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- Kivisakk, P, et al.
(författare)
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Neutralising and binding anti-interferon-beta-I b (IFN-beta-I b) antibodies during IFN-beta-I b treatment of multiple sclerosis
- 1997
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 3:3, s. 184-190
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Tidskriftsartikel (refereegranskat)abstract
- Interferon-β-1b (IFN-β-1b) is an immunomodulatory therapy of multiple sclerosis (MS), reducing the numbers and severity of exacerbations and the total lesion load measured by magnetic resonance imaging of the brain. The benefits of IFN-β-1b could be hampered by the development of neutralising antibodies against the compound. Our results confirmed earlier studies, showing that 42% of MS patients treated with IFN-β-1b for more than 3 months had developed neutralising antibodies. The occurrence of binding anti-IFN-β-1b antibodies, presently not believed to impede the clinical efficacy of IFN-β-1b, were demonstrated by an immunoassay in some patients already after I month of treatment and in 78% after 3 months. The development of binding antibodies seemed to be an early phenomenon, preceding the appearance of neutralising antibodies. Antibodies crossreacting with IFN-β-1a and natural IFN-β were also found in a majority of IFN-β-1b treated patients with high titres of binding antibodies. Employing a solid-phase enzyme-linked immunospot (ELISPOT) assay, 68% of MS patients treated with IFN-β-1b for 1 -23 months had elevated numbers of anti-IFN-β-1b-antibody secreting cells in blood, compared to 18% of untreated MS patients and 20% among patients with other neurological diseases. Thus, our findings confirm that IFN-β-1 b is immunogenic in MS patients. High levels of anti-IFN-β-1b antibody secreting cells were, however, also found in two untreated control patients with inflammatory diseases, suggesting that anti-IFN-β-1b antibodies might also occur spontaneously.
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- Lövgren, Janita, et al.
(författare)
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Production and activation of recombinant hK2 with propeptide mutations resulting in high expression levels
- 1999
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Ingår i: Eur J Biochem. ; 266:3, s. 5-1050
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Tidskriftsartikel (refereegranskat)abstract
- Human glandular kallikrein 2 (hK2) is a serine protease expressed mainly by the prostate gland with 80% identity in primary structure to prostate specific antigen (PSA). hK2 has proven to be a useful marker of prostate cancer which can be used in combination with PSA to better discriminate between prostate cancer and benign prostate hyperplasia. The studies on hK2 have been hampered by its very low phyciological levels (6 microgram.mL-1), its close similarity to PSA, and the low expression levels obtained using recombinant procedures to produce hK2 (0.7 mg.L-1). We have now generated propeptide mutations of hK2 which can be used to isolate stable, inactive prohK2 mutants. Compared with wild-type hK2, expression of the propeptide hK2 mutants increases the expression levels up to 15-40-fold giving 10-30 mg hK2.L-1. These results indicate that the low expression levels of wild-type hK2 are related to the activation or autoactivation of the wild-type enzyme and the instability of the active protease in cell culture and possibly also in tissue. The purified mutant hK2 may be activated by either enterokinase or factor Xa to generate an enzyme for use in functional studies with the characteristics of the original wild-type protein. Further, the stable inactive mutant hK2 protein may be used for immunizations to generate novel monoclonal antibodies, used as standard material for clinical assays or in crystallization studies where large quantities of protein are required.
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