Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG

Rheumatoid arthritis (RA) is a widely prevalent (1-3%) chronic systemic disease thought to have an autoimmune component; both humoral and cellular mechanisms have been implicated. Primary osteoarthritis (OA) is considered to be distinct from rheumatoid arthritis, and here damage is thought to be secondary to cartilage degeneration. In rheumatoid arthritis, immune complexes are present that consist exclusively of immunoglobulin, implying that this is both the 'antibody' (rheumatoid factor [RF]) and the 'antigen' (most commonly IgG). Autoantigenic reactivity has been localized to the constant-region (C gamma 2) domains of IgG. There is no evidence for a polypeptide determinant but carbohydrate changes have been reported. We have therefore conducted a study, simultaneously in Oxford and Tokyo, to compare in detail the N-glycosylation pattern of serum IgG (Fig. 1) isolated from normal individuals and from patients with either primary osteoarthritis or rheumatoid arthritis. The results, which required an evaluation of the primary sequences of approximately 1,400 oligosaccharides from 46 IgG samples, indicate that: (1) IgG isolated from normal individuals, patients with RA and patients with OA contains different distributions of asparagine-linked bi-antennary complex-type oligosaccharide structures, (2) in neither disease is the IgG associated with novel oligosaccharide structures, but the observed differences are due to changes in the relative extent of galactosylation compared with normal individuals. This change results in a 'shift' in the population of IgG molecules towards those carrying complex oligosaccharides, one or both of whose arms terminate in N-acetylglucosamine. These two arthritides may therefore be glycosylation diseases, reflecting changes in the intracellular processing, or post-secretory degradation of N-linked oligosaccharides.     

Genes for the major protein antigens of the leprosy parasite Mycobacterium leprae

Leprosy, a chronic infectious disease afflicting between 10 and 15 million people, is caused by the obligate intracellular parasite Mycobacterium leprae. Although M. leprae was the first identified bacterial pathogen of man, basic biochemical, immunological, diagnostic and therapeutic investigations have been severely limited because it remains one of the few human pathogens that have not been cultured in vitro. An M. leprae recombinant DNA expression library was constructed to provide a source of genes encoding proteins relevant for such studies. Monoclonal antibodies directed against M. leprae specific antigens have been used to isolate the genes encoding the five most immunogenic protein antigens of the leprosy bacillus. We report here that M. leprae specific epitopes recognized by all of 13 monoclonal antibodies tested were produced by recombinant phage in Escherichia coli.     

Single injections of triazolam,a short-acting benzodiazepine,lengthen the period of the circadian activity rhythm in golden hamsters

Single injections of the benzodiazepine, triazolam, induce phase shifts and cause a lengthening of the circadian activity rhythm in the golden hamster. The effect of triazolam on period depends on the phase of injection, but is not dependent on the direction of the phase shifts. Triazolam injections caused increases in period that were associated with phase advances as well as phase delays in the activity rhythm. This relationship between triazolam-induced phase shifts and changes in period is different from the relationship between light-induced phase shifts and period changes.     

Secondary metabolites of the chemically rich ascoglossanCyerce nigricans

Summary Two new metabolites of an apparent propionate origin have been isolated from the organic extract of the ascoglossan molluscCyerce nigricans. The proposed structures for the new natural products are based on interpretation of their physical and spectral properties. The new compounds isolated lacked the potent ichthyodeterrent properties of the whole animal extract suggesting that other molecules are involved in the defense of this shell-less mollusc.     

Isoprenaline-like effects of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine on mechanical, biochemical and electrophysiological parameters in the mammalian heart

The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) mimicked the effects of isoprenaline on the force of contraction, the cAMP content and the slow Ca++ inward current (Isi) in isolated guinea pig papillary muscles. The results support the hypothesis that phosphodiesterase inhibitors and beta-adrenoceptor agonists exert their positive inotropic effects by increasing Isi via the common mediator cAMP.     

Verapamil和Propranolol对非胰岛素依赖型糖尿病透析患者物质代谢的影响

比较Ｖｅｒａｐａｍｉｌ和Ｐｒｏｐｒａｎｏｌｏｌ对患有胰岛素非依赖型糖尿病及轻度至中度高血压的透析患者的血糖和物质代谢的影响。方法：４６例患有非胰岛素依赖型糖尿病及轻度至中度高血压的透析患者，为德国福尔达市ＫｆＨ血透中心和柏林ＫｆＨ血透中心的透析病人。分别经Ｖｅｒａｐａｍｉｌ和Ｐｒｏｐｒａｎｏｌｏｌ治疗三个月后测空腹血糖、血红蛋白Ａ１ｃ、果酸、胰岛素、胆固醇和甘油三脂，同时记录透析前心率和血压。结果：Ｖｅｒａｐａｍｉｌ对血糖及物质代谢无不良影响，Ｐｒｏｐｒａｎｏｌｏｌ可引起血糖、果酸和血红蛋白Ａ１ｃ升高。结论：在糖尿病透析患者，Ｐｒｏｐｒａｎｏｌｏｌ具有引起和／或加重小动脉血管病病以及脑血管意外的危险性