Article abstract-The authors report the use mycophenolate mofetil (MM) in the treatment of neuromuscular diseases. Thirty-eight patients (32 with MG, three with inflammatory myopathy, and three with chronic acquired demyelinating neuropathy) were treated with MM for an average duration of 12 months. All patients tolerated MM without major side effects. Twenty-four patients improved either in their functional status or in their ability to reduce corticosteroid dose. Mean time to improvement was 5 months.

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ObjectiveThe authors evaluated the response to extended cervicomediastinal thymectomy as a component of the integrated management of patients with myasthenia gravis in a large series of patients from a single institution. The authors evaluated the response to therapy with respect to a graded, multivariate, ordinal scale chosen to reflect the full range of the disease's manifestations. Summary Background DataA number of series, of varying sizes, describe the response of patients with myasthenia gravis to thymectomy primarily with respect to the bivariate endpoint of the presence or absence of "remission." These studies fail to describe the full spectrum of postoperative disease severity and have been unable to quantify definitively the influence of putative prognostic variables, nor to assess definitively the statistical significance of apparent improvements over time. MethodsThe authors evaluated 202 consecutive patients who underwent trans-sternal thymectomy for symptomatic myasthenia gravis from 1969 through 1996 at the Johns Hopkins Hospital. The response to surgery, combined with postoperative medical therapy, was evaluated by a standardized scale reflecting the full spectrum of the disease. These data were analyzed by a novel mean multivariate regression analysis, which allowed the quantification of the statistical significance of apparent responses over time and the evaluation of the independent influence of each of nine putative prognostic indicators. ResultsThere was no perioperative mortality and a 33% perioperative morbidity. There was a marked clinical response at 6 months to 1 year after surgery that was sustained for at least 10 years thereafter. The median increment of improvement was two (of five) classes. Eighty-six percent and 83% of the patients had improved by at least one class at 5 and 10 years, respectively. These changes were statistically significant (p < 0.001). Whereas the use of extended cervicomediastinal thymectomy was associated with a greater than 324

The large majority of patients with the autoimmune disease myasthenia gravis characteristically have detectable antibodies against the acetykcholine receptor (AChR). We used synthetic peptides to identify antibodies in sera of myasthenia gravis patients reactive with the human acetycholine receptor (HuAChR) a-subunit, residues 160-167. Affinity purification of these antibodies, using the HuAChR a-subunit 157-170 peptide immobilized on thiopropyl-Sepharose, yielded IgG antibodies that bound to the native AChR and inhibited the binding of a-bungarotoxin to the receptor. The HuAChR a-subunit 160-167 peptide demonstrated specific immunological crossreactivity with a shared homologous domain on herpes simplex virus glycoprotein D, residues 286-293, by both binding and inhibition studies. Thus, HuAChR a-subunit, residues 160-167, elicits antibodies in myasthenic patients that binds to the native AChR protein and is capable of eliciting a biologic effect. Immunologic cross-reactivity of this "self" epitope with herpes simplex virus suggest that this virus may be associated with the initiation of some cases of myasthenia.

The insertion of axonally transported fucosyl glycoproteins into the axolemma of regenerating nerve sprouts was examined in rat sciatic motor axons at intervals after nerve crush .[3H]Fucose was injected into the lumbar ventral horns and the nerves were removed at intervals between 1 and 14 d after labeling . To follow the fate of the "pulse-labeled" glycoproteins, we examined the nerves by correlative radiometric and EM radioautographic approaches.The results showed, first, that rapidly transported [3H]fucosyl glycoproteins were inserted into the axolemma of regenerating sprouts as well as parent axons. At 1 d after delivery, in addition to the substantial mobile fraction of radioactivity still undergoing bidirectional transport within the axon, a fraction of label was already associated with the axolemma. Insertion of labeled glycoproteins into the sprout axolemma appeared to occur all along the length of the regenerating sprouts, not just in sprout terminals . Once inserted, labeled glycoproteins did not undergo extensive redistribution, nor did they appear in sprout regions that formed (as a result of continued outgrowth) after their insertion . The amount of radioactivity in the regenerating nerves decreased with time, in part as a result of removal of transported label by retrograde transport . By 7-14 d after labeling, radioautography showed that almost all the remaining radioactivity was associated with axolemma . The regenerating sprouts retained increased amounts of labeled glycoproteins ; 7 or 14 d after labeling, the regenerating sprouts had over twice as much of radioactivity as comparable lengths of control nerves or parent axons.One role of fast axonal transport in nerve regeneration is the contribution to the regenerating sprout of glycoproteins inserted into the axolemma ; these membrane elements are added both during longitudinal outgrowth and during lateral growth and maturation of the sprout .Regeneration ofa transected axon requires both the restoration of a substantial volume of axoplasm and the addition of new axolemma to the regenerating sprouts. Because the axon itself is unable to synthesize significant amounts of protein, transfer of new protein from the cell body to both axoplasm and axolemma must be mediated by the axonal transport systems. Slow axonal transport provides the bulk ofthe axoplasmic and cytoskeletal proteins (15,18,24,25), whereas several lines of evidence suggest that fast transport contributes elements to the axolemma (4,12,13,19) . During regeneration, fast axonal transport continues at the normal rates (2,13,19,30,32), passing unimpeded through the site of axotomy into regenerating sprouts (2,17,19,31). Rapidly transported materials THE JOURNAL OF CELL BIOLOGY " VOLUME 88 JANUARY 1981 205-214 © The Rockefeller University Press " 0021-9525/81/01/0205/10 $1 .00 accumulate in the distal regions of the regenerating sprouts soon after delivery (17,19,28,31,33,38) . The subsequent disposition of rapidly transported materials, however, is poorly understood.The pre...