Some significant changes in the BILAG disease activity index to assess patients with SLE are proposed. The process of demonstrating validity and reliability has started with these two exercises assessing real patients. Further validation studies are under way. BILAG 2004 is likely to be valuable in clinical trials assessing new therapies for the treatment of SLE, as it provides a more comprehensive system-based disease activity measure than has been available previously.
Circulating anticardiolipin antibodies are associated with recurrent thrombosis, fetal loss and thrombocytopenia. We have identified four patients with SLE or lupus-like disease who have high circulating levels of ACLA, repeated thrombosis and evidence of renal disease. Their clinical signs and symptoms of lupus activity were minimal, yet all had renal insufficiency with GFR 50 ml/min or less despite no history nor evidence of overt nephritis (proteinuria less than 0.5 g/day and no haematuria). Renal biopsy specimens showed focal ischaemic lesions with no evidence of active lupus nephritis. We describe a new lesion of renal ischaemia secondary to non-inflammatory vascular pathology associated with circulating ACLA.
Transcripts of Saccharomyces cerevisiae nuclear tRNA genes are normally terminated within a few nucleotides of the tRNA coding region, in contrast to mitochondrially encoded tRNAs, which are contained within polycistronic transcripts and thus require 3'-processing by mitochondrial endonucleases. We show that 3'-processing activities capable of removing artificially extended 3'-trailer sequences from some tRNA substrates are also present in the yeast nucleus. Correct 3'-processing in vivo resulted in the formation of functional suppressor tRNA. The 3'-processing activities were also identified in vitro through analysis of transcription-processing products in cell-free yeast S-100 extracts. Comparison of several pre-tRNA substrates showed that the tRNA structure played a major role in determining the processability of a substrate but that the nature of the 3'-trailer sequence also modulated the rate of 3'-processing. Pre-tRNA containing mitochondrial tRNA(Val) sequence was a good substrate for in vitro processing, independent of its 3'-trailer. A 200-nt-long pre-tRNA, encoding the nuclear SUP4 tRNA gene and a mitochondrial 3'-trailer, was processed in yeast S-100 extract in a multistep pathway into mature-sized tRNA(Tyr). Part of the 3'-processing was due to an endonuclease which cleaved near or precisely at the 3'-end of the coding region of the tRNA. A short sequence around this endonucleolytic 3'-cleavage site was crucial for the formation of active suppressor tRNA in vivo. A 9-nt-long sequence motif derived from the mitochondrial 3'-trailer allowed processing, while sequences derived from lacZ or pBR322 DNA were processed neither in vitro nor in vivo.
The changes to junior doctors' hours, the working patterns of doctors and service commitments have all affected the quality and time available for certain aspects of rheumatological training. A major effort to enhance quality is necessary to ensure that the objectives of training are met within the intended training budget.
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