To clarify the role of cell-mediated versus humoral immune effector responses in myasthenia gravis (MG), we examined the occurrence of inflammatory cells in muscle from 30 patients with MG, determined the site of accumulation of the cells (at or remote from end-plates), enumerated and immunophenotyped those cells at the end-plate, and evaluated the frequency of deposition of the complement membrane attack complex (MAC) at the end-plate. Seven of 30 patients had well-defined collections of mononuclear cells in muscle (lymphorrhages), but these were not topographically related to the end-plates. Twenty of 30 patients had inflammatory cells (mostly macrophages and T cells) at or near end-plates, but these cells were present at less than 10% of the end-plates, and only seldom was there more than one cell at any end-plate. None of the inflammatory cells penetrated the muscle fiber near the end-plate. All end-plates of all patients immunostained for MAC. The findings reconfirm that the predominant immune effector response in MG is humorally mediated. The lymphorrhages in muscle and other tissues are probably a nonspecific indicator of disturbed immune regulation in MG.

The proline-rich motif in proteins is known to function as a ligand sequence that binds to protein modules such as SH3, WW, and several other protein interaction domains. These proline-rich ligand-mediated protein-protein interactions (abbreviated PLPI) are important in many signaling pathways that are involved in various diseases. Our previous studies showed that UCS15A, produced by Streptomyces species, inhibited PLPI. Here we report on synthetic analogs of UCS15A that show more potent activity than UCS15A in inhibiting PLPI. A synthetic analog, compound 2c, blocked in vitro PLPI of Sam68-Fyn-SH3 as well as in vivo PLPI of Grb2-Sam68 and Grb2-Sos1. Activation of MEK was also inhibited by compound 2c. Unlike UCS15A, compound 2c was an order of magnitude less cytotoxic and did not cause morphological changes in treated cells.

The prevalence of EF is relatively high in neonatal cardiac surgery. The etiologies can be diverse. Extubation of neonates at high risk after cardiac surgery, based on these possible risk factors, requires more diligent approaches.

Anti-protozoan, LL-Z1640-2 has been stereoselectively synthesized from d-ribose through Sonogashira coupling, Tsuji hydrogenolysis, and Mukaiyama lactonization.

No abstract