Biomedical subjects

Gareth Denyer

Publications and source records attributed to Gareth Denyer.

8 recordsLinked to original sources

PubMed2006

The effects on saturated fat purchases of providing internet shoppers with purchase- specific dietary advice: a randomised trial.

OBJECTIVES: The supermarket industry now services many customers through online food shopping over the Internet. The Internet shopping process offers a novel opportunity for the modification of dietary patterns. The aim of this study was to evaluate the effects on consumers' purchases of saturated fat of a fully automated computerised system that provided real-time advice tailored to the consumers' specific purchases recommending foods lower in saturated fat. DESIGN: This study was a blinded, randomised controlled trial. SETTING: The study was conducted in Sydney, New South Wales, Australia. PARTICIPANTS: The participants were consumers using a commercial online Internet shopping site between February and June 2004. INTERVENTIONS: Individuals assigned to intervention received fully automated advice that recommended specific switches from selected products higher in saturated fat to alternate similar products lower in saturated fat. Participants assigned to control received general non-specific advice about how to eat a diet lower in saturated fat. OUTCOME MEASURES: The outcome measure was the difference in saturated fat (grams per 100 g of food) in shopping baskets between the intervention and control groups. RESULTS: There were 497 randomised participants, mean age 40 y, each shopping for an average of about three people. The amount of saturated fat in the foods purchased by the intervention group was 0.66% lower (95% confidence interval 0.48-0.84, p < 0.001) than in the control group. The effects of the intervention were sustained over consecutive shopping episodes, and there was no difference in the average cost of the food bought by each group. CONCLUSIONS: Fully automated, purchase-specific dietary advice offered to customers during Internet shopping can bring about changes in food purchasing habits that are likely to have significant public health implications. Because implementation is simple to initiate and maintain, this strategy would likely be highly cost-effective.

Journal Article↗

PubMed2006

Obesity and risk of low self-esteem: a statewide survey of Australian children.

OBJECTIVE: There is variation in the psychological distress associated with child obesity. Low self-esteem, when observed, provides very little information about the nature of the distress and no indication of the proportion of obese children affected. This study used a domain approach to self-competence to evaluate self-esteem in a representative sample of Australian children. PARTICIPANTS AND METHODS: A total of 2813 children (mean age: 11.3 years) took part in the study. They were recruited from 55 schools and were all in the last 2 years of primary school. Participants completed the Self-perception Profile for Children, a measure of body shape perception, and their height and weight were measured. RESULTS: Obese children had significantly lower perceived athletic competence, physical appearance, and global self-worth than their normal weight peers. Obese girls scored lower in these domains than obese boys and also had reduced perceived social acceptance. Obese children were 2-4 times more likely than their normal weight peers to have low domain competence. In terms of prevalence, 1 of 3 obese boys and 2 of 3 obese girls had low appearance competence, and 10% and 20%, respectively, had low global self-worth. Body dissatisfaction mediated most of the association between BMI and low competence in boys but not in girls. CONCLUSIONS: Obesity impacts the self-perception of children entering adolescence, especially in girls, but in selected areas of competence. Obese children are at particular risk of low perceived competence in sports, physical appearance, and peer engagement. Not all obese children are affected, although the reasons for their resilience are unclear. Quantifying risk of psychological distress alongside biomedical risk should help in arguing for more resources in child obesity treatment.

Adolescent↗

PubMed2005

Annotation of androgen dependence to human prostate cancer-associated genes by microarray analysis of mouse prostate.

In silico methods and array technologies have identified genes differentially expressed in prostate cancer. Biological functions of the identified genes are often unclear. Considering the biological significance of androgens in prostate cancer, we profiled the prostate transcripts of congenital androgen-deficient mice with or without androgen replacement in vivo using murine gene expression array. In parallel genes differentially expressed in human prostate cancer were identified by Digital Differential Display and the Serial Analysis of Gene Expression. Androgen dependence of the identified genes was then determined by the steady-state mRNA levels of the murine orthologs in response to androgen treatment. The annotation is supported by the finding that some of the androgen target genes have been reported previously with independent experiments.

Androgens↗

PubMed2004

Increases in leukocyte cluster of differentiation antigen expression during cardiopulmonary bypass in patients undergoing heart transplantation.

Cardiopulmonary bypass (CPB) is essential in heart transplantation surgery. It is also used in coronary artery grafting surgery where it has been associated with a postoperative inflammatory response. This manifests as an increase in pro-inflammatory proteins like interleukin-8 and tumour necrosis factor alpha accompanied by increases in neutrophil populations and increased expression of cluster of differentiation (CD) antigens. The latter have been investigated using flow cytometry, which is limited to the measurement of three to four CD antigens simultaneously. We have developed a novel antibody array that can simultaneously measure the expression of 72 different CD antigens. The purpose of this study was to use this technology to measure CD antigen expression in patients undergoing CPB during heart transplantation. Twelve patients undergoing this operation were studied. A preoperative sample acted as an internal control while a second sample taken during CPB was the comparator. No previous studies have examined changes in CD antigen expression during heart transplantation. We report an increase in the expression of 10 different CD antigens across all patients between the two time points.

Antigens, CD19↗

PubMed2004

Microarray transcript profiling distinguishes the transient from the acute type of megakaryoblastic leukaemia (M7) in Down's syndrome, revealing PRAME as a specific discriminating marker.

Transient myeloproliferative disorder (TMD) is a unique, spontaneously regressing neoplasia specific to Down's syndrome (DS), affecting up to 10% of DS neonates. In 20-30% of cases, it reoccurs as progressive acute megakaryoblastic leukaemia (AMKL) at 2-4 years of age. The TMD and AMKL blasts are morphologically and immuno-phenotypically identical, and have the same acquired mutations in GATA1. We performed transcript profiling of nine TMD patients comparing them with seven AMKL patients using Affymetrix HG-U133A microarrays. Similar overall transcript profiles were observed between the two conditions, which were only separable by supervised clustering. Taqman analysis on 10 TMD and 10 AMKL RNA samples verified the expression of selected differing genes, with statistical significance (P < 0.05) by Student's t-test. The Taqman differences were also reproduced on TMD and AMKL blasts sorted by a fluorescence-activated cell sorter. Among the significant differences, CDKN2C, the effector of GATA1-mediated cell cycle arrest, was increased in AMKL but not TMD, despite the similar level of GATA1. In contrast, MYCN (neuroblastoma-derived oncogene) was expressed in TMD at a significantly greater level than in AMKL. MYCN has not previously been described in leukaemogenesis. Finally, the tumour antigen PRAME was identified as a specific marker for AMKL blasts, with no expression in TMD. This study provides markers discriminating TMD from AMKL-M7 in DS. These markers have the potential as predictive, diagnostic and therapeutic targets. In addition, the study provides further clues into the pathomechanisms discerning self-regressive from the progressive phenotype.

Acute Disease↗

PubMed2003

Endothelial cells preparing to die by apoptosis initiate a program of transcriptome and glycome regulation.

The protein-based changes that underlie the cell biology of apoptosis have been extensively studied. In contrast, mRNA- and polysaccharide-based changes have received relatively little attention. We have combined transcriptome and glycome analyses to show that apoptotic endothelial cell cultures undergo programmed changes to RNA transcript abundance and cell surface polysaccharide profiles. Although a few of the transcriptome changes were protective, most appeared to prepare cells for apoptosis by decreasing the reception and transduction of pro-survival signals, increasing pro-death signals, increasing abundance of apoptotic machinery, inhibiting cellular proliferation, recruiting phagocytes to regions of cell death, and promoting phagocytosis. Additional transcriptomal changes appeared to alter the synthesis and modification of cell surface glycosaminoglycans. The resultant reduced abundance of sulphated cell surface glycosaminoglycans may further promote cell death by inhibiting the presentation of extracellular matrix-tethered survival factors to their receptors on dying cells. We propose that the transcriptome and glycome regulation presented here synergize with previously described protein-based changes to guide the apoptotic program.

Apoptosis↗

PubMed2002

Microarray analysis of insulin and insulin-like growth factor-1 (IGF-1) receptor signaling reveals the selective up-regulation of the mitogen heparin-binding EGF-like growth factor by IGF-1.

Insulin and insulin-like growth factor-1 (IGF-1) act through highly homologous receptors that engage similar intracellular signaling pathways, yet these hormones serve largely distinct physiological roles in the control of metabolism and growth, respectively. In an attempt to uncover the molecular mechanisms underlying their divergent functions, we compared insulin receptor (IR) and IGF-1 receptor (IGF-1R) regulation of gene expression by microarray analysis, using 3T3-L1 cells expressing either TrkC/IR or TrkC/IGF-1R chimeric receptors to ensure the highly selective activation of each receptor tyrosine kinase. Following stimulation of the chimeric receptors for 4 h, we detected 11 genes to be differentially regulated, of which 10 were up-regulated to a greater extent by the IGF-1R. These included genes involved in adhesion, transcription, transport, and proliferation. The expression of mRNA encoding heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent mitogen, was markedly increased by IGF-1R but not IR activation. This effect was dependent on MAPK, but not phosphatidylinositol 3-kinase, and did not require an autocrine loop through the epidermal growth factor receptor. HB-EGF mitogenic activity was detectable in the medium of 3T3-L1 preadipocytes expressing activated IGF-1R but not IR, indicating that the transcriptional response is accompanied by a parallel increase in mature HB-EGF protein. The differential abilities of the IR and IGF-1R tyrosine kinases to stimulate the synthesis and release of a growth factor may provide, at least in part, an explanation for the greater role of the IGF-1R in the control of cellular proliferation.

3T3 Cells↗

PubMed2002

Creatine supplementation alters insulin secretion and glucose homeostasis in vivo.

Dietary creatine supplementation has been used to improve skeletal muscle performance. However, dietary creatine manipulation also affects glucose homeostasis. The aim of this study was to investigate the effect of dietary creatine supplementation on insulin secretion, glucose tolerance, and quadriceps glycogen metabolism in chow-fed rats. Forty-eight rats in total were divided into 2 groups of 24 and were then subdivided into 6 groups of 8. Rats were fed a diet supplemented with 0% (CON) or 2% (CREAT) creatine for 2, 4, or 8 weeks. At these 3 time points an oral glucose tolerance test was performed. Two days later, rats were euthanized and the pancreas and quadriceps muscles were collected. The peak insulin response to a glucose challenge was significantly elevated after both 4 (CON 327 +/- 72 v CREAT 735 +/- 140 pmol/L, P =.01) and 8 (CON 248 +/- 48 v CREAT 588 +/- 136 pmol/L, P =.02) weeks. Fasting insulin levels were also increased by creatine supplementation for 8 weeks (CON 78 +/- 14 v CREAT 139 +/- 14 pmol/L, P =.01). Glucose tolerance was not affected until 8 weeks at which point the peak plasma glucose was elevated in the creatine supplemented group (CON 10.1 +/- 0.6 v CREAT 13.5 +/- 1.5 mmol/L, P =.05). A significant increase in pancreatic total creatine content was seen in supplemented animals at 2 (CON 1.2 +/- 0.1 v CREAT 2.7 +/- 0.1 micromol/g wet wt, P =.005), 4 (CON 1.5 +/- 0.2 v CREAT 2.7 +/- 0.3 micromol/g wet wt, P =.02) and 8 (CON 1.5 +/- 0.1 v CREAT 2.6 +/- 0.1 micromol/g wet wt, P =.005) weeks, whereas no change in quadriceps total creatine or glycogen content was observed at any individual time point. This study shows that prolonged creatine supplementation induces abnormalities in pancreatic insulin secretion and changes in glucose homeostasis.

Animals↗