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We have previously reported linkage of systemic lupus erythematosus to chromosome 2q37 in multicase families from Iceland and Sweden. This locus (SLEB2) was identified by linkage to the markers D2S125 and D2S140. In the present study we have analyzed additional microsatellite markers and SNPs covering a region of 30 cM around D2S125 in an extended set of Nordic families (Icelandic, Swedish, and Norwegian). Two-point linkage analysis in these families gave a maximum lod score at the position of markers D2S2585 and D2S2985 (Z= 4.51, PIC = 0.65), by applying a “model-free” pseudo-marker linkage analysis. Based on multipoint linkage analysis in the Nordic families, the most likely location of the SLEB2locus is estimated to be in the interval between D2S125 and the position of markers D2S2585 and D2S2985, with a peak multipoint lod score of Z= 6.03, assuming a dominant pseudo-marker model. Linkage disequilibrium (LD) analysis was performed using the data from the multicase families and 89 single-case families of Swedish origin, using the same set of markers. The LD analysis showed evidence for association in the single-case and multicase families with locus GAAT3C11 (P< 0.0003), and weak evidence for association was obtained for several markers located telomeric to D2S125 in the multicase families. Thirteen Mexican families were analyzed separately and found not to have linkage to this region. Our results support the presence of the SLEB2locus at 2q37.

Objective. The development of systemic lupus erythematosus (SLE)-related syndromes during treatment with sulphasalazine has been described and demonstrated to be influenced by genetic factors. The prevalence of this drug-induced condition and the immunological mechanisms involved are less known. The aim of this study was to determine the prevalence of sulphasalazine-induced lupus-like reactions in a well-defined early rheumatoid arthritis (RA) cohort and to analyse the roles of HLA haplotypes, autoantibodies and the B-cell stimulating cytokine interleukin-10 (IL-10) as possible underlying risk factors.
Patients and methods. Forty-one consecutive patients with early RA, in whom sulphasalazine was used as the first disease-modifying anti-rheumatic drug in single therapy and was maintained for at least 6 months, were investigated for the occurrence of lupus-related events. Longitudinal analyses of rheumatoid factor (RF), antinuclear antibodies (ANA), anti-double-stranded DNA antibodies and serum IL-10 (ELISA) and the typing of HLA DR and DQ alleles were performed.
Results. Four of the 41 patients developed lupus-like disease. Three of four patients who had lupus-related events vs four of 37 patients without side-effects had an HLA DR 0301 haplotype. The patients developing lupus-related side-effects had increased levels of serum IL-10 and a high frequency of ANA in speckled patterns before the onset of therapy.
Conclusion. The development of SLE-like symptoms and SLE-related autoantibody production was observed more commonly than expected, with an increased risk in patients with SLE-related HLA haplotypes, increased serum IL-10 levels and ANA in speckled patterns. The data suggest that immunomodulation associated with sulphasalazine treatment may contribute to the development of lupus-related reactions in genetically predisposed individuals.

³H and ¹⁴C-Sch 27899 have been prepared by fermentation using the Micromonospora carbonacea organism. In the case of ³H-Sch 27899, the label was incorporated by a single addition of 100 mCi of 70Ci/mmole L-[³H-methyl]-methionine to two flasks. For ¹⁴C-Sch 27899, 48 mCi of 55 mCi/mmole L-[¹⁴C-methyl]-methionine was added in five aliquots to five flasks over a five day period. Both batches were isolated by solvent extraction, oxidized and purified by column chromatography and hplc. An overall incorporation of 7.8% was found from L-[³H-methyl]-methionine and 18.7% from L-[¹⁴C-methyl]-methionine. The in vivo stability of label of ³H and ¹⁴C-Sch 27899 was determined, with ¹⁴C-Sch 27899 found to be a better choice for use in in vivo metabolism studies. Copyright © 1999 John Wiley & Sons, Ltd.

Summary Sch 40873, a novel antifungal compound isolated from the fermentation broth of anActinomadura spp. was discovered in an assay designed to detect compounds with preferential activity against the invasive mycelial form ofCandida albicans. The geometric mean MIC of Sch 40873 against sevenCandida spp. in Sabouraud dextrose broth (yeast phase) was =58 µg/ml and in Eagles minimum essential medium (mycelial phase) was <0.03 µg/ml. Sch 40873 demonstrated slight in vivo topical activity in a hamster vaginal model.

A 73 year-old woman with ulcerative colitis developed skin rashes after long-standing sulphasalazine treatment. After a switch to olsalazine, she developed a severe SLE with multiorgan involvement. When the treatment was terminated, the disease manifestations and serological findings resolved.