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Biomedical subjects

C J Moore

Publications and source records attributed to C J Moore.

At least 73 records · Page 4Linked to original sources

Rejection by pigs of mouldy grain containing deoxynivalenol.

Weaner pigs on a farm near Beaudesert in south eastern Queensland refused to eat feed comprised largely of wheat and barley. Older pigs consumed small amounts and some prepubertal gilts subsequently displayed enlarged and reddened vulvas. Wheat, barley and triticale were grown on the farm during 1983, which was unusually and persistently wet. The wheat and triticale were harvested and stored for about 3 weeks with moisture contents above 14% before being fed. Samples of the wheat and triticale contained pale pink grains, which can indicate infection by the fungus Fusarium graminearum Schw. On analysis 2 mycotoxins known to be produced by F. graminearum were detected, deoxynivalenol (vomitoxin) which causes feed refusal and vomiting, and zearalenone which causes oestrogenic effects. Concentrations of deoxynivalenol in the wheat, triticale and barley were 34, 10, and less than 0.1 mg/kg respectively. Concentrations of zearalenone were 6.2, 2.8 and 0.1 mg/kg respectively. Subsequently, F. graminearum was isolated from grains and crop residues. Although the wet weather contributed to F. graminearum infection of the crops before harvest, most of the toxins probably developed during storage.

Animal Feed↗

Diagnostic imaging, a "parallel" discipline. Can current technology provide a reliable digital diagnostic radiology department?

Only recently has any detailed criticism been voiced about the practicalities of the introduction of generalised, digital, imaging complexes in diagnostic radiology. Although attendant technological problems are highlighted we argue that the fundamental causes of current difficulties are not in the generation but in the processing, filing and subsequent retrieval for display of digital image records. In the real world, looking at images is a parallel process of some complexity and so it is perhaps untimely to expect versatile handling of vast image data bases by existing computer hardware and software which, by their current nature, perform tasks serially. Successes in applying new imaging devices using digital technology, numerical methods and more easily available computing power are directing radiology towards the concept of all-digital departmental complexes. Hence a critical discussion of fundamental problems should be encouraged, to promote a thorough understanding of what may be involved (Gray et al, 1984) in following such a course. It is equally important to gain some perspective about the development possibilities for existing, commercially available equipment being offered to the medical community.

Computers↗

Differences in mediated mutagenesis and polycyclic aromatic hydrocarbon metabolism in mammary cells from pregnant and virgin rats.

The physiological state of pregnancy confers significant resistance to polycyclic aromatic hydrocarbon (PAH)-induced mammary tumorigenesis. We have tested the abilities of primary mammary cells from pregnant and virgin rats cultured on collagen-coated plates to metabolize PAHs and convert these carcinogens to mutagenic derivatives. Using a cell-mediated mutagenesis assay, we found that mammary epithelial cells from pregnant rats produced half the levels of mutagenic 7,12-dimethylbenz[a]anthracene (DMBA) metabolites formed by cells from virgin rats. Pregnant-derived mammary cells also showed consistently lower levels of metabolism of DMBA and benzo[a]pyrene (B[a]P) than cells from virgin rats. H.p.l.c. analysis of B[a]P metabolism by these cell populations indicated no significant qualitative differences in the extracellular and intracellular metabolites formed. We have previously shown that mammary cells from rat strains exhibiting significant differences in susceptibility to PAH-induced tumors have equivalent qualitative and quantitative abilities to metabolize PAH carcinogens. Our current data suggest that modifications in mammary tumor susceptibility found in various physiological states, unlike genetically determined differences, may be related in part to an altered ability to activate chemical carcinogens within the mammary gland.

Animals↗

Metabolism of benzo[a]pyrene by cultured human hepatocytes from multiple donors.

Primary hepatocyte cultures from six human donors were established and their abilities to metabolize the polycyclic aromatic hydrocarbon carcinogen benzo[a]pyrene (B[a]P) were examined. Cells from each donor were plated at similar densities (1 X 10(7) cells/100 mm dish). All cultures metabolized B[a]P to a significant extent (24-35 nmol in 24 h) and h.p.l.c. profiles of the organic solvent-soluble and glucuronidated B[a]P metabolites were obtained for all donors. The predominant extracellular organic solvent-soluble B[a]P metabolites were the 9,10- and 7,8-dihydrodiols, 9-hydroxy-B[a]P, and a mixture of tetrols, but the general ratios of these metabolites varied widely among the cells from different donors. In contrast, profiles were highly reproducible in cells from the same donor treated with B[a]P at either 8 or 24 h after initial plating. There was less variability in the amounts of specific B[a]P metabolites conjugated to glucuronic acid by cells from various donors. This variability could not be correlated with cell viability or overall levels of B[a]P metabolism. In addition, B[a]P metabolism by fresh and cryopreserved hepatocytes from the same donor was compared. While there was only a small reduction in the level of total B[a]P metabolism after cell freezing, there was a 3- to 5-fold increase in production of B[a]P-7,8-dihydrodiol, found both in the extracellular medium and as glucuronic acid conjugates, by the cryopreserved cells tested.

Adolescent↗

Zearalenone intoxication of pigs.

Mycotoxicosis due to ingestion of zearalenone was detected on 2 pig farms on the Atherton Tableland in northern Queensland. In one herd of 200 pigs, this resulted from feeding maize which had been stored with a high moisture content. In the other herd of 1400 pigs, it resulted from feeding sorghum grain which was rain affected before harvest. Concentrations of zearalenone in the feeds ranged up to 8 mg/kg. Most prepubertal gilts in the herds displayed enlarged teats and signs of oestrus such as having red, swollen vulvas. In several cases both rectal and vaginal prolapses occurred. On one of the farms, 25 pigs died as a direct result of prolapses. Autopsy of a 3-month-old gilt revealed apparently enlarged ovaries and uterine horns. Sows and boars seemed to be unaffected. Four gilts failed to conceive following mating during the period of zearalenone ingestion, but apart from this and the deaths from prolapses, production of the herds appeared to be unaffected.

Animals↗

The use of Selectron afterloading equipment to simulate and extend the Manchester System for intracavitary therapy of the cervix uteri.

When Selectron afterloading machines were introduced in the Christie Hospital the first aim was to reproduce, as closely as possible, the isodose distributions achieved with the traditional Manchester Radium System. This resulted in the establishment of standard pellet loading patterns, and standard treatment times, for programming the Selectron channels. However, the availability of whole-body CT scanning facilities provides a method of accurately locating the source positions with respect to the local anatomy and hence the possibility of dosage control based on doses to specific pelvic structures. Various computer programs have been written to extract source position data from the CT images, to allow the operator to propose pellet loading patterns and treatment times, and ultimately to display the resultant isodose distribution superposed on the cross-sectional scans. The effects on the dose distribution arising from changing the number of pellets, the pellet positions within the applicators, and the treatment times, are briefly discussed.

Brachytherapy↗

Relationship of mammary tumor susceptibility, mammary cell-mediated mutagenesis, and metabolism of polycyclic aromatic hydrocarbons in four types of rats.

Mammary tumorigenesis by 7,12-dimethylbenz(a)anthracene (DMBA) was tested in two rat stocks and two rat strains: outbred Sprague-Dawley and Long-Evans and inbred Wistar/Furth (WF) and Fischer F344 (F344) rats. Both Sprague-Dawley and WF rats showed comparably high susceptibility to tumorigenesis, whereas Long-Evans and F344 rats proved relatively resistant to tumorigenesis. Cultured mammary stromal and parenchymal cell populations from these four types of rats were used in a cell-mediated mutagenesis assay, and all were found to produce comparable levels of mutagenic metabolites from DMBA. Metabolisms of DMBA and benzo(a)pyrene (BP) were also examined in these cell populations, and similar patterns were found in mammary cells from both susceptible and resistant rat types. The stromal cell populations metabolized both carcinogens at a faster rate than the epithelial cells, but high-pressure liquid chromatographic analysis of ethyl acetate-soluble BP metabolites indicated that both cell types produced similar profiles of BP metabolites in all four rat types. Epithelial cells generally maintained higher intracellular concentrations of carcinogen compared to those of stromal cell populations. The four types were indistinguishable in the amounts and identities of glucuronic acid conjugates of BP that were formed by the mammary cells. The data demonstrate that the rat type-specific susceptibility to polycyclic aromatic hydrocarbon-induced tumorigenesis does not reside in the ability of the mammary cells to metabolically activate these carcinogens.

9,10-Dimethyl-1,2-benzanthracene↗

Field cases of aflatoxicosis in pigs.

Five cases of aflatoxicosis in pigs in southern Queensland are described. One peracute case where aflatoxin concentrations of up to 5000 micrograms aflatoxin B1/kg were demonstrated in stomach contents was presumed to be caused by consumption of mouldy bread. High levels of toxins were also present in the livers. Two cases of acute toxicity were caused by feeding mouldy peanut screenings containing 22000 micrograms aflatoxin B1/kg. One case of subacute and one of chronic toxicity were caused by sorghum grain based rations with lower aflatoxin levels (4640 and 255 micrograms/kg). Peracute toxicity caused collapse and deaths within several hours, acute toxicity caused deaths within 12 h and with subacute toxicity deaths occurred after 3 weeks on a toxic ration. Anorexia and ill thrift affecting only growing animals were seen with chronic toxicity. Extensive centrilobular liver necrosis and haemorrhage occurred with peracute toxicity and in cases of acute poisoning there was hepatic centrilobular cellular infiltration, hepatocyte swelling and bile stasis. With subacute toxicity hepatocyte vacuolation together with bile stasis and bile ductule hyperplasia were seen.

Animals↗

Human breast cell-mediated mutagenesis of mammalian cells by polycyclic aromatic hydrocarbons.

A system has been developed in which human breast cells activate chemical procarcinogens to mutagenic compounds. The degree of activation is quantitated by the estimation of induction of 6-thioguanine-resistant specific locus mutants in a cocultured Chinese hamster V-79 cell population which does not activate carcinogens. Both mammary stromal and parenchymal cells could activate the procarcinogen 7,12-dimethylbenz(a)anthracene. In addition, it is shown that the two mammary cell populations converted both 7,12-dimethylbenz(a)anthracene and benzo(a)pyrene to water-soluble metabolites. The stromal cells produced substantial amounts of glucuronic acid conjugates, but the parenchymal cells did not. Both cell types metabolize benzo(a)pyrene to the organic-soluble metabolites 9,10- and 7,8-dihydrodiol and both 9- and 3-hydroxybenzo(a)pyrene. These results suggest that the human breast may be a target for polycyclic aromatic hydrocarbon carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

A calibration protocol for serum-based secondary standards.

In this procedure, tentative calibration values are assigned to secondary standards by analysis of that material with the routinely used instrument calibrated by use of the former lot of material. Aliquots of serum from patients are then analyzed by the routine method and an appropriate calibration method in which primary standards are used. If the patient-sera results by both methods are the same, the assigned calibration value is assumed to be correct; if not, the calibration value of the secondary-standard material is adjusted to produce agreement in patient-sera results between the two methods. Thus, calibration of the routine method is linked via the calibration method to primary standards as the criterion of accuracy. This approach corrects for matrix interference of serum-based secondary standards. All that is expected for the secondary standard to obtain an accurate result for patient sera is to produce an analytical signal (irrespective of the origin of the signal) that is equivalent to the calibration value. Differences were significant between the secondary-standard calibration value we determined by this procedure and that assigned by the manufacturer for bilirubin, calcium, phosphorus, chloride, CO2, creatinine, glucose, sodium, uric acid, and commonly measured enzymes.

Autoanalysis↗

A suggested theory of the conventional tomographic imaging process.

An attempt is made to re-examine the well established theoretical basis of conventional tomography in the light of more detailed techniques being applied elsewhere in image analysis. Transfer function theory has been used to quantify the amount of edge detail reproduced by this process and the information in a tomogram is investigated in terms of edge detail associated with well resolved (unblurred) detail and also that associated with particular anatomical layers within the tomographed object, the theory has been used to define a cut plane thickness. A variety of different tube movements have been considered and calculated values of cut plane thickness are compared with those predicted by a simple geometric model. Besides the blurring associated with the tube movement the effect of x-ray focal spot, film-screen combination and also visual response of the observer have been included and their importance in the definition of cut plane thickness highlighted. One advantage of this approach appears to be the facility to quantify the performance of different tomographic tube movements and highlight the role of tomographic detail reproduced from body sections well removed from the cut plane.

Humans↗

Metabolism of carcinogenic 2-hydroxybenz.

The rates of metabolism of the carcinogenic 2-hydroxybenzo[a]pyrene (2-OH-B[a]P) and the non-carcinogenic 3- and 9-hydroxybenzo[a]pyrenes in cultured cell systems have been studied and compared. While 70-80% of the non-carcinogens are converted to water-soluble derivatives by hamster embryo fibroblasts in 24 h, carcinogenic 2-OH-B[a]P is metabolized at a slower rate (45% in 24 h), comparable to that for the parent hydrocarbon, benzo[a]pyrene (B[a]P). Analysis of extracellular organic solvent-soluble metabolites of 2-OH-B[a]P in cultured hamster embryo fibroblasts, using h.p.l.c., indicates the presence of a single major metabolite, which has been identified by mass spectroscopy as a dihydroxy derivative of B[a]P. At least one additional major organic solvent-soluble metabolite is formed in cultures of either mouse epidermal epithelial cells or human foreskin fibroblasts, indicating a different balance of metabolic pathways in these cell systems. The greater persistence of carcinogenic 2-OH-B[a]P in cells and its higher concentration in the cell cytoplasm compared with the non-carcinogenic phenols may be related to its relatively high biological activity. Differences in metabolism of 2-OH-B[a]P in several cultured cell systems indicate the importance of an appropriate choice of activating system in understanding the relationship between metabolism and carcinogenesis.

Animals↗

Metabolism and macromolecular binding of carcinogenic and noncarcinogenic metabolites of benzo(a)pyrene by hamster embryo cells.

The metabolism and macromolecular binding of four metabolites of benzo(a)pyrene in hamster embryo fibroblasts has been studied. Two noncarcinogenic phenolic derivatives, 3-hydroxybenz(a)pyrene and 9-hydroxybenzo(a)pyrene, are rapidly metabolized, primarily to their respective glucuronic acid conjugates and other H2O-soluble conjugates (78.4 to 80.8% of total radioactivity). Water-soluble conjugates were also formed from the carcinogenic phenol, 2-hydroxybenzo(a)pyrene, and from 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene, but in lower amounts (36.8 to 43.8% of total radioactivity. With each of the compounds, from 10 to 20% of the radioactivity was converted to ethyl acetate-soluble metabolites. The amount of unmetabolized 2-hydroxybenzo(a)pyrene recovered intracellularly was 20-fold higher than that recovered in incubations with the other phenols. Covalent binding to nuclear macromolecules was monitored after isopyknic separation. Binding of the three phenols tested was similar and was lower than the binding of benzo(a)pyrene to nuclear DNA, RNA, and protein. In contrast to the results with the monohydroxybenzo(a)pyrenes, high levels of covalent binding were observed with 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene; binding to DNA was 8-fold higher (315 pmol bound per mg DNA) than binding of benzo(a)pyrene to DNA.

Animals↗

Inverse correlation between species life span and capacity of cultured fibroblasts to metabolize polycyclic hydrocarbon carcinogens.

Many investigators have hypothesized that the aging process may result from an accumulation of DNA damage, and, if valid, this necessitates a means by which this accumulation can be related to the potential life span of an organism. Using an assay for cell-mediated mutagenesis, we have tested multiple diploid fibroblast strains from six mammalian species of widely differing life spans, and found a very good inverse correlation between species life span and ability to activate 7,12-dimethylbenz(a)anthracene (DMBA) to mutagenic forms. We have also found a very good inverse correlation between species life span and ability to activate DMBA to forms capable of covalent binding to DNA. Since the polycyclic hydrocarbon carcinogens such as DMBA and benzo(a)pyrene (BP) are chemically non-reactive in their native forms and must be metabolically activated by mixed-function oxidases to their biologically active forms, these data indicate that the capacity of fibroblasts to activate polycyclic hydrocarbon carcinogens to DNA-damaging forms is a species property related to potential life span. To determine the role of carcinogen metabolism in this phenomenon the capacity of diploid fibroblasts from eight mammalian species to convert BP and DMBA to water-soluble metabolites was then determined. This rate of conversion varies widely among different species and shows a very good inverse correlation with species life span. As a whole, these findings suggest that the ability of cultured cells to metabolize the polycyclic hydrocarbon carcinogens is related to species life span, and may be important in the occurrence of spontaneous cancer.

9,10-Dimethyl-1,2-benzanthracene↗