Nonulcer dyspepsia (NUD) is an enigmatic disorder which likely has heterogeneous etiologies. Helicobacter pylori-associated gastritis has been identified in a large number of patients with NUD, raising speculation that chronic infection with this organism may cause dyspepsia in some patients. Prospective case-control and cohort studies however do not suggest that H. pylori prevalence is greater in NUD than in asymptomatic controls. Limited therapeutic trials of H. pylori-eradication therapy have not shown a convincing symptomatic improvement compared with placebo treatment. Definition of the role of H. pylori in NUD awaits further well-designed, well-controlled epidemiologic and therapeutic studies. Until such information is available, routine endoscopic gastric biopsies looking for H. pylori in patients with NUD should be abandoned.

The cytokine interleukin 1 alpha (IL-1 alpha) is a critical mediator of the immune and inflammatory responses. A unique determinant of its activity as compared with IL-1 beta may be its association with the plasma membrane. While the biologic activity of "membrane IL-1" has been extensively reported, the mechanism of membrane binding remains unclear. We report that the N terminus of the 31-kDa IL-1 alpha precursor is myristoylated on specific internal lysine residues. Immunoprecipitation of [3H]myristic acid-radiolabeled human monocyte lysates with IgG antibodies to the 31-kDa IL-1 alpha precursor recovered a protein with the physicochemical properties of the IL-1 alpha N-terminal propiece (16 kDa, pI 4.45). Glycyl N-myristoylation of this protein is precluded by the absence of a glycine residue at position 2, suggesting that the propiece is myristoylated on epsilon-amino groups of lysine. To determine which lysine(s) are acylated, a series of synthetic peptides containing all lysines found in the IL-1 alpha N-terminal propiece were used in an in vitro myristoylation assay containing peptide, myristoyl-CoA, and monocyte lysate as enzyme source. Analysis of the reaction products by reverse-phase HPLC and gas-phase sequencing demonstrated the specific myristoylation of Lys-82 and Lys-83, yielding predominantly monoacylated product. A conserved sequence in the IL-1 beta propiece was myristoylated with at least 8-fold less efficiency. Acylation of the IL-1 alpha precursor by a previously unrecognized lysyl epsilon-amino N-myristoyl-transferase activity may facilitate its specific membrane targeting.