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Biomedical subjects

M Anderson

Publications and source records attributed to M Anderson.

At least 379 records · Page 21Linked to original sources
PubMed1986

Verapamil hypersensitivity of vincristine resistant Chinese hamster ovary cell lines.

Vincristine resistant CHO cell lines, obtained by prolonged selection in semi-inhibitory drug concentrations show considerable hypersensitivity to verapamil. Their D10 values are around 0.2 micrograms/ml compared to 23 micrograms/ml for unselected controls. Reversion of vincristine resistance during growth in vincristine free medium is correlated with reversal of verapamil sensitivity indicating that the two aspects of the cells' phenotype have a common underlying cause. The rate of uptake of calcium in the absence and presence of verapamil is similar in the vincristine resistant cells and the controls. The correlation of verapamil sensitivity with vincristine resistance is not a universal feature of CHO cell lines resistant to antimicrotubular drugs, since it was found that other resistant cell lines which have been selected by short term exposure to high drug concentrations were not verapamil hypersensitive.

Animals↗
PubMed1986

Glucagon: endocrine effects and calcium involvement in cardiovascular actions in dogs.

Although the cardiovascular effects of glucagon are understood, its mechanism(s) of action remains unclear. We studied the effects of increasing doses of glucagon (0.001, 0.01, 0.1 mg/kg) on cardiovascular responses in dogs relative to concurrent measurements of circulating glucagon, cyclic AMP, glucose, norepinephrine, epinephrine, triiodothyronine, thyroxine, and cortisol levels. Glucagon-induced increases in plasma cyclic AMP, glucose, and catecholamine concentrations paralleled the heart rate response to glucagon administration. Further studies were conducted to evaluate the role of beta-adrenergic function as well as calcium in mediating glucagon's actions. The tachycardic effects of glucagon (0.01 mg/kg) were unaltered by prior beta-adrenergic receptor blockade with propranolol (3.5 mg/kg total dose). The calcium antagonist verapamil (0.2 mg/kg bolus then 7.5 micrograms/kg/min/infusion) prevented glucagon-induced increases in heart rate. However, the coadministration of glucagon (0.01 mg/kg) with calcium (1.0, 5.0, 10.0, or 50.0 mg/kg) did not alter glucagon's cardiovascular effects. These data indicate that glucagon is a potent tachycardiac agent that also elevates circulating endocrine-related substances. The antagonism of glucagon's tachycardiac effects by verapamil suggests that glucagon's action may be via glucagon-induced calcium movement through calcium channels, although extracellular calcium changes do not alter glucagon's effect. Furthermore, the persistence of glucagon's cardiovascular actions following beta-adrenergic blockade indicates the potential clinical utility of glucagon in reversing the adverse effects of beta-blocker overdoses, and its potential usefulness in treating circulatory shock in "beta-blocked" patients.

Animals↗
PubMed1986

Accumulation and persistence of DNA adducts in respiratory tissue of rats following multiple administrations of the tobacco specific carcinogen 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone.

4-(N-Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a major nitrosamine formed in tobacco smoke, induces a high incidence of lung, liver, and nasal cavity tumors in rats. Since alpha-hydroxylation of NNK by target tissues can lead to the generation of a methylating agent, the formation and removal of 7-methylguanine and the promutagenic lesions O6-methylguanine (O6mGua) and O4-methyldeoxythymidine were determined over 12 days of NNK administration to rats (100 mg/kg/day). DNA alkylation was greatest in the nasal mucosa, followed by liver and lung after 1 dose of NNK. No DNA adducts were detected in kidney and brain under these conditions. The concentration of O6mGua increased steadily in lung throughout the treatment regimen, while O6-methylguanine-DNA methyltransferase decreased to less than 5% of control. The concentration of O4-methyldeoxythymidine in lung DNA reached a steady state after 4 days of carcinogen treatment. After NNK treatment was discontinued, O6mGua persisted, while O4-methyldeoxythymidine was removed rapidly in the lung, suggesting that different repair pathways exist for the removal of these adducts in vivo. In hepatocytes, nonparenchymal cells, and nasal mucosa, O6mGua concentrations were maximal after 1-2 days and declined by 50-80% during the remaining 10 days of treatment. The decrease in O6mGua levels in nasal mucosa paralleled a decline in O6-methylguanine-DNA methyltransferase activity and was associated with marked cytotoxicity to Bowman's glands, portions of the lateral nasal gland, and the olfactory and respiratory mucosa during carcinogen treatment. In contrast, the decline in O6mGua in hepatocytes was attributed to the induction of O6-methylguanine-DNA methyltransferase activity, since an 18-fold reduction in the ratio of O6mGua:7-methylguanine was observed over the 12 days of treatment. These studies have demonstrated a marked accumulation of promutagenic DNA adducts in target tissues during repeated exposure to NNK.

Animals↗
PubMed1985

Rat liver 4-hydroxy-2-ketoglutarate aldolase: purification and kinetic characterization.

The enzyme 4-hydroxy-2-ketoglutarate aldolase (4HKG aldolase), which catalyzes the reversible cleavage of 4-hydroxy-2-ketoglutarate to form pyruvate and glyoxylate, was isolated from rat liver. The purification scheme as well as a study of several of the physical and kinetic properties of the enzyme are presented. The effects of anions, various buffers, and possible physiologically relevant effectors on the kinetic parameters of the aldolase were also investigated. It was found that pyruvate analogs inhibited the aldolase. Oxaloacetate was a competitive inhibitor of the aldolase, and in addition caused synergistic inhibition with respect to pyruvate analogs at low substrate concentration. These results are discussed in terms of possible regulation of the aldolase.

Animals↗
PubMed1985

Calcium-containing granules in myoepithelial cells of the polychaete Syllis spongiphila: possible ionic modulators.

Myoepithelial cells of the polychaete Syllis spongiphila have a central core containing abundant membrane-bound granules. Examination of isolated and in situ granules using radioactive labelling, X-ray energy dispersive spectrometry, and scanning and transmission electron microscopy indicated that the granules contain high levels of Ca and P, and take up free Ca ions with a time course of 15-30 min. The granules appear to contribute to the dynamic calcium metabolism of the myoepithelial cells.

Animals↗
PubMed1985

Wound care.

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Bandages↗
PubMed1984

Resistance to the mitotic inhibitor NY 3170 in Chinese hamster ovary cells.

Mutant CHO cells have been isolated which are resistant to NY 3170, a member of the metahalone group of antimitotic drugs. One NY 3170 resistant mutant is hypersensitive to the microtubule-stabilising drug, taxol, but there is not a reciprocal relationship between levels of resistance to these drugs in CHO cells, since it was found that sixteen other mutants isolated on the basis of taxol resistance had wild type levels of NY 3170 resistance. Our NY 3170 resistant mutants are cross-resistant to vincristine and other mutants, selected on the basis of vincristine resistance, are cross-resistant to NY 3170.

Animals↗
PubMed1984

Lipid composition of milks from cows with experimentally induced mastitis.

Changes in milk lipid composition were measured during the course of mastitis infections induced in cows by infusion of either Escherichia coli endotoxin or Streptococcus agalactiae into 2 quarters of the udder; untreated quarters were used as controls. Experiments were divided into 3 distinct phases: a pre infusion period during which several samples were collected before infusion; a post infusion period following infusion and corresponding to the occurrence of elevated cell counts in milk from infused quarters; a recovery period followed after a short pause and represented the return of the cell count in milk from infused quarters to the level in the corresponding controls. Milk total fatty acid composition was unaffected by the infusion. Free fatty acid (FFA) composition did, however, undergo some alteration. There was a significant increase in long-chain saturated acids in milk from infused quarters relative to the corresponding controls during the post infusion period. FFA concentration (mequiv./100 g fat) also increased significantly during this period although the net increase was only slight. Phospholipid and cholesterol concentrations were significantly higher post infusion in milk of infused quarters. The results suggest that changes in concentration and composition of those milk constituents synthesized and secreted by the mammary epithelium occur after secretion in the alveolar lumen and milk ducts.

Animals↗
PubMed1983

Development and operation of a pharmacy-based intravenous cytotoxic reconstitution service.

An intravenous cytotoxic reconstitution service has proved extremely popular with both medical and nursing staff. Since the pharmacy has taken over the responsibility for presenting these medicines in a readily usable form, many potential hazards to inexperienced medical staff have been eliminated, and much time and money have been saved. The pharmacists are in an excellent position to offer advice on many aspects of excellent position to offer advice on many aspects of cytotoxic treatment and are well equipped to spot prescription errors. They are often asked to supply information concerning rates and methods of administration as well as compatibility data of different diluents with various cytotoxic agents. The eventual objective of the service is to provide reconstituted cytotoxic drugs for all patients in the pharmaceutical district receiving chemotherapy. As it is not practical to have pharmacists available 24 hours a day, some form of batch production of syringe-loaded drugs could be used. In the immediate future the practicality of storing syringe-loaded drugs in a deep freeze (at -20 degrees C) with rapid thawing will be considered.

Antineoplastic Agents↗