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Biomedical subjects

D B Drachman

Publications and source records attributed to D B Drachman.

At least 19 recordsLinked to original sources
PubMed1979

Isaacs syndrome with laryngeal involvement: an unusual presentation of myokymia.

A woman with widespread myokymia presented initially at age 19 with hoarseness and mild dyspnea on exertion. The diagnosis of Isaacs syndrome was suggested by the clinical findings of widespread continuous muscle activity and depressed tendon reflexes, although she lacked the usually prominent increased muscle tone. The diagnosis was confirmed by the electromyographic demonstration of continuous spontaneous muscle action potentials that were abolished by neuromuscular blockade but not by local nerve blockade. Pulmonary function tests were consistent with fixed extrathoracic obstruction. The vocal cords were closely approximated. Electromyographic studies of the laryngeal muscles under general anesthesia revealed continuous muscle activity, which accounted for the hoarseness and much of the exertional dyspnea. The patient responded well to treatment with phenytoin and carbamazepine. This unusual syndrome should be considered in the differential diagnosis of patients with respiratory complaints and muscle fasciculations, even though they have normal muscle tone.

Action Potentials↗
PubMed1978

Effect of myasthenic immunoglobulin on acetylcholine receptors of intact mammalian neuromuscular junctions.

Degradation of acetylcholine receptors of intact mouse neuromuscular junctions was determined in vivo and in vitro by the release of radioactivity from mouse diaphragms labeled with 125I-alpha-bungarotoxin. Treatment of mice with immunoglobulin from myasthenic patients accelerated the degradation rate to approximately three times normal, in both intact animals and organ cultures. The released radioactivity was in the form of [125I]tyrosine, confirming the nature of the degradative process. Accelerated degradation of acetylcholine receptors at neuromuscular junctions may represent an important antibody-mediated mechanisms in myasthenia gravis.

Animals↗
PubMed1978

Myasthenic antibodies cross-link acetylcholine receptors to accelerate degradation.

The decrease of acetylcholine receptors at neuromuscular junctions of myasthenic patients has been attributed to an antibody-mediated autoimmune process that accelerates receptor degradation. We studied the mechanism of this process in skeletal-muscle cultures, using intact antibodies and antibody fragments. Addition of myasthenic IgG or its divalent fragment, F(ab')2, to cultures accelerated the rate of acetylcholine-receptor degradation threefold. By contrast, the monovalent fragment, Fab, from myasthenic serum had no effect on degradation, although it bound to acetylcholine receptors. Addition of a second, "piggyback" antibody to cross-link the Fab:receptor complexes resulted in a threefold increase of the degradation rate. Similarly, when acetylcholine receptors with bound alpha-bungarotoxin were cross-linked by the addition of specific antibody against alpha-bungarotoxin, the degradation rate increased approximately threefold. The effect of myasthenic patients' antibodies in accelerating degradation of acetylcholine receptors is attributed to their ability to cross-link the receptors.

Autoantibodies↗
PubMed1978

Motor nerve sprouting and acetylcholine receptors.

Sprouting of motor nerve terminals was evoked by functional denervation of skeletal muscles brought about by presynaptic blockade or disuse. The amount of sprouting, determined by morphometric measurement, was correlated with the level of extrajunctional acetylcholine receptors. Sprouting was inhibited by blockade of acetylcholine receptors with alpha-bungarotoxin. Extrajunctional acetylcholine receptors may play an important role in eliciting motor nerve terminal sprouting.

Acetylcholine↗
PubMed1978

Effect of myasthenic patients' immunoglobulin on acetylcholine receptor turnover: selectivity of degradation process.

Antibodies in the sera of patients with myasthenia gravis are believed to play an important role in the pathogenesis of the disorder. They have recently been shown to accelerate the degradation of acetylcholine receptors in cultured mammalian skeletal muscle and at intact neuromuscular junctions. To elucidate the mechanism of the antibody-accelerated degradation process, we have prepared cultures in which one set of acetylcholine receptors was exposed to myasthenic immunoglobulin while a second set of acetylcholine receptors, newly incorporated after exposure to the immunoglobulins, was not. The set of acetylcholine receptors with bound myasthenic immunoglobulin was degraded at 2 to 3 times the normal rate, while the second set of acetylcholine receptors without bound immunoglobulin was degraded at the control rate. This suggest that the binding of antibody from myasthenic patients alters the acetylcholine receptors in some way that causes them to be selected for preferential degradation by the muscle cells. New synthesis and incorporation of the acetyl-choline receptors into the surface membrane of cultured skeletal muscle was unaffected by exposure to myasthenic immunoglobulin.

Antigen-Antibody Reactions↗
PubMed1978

The effect of disuse on cholinergic enzymes.

1. The effects of disuse on the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) have been investigated in the sciatic nerve and leg muscles of the rat. 2. Disuse was produced by blockade of nerve conduction by repeated subperineurial injection of tetrodotoxin (TTX), and the effects were compared to those of denervation. 3. After 8 days of disuse there was no change in neural ChAT activity in the sciatic nerves, anterior roots or intramuscular terminals. By contrast, surgical section of the sciatic nerve resulted in a marked decrease of ChAT in the nerve terminals. 4. Similarly, after 8 days of disuse there was no change in neural AChE activity in the sciatic nerves or anterior roots. 5. AChE activity in the disused muscles decreased by more than 50%, which was comparable to the effect of surgical denervation. 6. These results indicate that disuse produced by TTX blockade of nerve conduction does not affect the cholinergic enzymes ChAT and AChE in nerves, but does lead to a significant decrease in muscle AChE.

Acetylcholinesterase↗
PubMed1977

Myasthenic immunoglobulin accelerates acetylcholine receptor degradation.

Degradation of acetylcholine receptors by cultured rat skeletal muscle cells was determined from the release of 125I from bound 125I-labeled alpha-bungarotoxin. Addition of immunoglobulin from patients with myasthenia gravis to the culture medium accelerated the degradation rate to a mean of 8.51 +/- 0.44 percent per hour, compared with the mean control rate of 3.97 +/- 0.14 percent per hour (P less than .001). A similar mechanism may possibly be involved in the autoimmune pathogenesis of myasthenia gravis in man.

Acetylcholine↗
PubMed1977

Myasthenia gravis. Study of humoral immune mechanisms by passive transfer to mice.

To study the role of humoral factors in the pathogenesis of myasthenia gravis, we employed passive transfer of human serum fractions to mice. Immunoglobulins from 16 patients with myasthenia gravis were injected into mice daily for one to 14 days. Typical myasthenic features of reduction in amplitude of miniature end-plate potentials (mean change more than 50 per cent, P less than 0.005) or reduction in acetylcholine receptors at neuromuscular junctions (mean change more than 50 per cent, P less than 0.005) (or both) were produced by immunoglobulin from 15 of the 16 patients. Some mice showed weakness or decremental responses to repetitive nerve stimulation as well. The active fraction was identified as IgG by three different purification methods. Its effect was enhanced by the third component (C3) of the complement system, but the fifth component (C5) had no effect. These data suggest that the pathogenesis of myasthenia gravis often involves and antibody-mediated autoimmune attack on the acetylcholine receptors of the neuromuscular junction.

Acetylcholine↗
PubMed1977

Thymic muscle cells bear acetylcholine receptors: possible relation to myasthenia gravis.

Culture of dissociated thymus from rats and humans yielded cells identical to skeletal muscle with respect to morphology, contractility, electrophysiological properties, and the presence of acetylcholine receptors. These cells, strategically located in the thymus, may play a role in initiation of the autoimmune response against acetylcholine receptors, which is characteristic of myasthenia gravis.

Acetylcholine↗