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Biomedical subjects

O Vos

Publications and source records attributed to O Vos.

At least 37 records · Page 2Linked to original sources

Further studies on mobilization of CFUs.

Mobilization of CFUs from haemopoietic tissues into circulation was studied after injection of different bacterial lipopolysaccharides (LPS), zymosan, phytohaemagglutinin (PHA), concanavalin A (Con A), trypsin and di-isopropyl-fluorophosphate-inhibited trypsin. All bacterial LPS used gave an increase of CFUs in the peripheral blood at 1 h after i.v. injection. Some variation in activity could not be excluded. As with Salmonella typhosa LPS, zymosan gave an increase in circulating CFUs during the first few hr and a second peak a few days later. After injection of zymosan as well as S. typhosa LPS the second peak in the blood was accompanied by a large increase in CFUs numbers in the spleen. PHA gave an immediate mobilization of CFUs, but the mobilization after injection of Con A during the first few hr occurred more slowly. After injection of S. typhosa LPS, zymosan and PHA the blood C3 level was found to be depressed considerably. This might indicate that the complement system is involved in the early mobilization of CFUs. Dexamethasone, a synthetic hormone which has been reported to give sequestration of several cell types in the bone marrow, did not inhibit the early and late mobilization of CFUs which normally occurs after injection of S. typhosa LPS.

Animals↗

Studies on the mechanism of haemopoietic stem cell (CFUs) mobilization. A role of the complement system.

A variety of substances can mobilize haemopoietic stem cells (CFUs) into the peripheral blood. In this study the involvement of the complement system in the mobilization process was investigated. Pretreatment of mice with the complement-activating factor of cobra venom (CoF), which lowered the serum C3 levels to 10-25% of the normal value, could completely prevent CFUs mobilization induced by high doses of CoF, endotoxin (ET) from Salmonella typhosa, inulin, zymosan and the proteolytic enzymes proteinase and trypsin. On the other hand, mobilization induced by the polyanions dextran sulphate and the copolymer of polymethacrylic acid and styrene could not be prevented, or at least affected only slightly. There appears to be a relationship between the extent of decomplementation by CoF and the extent of CFUs mobilization induced by ET. The results indicate that certain agents mobilize CFUs via the complement system, whereas other agents induce CFUs mobilization independent of the availability of complement components.

Animals↗

Effect of bacterial lipopolysaccharide on proliferation of CFU-S.

Multiple injections of S. typhosa LPS increased the number of CFU-S in the spleen 20-50 fold and decreased the number in the femur to one half or less. LPS injections did not affect the growth rates of CFU-S in the spleen or femur of lethally irradiated mice. The plateau levels which were attained in these mice after proliferation, corresponded with the levels in LPS-treated non-irradiated mice. Local irradiation of the spleen with 3000 rad hardly affected the capacity of the spleen to accommodate the increased CFU-S numbers after LPS injection. These results suggest that irradiation resistant microenvironmental factors in the spleen determine the CFU-S accumulation in this organ after injection of Salmonella typhosa LPS. The increased number of CFU-S in the blood after LPS injection was maintained in splenectomized mice as well as in mice which received a local splenic x-irradiation with 3000 rad, indicating that this rise of blood CFU-S numbers is independent of the spleen.

Animals↗

Mobilization of B and T lymphocytes and haemopoietic stem cells by polymethacrylic acid and dextran sulphate.

The leucocytosis which can be evoked by the polyanions dextran sulphate (DS), polymethacrylic acid (PMAA) and the copolymer of PMAA and styrene (PMAA--STYR) was studied in mice. After intravenous administration of these polyanions peak numbers of leucocytes were found in the peripheral blood 3 hr after injection. All three types of polyanions increased the number of lymphocytes, granulocytes and monocytes. Dose--response studies revealed that the nature of the polyanion determined the degree of leucocyte mobilization. The most potent mobilizer was found to be DS. This polyanion could evoke a six-fold increase of the number of peripheral blood leucocytes. By means of the membrane fluorescence technique it could be demonstrated that optimal doses of DS, PMAA and PMAA--STYR mobilized both B and T lymphocytes. The ratio between the number of B and T cells mobilized was greater for DS than for the other two polyanions. Intravenous injection of DS, PMAA and PMAA--STYR also increased the number of circulating haemopoietic stem cells (CFU-S). The most potent stem cell mobilizer appeared to be PMAA--STYR. This polyanion evoked a twenty-five-fold increase in the number of CFU-S.

Acrylic Resins↗

Kinetics of erythropoiesis in the liver induced in adult mice by phenylhydrazine.

Phenylhydrazine treatment of normal mice elicited a rise in the numbers of CFU-S in blood, spleen and liver. High numbers of CFU-S were found in blood and liver 4 d after the first phenylhydrazine injection. CFU-S in the liver decreased slowly and were absent after 2 weeks. Blood CFU-S returned to normal levels by day 6, whereas spleen CFU-S numbers remained high upto day 12 with a 20-fold increase being apparent between days 5 and 8. Bone marrow CFU-S numbers were relatively unaffected except for a dip between days 4 and 7 with a nadir at day 5 where numbers decreased to 50% of the control levels. Approximately 40% of liver, spleen and blood CFU-S present on the 4th d after initiation of phenylhydrazine treatment, were killed with a single dose of hydroxyurea whereas bone marrow CFU-S numbers were not significantly reduced by the drug. Splenectomy performed before (21 d) or during phenylhydrazine treatment did not diminish the number of CFU-S found in theliver on day 4. A 3 d interval was observed between peak numbers of CFS-U and erythroblasts in the liver which suggests that hepatic CFU-S are able to undergo differentiation along the erythroid pathway. The presence of maceophages was correlated with that of erythroblasts in the hepatic central veins. These macrophages may be essential to the liver environment for induction of erythropoiesis.

Animals↗

Radiosensitization of mammalian cells by diamide.

The effect of diamide on the radiosensitivity of T-cells was investigated under oxic and anoxic conditions. The compound was found to sensitize the cells under both conditions. Under oxic conditions, exposure for 10 min before and during irradiation to 0.1, 0.5 and 1.0 mM diamide produced dose-modifying factors of 0.81, 0.60 and 0.55, respectively. Under anoxic conditions, exposure for 10 min before and during irradiation to 0.5 mM produced a dose-modifying factor of 0.34. When the cells in oxic conditions were exposed for just 20 min before irradiation, the sensitizing effect was smaller, but some sensitization effect was still apparent after a 120 min interval between diamide treatment and irradiation. Diamide also sensitized the cells after irradiation, but this effect was less than when it was present during irradiation. The presence of whole rat-blood in the incubation medium prevented sensitization. No sensitization could be detected in the whole animal. It is proposed that sensitization is due to lack of capacity for repair of radicals by hydrogen transfer and biochemical repair processes.

Animals↗

In vitro evaluation of some latent radioprotective compounds.

In tissue culture, protection against X-irradiation by a number of cysteamine derivatives was studied and the results were compared with data obtained in mice. Compounds with a covered SH group, like WR 638, cysteamine phosphate, WR 2721, and AE 48527, showed practically no protection when dissolved in tissue-culture medium, but developed a protective activity when dissolved in rat blood. Thiol measurements demonstrated that in rat blood the compounds were partly hydrolysed to thiols. C511 was also hydrolysed in culture medium and was slightly less effective than cysteamine in culture medium. Cysteamine phosphate was hydrolsed more easily than cysteamine sulphate and the protective activity in rat blood was better. WR 2721 was also partly hydrolysed in rat blood. The in vitro protection of this compound was disappointing when compared with results in vivo. Its SH form (WR 1065) also showed less protection than expected from in vivo experiments. Thus, the little protection by WR 2721 in vitro in rat blood is not only due to its incomplete conversion into its thiol. Longer incubation times and the use of rat blood as a solvent brought the protective activity of WR 1065 almost up to the level of cysteamine. This may indicate that WR 1065 penetrates the cells poorly. WR 1065 was the only compound we studied whose protective activity in vitro was improved appreciably by dissolving it in rat plasma.

Amifostine↗

Influence of rat blood on radiation protection of mammalian cells by cysteamine and cystamine in vitro.

The protective effect of cystamine and cystamine on T-cells in normal growth-medium was studied in the presence of whole rate blood (WRB). The protective effectiveness of both agents was increased by the addition of WRB, but much less so on the activity of cystamine. In the presence of WRB a dose-reduction factor of 1-5 was obtained at the low concentration of 0-05 mM cysteamine. The increase in protection was not due to induction of anoxia or to a release of glutathione from the rat red cell. The increase in protection may be due to protector RS radicals reacting with rat red cells.

Animals↗

The influence of genetic resistance on CFU growth kinetics in spleen and femur.

An impaired colony formation of C57BL marrow cells transplanted into F1 (C57BL TIMES CBA) mice was observed. In accordance with the literature this phenomenon has been designated as "genetic resistance". Studies to elucidate the mechanism of the genetic resistance demonstrated that the multiplication phase of the CFU growth curve started in the semi-isogeneic combination about 48 hr later than in the isogeneic combination. In the spleen this resulted in a lower "dip". For the spleen as well as for the femur similar CFU doubling times were found during the multiplication phase when both transplantation combinations were compared. Furthermore the percentage of CFU in S-phase (assessed with the 3-H-TdR suicide technique) during the first days after transplantation were similar in both combinations. When the spleen was removed 5-6 months before irradiation and bone marrow transplantation was performed the growth curve of parental CFU in the femur was identical with the growth curve of isogeneic CFU (no delay was observed). These results are discussed and a few theories explaining the observations are proposed.

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