Background: Increased serum levels of proinflammatory cytokines may contribute to the organ damage in active antineutrophil cytoplasmic antigen (ANCA)-positive renal vasculitis. Plasma exchange (PE) may influence the activity of vasculitis not only by removing pathogenic autoantibodies, but also by lowering the serum levels of circulating cytokines. Methods: Serum levels of IL-1β, IL-1ra, IL-6, IL-8, ICAM-1 and VCAM-1 were measured using ELISA in 10 patients with active ANCA-positive renal vasculitis (5 patients with Wegener’s granulomatosis, WG, and 5 patients with microscopic polyangiitis, MPA) during the course of therapeutic PE. Cytokines and adhesion molecules were measured in samples of serum obtained at the beginning and at the end of the 1st, 3rd and 5th PE and in samples of filtrate obtained during the same PE. Results: In comparison with controls, patients with ANCA had higher serum levels of IL-1ra, IL-8, ICAM-1 and VCAM-1 before the 1st PE. Serum levels of IL-6, IL-8, ICAM-1 and VCAM-1 were increased in patients with MPA, and the serum levels of all the cytokines and adhesion molecules measured in patients with WG were increased. At the end of the PE course there were decreases in the serum levels of IL-1ra and VCAM-1 in ANCA patients and IL-1ra and ICAM-1 in WG patients. Single PE in ANCA patients led only to a decrease in serum levels of ICAM-1 and VCAM-1. On the other hand, there was no change in serum levels of IL-1β and IL-8, and the serum levels of IL-1ra and IL-6 even increased at the end of a single PE, in spite of high levels of all cytokines and adhesion molecules in the plasma filtrate. Conclusion: Serum levels of soluble adhesion molecules decrease after PE, but serum levels of proinflammatory cytokines are not reduced even by a PE course. Removal of these substances by PE is obviously counteracted by their increased production, possibly further stimulated by the contact of blood with the synthetic membrane. The insufficient influence of PE on the elimination of proinflammatory cytokines may partially explain its limited effect in some patients with ANCA-positive renal vasculitis.

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Addition of ammonium salts to E. coli cells grown on a medium with glutamate as the sole nitrogen source is followed by rapid inactivation of glutamine synthetase (GS) I1 The active form of the enzyme (GSa) and the inactive form (GSb) have been isolated.2 Both forms behave similarly in the analytical ultracentrifuge, electrophoresis, and ion exchange chromatography. 2 In a cell-free system GSa is converted to GSb by an "inactivating enzyme"3 in the presence of adenosine 5'-triphosphate (ATP), Mg2+, and glutamine.4 The inactivating enzyme catalyzes an adenylylation of GSa5-7 in the presence of glutamine or certain related metabolites as allosteric effectors.8 Kingdon and Stadtman9' 10 also reported the isolation of two forms of glutamine synthetase from E. coli cells grown on a medium containing either glutamate or ammonia, respectively, as sole nitrogen source. Both forms show characteristic differences in their responses to feedback inhibitors. In the present paper it will be shown that our GSa preparation behaves like the "ammonia preparation" and the GSb preparation like the "glutamate preparation" of Kingdon and Stadtman. As will be shown, in the late logarithmic or in the stationary growth phase, the "ammonia medium" contains no more ammonia, whereas the "glutamate medium" contains large amounts of ammonia. There is a striking parallelism between the appearance or disappearance of ammonia in the culture medium and the formation of GSb or GSa. The "ammonia preparation" of Kingdon and Stadtman is isolated from cultures with very low ammonia concentrations, and the "glutamate preparation" from cultures with high concentrations of ammonia. Both our previous data and those of Kingdon and Stadtman therefore suggest that ammonia controls the ratio GSa: GSb by causing formation of GSb from GSa. Results.-Growth (as recorded by optical density at 650 mM), specific activity of glutamine synthetase, ratio of glutamine synthetase to glutamyltransferase

The aim of our study was to evaluate antibodies against thyroglobulin (anti-TG) and thyroid peroxidase (anti-TPO) - markers of autoimmune thyroiditis - in several groups of adult patients with type 1 and type 2 diabetes mellitus (DM). We were particularly interested whether the presence of thyroid antibodies is related to the positivity of glutamic acid decarboxylase antibodies (anti-GAD). We found elevated anti-GAD in 46 % (97/210) patients with type 1 DM. All patients with type 2 diabetes were anti-GAD-negative. At least one thyroid antibody (anti-TG and/or anti-TPO) was found in 30 % (62/210) patients with type 1 DM and 27 % (22/83) type 2 diabetes patients. The patients with type 1 DM were further grouped according to their anti-GAD status. The anti-GAD-positive patients had a higher prevalence of anti-TG antibodies than the anti-GAD-negative patients (25 % vs. 12 %, p=0.03) as well as anti-TPO antibodies (32 % vs. 12 %, p<0.001). At least one thyroid antibody was detected in 39 % (38/97) of anti-GAD-positive but only in 21 % (24/113) of anti-GAD-negative patients with type 1 DM (p=0.006). No significant difference in the frequency of thyroid antibodies was found between anti-GAD-negative patients with type 1 and type 2 DM (21 % vs. 27 %, p=0.4). The groups with or without thyroid antibodies in both type 1 and type 2 diabetic patients did not differ in actual age, the age at diabetes onset, duration of diabetes, body mass index or HbA1c level. Patients with elevated thyroid antibodies had significantly higher levels of TSH than those without thyroid antibodies (1.86 vs. 3.22 mIU/l, p=0.04 in type 1 DM; 2.06 vs. 4.89 mIU/l, p=0.003 in type 2 DM). We conclude that there is a higher frequency of thyroid-specific antibodies in anti-GAD-positive adult patients with type 1 DM than in anti-GAD-negative patients or in patients with type 2 DM. Patients with or without thyroid antibodies do not differ in age, DM onset and duration, BMI or HbA1c. Thyroid antibodies-positive patients have higher levels of thyroid stimulating hormone (TSH).

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