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Biomedical subjects

R D Gill

Publications and source records attributed to R D Gill.

31 records · Page 2Linked to original sources
PubMed1984

The action of various hormones and metabolites upon glucose production by isolated hepatocytes from lactating and non-lactating ewes.

Glucose production was measured from hepatocytes isolated from the livers of non-mated, 20- and 50-day lactating ewes (4 animals/group) in the presence and absence of various substrates and hormones. The output of glucose was reduced at peak lactation (20-day) compared to both the unmated (P less than 0.05) and 50-day lactating groups (P less than 0.05). There was no significant difference in glucose production between the unmated and 50-day lactating groups. In the presence of glucagon (1 uM), glucose production was stimulated above control levels (P less than 0.05). However, insulin (1 uM) did not reduce glucose production compared to controls, while the effect of insulin and glucagon combined (1:1 uM) was not significantly higher than control values. Propionate, acetate and butyrate (10 mM) significantly increased glucose output above control values (P less than 0.05), in all three groups of animals. Glucose output was relatively unchanged in the presence of alanine and glutamate (10 mM), while fructose supplementation (10 mM) resulted in a significantly reduced glucose output compared to the controls (P less than 0.05).

Animals↗
PubMed1982

Hepatic receptors for insulin and glucagon in relation to plasma hormones and metabolites in pregnant and unmated ewes.

Glucagon and insulin receptors were examined in relation to plasma concentrations hormones and metabolites in unmated and in 110- and 140-day pregnant ewes (four animals per group). The concentrations of insulin, growth hormone and non-esterified fatty acids in the circulation, together with the maintenance of body weight, suggested that the animals were in energy surplus. When compared with the unmated group the binding insulin to isolated hepatocytes increased by 110 days of pregnancy, attaining statistical significance (P less than 0.02) after 140 days. Conversely, glucagon binding was reduced by 110 days of pregnancy, also attaining statistical significance (p less than 0.02) after 140 days. The changes in both insulin and glucagon binding were primarily due to changes in the number of receptors on each hepatocyte, although some fluctuation in receptor affinity were also found. These observations suggested that the number of hepatic insulin and glucagon receptors are altered during the metabolic demands of pregnancy in sheep, but unlike the changes reported during lactation in the ewe and restricted energy intake in the goat, they are not related either to energy deficit or to changes in the concentration on insulin, and probably of glucagon, in the circulation.

Animals↗
PubMed1981

Insulin and glucagon binding to hepatocytes in relation to circulating hormones and metabolites in goats maintained on different diets.

Insulin and glucagon receptors were measured on hepatocytes in relation to circulating hormones (insulin, glucagon and growth hormone) and metabolites (non-esterified fatty acids, volatile fatty acids, glucose, total lipids, urea and alpha-amino nitrogen), in twelve, two-year old, castrated male goats, fed rations of different composition and dietary energy. The goats were separated into four groups; group 1 was fed a restricted ration of 600 g clover hay/day, group 2 a ration high in carbohydrate (rolled barley), group 3 a ration high in fat (protected tallow) and group 4 a ration high in protein (fish meal). Rations in groups 2 - 4 were fed at 1300 g/day supplemented with 600 g of clover hay. The binding of insulin to hepatocyte receptors was increased by restricting dietary intake when compared to the high energy intake groups (p less than 0.01). There was no significant difference between the insulin binding of groups 2 -4. Glucagon receptor binding was increased on the high protein diet in comparison with th ration high in carbohydrate (p less than 0.05) or in fat (p less than 0.01). The glucagon binding was reduced by restricting feed intake when compared wih feeding high protein (p less than 0.02), but slightly increased when compared with feeding diets high in both carbohydrate or fat (p less than 0.02). There was no significant difference between the high carbohydrate or high fat fed groups. These changes in hormone receptors were accompanied by inverse changes in plasma insulin and glucagon.

Animals↗
PubMed1980

Properties of insulin and glucagon receptors on sheep hepatocytes: a comparison of hormone binding and plasma hormones and metabolites in lactating and non-lactating ewes.

A method is described for the isolation of viable hepatocytes from sheep liver. The characteristics of insulin and glucagon binding to the cells were investigated by the use of mono-iodinated hormone, and from these data the optimum in-vitro incubation conditions for hormone-receptor binding were established. Glucagon and insulin receptors were examined in relation to plasma concentrations of hormones and metabolites in non-mated, and 20- and 50-day-lactating ewes (six animals/group). Measurements of insulin, growth hormone and non-esterified fatty acids in the circulation, together with a fall in body weight, suggested that a peak lactation (20 days) the ewes were in energy-deficit and were mobilizing body tissue. The percentage binding of insulin was higher in hepatocytes after 50 days of lactation when compared with that in both the unmated (P less than 0.05) and 20 day-lactating animals. No changes in insulin binding were found between the unmated and 20-day-lactating groups. Glucagon binding was reduced in the 20- (P less than 0.02) and increased in the 50-day-lactating group (P less than 0.001) when compared with the unmated control animals. The binding of glucagon was higher at 50 days as compared with 20 days of lactation (P less than 0.001). The changes in insulin binding resulted primarily from altered receptor numbers whereas changes in the binding of glucagon were due to alterations in both receptor numbers and affinity. Our results indicated that the binding of insulin and glucagon to isolated hepatocytes was altered during lactation in sheep and that these changes might modulate the sensitivity of the cells to the actions of the hormones.

Animals↗
PubMed1976

A simple cooling circuit for topical cardiac hypothermia.

Rapid uniform cooling of the heart is the most important requirement of any method using local hypothermia for protection of the myocardium during open intracardiac surgery. We report the construction and operation of a recirculation cooling circuit comprising a reservoir, pump, and heat-exchanger for this purpose. It is operated by the perfusionist and can deliver up to 1 litre of fluid per minute at 4 degrees C into the pericardium or interior of the heart. Advantages of the system include rapid cooling of the myocardium, simplicity of operation, and applicability to all routine cardiac surgical procedures.

Aortic Valve↗
PubMed1975

Performance of heat exchangers used in whole body perfusion circuits.

The performance of some commonly used heat exchangers has been investigated with particular reference to the effect of varying the water flow. The results demonstrate that there is considerable variation in the performance of most units when the water flow is changed. It is suggested that more information should be provided by the manufacturers of heat exchangers and that there should be a supply of water in cardiothoracic theatres at a sufficient pressure to allow the full performance of the heat exchangers to be realized.

Blood Flow Velocity↗
PubMedDate not supplied

Non-response models for the analysis of non-monotone ignorable missing data.

We discuss a new class of ignorable non-monotone missing data models-the randomized monotone missingness (RMM) models. We argue that the RMM models represent the most general plausible physical mechanism for generating non-monotone ignorable data. We show that there exists ignorable missing data processes that are not RMM. We argue that it may therefore be inappropriate to analyse non-monotone missing data under the assumption that the missingness mechanism is ignorable, if a statistical test has rejected the hypothesis that the missing data process is RMM representable. We use RMM models to analyse data from a case-control study of the effects of radiation on breast cancer.

Algorithms↗
PubMedDate not supplied

Characterization of DNA adducts derived from (+/- )-trans-3,4-dihydroxy-anti-1,2-epoxy-1,2,3,4- tetrahydrodibenz[a,j]anthracene and (+/- )-7-methyl-trans-3,4-dihydroxy- anti-1,2-epoxy-1,2,3,4-tetrahydrodibenz[a,j]anthracene.

Structural characterizations of the DNA adducts derived from reaction of the racemic bay region anti-diol epoxides of dibenz[a,j]anthracene and 7-methyldibenz[a,j]anthracene with calf thymus DNA are presented. Quantities of adducts necessary for spectroscopic characterization were obtained from reactions of the respective diol epoxides with individual deoxyribonucleotides. Both hydrocarbon diol epoxides showed similar adduct profiles upon reaction with calf thymus DNA in vitro which were composed mainly of three deoxyguanosine and four deoxyadenosine adducts. No significant modification of pyrimidine bases in DNA was detected with either of the diol epoxides. Approximately 3 times more deoxyguanosine than deoxyadenosine residues in the DNA were found to be modified by both diol epoxides. The DNA reactions showed very similar stereo- and enantioselectivities with both diol epoxides. The stereochemistries of addition of the purine bases to the diol epoxides were determined from analysis of the NMR spectra of individual adducts. The predominant adducts formed were products of trans addition of the exocyclic amino group of purines to the diol epoxides. The enantiomeric nature of the various adducts was determined from reaction of the individual deoxyribonucleotides with the pure (+)-anti-diol epoxide of dibenz[a,j]anthracene. The major deoxyguanosine and deoxyadenosine adducts from reactions with DNA were found to arise from the (+)-enantiomer of both hydrocarbon diol epoxides. The high reactivities of both diol epoxides (24-38%) with DNA in solution are consistent with the high tumor-initiating activity exhibited by the diol epoxide of dibenz[a,j]anthracene relative to the parent hydrocarbon.

Animals↗
PubMedDate not supplied

Characterization of covalently modified deoxyribonucleosides formed from dibenz[a,j]anthracene in primary cultures of mouse keratinocytes.

Identification of various deoxyribonucleoside adducts formed in primary cultures of mouse keratinocytes exposed to dibenz[a,j]anthracene (DB[a,j]A) is presented. A preliminary analysis of the DNA adducts formed from 7-methyldibenz[a,j]anthracene (7MeDB[a,j]A) also is presented. Cultures of keratinocytes obtained from dorsal skins of female SENCAR mice were exposed to 0.5 microgram of tritium-labeled hydrocarbons/mL of medium for 24 h. The total DNA binding was 2.23 +/- 0.54 and 5.28 +/- 0.97 pmol of hydrocarbon/mg of DNA for DB[a,j]A and 7MeDB[a,j]A, respectively. These binding values represented the radioactivity associated with the modified deoxyribonucleosides separated from the normal deoxyribonucleosides on Sephadex LH-20 columns following enzymatic digestion of isolated DNA. Treatment of keratinocytes with DB[a,j]A produced adduct peaks corresponding to marker adducts derived from trans addition of both deoxyguanosine as well as deoxyadenosine residues to the (+) enantiomer of the anti-diol epoxide where the deoxyadenosine adducts were predominant. In addition, DNA adduct peaks corresponding to markers of trans and cis addition, respectively, of deoxyguanosine and deoxyadenosine to the (+)-syn-diol epoxide were also noted in these chromatograms. A major DNA adduct in cells exposed to DB[a,j]A was tentatively identified as resulting from the addition of deoxyadenosine to DB[a,j]A-5,6-oxide. Several other later eluting DNA adduct peaks, not corresponding to any of the marker adducts, were also present in these chromatograms. In comparison, when cells were exposed to the more biologically potent 7-methyl analogue, at least 12 DNA adduct peaks were consistently observed in HPLC chromatograms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Construction of Escherichia coli vectors containing deoxyadenosine and deoxyguanosine adducts from (+)-anti-dibenz[a,j]anthracene diol epoxide at a defined site.

Dibenz[a,j]anthracene (DB[a,j]A) is a carcinogenic polycylic aromatic hydrocarbon, which is metabolically activated through the formation of bay region diol epoxides. Site-specifically modified M13mp19-based vectors containing a single (+)-anti-dibenz[a,j] anthracene diol epoxide [(+)-anti-DB[a,j[A-DE]-deoxyguanosine (dGuo) or -deoxyadenosine (dAdo) adduct were constructed. Four-base oligonucleotides, 5'-HOTGCA-3' and 5'-HOCATG-3', corresponding to the central four base pairs in the PstI and SphI restriction endonuclease sites, respectively, in the multiple cloning region of M13mp19, were reacted in solution with (+/-)-anti-DB[a,j]A-DE. The resulting adducted oligonucleotides were separated and purified using reverse-phase HPLC. Several different singly adducted oligonucleotides were isolated, consisting of the various cis and trans addition products of the (+) and (-) enantiomers of the diol epoxide bound to dGuo or dAdo in the oligonucleotides. 5'-HOTGCA-3' containing the (+)-anti-DB[a,j]A-trans-N2-dGuo adduct [T(DB[a,j]A-N2)GCA] and 5'-HOCATG-3' containing the (+)-anti-DB[a,j]A-trans-N6-dAdo adduct [C(DB[a,j]A-N6)ATG) were selected for subsequent ligation into M13mp19 vectors that had been constructed with a corresponding four base gap in the minus strand. Both unmodified and adducted oligonucleotides were successfully ligated into the M13mp19 vectors, [yields: unmodified -TGCA-M13mp19 (approximately 32%) and -CATG- M13mp19 (approximately 42%); adducted T(DB[a,j]A-N2)GCA-M13mp19 (approximately 13%) and C(DB[a,j]A-N6)ATG-M13mp19 (approximately 12%)]. The dAdo adduct-containing vector was characterized. The presence of a dAdo-DNA adduct at the recognition site of SphI inhibited restriction by SphI.(ABSTRACT TRUNCATED AT 250 WORDS)

Benz(a)Anthracenes↗