European journal of clinical investigation
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Eur. J. Clin. Invest. · Apr 1994
Association between biosynthesis of nitric oxide and changes in immunological and vascular parameters in patients treated with interleukin-2.
Hypotension is a dose-limiting side effect of interleukin-2 (IL-2) therapy. This may be due to increased biosynthesis of the potent vasodilator nitric oxide (NO) induced by cytokines such as tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), which are known to be generated during IL-2 therapy. We describe the relationship between NO biosynthesis and changes in immunological and vascular parameters during IL-2 therapy in 13 patients with metastatic cancer. ⋯ As plasma NOx concentrations increased, systolic blood pressure fell, reaching a minimum at day 3 despite a continued rise in NOx concentrations. These changes were accompanied by a continuous increase in pulse rate throughout the infusion period. These findings indicate that induction of NO biosynthesis contributes to hypotension induced during IL-2 therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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Eur. J. Clin. Invest. · Apr 1994
Systemic lupus erythematosus is associated with increased auto-antibody titers against calreticulin and grp94, but calreticulin is not the Ro/SS-A antigen.
Auto-antibodies against purified human calreticulin were determined by an ELISA in sera from patients with systemic lupus erythematosus (SLE) and from healthy persons or patients without an autoimmune disease. More than 80% of patients with SLE had titers exceeding the highest value obtained in the group without SLE. Almost 30% of the patients had also elevated auto-antibody titers against purified rat grp94, another resident ER-protein of the KDEL-protein family, but not against rat ERp72 (CaBP2), an ER-resident protein of the proteindisulfide isomerase family. It could, however, be excluded that calreticulin is the Ro/SS-A antigen on the basis of the following observations: 1) Calreticulin purified from rat, bovine or human liver contained far less than 1 mol of phosphate per mol of calreticulin, showed an E280/E260-absorption ratio of about 2.0, and did not contain extractable RNA; 2) Sera from patients with SLE did not react with or precipitate endogenous calreticulin from Hep G2 cells; they did, however, precipitate hY-RNA from these cells; 3) Sera from SLE-patients, but not anti-calreticulin antisera precipitated [32P]-hY-RNA from [32P]-labelled Hep G2 cells.