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Biomedical subjects

W Berthold

Publications and source records attributed to W Berthold.

38 records · Page 3Linked to original sources
PubMedDate not supplied

Rational design of a potent, long-lasting form of interferon: a 40 kDa branched polyethylene glycol-conjugated interferon alpha-2a for the treatment of hepatitis C.

A potent, long-lasting form of interferon alpha-2a mono-pegylated with a 40 kilodalton branched poly(ethylene glycol) was designed, synthesized, and characterized. Mono-pegylated interferon alpha-2a was comprised of four major positional isomers involving Lys31, Lys121, Lys131, and Lys134 of interferon. The in vitro anti-viral activity of pegylated interferon alpha-2a was found to be only 7% of the original activity. In contrast, the in vivo antitumor activity was severalfold enhanced compared to interferon alpha-2a. Pegylated interferon alpha-2a showed no immunogenicity in mice. After subcutaneous injection of pegylated interferon alpha-2a, a 70-fold increase in serum half-life and a 50-fold increase in mean plasma residence time concomitant with sustained serum concentrations were observed relative to interferon alpha-2a. These preclinical results suggest a significantly enhanced human pharmacological profile for pegylated interferon alpha-2a. Results of Phase II/III hepatitis C clinical trials in humans confirmed the superior efficacy of pegylated interferon alpha-2a compared to unmodified interferon alpha-2a.

Animals↗
PubMedDate not supplied

IFN-gamma is not the only mediator of suppressed myelopoiesis produced by mononuclear cells from aplastic anemia patients.

Peripheral blood mononuclear cells (PBMC) from patients with aplastic anemia (AA) and healthy donors were compared with regard to their ability to produce soluble factors with inhibitory activity on in vitro granulopoiesis (GM-CFC). Although PBMC from AA patients produced enhanced levels of IFN-gamma as compared to controls, this lymphokine was found not to be the main inhibitor of in vitro granulopoiesis. Other, non-IFN related factors were potent inhibitors of both the mature and the immature precursors for GM-CFC, could act across the species barrier and were of low molecular weight. Also PBMC from healthy donors produced a non-IFN mediated GM-CFC inhibitory factor, but to a lesser degree and acting only on one type of myeloid precursors. The possible implications of these findings in relation to the etiology of AA will be discussed.

Adult↗