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Biomedical subjects

G J Dutton

Publications and source records attributed to G J Dutton.

At least 19 recordsLinked to original sources
PubMed2006

Infectivity and persistence of an outbreak strain of Salmonella enterica serotype Typhimurium DT160 for house sparrows (Passer domesticus) in New Zealand.

AIM: To examine the infective dose, incubation period and disease progression of an isolate of Salmonella enterica serotype Typhimurium definitive type 160 (DT160) originating from a naturally-infected house sparrow (Passer domesticus) during an outbreak of the disease in New Zealand. METHODS: Thirty-six house sparrows captured from the wild and free of Salmonella spp were divided into six groups of six birds, housed individually, and inoculated orally with phosphate buffered saline (PBS) or 10(1), 10(2), 10(3), 10(5), 2 x 10(8) colony forming units (cfu) of the outbreak strain of S. Typhimurium DT160. The birds were observed for 10 days for clinical signs and/or mortality, and faecal samples were collected to determine excretion of S. Typhimurium. The birds were euthanised 11 days post-inoculation (p.i.) and a wide range of tissue samples were collected for histopathological examination, and culture and typing of Salmonella spp. Macro-restriction profiling by pulsed-field gel electrophoresis (PFGE) using XbaI was performed for the epidemiological typing of S. Typhimurium DT160 isolates. RESULTS: Mortality in house sparrows inoculated with S. Typhimurium DT160 was dose-dependent, and 2/6 birds inoculated with 10(5) cfu and all six birds inoculated with 2 x 10(8) cfu died during the study. Infected sparrows displayed few clinical signs, apart from diarrhoea and/or polyuria, fluffed plumage, and sitting on the floor of the cage. Faecal excretion of DT160 occurred briefly in two birds inoculated with 10(2) cfu and four birds inoculated with 10(3) cfu, on most days in five birds inoculated with 10(5) cfu, and continuously in six birds inoculated with 2 x 10(8) cfu. DT160 was isolated from the livers of three birds which received 10(3) cfu, five birds dosed with 10(5) cfu, and all six birds given 2 x 10(8) cfu. Following necropsy, histopathological lesions similar to those seen in the natural disease were observed in the liver or spleen of three birds which received 10(3) cfu, and all birds dosed with > or =10(5) cfu. CONCLUSION: The results indicate that an isolate of S. Typhimurium DT60 originating from house sparrows in New Zealand is pathogenic to these birds and that the response is dose dependent. The persistence and excretion of the pathogen may last for at least 10 days. This confirms that sparrows infected with DT160 could be a source of infection to humans and other in-contact animals.

Animals↗
PubMed1983

The temporary postnatal decline in glucuronidation of certain phenols by rat liver.

A temporary but marked postnatal decline in UDP-glucuronosyltransferase activity occurs in homogenates and microsomes from rat liver. The profile of this trough and its time of occurrence (maximal over 13-16 days) are almost identical with the two substrates 2-aminophenol and 1-naphthol, whose rates of glucuronidation differ 10-fold. The trough is greatest with digitonin-activated preparations, least with fresh latent ('native') enzyme and intermediate when the native enzyme is treated with its specific activator UDP-N-acetylglucosamine (UDP-GlcNAc). Less detailed evidence supports similar conclusions with 4-nitrophenol as substrate. The trough is not due to the presence of an inhibitor of the transferase in rat liver at 15 days of age. Over the whole perinatal period, including the time of the trough, the enzyme in homogenates can be activated by UDP-GlcNAc; the microsomal enzyme is activated to a rather lesser degree perinatally, and evidence suggests this may be due to artefacts introduced during tissue fractionation. When the overall process of glucuronidation is studied in snips of intact liver offered high concentrations of the two different phenols, the trough is again evident over the same period as observed with broken cells, and of equal depth for both substrates. The infant rat is therefore probably less able to glucuronidate hepatically these phenols over the suckling or early weaning period than are the adult, late foetus or newborn, and may be especially incompetent at 13-16 days of age.

Aminophenols↗
PubMed1982

Liver snips. A simple, rapid and reproducible method for studying metabolism in small fragments of tissue, as applied to glucuronidation in rat liver.

A simple, rapid method is described of preparing intact cells as small (about 2mm) pieces of organized tissue capable of performing synthetic metabolic functions. It has been applied to the study of glucuronidation in rat liver. In this process, snips appear less damaged, more versatile and more active than tissue slices and yield results of reproducibility comparable with those with homogenates. From a comparison with the literature, snips glucuronidate the substrates employed at a rate much the same as in perfused preparations and some 30% less than the rate in isolated-hepatocyte suspensions; the advantages they offer in certain situations over these two techniques are discussed.

Aminophenols↗
PubMed1982

Interrelationship of carcinogen and glucocorticoid in perinatal enzyme induction.

Polycyclic aromatic hydrocarbons such as 3-methylcholanthrene can interrelate certain of their effects with those of glucocorticoid in the fetomaternal unit and the infant. We describe the induction by both classes of compounds in perinatal rat liver of enzymes that modify their biologic activity, and present further evidence for glucocorticoid-mimetic effects of 3-methylcholanthrene. We suggest that some degree of fetal teratogenicity and imprinting of postnatal events can arise from these mimetic effects, which should be taken into consideration along with the more direct perinatal toxicity of these mutagens.

Adrenalectomy↗
PubMed1979

The formation and distribution of bilirubin monoglucuronide and diglucuronide in rat liver slices.

1. Bilirubin conjugation in rat liver slices was reassessed by using analysis of ethyl anthranilate azopigments to estimate separately the formation of bilirubin mono- and di-glucuronides. 2. Conjugation in slices resembles the situation in vivo more closely than does microsomal conjugation, in that diglucuronide is formed in appreciable quantity. 3. Both bilirubin mono- and di-glucuronides were present in slices in approximately equal amounts, but the monoglucuronide was the major product found in the incubation medium. 4. These results are discussed in relation to recent theories on the relationship between bilirubin mono- and di-glucuronide formation in vivo.

Animals↗
PubMed1979

Differential stimulation of hepatic mono-oxygenase and glucuronidating systems in chick embryo and neonatal rat by glucocorticoids.

White Leghorn embryos infused with corticosterone precociously reproduced the hatching surges of hepatic UDPglucuronosyltransferase activity to 2-aminophenol, aminopyrine N-demethylase activity and cytochrome P-450 concentration. Onset of transferase activity followed that of the others by 48 h over hatching and on infusion. Competence of demethylase and transferase to respond to corticosterone appeared over days 12--14. Glucocorticoids are suggested as the natural triggers of both transferase and monooxygenase activities in chick and both processes may share a further control. Exposure of CD rat foetuses at 18 1/2 days to dexamethasone by maternal injection evoked precocious onset of transferase activity to 2-aminophenol but not to bilirubin, nor of demethylase activity or cytochrome P-450 content. Injection of hour-old or infant rats with dexamethasone did reproduce precociously onset of the three latter and stimulated the former. Competence for glucocorticoid response thus appeared before birth for transferase activity to 2-aminophenol and at birth for the others. Onset of transferase following hatching or glucocorticoid lagged behind that of demethylase or cytochrome P-450 by 48 h in chick embryo and 36 h in newborn and infant rats; only in foetal rat was response of transferase rapid to administered glucocorticoid.

Aminophenols↗
PubMed1977

Regulation of onset of development of UDP-glucuronosyltransferase activity towards o-aminophenol by glucocorticoids in late-foetal rat liver in utero.

1. A precocious development of UDP-glucuronosyltransferase activity (EC 2.4.1.17) towards o-aminophenol is demonstrated in 15-17 day foetal rat liver in utero after dexamethasone administration to the mother. 2. This stimulation of liver transferase activity in utero is directly proportional to the dose of dexamethasone infected. 3. Precocious development of transferase activity in utero can also be effected with the natural glucocorticoid cortisol by multiple injections of large amounts of this hormone into the mother. 4. Transferase activity towards o-aminophenolin foetal lung, kidney and upper alimentary tract can also be precociously stimulated by dexamethasone in 17-day foetuses in utero. 5. Natural development of hepatic transferase activity between days 18 and 20 of gestation is retarded after foetal hypophysectomy by decapitation in utero. 6. Overall glucuronidation of o-aminophenol, as observed in foetal rat liver, is also precociously stimulated by dexamethasone. 7. From this and from evidence previously presented we suggest that glucocorticoids, which are known to increase in rat foetuses between days 17 and 20 of gestation, trigger the normal development in utero of hepatic transferase activity towards o-aminophenol which occurs at that time. We also suggest that these hormones are responsible for the rise in activity of the enzyme in foetal lung, kidney and upper alimentary tract which occurs during the same gestational period.

Aniline Compounds↗
PubMed1977

Precocious development of uridine diphosphate glucuronosyltransferase activity during organ culture of foetal rat liver in the presence of glucocorticoids.

1. Precocious development of mammalian UDP-glucuronosyltransferase (EC 2.4.1.1.7) induced by endogenous compounds of known chemical composition is reported for the first time. 2. This development occurs in cultured explants of foetal rat liver when exposed to corticosteroids possessing a pregn-4'-ene structure and a hydroxy or an oxo group at C-11. 3. Explants from 14-day foetuses cultured for 3 days in a chemically defined medium containing dexamethasone exhibited transferase activities towards o-aminophenol within adult male values. Those liver transferase activities attained in utero by 17 days were still negligible. 4. Evidence from several approaches indicated that the explants required glucocorticoids for expression of the transferase, not for maintenance of viability. 5. Glucocorticoid-dependent stimulation of transferase activity required incorporation of L-[14C]leucine into protein, as judged from the pulsing of cultures with cycloheximide. 6. The relevance of these culture experiments to the situation in vivo is discussed.

Amino Acids↗