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Biomedical subjects

H E Rugstad

Publications and source records attributed to H E Rugstad.

At least 91 records · Page 5Linked to original sources
PubMed1983

Cultured human cells with a high content of metallothionein show resistance against gold-chloride.

Resistance to gold(III)chloride was tested in cultures of human epithelial cells derived from normal skin. Two cell strains were used, a 'wild type' (HE) and a substrain, previously made resistant to 100 mumol/l of CdCl2 (HE100), with a high content of the cysteine-rich cytoplasmic protein, metallothionein. Cell growth was studied for a period of 4 days during exposition to gold-chloride (100-400 mumol/l of HAuCl4 X 4H2O). Gold-chloride produced a dose-dependent inhibition of cell proliferation of both cell strains. Compared with untreated control cells, however, the percentage survival after 4 days' treatment with 400 mumol/l was only 11% of HE cells, vis-à-vis 44% of the HE100 cells. After 24 hours' exposition to 200 mumol gold-chloride/l, the subcellular distribution of gold was determined by gel-filtration of cytosols, and subsequent analyses for Au by flame atomic absorption spectrophotometry. In the HE100 cells 30% of the cytosolic gold co-eluted with the metallothionein. In the HE cells, which do not contain detectable amounts of metallothionein, only traces of gold were found in the corresponding eluate fractions. The total amount of intracellular gold was 15% higher in HE100 than in HE cells. This study renders it probable that the binding of gold to pre-existing metallothionein in HE100 cells affords protection against otherwise lethal gold concentrations. The significance of the results is briefly discussed in relation to therapeutic use of gold substances.

Binding, Competitive↗
PubMed1983

Increased resistance to chlorambucil in cultured cells with a high concentration of cytoplasmic metallothionein.

Cultured cells with elevated levels of cytoplasmic metallothionein (MT), a small-molecular-weight protein extremely rich in cysteine, showed resistance against the alkylating drug chlorambucil. One human epithelial line (HE) and one mouse fibroblast line (Cl 1D) were used, as well as substrains of both cell lines (HE100 and Cl 1D100). The substrains contain large amounts of MT. Dose-survival curves obtained from cloning studies with the murine cells after exposure to chlorambucil for 1 hr revealed that Cl 1D100 was approximately 3-fold more resistant than were Cl 1D cells (D0 = 32.9 and 11.6 micrograms/ml, respectively); this difference was highly significant (p less than 0.001; t test). In growth rate studies, both MT-containing strains showed resistance against chlorambucil over the total dose range of 0.5 to 100 micrograms/ml compared to the parent strains. After 4 days treatment with 25 micrograms/ml, the growth inhibition of Cl 1D was 67%, but only 13% in Cl 1D100. For HE and HE100, 50 micrograms/ml gave growth inhibitions of 83 and 65%, respectively. Following 1- and 24-hr incubations of cells with [14C]chlorambucil and subsequent ultracentrifugation and gel filtration of the cytosols, about 20 to 40% of the 14C-derived radioactivity coeluted with the MT from the resistant strains. The results indicate that intracellular MT sequesters chlorambucil or its toxic metabolites and that the protein thus contributes to the resistance against this drug.

Animals↗
PubMed1982

Radioresistance in cells with high content of metallothionein.

An endogenous cytoplasmic protein, metallothionein (MT) apparently gave rise to radioresistance in 2 different cell lines. A dose reduction factor of 1.9 was achieved in MT-containing cells. MT accounted for a 3-4 fold increase of total sulfhydryl groups in the resistant cell strains, compared to the non-resistant lines from which they were derived. The protein is rich in cysteine (30%), an amino acid known to give radioprotection when administered exogenously. Glutathione levels and cell-cycle phase distribution showed no marked difference between resistant and corresponding non-resistant cells.

Animals↗
PubMed1982

The absorption and excretion of methyldopa ingested concomitantly with amino acids or food rich in protein.

Absorption and urinary excretion of 2-14C-L-alpha-methyldopa (alpha MD) were investigated in 5 healthy human volunteers. The drug was administered alone, with a mixture of amino acids and with a meal consisting of roast beef. The radioactivity in plasma and urine was not decreased significantly by either treatment, and it was concluded that the overall absorption of the drug was virtually unchanged. The amount of unconjugated alpha MD in plasma and urine, however, was significantly decreased following administration of the drug with roast beef. As the acid labile conjugates of alpha MD were practically unchanged an increased biotransformation to other metabolites owing to the protein rich meal was suggested more probable than competition between alpha MD and amino acids in the specific transport systems.

Adult↗
PubMed1982

Ultrastructural changes in the nucleus of a human epithelial cell line exposed to cytotoxic agents. The effect of PUVA and cadmium.

An established human epithelial cell line was exposed to cytotoxic doses of photo-activated 8-methoxy psoralen (PUVA) and to cadmium (Cd++) and the cells' nuclear ultrastructure were compared with controls. PUVA and Cd++ have some common biological features. Both substances induced nuclear indentations and cytoplasmic invaginations, while only PUVA caused an increase in nuclear bodies. After cadmium exposure, clusters of large-sized perichromatin granules (PG) were seen as well as an increase in chromatin margination. After PUVA, an increase in singularly distributed PGs was observed. The nuclear envelope was not affected by PUVA while Cd caused extensive disruption of this membrane. A strain of the epithelial cell line was made resistant to 100 mumol Cd/l and its nuclear ultrastructure was examined. An increase in chromatin margination was seen compared with its parent line. When this Cd resistant cell strain was exposed to 200 mumol Cd/l no ultrastructural changes took place. An attempt to produce a PUVA resistant epithelial cell strain was unsuccessful. Some functional aspects of the different morphological parameters observed are discussed.

Cadmium↗
PubMed1981

Effects of PUVA on a human skin epithelial cell line.

An established human epithelial cell line was exposed to photoactivated 8-methoxy psoralen (PUVA) during exponential growth. Effects of PUVA treatment on cell growth were measured by cell kinetic methods (counting of cell numbers, flow cytometric measurements (FCM) of DNA and calculations of labelling indices (LI)). Doses of 8-methoxy psoralen and UVA were comparable to those used in patients. The cell number in PUVA treated cultures remained almost constant, and very few mitoses were seen for 144 h. About 9 h after PUVA, both FCM and LI showed an increase in the fraction of cells in S-phase, reaching a maximum of 85-90% after 24 h. DNA synthesis took place at a low rate in these cells. FCM showed an increasing fraction of polyploid cells after PUVA treatment. The possibility that inhibition of cell proliferation is one of the main effects of PUVA, is discussed.

Cell Count↗
PubMed1981

Comparison of two soft-agar methods for assaying chemosensitivity of human tumours in vitro: malignant melanomas.

Two soft-agar methods for assaying chemosensitivity of human cancers in vitro were compared with respect to colony morphology, plating efficiency (PE) and chemosensitivity of human melanomas. In 9 xenografts and 9 patients' biopsy specimens Method A (essentially that of Courtenay & Mills, 1978) gave considerably higher PE that Method B (essentially that of Hamburger & Salmon, 1977) and, in contrast to Method B, the number of colonies was proportional to the number of cells plated. Evidence was obtained that the observed differences in PE could be attributed to the low O2 concentration and the presence of rat red blood cells in Method A. Colony morphology was similar in the 2 assays. When cells from 4 xenografted melanomas were treated in vitro with DTIC, CCNU, vinblastine and abrin, and the inhibition of colony formation was assayed concurrently in the 2 soft-agar methods, the tumour cells appeared to be more sensitive to 3 of the drugs in Method B than in A. The results demonstrate that chemosensitivity data obtained with the 2 assays cannot be directly compared.

Abrin↗
PubMed1981

Influence of certain chelating agents on egress of cadmium from cultured epithelial cells containing high amounts of metallothionein: a screening of Cd-releasing and toxic effects.

Cells cultures have been used to study the effect of 6 different metal chelating compounds on the efflux of Cadmium (Cd) from the cells and on cell growth. The cells had previously been made resistant to high levels of Cd (100 mumol/1) in the medium. They contain large amounts of intracellular Cd (40-50 nmol Cd/mg cell protein), the main part of which is bound to cytoplasmic metallothionein. Among the different monothiol and dithiol compounds tested are some old, well-known and to some extent therapeutically tried substances, i.e. 2,3-dimercapto-1-propanol (BAL), D-penicillamine (PA), N-acetyl-DL-penicillamine (NAPA) and some newer metal chelators, i.e. 2,3-dimercaptopropane-1-sulphonate (BAL-Sulph), mercaptosuccinic acid (MSA) and meso-2,3-dimercaptosuccinic acid (DMSA). The three latter ones all showed better effect on the egress of Cd than PA and NAPA and less toxic effect than BAL on an equimolar basis. All the agents tested increased the efflux of Cd from metallothionein-containing cell cultures which seem to be justified as a test system for primary screening of effect and toxicity of new chelators.

Cadmium↗
PubMed1981

Uptake and egress of cadmium in cultures of cadmium-resistant and the corresponding "wild-type" cells.

Development of resistance against the highly toxic Cd++ion has been described earlier both in animals, cell cultures and in bacteria. In this paper we have tested if decreased intracellular concentration of Cd plays a role in resistance to Cd in three mammalian cell cultures. The cells originated from different tissue and from two different species. Cd-resistant and corresponding "wild-type" strains were used. The results from all three lines show essentially the same, namely that there is no significant difference in Cd content between the Cd-resistant and the non-resistant cells. The resistant cells from all three lines grow continuously with a cellular Cd-content which is several times higher than that killing all cells of the non-resistant "wild-type".

Animals↗
PubMed1981

Evaluation of a new sustained-release theophylline tablet for children.

A new, low dose sustained-release tablet of theophylline has been developed in order to facilitate a correct dose regimen in asthmatic children treated with theophylline. The formulation (Euphyllin retard mite w/groove) contains 128 mg of theophylline, and can easily be divided. The extent of bioavailability in adults is 0.91, and the peak serum concentration is reached after 8.7 h. 25 children treated with plain theophylline tablets were followed when changing to the sustained-release tablets. Compared to the plain tablets, the serum theophylline concentration before the morning dose was 29 mumol/l higher (range 12-51) when the same daily dose was given as a sustained-release preparation. The serum concentration fluctuations during one dosing interval were reduced with 13 mumol/l (0-26). Mild gastrointestinal side effects reported by the children when using the plain theophylline tablets all disappeared on changing to the sustained-release tablets.

Adolescent↗
PubMed1981

Characterization of a human epithelial cell line with special reference to its ultrastructure.

A commercially available cell line (NCTC 2544) originating from presumably normal human skin was chosen as an in vitro model system for subsequent studies of the effects of different agents on human epithelial cells. The cell line, therefore, was ultrastructurally and otherwise characterized at intervals by techniques which allow standardized controls of the model. The cell line was classified as epithelial both by phase contrast microscopy and transmission electron microscopy. The cells were polygonal, fully developed desmosomes were demonstrated and no extracellular filamentous material was observed. Specific epidermal markers like keratohyalin granules or keratinosomes were not demonstrated. Comparison of the nuclear morphology of cells from 1, 3 and 6 days old cultures revealed that only minor changes took place. The same was true for cytoplasmic features. Thus this cell line has a well-defined ultrastructural morphology. Flow cytometry studies showed the cell line to be tetraploid, with no sub-populations with other ploidies. Surface antigens were typed by a microcytotoxicity assay using 12 different antisera. The electrophoretic patterns of the isoenzymes lactate dehydrogenase and glutathione reductase were human. The cells did not form colonies in soft agar. Though several parameters indicate that this cell line is not a HeLa cell contaminant, this possibility cannot, however, be totally excluded.

Antigens, Surface↗
PubMed1981

Immunosuppressive treatment policies. A) Glucocorticoids: absorption of prednisolone. I. The effect of fasting, food, and food combined with antacids.

Serum concentrations of prednisolone have been measured by radioimmunoassay in 19 healthy volunteers after ingestion of 20 mg prednisolone as four 5 mg tablets. Thirteen subjects were fasting, and 6 had taken a light breakfast. Repeat studies were performed with coadministration of antacid in the 6 non-fasting subjects. The maximum serum concentration of prednisolone was higher, (mean Cmax; fasting: 597 +/- 101 ng/ml, non-fasting: Cmax 489 +/- 56 ng/ml) and the rate of absorption more rapid in the fasting than in the non-fasting subjects (absorption t1/2 fasting: 15.7 +/- 7 minutes, non-fasting: 20 +/- 11.5 minutes). The extent of bioavailability of prednisolone and the rate of elimination were the same in both groups. In the non-fasting groups, the intake of antacid with the tablets had no significant effect on these parameters. This study shows that antacid may safely be coadministered with prednisolone tablets in non-fasting subjects without reducing the rate and extent of bioavailability of prednisolone. It is not known whether the reduction in maximum prednisolone concentration found when the tablets were taken after a meal has any clinical significance.

Absorption↗