenfold increase in protein concentration. Despite its protective effect, antibody feeding was associated with late levels of serum anti-AchR considerably above those in immunized controls. The hypothesis presented is that the tolerance results from enhanced anti-idiotype production.

Attenuation of local tetanus by treatment of ipsilateral sciatic nerve with colchicine

Abstract A study of local tetanus in the hindlimb muscles of albino rats has shown that the toxins clinical and electromyographic effects can be reduced by using colchicine to inhibit centripetal intraaxonal flow. We have not found significant defects in any aspect of neuromuscular transmission, but involved muscles show fibrillation, a tendency toward slower twitches, and profound weight loss, as if denervated. This is interpreted to mean that tetanus toxin damages the motoneuron so that it cannot synthesize or transport materials required for peripheral neurotrophic regulation of muscles. Phasic (type II) muscles are more involved than the tonic (type I) muscles. Joint adhesions were found to cause some of the late manifestations of local tetanus at a time when the spasms had subsided.