The lymphocyte and the immune response.
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Biomedical subjects
Publications and source records attributed to M Holub.
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Phagocytosis of synthetic microspheres was determined by peritoneal macrophages and omental dendritic cells of nu/nu and nu/+ BALB/c and C57BL/10.LP mice during ontogenetic development. The macrophages of nu/nu mice phagocytized comparably to those of the nu/+ littermates till day 10 of their life. On day 25, the phagocytic activity of nu/nu mice sharply decreased but returned to normal and higher values at the age of 2 months. Omental dendritic cells showed similar ontogenetic behaviour in their ability to engulf microspheres as was found for free peritoneal macrophages.
The soluble IL-6 receptor (sIL-6R) occurring in various body fluids of healthy persons and patients with various diseases is an agonist since its complex with IL-6 binds to gp130 making IL-6 receptor negative cells responsive for IL-6. The generation as well as the functional role of soluble IL-6 receptor is poorly understood. We measured the sIL-6R levels by ELISA sandwich technology in sera and in supernatants of lymphocyte cultures without and after incubations with dexamethasone. Our results indicate, that the sIL-6R levels in sera of patients with inactive systemic lupus erythematosus (SLE) and active rheumatoid arthritis (RA) were higher than those of the control group, active SLE and inactive RA. In vitro dexamethasone treatment stimulated generation of sIL-6R in both healthy persons and in active SLE, however it strongly suppressed sIL-6R in both RA groups. At mRNA level, we found that in SLE both the mRNA coding the cell-bound and an alternatively spliced variant corresponding to soluble IL-6R transcript increases, however the strong decrease of sIL6R protein in RA was not found at mRNA level.
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Cytotoxicity of most of the 18 new sesquiterpene lactones (SL), derivatives of germacran, guaian, pseudoguaian, and selinan, and related glycosides was studied by tissue culture method on human KB and HeLa cell lines. Eleven compounds with ED50, activity values between 0.24 and 2.40 microgram/ml (9,2.10(-7)--9.1.10(-6) M) were qualified for further in vivo investigation. It seems that: a) unsaturated alpha-exo-methylene-gamma-lactone ring:-O-CO-C=CH2 conjugated with basic terpene carbocyclic skeleton plays the main role for cytotoxicity of SL. The next determinants of the activity are apparently: b) sesquiterpenoid carbocyclic grouping (germacranolides (GE), pseudoguaianolides (PGU), guaianolides (GU), c) the position of cyclization of gamma-lactone ring (C6--C12) or C8--C12), d) some substituents with an epoxide and/or keto-function in different positions of sesquiterpenoids. The natural and modified alpha-exo-methylene-guaianolide-C3-glycosides (GUG) are not significantly more potent than the remaining alpha-exo-methylene-gamma-lactones.