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Biomedical subjects

A M Cameron

Publications and source records attributed to A M Cameron.

At least 55 records · Page 3Linked to original sources
PubMed1984

Developmental regulation and properties of the cGMP-specific phosphodiesterase in Dictyostelium discoideum.

A simple assay has been developed to measure cGMP-specific phosphodiesterase (cGPD) activity in crude soluble extracts of amoebae of Dictyostelium discoideum. When amoebae of different wild-type strains were starved on buffered agar, all strains exhibited an 8- to 12-fold increase in cGMP-specific hydrolyzing activity during development, with the major increase occurring at aggregation. cGMP-specific activity was found in both prestalk and prespore cells. To determine if the elevated cGMP-specific hydrolyzing activity observed during late development was associated with the same enzyme present in vegetative cells, cGMP-specific activities were partially purified from cells at different developmental stages and characterized. Activity in vegetative cells was fractionated by gel filtration into three components with molecular weights of approximately 172,000, 115,000 and 56,000. In contrast, cells starved 4 hr in suspension or 18 hr on agar possessed only the 172,000 or 115,000 Mr forms, respectively. The low-molecular-weight enzyme differed from the two larger forms in kinetic properties and in sensitivity to sulfhydryl reagents. Nevertheless, the three activities probably represent different forms of the same enzyme because mutants defective at the stmF locus lacked appreciable cGMP-specific hydrolyzing activity throughout development. These results indicate that D. discoideum produces a single cGPD which is strongly developmentally regulated. These findings further suggest that intracellular cGMP might be involved in regulating postaggregative as well as preaggregative development.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1983

Acetaminophen-induced hepatic glycogen depletion and hyperglycemia in mice.

Two hours following administration of a hepatotoxic dose of acetaminophen (500 mg/kg, i.p.) to mice, liver sections stained with periodic acid Schiff reagent showed centrilobular hepatic glycogen depletion. A chemical assay revealed that following acetaminophen administration (500 mg/kg) hepatic glycogen was depleted by 65% at 1 hr and 80% at 2 hr, whereas glutathione was depleted by 65% at 0.5 hr and 80% at 1.5 hr. Maximal glycogen depletion (85% at 2.5 hr correlated with maximal hyperglycemia (267 mg/100 ml at 2.5 hr). At 4.0 hr following acetaminophen administration, blood glucose levels were not significantly different from saline-treated animals; however, glycogen levels were still maximally depleted. A comparison of the dose-response curves for hepatic glycogen depletion and glutathione depletion showed that acetaminophen (50-500 mg/kg at 2.5 hr) depleted both glycogen and glutathione by similar percentages at each dose. Since acetaminophen (100 mg/kg at 2.5 hr) depleted glutathione and glycogen by approximately 30%, evidence for hepatotoxicity was examined at this dose to determine the potential importance of hepatic necrosis in glycogen depletion. Twenty-four hours following administration of acetaminophen (100 mg/kg) to mice, histological evidence of hepatic necrosis was not detected and serum glutamate pyruvate transaminase (SGPT) levels were not significantly different from saline-treated mice. The potential role of glycogen depletion in altering the acetaminophen-induced hepatotoxicity was examined subsequently. When mice were fasted overnight, hepatic glutathione and glycogen were decreased by 40 and 75%, respectively, and fasted animals showed a dramatic increase in susceptibility to acetaminophen-induced hepatotoxicity as measured by increased SGPT levels. Availability of glucose in the drinking water (5%) overnight resulted in glycogen levels similar to those in fed animals, whereas hepatic glutathione levels were not significantly different from those of fasted animals. Fasted animals and animals given glucose water overnight were equally susceptible to acetaminophen-induced hepatotoxicity, as quantitated by increases in SGPT levels 24 hr after drug administration. The potential role of a reactive metabolite in glycogen depletion was investigated by treating mice with N-acetylcysteine to increase detoxification of the reactive metabolite. N-Acetylcysteine treatment of mice prevented acetaminophen-induced glycogen depletion.

Acetaminophen↗
PubMed1983

Inhalation of enflurane and halothane at subanesthetic concentrations and effects on circulating serum testosterone, luteinizing hormone and follicle-stimulating hormone in the male rat.

The present study was carried out in order to investigate the effects of inhaled volatile anesthetic gases in subanesthetic concentrations on circulating hormones essential for normal male reproduction. Male mature rats were exposed daily, up to 11 days, to halothane or enflurane in concentrations up to 500 and 1000 ppm, respectively, and thereafter examined for changes in the serum concentration of circulating testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). No significant changes were found for any of the investigated hormones. Based on our results and other reports it is suggested that short-term repeated exposure to halothane and enflurane at subanesthetic concentrations is not associated with any appreciable acute toxicity on male reproductive functions.

Animals↗
PubMed1982

The antispasmogenic action on guinea-pig ileum of a fraction obtained from the toxic skin secretion of the stonefish, Synanceia trachynis.

The toxic skin tubercle gland secretion of the stonefish, Synanceia trachynis, contains a smooth muscle antispasmogen that is readily distinguished from papaverine, verapamil and both alpha and beta adrenoreceptor agonists. At 15 micrograms/ml, the toxin containing fraction markedly inhibited the phasic response and had a lesser inhibitory effect on the tonic response of acetylcholine-and KCl-induced contractures of guinea-pig ileum, while at 50 micrograms/ml, the toxin markedly inhibited both responses. Over the same dose range the toxin fraction markedly inhibited BaCl2-induced contractile responses but did not distinguish between the phasic and tonic components. Whereas the toxin fraction markedly reduced the tone of previously induced supramaximal KCl and acetylcholine responses of guinea-pig ileum, it had little effect on the tone of previously induced BaCl2 responses. The toxin non-competitively inhibited acetylcholine-induced contractions of guinea-pig ileum and similarly non-competitively inhibited the response induced by Ca2+ in high-[K+] Ringer. The toxin is not a chelating agent for Ca2+ or Mg2+ and it does not affect ATP-induced contracture of glycerinated guinea-pig ileum. The antispasmogenic effect of the toxin contained in the fraction does not result from inhibition of cAMP phosphodiesterase activity.

Acetylcholine↗
PubMed1982

Accelerated appearance of chemically induced mammary carcinomas in obese yellow (Avy/A) (BALB/c X VY) F1 hybrid mice.

Latent periods and cumulative incidence of mammary carcinomas (MT) up to 50 wk after initial gavage with 7.12-dimethylbenz[a]anthracene (DMBA) were determined in virgin yellow (Avy/A) and agouti (A/a) (BALB/cStCrlfC3Hf/Nctr X VY/WffC3Hf/Nctr-Avy) F1 hybrid female mice. When subcutaneous masses reached 5-10 mm in diameter, the mice were killed and necropsied, and the tissues examined histologically. No MT were found in control mice. Cumulative MT incidence in the 1.5-mg DMBA group (A) was 43% (41/95) among yellow mice, and 33% (32/96) among agoutis. In the 6.0-mg DMBA group (B), corresponding MT incidences were 86% (83/96) and 71% (67/95). In group A, the first percentile of MT detection was 13.0 wk after initial carcinogen treatment in yellow mice; it was 18.0 wk in agoutis. Corresponding latent periods for the 20th percentile were 34.3 and 47.0 wk. In group B, latencies for the first percentile were 8.3 and 9.0 wk. Corresponding latencies for the 20th percentile were 15.3 and 16.0 wk. Within genotypes and dose groups, rates of weight gain of mice that developed MT and those that did not were similar. We conclude that MT induced by low doses of DMBA arise more rapidly in yellow mice than in nonyellow littermates. The absence of spontaneous MTs, acceleration of chemically induced MT formation at a low dose level that does not induce general toxicity, and availability of genetically identical (except for one gene) normal control animals make this experimental system suitable for development of an assay to efficiently test the carcinogenic potential of low dose levels of chemical substances.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Influence of cause-of-death assignment on time-to-tumor analyses in animal carcinogenesis studies.

The importance of cause-of-death determination in an animal carcinogenesis study with respect to estimation of time-to-tumor distributions of internally occurring (occult) tumors is discussed. A nontechnical description of time-to-tumor estimation is presented. The information obtained from time-to-tumor estimation when cause-of-death designation was used is illustrated for liver tumors in female mice of the inbred strain BALB/cStCrlfC3Hf/Nctr from the ED01 study with N-2-fluorenylacetamide done at the National Center for Toxicological Research. A time-to-tumor analysis of reticulum cell sarcoma data from the same study has provided insight into some difficulties involved in routine case-by-case determination of cause of death. A more flexible system for assigning of cause of death to dead animals and cause of morbidity to moribund animals is described as a way to improve cause-of-death assignment.

2-Acetylaminofluorene↗
PubMed1979

radE, a new radiation-sensitive locus in Dictyostelium discoideum.

Dictyostelium discoideum strain M28, which has been used widely in genetic studies, was found to carry a radiation-sensitive mutation. This allele, termed rad-100, was recessive in heterozygous diploids and mapped in linkage group III. Complementation analysis and survival studies on strains carrying rad-100 suggested that this allele defines a new radiation-sensitive locus in D. discoideum, and this locus has been designated radE. radE strains were moderately sensitive to ultraviolet light (D10 90 J m-2) and slightly sensitive to 137Cs gamma rays D10 255 krad). radE strains also exhibited increased sensitivity to killing by N-methyl-N'-nitro-N-nitrosoguanidine but not by other alkylating agents such as ethyl methanesulphonate or methyl methanesulphonate. The frequency of spontaneous methanol-resistant (acrA) mutants was approximately the same in cultures of radE and radE+ strains. However, when amoebae of these strains were irradiated with ultraviolet light, the frequency of induced mutants was significantly lower in cultures of the radE strain. Furthermore, when amoebae of wild-type strain NC4 were plated in the presence of caffeine after ultraviolet-irradiation, the survival curves were very similar to the curves obtained for amoebae of radE strains in the presence or in the absence of caffeine. These results suggest that the radE100 mutation and caffeine interfere with an error-prone DNA repair pathway in D. discoideum.

Alleles↗
PubMed1977

Differential distribution of ciliated epithelial cells in the trachea of hamsters: implications for studies of pathogenesis.

The morphology of the inner aspect of the adult hamster trachea was examined by scanning electron microscopy. Relatively large patches of unciliated cells were observed in the epithelial layer. The patches, which covered several hundreds to thousands of square microns, were most conspicuous on the ventral surface of the trachea, especially in the middle third. The frequency of these areas of unciliated cells, both isolated and in patches, was much greater in hamsters than in mice, rats, or cats. Greatest ciliation in the hamster trachea was observed over the strip of trachealis muscle between the open ends of the cartilaginous rings. Areas with the heaviest ciliation also had the greatest activity of cellular metabolism, as measured by the tetrazolium reduction assay. The attachment of tritium-labeled cells of Mycoplasma pneumoniae was inversely correlated with extensive ciliation, since the greatest numbers of counts were found on the middle third and ventral regions of the tracheal surface. The results of this study suggest that the regional differences in ciliation of respiratory epithelium in hamsters may influence studies of pathogenesis and isolation of M. pneumoniae and that these differences should therefore be considered and controlled in the experimental design.

Animals↗
PubMed1976

Papillary carcinoma of apocrine sweat glands in a capuchin monkey (Cebus albifrons).

A tumor removed from the skin of the right pectoral region of a 19-year-old male Capuchin monkey (Cebus albifrons) was morphologically classified as a papillary carcinoma of apocrine sweat gland origin. The designation of malignancy was based primarily on cellular pleomorphism and stromal invasion. This is believed to be the first report of this neoplasm in nonhuman primates. There has been no evidence of recurrence nor metastasis in the 12 months following excision.

Animals↗
PubMed1974

Cytotoxicity of Mycoplasma pneumoniae Membranes.

Organ cultures of adult hamster trachea were used to evaluate the cytotoxic potential of cell fractions of Mycoplasma pneumoniae. Cytoplasm was essentially devoid of activity, whereas viable cells and membrane preparations, at a level of 25 mug of protein per ml, induced necrosis. Damage, as revealed by light and electron microscopy, included ciliostasis, vacuolization, loss of ciliated respiratory epithelial cells, disorganization, and a loss of polarity. Dose response data indicated that the speed and degree of cytotoxicity was directly related to the concentration of membranes. Doses of 30 to 60 mug of protein per ml could reduce relative ciliary activity to 20% of the control level within 4 days. Membranes prepared after freeze-thaw lysis of cells were almost twice as active as those isolated after a combination of osmotic and sonic shock. Membranes of M. fermentans were inactive, though both the FH and M129 strains of M. pneumoniae were toxic. These data indicate that the toxic factor responsible for M. pneumoniae may be located in the cell membrane.

Journal Article↗