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Biomedical subjects

S A Gibson

Publications and source records attributed to S A Gibson.

At least 19 recordsLinked to original sources
PubMed2000

Transient high temperatures in mantle plume heads inferred from magnesian olivines in Phanerozoic picrites.

Both scaled laboratory experiments and numerical models of terrestrial mantle plumes produce 'balloon-on-a-string' structures, with a bulbous head followed by a stem-like tail. Discussions have focused on whether their initial upwelling heads are hotter than the tails or cooler, as a result of entrainment of ambient mantle during ascent, and also on whether initial plume upwelling is a newtonian or non-newtonian process. The temperature of the mantle delivered to the base of the lithosphere is a critical parameter in such debates. Dry continental magmas can normally contribute little to this topic because their hottest (ultramafic) examples can be expected to be trapped, owing to their density, beneath the Moho. Here we report a rare case in which olivine (with 93.3% forsterite; Mg2SiO4) phenocrysts, precipitated from an unerupted komatiitic melt (approximately 24% MgO) of the Tristan mantle plume head 132 Myr ago, were carried to upper-crust levels in northwest Namibia by less Mg-rich (9.6-18.5% MgO) magmas. We infer that the hidden melt, generated when the plume impinged on the base of the lithosphere, originated in the mantle with a potential temperature of approximately 1,700 degrees C. This is approximately 400 degrees C above ambient and much hotter than the temperatures previously calculated for steady-state Phanerozoic mantle plumes. Published data show that the same conclusion can be reached for the initial Iceland and Galapagos plumes.

Journal Article↗
PubMed2000

Breakfast cereal consumption in young children: associations with non-milk extrinsic sugars and caries experience: further analysis of data from the UK National Diet and Nutrition Survey of children aged 1.5-4.5 years.

OBJECTIVE: This study examined the relationship between breakfast cereal consumption and non-milk extrinsic sugars (NMES) intake and the possible implications of this for caries in preschool children. METHODS: Data from the 1995 UK National Diet and Nutrition Survey (NDNS) of children aged 1.5-4.5 years were reanalysed. Four-day weighed food records and dental examinations were available on 1450 children living in private households in Britain. Children were classified by tertiles (age-adjusted) according to the proportion of energy derived from breakfast cereals, and the amount of NME sugar from cereals. There were no significant differences in social class background between any of the groups. RESULTS: Children with diets high in breakfast cereals as a proportion of total energy (top third) had lower proportional intakes of NMES, compared with low consumers of cereals (lowest third). Consumption of sweetened cereals was positively associated with NMES intake. However, caries experience was unrelated to breakfast cereal consumption, whether presweetened or not. CONCLUSIONS: Although presweetened cereals are relatively high in NMES, their cariogenic potential is probably minimal in the circumstances in which they are normally consumed.

Chi-Square Distribution↗
PubMed2000

Associations between energy density and macronutrient composition in the diets of pre-school children: sugars vs. starch.

OBJECTIVE: To investigate the associations between energy density (ED) and macronutrient composition in the National Diet and Nutrition Survey of Children aged 1(1/2)-4(1/2) y, hypothesizing that high-ED diets tend to be high in sugars as well as fat. DESIGN: Further analysis of data from a cross-sectional dietary survey of 1675 children with complete 4-day weighed dietary records. Differences in diet composition and food choice between children with diets of high, medium and low ED (defined as kJ/g of all food and drink) were identified. The possibility of confounding by water, or by soft drinks, was also explored in age-adjusted correlations. RESULTS: High-ED diets (>3.7 kJ/g of total diet) were proportionately richer in fat and lower in carbohydrate, compared with diets of low ED (<2.9 kJ/g). In contrast to the hypothesis, high-ED diets were found to be proportionately lower in sugars, and higher in starch. Children with high-ED diets consumed more of a whole range of foods: meat, eggs, potatoes, cereal products, confectionery, sugar/preserves and savoury snacks, but consumed less soft drinks, water and fruit. CONCLUSION: The inverse relationship observed between sugars and energy density may be partly attributable to the reciprocal relationship between sugars and fat, expressed as a proportion of energy. It may also reflect developing preferences in young childhood for a more adult-type, energy-dense, diet. Further work is required to verify ED/macronutrient relationships in other age groups, as the results have potential implications for obesity prevention and for food product development.

Child↗
PubMed2000

Induction of apoptosis in oral cancer cells by an anti-bcl-2 ribozyme delivered by an adenovirus vector.

Human oral cancer cells may have any of several genetic changes, but the role of the bcl-2 oncogene is relatively unexplored. To find out if this gene plays a significant role and whether it could act as a target for gene therapy of oral cancer, we have examined the effects of an anti-bcl-2 ribozyme on the phenotype of oral cancer cells. A hammer-head ribozyme was designed to cleave the bcl-2 transcript after nucleotide 279 and was confirmed to be effective against a synthetic bcl-2 transcript. A gene encoding the ribozyme was cloned into an adenovirus vector and transferred to the human oral cancer cell lines 686LN, 1483, and Tu183. Over a 6-day period, the growth of each cancer cell line was reduced, whereas growth of the fibroblast cell line FS7 was less inhibited. Inhibition of the oral cancer cells could be attributed to apoptosis, as indicated by the detection of histone-associated DNA fragments in an immunoassay. Northern blots showed no detectable reduction in the level of bcl-2 mRNA of Tu183 cells, but Western blots showed a reduction of Bcl-2 protein at 24 h after infection with the ribozyme-expressing adenovirus vector. The results imply that (a) expression of the bcl-2 oncogene is necessary for the survival of oral cancer cells, (b) the bcl-2 gene transcript presents a target for gene therapy by ribozymes, and (c) an adenovirus vector is a suitable method for transfection of the ribozyme-expressing gene.

Adenoviridae↗
PubMed1999

Iron intake and iron status of preschool children: associations with breakfast cereals, vitamin C and meat.

OBJECTIVE: To examine associations between breakfast cereal consumption and iron status and identify dietary patterns that might improve iron status in this vulnerable group. DESIGN: Analysis of data from the UK National Diet and Nutrition Survey (NDNS) of children aged 1.5-4.5 years, including dietary intakes calculated from 4-day weighed records. SUBJECTS: Data were used from 904 children with haematological measurements, excluding those taking iron supplements; 20% had low iron stores (ferritin < 10 microgl-1) while 8% were anaemic (Hb < 11 g dl-1). RESULTS: High cereal consumers had significantly higher iron intakes than low cereal consumers (classified by tertiles) but the 10% difference in mean ferritin levels was not significant (P= 0.067). Lower intakes of vitamin C and meat among high consumers of cereal may have diluted the impact of cereal iron on iron status. When children were reclassified according to their intakes of vitamin C and iron from meat and breakfast cereals, the group with high (above median) intakes of two or more factors had a higher mean haemoglobin (Hb) level and a lower prevalence of anaemia compared with the group with low (below median) intakes of all three dietary constituents. CONCLUSIONS: Nutritional advice that aims to improve iron status should emphasize not only rich sources of iron but also factors that may enhance or inhibit absorption. Strategies to optimize iron status in this vulnerable age group include consuming an iron-fortified breakfast cereal, vitamin C-rich fruit or drink at breakfast, and avoiding tea with (or after) meals.

Anemia, Iron-Deficiency↗
PubMed1998

Antiseptics: a forgotten weapon in the control of antibiotic resistant bacteria in hospital and community settings?

The aim of this study was to ascertain the activity of a selection of widely-used antiseptic/disinfectant agents against antibiotic resistant bacteria and strains isolated from patients infected with clinically significant species. Four antiseptic agents (Dettol, Dettol Hospital Concentrate, Savlon and Betadine) were tested against Staphylococcus aureus, Methicillin Resistant S. aureus (MRSA), Enterococcus hirae, Vancomicin Resistant Enterococcus sp (VRE), Escherichia coli and E. coli 0157. The antiseptics were applied at recommended use dilutions and at a half and a quarter of those concentrations in a standard suspension test (EST). Organic material was added to mimic the presence of blood, protein and other such contaminants to be found in the clinical situation. All antiseptics tested were effective against both the antibiotic sensitive and antibiotic resistant strains of S. aureus and E. hirae as well as normal and clinical strains of E. coli at recommended concentrations. All but Betadine were also effective against the antibiotic resistant bacteria at a half and a quarter of normal concentration. The iodine containing antiseptic, however, failed the test against MRSA at a half normal concentration and showed virtually no activity against MRSA at a quarter normal concentration.

Anti-Infective Agents, Local↗
PubMed1997

Ribozymes. Their functions and strategies for their use.

The ability to alter genes in order to regulate their expression has become an undeniable reality. This can be performed in vitro and in cells, and the possibility of treating diseases and even preventing them now exists through such gene manipulation. A particularly intriguing form of manipulation that has been investigated for just over a decade is one that involves the use of ribozymes. These are short segments of RNA that form complementary base-pairing with mRNA. However, it is their enzymatic properties that set them apart from other antisense RNA molecules and allow them to cleave and destroy mRNA in a very specific manner. The ribozyme then dissociates from the cleaved substrate RNa, and repeatedly hybridizes to and cleaves additional substrate RNA molecules. Problems being addressed as this technology evolves involve optimization of ribozyme:substrate binding efficiencies and their effective transmission into cells. This article points out the origin of ribozymes, analyzes and summarizes the current strategies for designing ribozymes, and outlines a basic procedure for ribozyme development.

Animals↗
PubMed1997

Non-milk extrinsic sugars in the diets of pre-school children: association with intakes of micronutrients, energy, fat and NSP.

Concern has been expressed that high dietary concentrations of non-milk extrinsic sugars (NMES) may potentially compromise nutrient intakes in population groups with low energy intakes (Department of Health, 1991). The objective of the present study was to examine data from the National Diet and Nutrition Survey of Children Aged 1.5 to 4.5 years (Gregory et al. 1995) for evidence of an inverse association between energy from NMES and micronutrient intakes, and if possible to quantify a level of NMES-energy at which micronutrient intakes may, theoretically, be compromised. Energy and nutrient intakes were compared across quintiles of NMES-energy for boys (n 848) and girls (n 827). As the concentration of NMES increased, energy intake rose (in boys only) while percentage energy from fat fell from 40 to 32% across quintiles 1 to 5. Intakes of most micronutrients also fell, while intakes of vitamin C rose. Mean intakes of most micronutrients (Ca, thiamin, riboflavin, niacin, folate and vitamin C) were adequate in comparison with dietary reference values. However, intakes of Fe, Zn and vitamin D were low at all levels of NMES-energy and fell below the estimated average requirement for Fe and Zn for NMES concentrations exceeding 24% of energy. Lower Intakes of milk, meat, bread and vegetables, and higher intakes of fruit juice largely explain the observed trends in micronutrient intake. It is concluded that the inverse association of NMES with micronutrient intakes is of most significance for the 20% of children with diets highest in NMES. However, further work is required to establish whether the associations observed have biological significance with regard to micronutrient status.

Animals↗
PubMed1996

Are high-fat, high-sugar foods and diets conducive to obesity?

Restriction of both dietary fat and extrinsic sugars is standard advice for weight reduction. It has been suggested that foods, and diets, that combine high levels of sugars and fat particularly contribute to overconsumption. Weighed dietary data on 1087 men and 1110 women aged 16-64 who took part in the Dietary and Nutritional Survey of British Adults were examined for evidence of this hypothesis. Consumption of the main sugary fatty foods (cakes, biscuits, confectionery and puddings) averaged 12% of energy for men, 14.9% for women. Intake of these foods (as a proportion of total energy) was inversely related to BMI (adjusted for age and smoking). After exclusion of the substantial number who were dieting or unwell or who may have under-reported their intakes, the association remained significant only in men. Consumption of sugary fatty foods showed a positive association with intakes of fibre, a negative association with vegetables and no relationship with percentage of energy from fat. For the investigation of diet composition, men and women were divided into four groups, high or low in extrinsic sugars energy (cut point 15%) and fat energy (cut point 40%). For men consuming high fat diets (> 40% energy) mean BMI was higher in the low sugar group. After exclusion of dieters and unwell, men with low sugar intakes still had a higher mean BMI than men with high sugar intakes. BMI and extrinsic sugars energy were still negatively but weakly correlated (r = -0.10; P < 0.05) after adjusting for age, smoking, energy, fat intake, and dieting/under-reporting. In conclusion, there is little evidence in this cross-sectional survey that either sugary fatty foods, or diets high in sugars, are associated with obesity. Rather, sugars appear to have a weak negative association with BMI that is not totally explained by confounders such as dieting, under-reporting or the inverse correlation between energy from sugars and fat.

Adolescent↗
PubMed1995

Breakfast cereal consumption patterns and nutrient intakes of British schoolchildren.

Breakfast cereals are nutrient-dense foods that are also low in fat. They could theoretically contribute to lowering the percentage energy from fat in the diet whilst enhancing the intake of certain nutrients. This project is based on a further analysis of dietary data (seven day weighed intakes) from 2705 British schoolchildren (DoH, 1989) and examines the relationship between breakfast cereal consumption and total daily nutrient intakes. The children were grouped according to amount of cereal consumed per day (none; less than 20 g; 20-40 g; over 40 g) and results examined for each age group (10-11 and 14-15 years) in boys and girls separately. For the nutrients examined there was a highly significant and graded increase in vitamin and mineral intake with increasing cereal consumption and a simultaneous reduction in energy from fat from 39-40% amongst non-consumers to 36-37% among children consuming a portion of cereal or more per day. Body mass index tended to be lower in the frequent breakfast cereal eaters. In conclusion, children who eat breakfast cereal tend to have more desirable nutrient intakes than those who do not.

Adolescent↗
PubMed1994

Confocal laser scanning microscopy of calcified bioprosthetic heart valves.

Calcification of bioprosthetic heart valves is a major factor limiting their long-term function. Current methods of microscopic examination of calcific deposits require dehydration and processing of the leaflet material, e.g. wax embedding, sectioning, gold coating. Confocal laser scanning microscopy is a new technique which allows serial optical sectioning of thick biological specimens in their normal hydrated state. The current study has examined bovine pericardium and porcine aortic valve materials calcified in vitro under static and dynamic conditions. A series of clinical explants of bovine pericardial and porcine aortic valve types has also been examined. The calcium-specific stain, Alizarin Red S, has been used as a fluorescent marker for calcium deposits. Fluorescent images, generated by Argon ion laser light at 488nm, have been obtained at varying depths into samples. These have been reconstructed to demonstrate the relationship between calcium deposits and autofluorescent collagen fibers. The patterns of calcification were similar in both in vitro and explant valve material. The calcification was of three main patterns: calcium depositing longitudinally on collagen fiber bundles; calcium forming a banded pattern perpendicular to the fiber direction and large, dense, focal deposits obliterating the underlying collagen structure. Involvement of collagen fibers in the calcification pattern was a consistent finding in all sample types. The method is a useful addition to the tools available for study of calcification processes. The potential exists for three-dimensional reconstruction of leaflet architecture and its inter-relationship with calcium deposition, in a normally hydrated state.

Adult↗
PubMed1993

Role of electron-donating cosubstrates in the anaerobic biotransformation of chlorophenoxyacetates to chlorophenols by a bacterial consortium enriched on phenoxyacetate.

A bacterial consortium that anaerobically mineralized phenoxyacetate, with transient production of phenol as an intermediate, was obtained from a methanogenic aquifer site near the Norman, OK municipal landfill. This consortium was able to convert the eight halogenated chlorophenoxyacetates tested to the corresponding chlorophenols. The chlorophenols were not subsequently metabolized. The addition of reduced substrates increased the rate of degradation of all chlorophenoxyacetates, with 78% of mono- and di-chlorinated substrates being transformed to chlorophenols in butyrate-amended cultures, compared to less than 37% transformed in unsupplemented cultures. Butyrate increased the transformation of 2,4,5-trichlorophenoxyacetate from 10% to 20%. An experiment evaluating the effects of several compounds on the side-chain cleavage reaction of 3-chlorophenoxyacetate showed that addition of compounds which readily act as hydrogen donors (butyrate, crotonate, ethanol, propionate, and hydrogen) resulted in 2 to 5 times the amount of 3-chlorophenoxyacetate transformed compared to controls with no amendment, formate had a slight stimulatory effect, and acetate and methanol had no effect. Butyrate addition also increased the rate of phenoxyacetate degradation, resulting in transient phenol accumulation not observed in butyrate-unamended controls. These results support the hypothesis that the side-chain cleavage of phenoxyacetate is a reductive process that is stimulated by the oxidation of reduced cosubstrates.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1990

Anaerobic biodegradation of 2,4,5-trichlorophenoxyacetic Acid in samples from a methanogenic aquifer: stimulation by short-chain organic acids and alcohols.

The herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) was dehalogenated in samples from a methanogenic aquifer to form 2,4- and 2,5-dichlorophenoxyacetic acids as the first detected intermediates. Further incubation of the aquifer slurries resulted in the formation of several intermediates including monochlorophenoxyacetic acids, di- and monochlorophenols, as well as phenol. No transformation of the parent substrate or production of intermediates was detected in autoclaved controls. The pattern of intermediate formation suggested that the anaerobic degradation of 2,4,5-T proceeded by a series of sequential dehalogenation steps with side-chain cleavage reactions occurring at some point before ring cleavage. The addition of short-chain organic acids or alcohols stimulated the onset and rate of 2,4,5-T dehalogenation and decreased the amount of parent substrate still detectable as halogenated intermediates at the end of the experiment. Sulfate addition had the opposite effect on dehalogenation regardless of whether supplemental carbon was added to the aquifer slurries. The inhibitory effect of sulfate on dehalogenation could sometimes be relieved with molybdate, although this effect seemed to be related to the supplemental carbon compound that was used.

Journal Article↗
PubMed1989

Significance of microflora in proteolysis in the colon.

Protease activities in human ileal effluent and feces were compared by using a variety of native and diazotized protein substrates. In many cases the diazotized proteins had altered susceptibilities to hydrolysis compared with the native proteins. Proteolytic activity was significantly greater than (P less than 0.001) in small intestinal effluent than in feces (319 +/- 45 and 11 +/- 6 mg of azocasein hydrolyzed per h per g, respectively). Moreover, fecal proteolysis was qualitatively different in that ileal effluent did not hydrolyze the highly globular protein bovine serum albumin, whereas all fecal samples tested degraded this substrate. Inhibition experiments provided further evidence that fecal protease activity differed from that in the small intestine. Physical disruption of fecal bacteria released large quantities of proteases, indicating that the lysis of bacteria in the colon may contribute to the extracellular proteolytic activity in feces. Protease inhibition studies with washed fecal bacteria showed that they produced serine, cystine, and metalloproteases, and experiments with synthetic p-nitroanilide substrates indicated that low levels of trypsin- and chymotrypsin-like activities were associated with whole cells. An elastase-like enzyme was bound to the outer membranes of some fecal bacteria.

Bacteria↗
PubMed1988

Studies on the proteolytic activity of Bacteroides fragilis.

The proteolytic activity of the intestinal bacterium Bacteroides fragilis NCDO 2217 was cell-bound during exponential growth, but was progressively released from the cells in stationary phase. Proteins hydrolysed included casein, trypsin, chymotrypsin, azocasein and the proteins in azosoya bean flour. Collagen, azocoll, elastin, gelatin, ovalbumin and bovine serum albumin were either weakly degraded or completely refractory to proteolysis. Arylamidase activity was exhibited against leucine p-nitroanilide (LPNA), leucine beta-naphthylamide, glycyl-proline p-nitroanilide and valyl-alanine p-nitroanilide. The bacterium grew with ammonia, peptone or casein as sole nitrogen source. Azocasein- and LPNA-hydrolysing activities were consistently higher when grown on casein. Cell-bound protease activity increased concomitantly with growth rate in both carbon- and nitrogen-limited continuous culture. Leucine arylamidase activity was also growth-rate-dependent, being 3-fold greater at D = 0.18 h-1 compared to D = 0.03 h-1. Extracellular proteolytic activity was only detected at low growth rates, accounting for about 25% of total protease activity.

Aminopeptidases↗
PubMed1988

Characterization of proteases formed by Bacteroides fragilis.

Bacteroides fragilis NCDO 2217 produced three major proteases, P1, P2 and P3 of estimated molecular masses 73, 52 and 34 kDa respectively. Protease P1 weakly hydrolysed azocasein but strongly hydrolysed valyl-alanine p-nitroanilide (VAPNA), glycyl-proline p-nitroanilide (GPRPNA), and to a lesser extent leucine p-nitroanilide (LPNA), indicating it to be an exopeptidase. Proteases P2 and P3 hydrolysed only azocasein and LPNA. The high protease:arylamidase ratios of these enzymes indicated that they were probably endopeptidases. Experiments with protease inhibitors suggested that P1 and P2 had characteristics of serine and metalloproteases respectively and that P3 was a cysteine protease. The proteolytic activity of whole cells was stimulated by divalent metal ions such as Mn2+, Ca2+ and Mg2+, but was strongly inhibited (about 95%) by Cu2+ and Zn2+. The temperature optimum for protein hydrolysis was 43 degrees C. Proteolysis was temperature sensitive, however (90% reduction at 60 degrees C) and was maximal at alkaline pH, with two broad peaks at pH 7.9 and pH 8.8. Cell fractionation showed that P1 was located intracellularly and in the periplasm, whereas P2 and P3 were largely associated with the outer membrane. Release of the membrane-bound proteases by treatment with 1 M-NaCl suggested that ionic interactions were involved in the association of these enzymes with the membranes.

Aminopeptidases↗
PubMed1988

Contribution of the microflora to proteolysis in the human large intestine.

Protease activities in human ileal effluent were approximately 20-fold greater than in normal faeces. Comparative studies with faeces from a person who did not have a pancreas suggested that a substantial proportion of the proteolytic activity in normal faeces was of bacterial origin. Thimerosal, iodoacetate, EDTA and cysteine significantly inhibited proteolysis in faeces, but not in small intestinal contents, showing that cysteine and metalloproteases were produced by bacteria in the large gut. These results, together with results from studies using p-nitroanilide substrates, demonstrated that faecal proteolysis was both qualitatively and quantitatively different from that in the small intestine. Studies with pure cultures of proteolytic gut bacteria indicated that the cell-bound proteases of Bacteroides fragilis-type organisms were likely to contribute significantly towards proteolytic activity associated with the washed cell fraction and washed particulate fraction of faeces. Extracellular proteases were formed by Streptococcus faecalis ST6, Propionibacterium acnes P6, Clostridium perfringens C16, Cl. bifermentans C21 and Cl. sporogenes C25. Inhibition results suggested that these bacteria, and similar organisms, may be partly responsible for the extracellular proteolytic activity found in the cell-free supernatant fraction of faeces.

Aminopeptidases↗