Objective. To clarify the clinical features and prognosis of systemic sclerosis (SSc) based on serum antinuclear antibodies (ANA). Methods. We studied 275 consecutive Japanese patients newly diagnosed as having SSc, who were first evaluated during the period 1971—1990. Eight SSc–related ANA were identified using indirect immunofluorescence, double immunodiffusion, or immunoprecipitation assays. Clinical and prognostic features were retrospectively analyzed in patient groups, categorized by their serum ANA. Results. Cumulative survival rates at 10 years after diagnosis of SSc were 93% in patients with anticentromere antibodies (ACA), 72% in those with anti—U1 RNP, 66% in those with anti—DNA topoisomerase I (anti—topo I), and 30% in those with anti‐RNA polymerases I, II, and III (anti‐RNAP). Major organ involvement linked to cause of death included biliary cirrhosis in patients with ACA, isolated pulmonary arterial hypertension and cerebral hemorrhage in those with anti—U1 RNP, pulmonary interstitial fibrosis in those with anti—topo I, and cardiac and renal involvement in those with anti‐RNAP. Conclusion. Determinations of serum ANA in SSc patients are useful in predicting organ involvement and long‐term outcome.

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Many flagellar proteins are exported by a flagellum-specific export pathway. In an initial attempt to characterize the apparatus responsible for the process, we designed a simple assay to screen for mutants with export defects. Temperature-sensitive flagellar mutants of Salmonella typhimurium were grown at the permissive temperature (30°C), shifted to the restrictive temperature (42°C), and inspected in a light microscope. With the exception of switch mutants, they were fully motile. Next, cells grown at the permissive temperature had their flagellar filaments removed by shearing before the cells were shifted to the restrictive temperature. Most mutants were able to regrow filaments. However, flhA,fliH, fliI, and fiN mutants showed no or greatly reduced regrowth, suggesting that the corresponding gene products are involved in the process of flagellum-specific export. We describe here the sequences offliH,fliI, and the adjacent gene,flij; they encode proteins with deduced molecular masses of 25,782, 49,208, and 17,302 Da, respectively. The deduced sequence of Fliu shows significant similarity to the catalytic 0i subunit of the bacterial FOF, ATPase and to the catalytic subunits of vacuolar and archaebacterial ATPases; except for limited similarity in the motifs that constitute the nucleotide-binding or catalytic site, it appears unrelated to the ElE2 class of ATPases, to other proteins that mediate protein export, or to a variety of other ATP-utilizing enzymes. We hypothesize that FliI is either the catalytic subunit of a protein translocase for flagellum-specific export or a proton translocase involved in local circuits at the flagellum.The bacterial flagellum is a complex structure comprising intracellular, envelope-spanning, and extracellular components. In Salmonella typhimurium, it is encoded by about 40 genes (39).Of those flagellar proteins located within the cell envelope or outside the cell, only the outer-ring (P and L) proteins appear to be exported by the primary signal peptide-dependent pathway (33,36,42). The rest (four rod proteins, a hook protein, three hook-associated proteins, and the filament protein, flagellin) are thought to be exported by a unique, flagellum-specific pathway (30,34,38,59), travelling through the hollow core of the nascent structure (70) and assembling at its distal end (19, 37) (Fig. 1). The process must be a highly organized one, in which protein subunits are incorporated into the growing flagellum in the correct order and stoichiometry (45). The export apparatus obviously must be selective in the proteins it recognizes for export. It may also have to supply energy for the process. Given that the physical path for export is through the nascent structure, it seems likely that the export apparatus is located at the flagellar base (Fig. 1).Essentially nothing is known about this apparatus; specifically, its genetic origin and biochemical composition are completely unknown. We describe here initial attempts to identify its components genetically by use of temperaturesensitive ...

We have identified a novel autoantibody reactive with all three classes of RNA polymerases, well-characterized nuclear enzymes, in sera from patients with systemic sclerosis (SSc).

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