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Biomedical subjects

E Smith

Publications and source records attributed to E Smith.

At least 361 records · Page 20Linked to original sources
PubMed1981

The age-dependent loss of cells from the rear of Dictyostelium discoideum slug is not tip controlled.

Young slugs of the cellular slime mould Dictyostelium discoideum drop small numbers of individual amoebae (approximately 10/mm) in the slime trail. With increased time of migration, slugs develop trailing tails and leave clumps of cells in their slime trails. Using reciprocal transplants between tips of young and old slugs and between a wild-type strain and an 'aged" mutant it was shown that this age-dependent cell loss is due to changes in the bulk of cells comprising the slug, rather than to changes in the effectiveness of the tip (organizer region). Another property of the slug, the decision to continue migrating or form a fruiting body which is controlled by the tip, was less affected by age. This raises the possibility that cell autonomous properties of the slug are more subject to ageing than is the tip.

Animals↗
PubMed1980

Influence of environmental chemicals on drug therapy in humans: studies with contraceptive steroids.

The effects have been studied of various environmental factors on the variability in response to oral contraceptive steroid therapy in women. Ten- to thirty-fold variations in plasma concentrations of norethisterone, L-norgestrel and ethinyloestradiol have been shown in samples taken 12 h after administration of oral contraceptives in mid-menstrual cycle. Factors shown to be responsible for this variation include passage into the enterohepatic circulation, a variable first-pass effect, and changes in metabolism in the gut wall or liver due to diet, disease, smoking or administration of drugs. Phenobarbitone and the antibiotic rifampicin increase both oestrogen and progestogen metabolism in women and in experimental animals by increasing hepatic and gut wall metabolism. In animals, other antibiotics (ampicillin, neomycin and lincomycin) suppress the gut flora that normally hydrolyse steroid conjugates excreted in bile; enterohepatic circulation or oral contraceptive steroids is thus reduced and their plasma concentrations lowered by up to 90%. In the human, ampicillin has a variable but less dramatic effect on elimination of oral contraceptives. Samples of gut wall mucosa obtained from patients with coeliac disease are defective in their ability to metabolize oral contraceptives. Cigarette smokers eliminate ethinyloestradiol more rapidly than non-smokers; an increased production of reactive steroid metabolites may thus be a cause of vascular disease in women who smoke and take contraceptive steroids.

Animals↗
PubMed1980

The interaction of phenobarbital and other anticonvulsants with oral contraceptive steroid therapy.

In a group of 5 women on long-term anticonvulsant and oral contraceptive therapy, the plasma ethynylestradiol (EE) concentration on 50 microgram EE daily was 11.1 +/- 4.5 pg/ml. These values were at the lower end of the range found in normal women in this laboratory taking 30 microgram EE daily (6-190 pg/ml). Four women have been studied prospectively for 3 months, over 1 cycle before and 2 cycles during phenobarbital 30 mg b.i.d. therapy. Significant falls in the plasma EE concentration were seen in two women (from 104.8 +/- 13.4 to 37.7 +/- 2.0 pg/ml and from 125.6 +/- 23.8 to 34.8 +/- 6.7 pg/ml p less than 0.01) and breakthrough bleeding was seen in both women. No changes in plasma concentrations of follicle stimulating hormone, progesterone, norethindrone or norgestrel were seen. There was a significant increase in the sex hormone binding globulin capacity from 100.7 +/- 5.8 to 133.3 +/- 1.2 nmoles/1 (p less than 0.05). These changes are consistent with the known microsomal enzyme inducing effect of phenobarbital.

Adolescent↗
PubMed1980

The effect of rifampicin on the pharmacokinetics of ethynylestradiol in women.

A single dose of Minovlar (50 microgram ethynylestradiol (EE) and 1 mg norethindrone acetate) was given to seven women during treatment with rifampicin (450-600 mg/day) and again one month after stopping rifampicin. Blood samples were taken at intervals over a 24-hour period. The area under the plasma EE versus time curve increased significantly on stopping rifampicin from 1014 +/- 317 pg/ml x h (mean +/- SE) to 1747 +/- 218 pg/ml x h (p less than 0.01). The terminal plasma half-life increased from 2.9 +/- 0.8 h to 6.3 +/- 1.4 h (p less than 0.005). The sex hormone binding globulin (S.H.B.G.) capacity was also reduced from 213.4 +/- 11.5 nmoles to 129.0 +/- 7.7 nmoles/1 after stopping rifampicin. In one patient starting rifampicin who was taking Minovlar as a long-term oral contraceptive, a fall in the plasma EE concentration was associated with a rise in the plasma follicle stimulating hormone concentration. These effects of rifampicin on EE pharmacokinetics are consistent with induction of the microsomal enzymes that metabolise EE.

Adolescent↗
PubMed1980

Cytotoxicity of adriamycin on aerobic and hypoxic chinese hamster V79 cells in vitro.

Mammalian cells (V79-379A) in suspension culture rendered chronically hypoxic showed greater resistance to Adriamycin than exponentially growing aerobic cells. Resistance to Adriamycin increased as a function of the time cells were held under hypoxic conditions, with maximal resistance after 6 h. Chronically hypoxic cells retained their resistance when reoxygenated, and did not return to their original sensitivity until they had been in air for 24 h. Uptake of Adriamycin was similar for chronically hypoxic and exponentially growing aerobic cells, but much more than for plateau-phase cells. These findings suggest that chronically hypoxic cells in tumours may be resistant to this drug.

Aerobiosis↗
PubMed1980

Rapidly fatal lymphangioma-like Kaposi's sarcoma.

A 34-year-old black South African male was treated for lymphangioma-like clinical Kaposi's sarcoma. The disease followed a rapidly fatal course and was characterized by unexplained recurrent pleural effusions and severe refractory anaemia due to the presence of dilated vascular channels in the bone marrow. Definitive diagnosis was only made at autopsy. Lymphangiomatous changes in the skin without spindle cell formation caused diagnostic difficulties.

Adult↗
PubMed1980

The interaction of misonidazole with radiation, chemotherapeutic agents, or heat: a preliminary report.

Survival of hypoxic cells exposed to misonidazole at 37 degrees C show an initial lag period after which survival decreases exponentially with time. Hypoxic cells incubated with misonidazole for a time equivalent to that of the lag period on the survival curve show increased sensitivity when subsequently given x-irradiation. This is consistent with previously published observations. In addition, preincubation of hypoxic cells with misonidazole ata 37 degrees C also renders cells more sensitive to subsequent treatments by heat or melphalan, mustine and cis-Pt(II). Preincubation must be in hypoxia for cells to become sensitive to a second insult; preincubation in air does not change cellular sensitivity even when this preexposure is 5 mM misonidazole for 3 days. The potential of exploiting a physiological property of most solid tumors, viz., hypoxia, in order to increase sensitivity of tumor cells to cytotoxic agents is discussed.

Animals↗
PubMed1980

Evidence for tip control of the 'slug/fruit' switch in slugs of Dictyostelium discoideum.

Reciprocal transplants were performed between slugs of two strains of Dictyostelium discoideum. Slugs of one strain (NP84 'slugger') showed prolonged migration, while slugs of the other strain (AX3 'fruiter') migrated for a short period only. The transplant experiments showed that the 'slug/fruit' characteristic is tip dependent, since an NP84 tip induced an AX3 rear to migrate for a prolonged period, while an AX3 tip induced the rear of a NP84 slug to fruit without migration. These findings are not consistent with the hypothesis that tips of all stages release only one signal which is interpreted differently by the rest of the cells in the aggregate at different stages. Rather, we propose that the tip of a D. discoideum aggregate may release a number of signals, one of which is stage dependent, and triggers the 'slug/fruit' switch.

Chimera↗
PubMed1979

The effect of rifampicin on norethisterone pharmacokinetics.

The pharmacokinetics of norethisterone have been studied in 8 women during and one month after treatment with rifampicin (450--600 mg/day). Rifampicin caused a significant reduction in the A.U.C. of a single dose of 1 mg norethisterone from 37.8 +/- 13.1 to 21.9 +/- 5.9 ng/ml X h (p less than 0.01). The plasma norethisterone half life (beta-phase) was also reduced from 6.2 +/- 1.7 to 3.2 +/- 1.0 h (p less than 0.0025). In one additional woman on long term oral contraceptive therapy the 12 hour plasma norethisterone concentration was reduced by rifampicin from 12.3 ng/ml to 2.3 ng/ml. Rifampicin caused a significant increase in antipyrine clearance, 6 beta-hydroxycortisol excretion and plasma gamma-glutamyltranspeptidase activity but there was no significant correlations between changes in these indices of liver microsomal enzyme induction. There was a significant correlation between the percentage increase in antipyrine clearance and the percentage decrease in norethisterone A.U.C. during rifampicin. The changes in norethisterone pharmacokinetics during rifampicin therapy are compatible with the known enzyme inducing effect of rifampicin.

Adolescent↗
PubMed1979

Mouse hybrid cell lines produce antibodies to herpes simplex virus type 1.

A solid-phase radioimmunoassay procedure has been devised for the assay of antibodies produced in the mouse to herpes simplex virus type 1 (HSV-1). It is based on the adsorption of virus to flexible micro-well plates and uses radio-iodine-labelled rabbit antibody against mouse immunoglobulin to assess antibody binding. Using this assay for screening, cell hybrids have been obtained which yield monoclonal antibody to HSV-1. The hybrids are between spleen cells from hyperimmune mice and an immunoglobulin-non-secreting, azaquanine resistant myeloma cell line (NS-1). From 480 hybrid cell lines initially examined, five stable cell lines were obtained which released HSV-1-specific antibody in vitro and in vivo. Mice carrying transplants of these cell lines yield binding titres in serum of up to 1/25000. Both IgG and IgM antibodies were obtained in this way.

Animals↗