Acetylcholine receptors are present in the sarcolemma of cultured skeletal muscle myotubes either as large clusters or in a diffuse distribution. Both the clustered and diffuse acetylcholine receptors are potentially removable from the membrane. Treatment of myotubes with globulin from patients with myasthenia gravis causes the loss of acetylcholine receptor clusters and the concomitant appearance of acetylcholine receptor microaggregates. The rate of acetylcholine receptor cluster loss is greater than the rate of acetylcholine receptor degradation, indicating that acetylcholine receptors are disrupted from clusters to form microaggregates before being removed from the plasma membrane.
Abstract A 26‐year‐old woman was in spontaneous clinical remission from myasthenia gravis (MG) for six months, yet gave birth to a full‐term infant with typical neonatal MG. It is believed that transplacental transfer of anti‐acetylcholine (ACh) receptor antibodies is responsible for neonatal MG; therefore, neonatal MG represents an in vivo assay of the pathogenic potential of anti‐ACh receptor antibodies in 2 human individuals. Anti‐ACh receptor antibodies were present in both mother and infant (titers 12.3 × 10 −9 and 4.4 × 10 −9 moles per liter, respectively) at the time of birth, and both mother's and infant's sera accelerated the degradation of ACh receptors in myotube cultures. This case suggests that “host factors” unique to the individual appear to modify or even determine whether the presence of anti‐ACh receptor antibodies will result in clinical myasthenia.
The rate at which profound hyponatremia should be corrected is the focus of a recent clinical debate. We prospectively studied neurological outcomes with serial magnetic resonance imaging in 13 hyponatremic subjects with serum sodium concentrations of less than 115 mmol/L (mean initial serum sodium concentration, 103.7; range, 93-113 mmol/L). All subjects were corrected to mildly hyponatremic levels at 24 hours and ultimately underwent an increase in serum sodium concentration of 25 mmol/L without development of hypernatremia. Magnetic resonance imaging revealed the development of pontine lesions in 3 patients. The correction rate of hyponatremia over the first 24 hours was significantly faster in patients with pontine lesions (mean +/- SD, 1.25 +/- 0.4 mmol/(L . hr) versus 0.74 +/- 0.3 mmol/(L . hr); p less than 0.05). Initial sodium concentration was also significantly lower in the pontine lesion group (97.3 +/- 6.7 vs 105.6 +/- 5.2 mmol/L, p less than 0.05). We conclude that the correction rate of hyponatremia plays a significant role in the pathogenesis of pontine lesions in individuals with profound hyponatremia who undergo large increases in sodium concentration as a result of severe initial hyponatremia.
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