Biomedical subjects

Paul D Taylor

Publications and source records attributed to Paul D Taylor.

18 recordsLinked to original sources

PubMed2006

Comparative anatomical study of internal brooding in three anascan bryozoans (Cheilostomata) and its taxonomic and evolutionary implications.

The anatomical structure of internal sacs for embryonic incubation was studied using SEM and light microscopy in three cheilostome bryozoans-Nematoflustra flagellata (Waters,1904), Gontarella sp., and Biflustra perfragilis MacGillivray, 1881. In all these species the brood sac is located in the distal half of the maternal (egg-producing) autozooid, being a conspicuous invagination of the body wall. It consists of the main chamber and a passage (neck) to the outside that opens independently of the introvert. There are several groups of muscles attached to the thin walls of the brood sac and possibly expanding it during oviposition and larval release. Polypide recycling begins after oviposition in Gontarella sp., and the new polypide bud is formed by the beginning of incubation. Similarly, polypides in brooding zooids degenerate in N. flagellata and, sometimes, in B. perfragilis. In the evolution of brood chambers in the Cheilostomata, such internal sacs for embryonic incubation are considered a final step, being the result of immersion of the brooding cavity into the maternal zooid and reduction of the protecting fold (ooecium). Possible reasons for this transformation are discussed, and the hypothesis of Santagata and Banta (Santagata and Banta1996) that internal brooding evolved prior to incubation in ovicells is rejected.

Animals↗

PubMed2005

Spatial contaminant heterogeneity: quantification with scale of measurement at contrasting sites.

Material within the terrestrial environment is rarely homogeneously distributed, either spatially or temporally. One consequence of heterogeneity is that uncertainty is usually generated in measurements that are taken with the aim of characterising the environment. For example, a measurement of analyte concentration within soil taken from one sampling location on contaminated land can vary substantially when compared against another sample taken at effectively the same nominal location. The measurement uncertainty arising from the heterogeneity can substantially limit the reliability of the interpretations made upon environmental investigations. The sampling uncertainty usually outweighs the analytical uncertainty from the laboratory, often by a factor of 20 or more. One approach to reducing the uncertainty is to design a more suitable sampling strategy. This might be achieved by predicting the degree of heterogeneity prior to the investigation, but this is often difficult to achieve accurately. Another approach, which was investigated here, is to actually characterise the heterogeneity prior to the main investigation using rapid and inexpensive technology, such as in situ measurement techniques. In situ portable X-ray fluorescence (PXRF) and X-ray microprobe (XMP) techniques were employed to test the feasibility of this approach. Two contrasting contaminated land sites were chosen to characterise the two-dimensional spatial heterogeneity of heavy metal contamination in topsoil at a range of scales (50 m to 0.001 m). The spatial heterogeneity of contaminants, expressed as relative standard deviations, was found to differ between the two sites by a factor of two, largely due to the mode of deposition of pollution. The study also indicated that the heterogeneity did not change systematically with the scale of measurement between sampling locations at either site.

England↗

PubMed2005

Developmental programming of aortic and renal structure in offspring of rats fed fat-rich diets in pregnancy.

Evidence from human and animal studies suggests that maternal nutrition can induce developmental programming of adult hypertension in offspring. We have previously described a model of maternal dietary imbalance in Sprague-Dawley rats whereby administration of a maternal diet rich in animal lard programmes the development of increased blood pressure, insulin resistance, dyslipidaemia, obesity and mesenteric artery endothelial dysfunction in adult offspring. To further characterize the mechanism of hypertension in this model we have examined vascular and renal structure in adult offspring of Sprague-Dawley rats fed a control diet (OC) or lard-rich diet (OHF) during pregnancy and suckling followed by a control diet post-weaning. To gain further insight, we assessed aortic reactivity and elasticity in an organ bath preparation and renal renin and Na+,K+-ATPase activity. Plasma aldosterone concentration was also measured. Stereological examination of the aorta in OHF demonstrated reduced endothelial cell volume and smooth muscle cell number compared with OC. Adult OHF animals showed increased aortic stiffness and reduced endothelium-dependent relaxation. Renal stereology showed no differences in kidney weight, glomerular number or volume in OHF compared with OC, but renin and Na+,K+-ATPase activity were significantly reduced in OHF compared with controls. Programmed alterations to aortic structure and function are consistent with previous observations that exposure to maternal high fat diets produces systemic vascular changes in the offspring. Despite normal renal stereology, altered renal Na+,K+-ATPase and renin activity offers further insight into the mechanism underlying the increased blood pressure characteristic of this model.

Animal Nutritional Physiological Phenomena↗

PubMed2005

Experimental models of developmental programming: consequences of exposure to an energy rich diet during development.

Studies in both humans and experimental animals addressing the 'Fetal Origins of Adult Disease' hypothesis have established a relationship between an adverse intrauterine environment and offspring disease in adult life. This phenomenon, termed 'fetal programming' describes a process whereby a stimulus in utero establishes a permanent response in the fetus leading to enhanced susceptibility to later disease. However, the environment, during periods of developmental plasticity in postnatal life, can also 'programme' function. Thus, the terms 'developmental programming' and the 'Developmental Origins of Adult Health and Disease' are preferentially utilized. The 'Thrifty Phenotype' hypothesis explained the association between insufficient in utero nutrition and the later development of Type 2 diabetes. Most recently the 'Predictive Adaptive Response' hypothesis proposes that the degree of mismatch between the pre- and postnatal environments is an important determinant of subsequent disease. Epidemiological studies have indicated that fetal growth restriction correlates with later disease, implying that fetal nutritional deprivation is a strong programming stimulus. This prompted the development of experimental animal models using controlled maternal calorie, protein or macronutrient deficiency during key periods of gestation. However, in many societies, maternal and postnatal nutrition are either sufficient or excessive. Here, we examine findings from a range of nutritional studies examining maternal and/or postnatal nutritional excess. There is supportive evidence from a limited number of studies to test the 'Predictive Adaptive Response' hypothesis. These suggest that maternal over-nutrition is deleterious to the health of offspring and can result in a phenotype of the offspring that is characteristic of metabolic syndrome.

Adaptation, Physiological↗

PubMed2004

Balancing measurement uncertainty against financial benefits: comparison of in situ and ex situ analysis of contaminated land.

The uncertainty of measurements taken for the purpose of characterizing contaminated land can subsequently cause decision errors, which can produce significant, financial consequences. Given the site-specific costs, such as those associated with the measurements or with site misclassification, the important question addressed is "Are the measurements of acceptable quality for that given objective or fit-for-purpose"? It is often considered by investigators that using a standard operating procedure (SOP) with an approved analytical method will give an acceptable level of uncertainty. This is despite evidence that sampling is usually the predominant source of uncertainty, not the chemical analyses, mainly as a result of the contaminant heterogeneity within sampling locations at a site. One in situ and one ex situ measurement technique were used to represent these two contrasting approaches to characterizing a site contaminated with lead in topsoil. The measurement uncertainty, from both sampling and analyses, was estimated for the two techniques, and its fitness-for-purpose was assessed using the innovative optimized contaminated land investigation (OCLI) method. It is objectively demonstrated by the OCLI method that the in situ method (portable X-ray fluorescence) was three times more cost-effective than the ex situ (AAS) method at characterizing a contaminated site, despite generating higher uncertainty on individual measurements.

Cost-Benefit Analysis↗

PubMed2004

Localization and quantification of cyclic changes in the expression of endocrine gland vascular endothelial growth factor in the human corpus luteum.

Angiogenesis is essential for normal growth and function of the corpus luteum. The roles of various angiogenic factors in these events are being elucidated. Endocrine gland vascular endothelial growth factor (EG-VEGF) has recently been described in the human ovary. To define the localization of EG-VEGF mRNA in the corpus luteum and determine changes in its expression, dated human corpora lutea were studied at the early, mid-, and late luteal phases. Quantitative RT-PCR was employed to determine changes in EG-VEGF mRNA and compare expression to its related factor prokineticin-2 and the established angiogenic factor, VEGF. In situ hybridization was used to localize sites of production of EG-VEGF. To investigate whether expression of EG-VEGF was under the influence of LH or progesterone, luteinized granulosa cells were stimulated with human chorionic gonadotropin in the presence or absence of a progesterone synthesis inhibitor. EG-VEGF mRNA increased throughout the luteal phase, whereas there was no change in VEGF mRNA. The relative abundance of RNAs based upon PCR signal intensity showed that VEGF and EG-VEGF were highly expressed, whereas expression of prokineticin-2 was low. EG-VEGF mRNA was localized predominantly to granulosa-derived cells of the corpus luteum. Human chorionic gonadotropin stimulated both VEGF and EG-VEGF mRNA in vitro, but the level of expression was not influenced by progesterone. These results establish that in the human corpus luteum EG-VEGF is principally derived from granulosa lutein cells and that its synthesis is highest during the mid- to late luteal phase.

Adult↗

PubMed2004

Developmental programming of the metabolic syndrome by maternal nutritional imbalance: how strong is the evidence from experimental models in mammals?

The incidence of the metabolic syndrome, a cluster of abnormalities focusing on insulin resistance and associated with high risk for cardiovascular disease and diabetes, is reaching epidemic proportions. Prevalent in both developed and developing countries, the metabolic syndrome has largely been attributed to altered dietary and lifestyle factors that favour the development of central obesity. However, population-based studies have suggested that predisposition to the metabolic syndrome may be acquired very early in development through inappropriate fetal or neonatal nutrition. Further evidence for developmental programming of the metabolic syndrome has now been suggested by animal studies in which the fetal environment has been manipulated through altered maternal dietary intake or modification of uterine artery blood flow. This review examines these studies and assesses whether the metabolic syndrome can be reliably induced by the interventions made. The validity of the different species, diets, feeding regimes and end-point measures used is also discussed.

Animals↗

PubMed2004

Impaired glucose homeostasis and mitochondrial abnormalities in offspring of rats fed a fat-rich diet in pregnancy.

We previously reported that prenatal and suckling exposure to a maternal diet rich in animal fat leads to cardiovascular dysfunction in young adult rat offspring with subsequent development of dyslipidemia and hyperglycemia. We have further investigated glucose homeostasis in adult female offspring by euglycemic-hyperinsulinemic clamp and by dynamic assessment of glucose-stimulated insulin secretion in isolated, perifused pancreatic islet cells. Additionally, given the link between reduced mitochondrial DNA (mtDNA) content and the development of type 2 diabetes mellitus, we have measured mtDNA in organs from young adult animals. Sprague-Dawley rats were fed a diet rich in animal fat or normal chow throughout pregnancy and weaning. Infusion of insulin (5 mU.kg(-1).min(-1)) resulted in a higher steady-state plasma insulin concentration in 1-year-old offspring of fat-fed dams (OHF, n = 4) vs. offspring of control dams (OC, n = 4, P < 0.01). Glucose-stimulated insulin secretion in isolated islets from 9-mo-old OHF was significantly reduced compared with OC (n = 4, P < 0.05). Transmission electron micrography showed altered insulin secretory granule morphology in OHF pancreatic beta-cells. Kidney mtDNA was reduced in 3-mo-old OHF [16S-to-18S gene ratio: OC (n = 10) 1.05 +/- 0.19 vs. OHF (n = 10) 0.66 +/- 0.06, P < 0.05]. At 6 mo, gene chip microarray of OHF aorta showed reduced expression of the mitochondrial genome. Prenatal and suckling exposure to a diet rich in animal fat leads to whole body insulin resistance and pancreatic beta-cell dysfunction in adulthood, which is preceded by reduced tissue mtDNA content and altered mitochondrial gene expression.

Adipose Tissue↗

PubMed2004

Doryporella smirnovi sp. nov. (Bryozoa: Cheilostomata) and its impact on phylogeny and classification.

A new species of Doryporella, D. smirnovi sp. nov. is described from the area of the Commander Islands. Inclusion of this species in a revised phylogenetic analysis of Doryporella and its relatives permits the recognition of a clade comprising Doryporella and Doryporellina. This clade is accorded family-level status as the Doryporellidae fam. nov., thereby removing Doryporella (and Doryporellina) from the large and paraphyletic Calloporidae.

Animals↗

PubMed2003

Handedness and schizotypy in a Japanese sample: an association masked by cultural effects on hand usage.

Previous research has shown a robust association between schizotypy and mixed/ambiguous-handedness, but little is known about the universality of this relationship outside Western cultures. The present paper examines this issue in a sample of 413 Japanese students administered (in Japan) the Annett handedness questionnaire and a schizotypy scale (STA). Conventional analyses of current hand preference, using several indices derived from the Annett scale, mostly failed to replicate previous findings. However, there was a significant tendency for greater use of either hand in highly schizotypal males. Furthermore, a significant association between schizotypy and non-right-handedness was found--again only in males--after correcting for the effects of early switching of hand usage, presumed to be due to cultural pressure against left-handedness in Japanese society. These results were found to be highly convergent with findings previously reported for clinical schizophrenia.

Adolescent↗

PubMed2003

BPROMPT: A consensus server for membrane protein prediction.

Protein structure prediction is a cornerstone of bioinformatics research. Membrane proteins require their own prediction methods due to their intrinsically different composition. A variety of tools exist for topology prediction of membrane proteins, many of them available on the Internet. The server described in this paper, BPROMPT (Bayesian PRediction Of Membrane Protein Topology), uses a Bayesian Belief Network to combine the results of other prediction methods, providing a more accurate consensus prediction. Topology predictions with accuracies of 70% for prokaryotes and 53% for eukaryotes were achieved. BPROMPT can be accessed at http://www.jenner.ac.uk/BPROMPT.

Bayes Theorem↗

PubMed2003

Gender-linked hypertension in offspring of lard-fed pregnant rats.

Epidemiological studies suggest an association between maternal nutrition and offspring cardiovascular disease. We previously demonstrated endothelial dysfunction and abnormal aortic fatty acid composition in adult female offspring of rats fed animal lard during pregnancy. We have now further investigated this model. Female Sprague-Dawley rats were fed a control breeding diet (5.3% fat) or a diet rich in lard (25.7% fat) 10 days before and throughout pregnancy and lactation. Male and female offspring were implanted with radiotelemeters for recording of blood pressure, heart rate, and activity at 80, 180, and 360 days of age. Reactivity to acetylcholine and to nitric oxide were assessed in isolated small mesenteric arteries from 80- and 180-day-old littermates. Systolic blood pressure (awake phase) was raised in female offspring (180 days: offspring of control, 130.7+/-1.6 mm Hg, n=5, versus offspring of lard-fed, 138.1+/-2.9, n=5, P=0.029; 360 days: offspring of control, 129.7+/-3.7 mm Hg, n=6, versus offspring of lard-fed, 142.1+/-3.2, n=6, P=0.005). Diastolic blood pressure was also raised at 180 days (offspring of control, 87.6+/-1.0 mm Hg, n=5, versus offspring of lard-fed, 94.7+/-2.6, n=5, P=0.011). Blood pressure was not raised in male offspring. Endothelium-dependent relaxation to acetylcholine was blunted in male and female offspring of lard-fed dams (80 and 180 days). Feeding a diet rich in lard to pregnant rats leads to gender-related cardiovascular dysfunction in normally fed offspring.

Animals↗

PubMed2002

Effects of a 'healthy' diet and of acute and long-term vitamin C on vascular function in healthy older subjects.

OBJECTIVE: Aging is associated with endothelial dysfunction. We studied the acute and longer-term effects of vitamin C compared to a 'Mediterranean-type' diet on endothelial function in healthy older subjects. METHODS: Bilateral venous occlusion plethysmography was used to measure forearm blood flow in subjects aged 57-80 years. Responses to cumulative intra-arterial doses of the endothelium-dependent dilator bradykinin (BK; n=56; 20, 40, 80 pmol/min) and the nitric oxide donor glyceryl trinitrate (GTN; n=54; 4, 8, 16 nmol/min), were determined alone and in the presence of vitamin C (25 mg/min). We then randomised 54 subjects to a 'healthy' diet (n=18), vitamin C (1 g/day; n=18) or placebo for 6 weeks and reassessed endothelial and smooth muscle function. RESULTS: Acute intra-arterial vitamin C did not alter dilatation to BK or GTN. Similar increases in plasma vitamin C occurred on oral vitamin C (83+/-4 to 135+/-8 micromol/l) and 'healthy' diet (84+/-5 to 135+/-27 micromol/l; P<0.01 for both), with no change seen on placebo. Treatment with a 'healthy' diet but not oral vitamin C improved endothelium-dependent (P=0.043) and endothelium-independent dilatation (P=0.011). CONCLUSIONS: A 'Mediterranean-type' diet rich in vitamin C improves vascular function. Neither acute intra-arterial nor sustained administration of oral vitamin C improves vascular function in healthy older subjects.

Administration, Oral↗

PubMed2002

Electron diffraction studies of the calcareous skeletons of bryozoans.

Electron microscopy and electron diffraction were used to investigate mineral crystallites dissociated from the skeletal walls of six species belonging to the Bryozoa, a phylum of predominantly marine colony-forming invertebrate animals. Four cheilostome bryozoans (Flustra foliacea, Membranipora membranacea, Thalamoporella novaehollandiae and Cellarinella foveolata) and two cyclostomes (Fasciculipora ramosa and Hornera robusta) were analysed. In each case, an attempt was made to relate the crystal morphology imaged in situ by scanning electron microscopy with the crystallographic orientation of isolated crystals determined by electron diffraction analysis in the transmission electron microscope. The results showed that the calcitic cheilostome and cyclostome skeletons consisted of closely packed arrays of plate-like Mg-containing calcite crystallites, and that the crystallographic a-axis was preferentially aligned perpendicular to the top and bottom surfaces of the flattened particles. The results suggest that calcite biomineralization occurs under similar crystallographic constraints in the five species studied even though the origins of cheilostomes and cyclostomes are separated by over 300 million years in the fossil record of the bryozoans. Similar studies for the aragonite crystallites in skeletons of M. membranacea indicated that the crystallographic b-axis was preferentially oriented perpendicular to the basal surfaces of irregular plate-like particles.

Animals↗

PubMed2002

Optimized contaminated land investigation at minimum overall cost to achieve fitness-for-purpose.

A methodology for optimized contaminated land investigation (OCLI) is described that balances the uncertainty of measurements against the cost of taking the measurements and the financial losses that may arise from misclassification of the land. Uncertainty from the sources of both field sampling and chemical analysis is estimated using existing techniques, based on the taking of duplicated samples. The actual costs of sampling and analysis and the expected costs that could arise from either 'false positive' or 'false negative' classification of areas of land were estimated. A loss function was constructed that calculates the expectation of financial loss that will arise for a given uncertainty of measurement. The function shows a clear minimum value of cost at an optimal value of uncertainty. Application of this OCLI technique to two case studies demonstrated this minimum value. Below the optimum value of uncertainty, the costs increased due to higher measurement costs. Above the optimum, the costs increased due to increasing risk of factors such as unnecessary remediation or potential litigation over undetected contamination. Many areas for further development of OCLI are identified, but the technique is demonstrated as a useful new approach to judging fitness-for-purpose of such measurements.

Cost Control↗

PubMed2002

Site-directed mutagenesis of exon 5 of p53: purification, analysis, and validation of amplicons for DHPLC.

Reversed-phase ion-pair chromatography is used in its three modes of operation--(1) non-denaturing, (2) partially denaturing, (3) fully denaturing - to isolate and characterize five site-directed mutant amplicons of exon 5 of the p53 gene (GenBank X54156). The mutant fragments were prepared using a simplified mutagenesis procedure without cloning and isolated in high purity under non-denaturing conditions. Then, under partially denaturing conditions, heteroduplices formed by hybridization of each of the five mutants with wild-type were all detected by denaturing reversed-phase high-performance chromatography (DHPLC). The fidelity of the PCR step was also assessed. Finally, the homogeneity of each mutant was confirmed by minisequencing under fully denaturing conditions. The versatility and facility of the method for DNA manipulations was exploited to demonstrate a strategy for validating amplicons for mutation detection by DHPLC.

Chromatography, High Pressure Liquid↗

PubMed2002

A new cheilostome bryozoan with gigantic zooids from the North-West Pacific.

Gontarella gigantea gen. et sp. nov. is described from two stations, one in the Sea of Okhotsk and the second on the Pacific side of the Small Kuril Arc. This membraniporiform anascan cheilostome bryozoan has very large zooids, the largest known among extant sheet-like encrusting anascans. Comparative data on similar sheet-like cheilostomes gathered from the literature shows that the new species represents a conspicuous outlier in size, with the surface area of the zooid being approximately twice that of the next largest species. Skeletal evidence, including the lack of ovicells, indicates that G. gigantea belongs within the malacostegan family Electridae. The gigantic ancestrula suggests that the species has a cyphonautes larva about 1 mm in maximum dimension.

Animals↗

PubMedDate not supplied

Selective binding of nucleotide probes by eosinophilic cationic protein during in situ hybridisation.

During in situ hybridisation on frozen and paraffin-embedded sections of bowel for IkappaB alpha, oligodeoxyribonucleotide probes were found to bind more avidly to eosinophils than target mRNA. This binding could not be obviated using strategies previously employed to block either binding of long DNA probes (200-mers) to eosinophils in bone marrow smears, or of riboprobes to eosinophils in sections of bowel, without removing specific hybridisation of probes. That this binding could arise through interaction of anionic oligodeoxyribonucleotides with eosinophil cationic protein, which has an unusually high pI, and is abundant in cytoplasmic granules of eosinophils, was demonstrated in vitro using real-time biomolecular interaction analysis with a BiacoreX instrument. Finally, a relationship between probe hydrophobicity, measured by reverse phase ion-pair high performance liquid chromatography, and in situ binding of individual probes to eosinophils was demonstrated. Effective tissue penetration by hydrophobic probes and subsequent strong probe-eosinophilic cationic protein interactions therefore may confound the interpretation of in situ hybridisation performed with oligonucleotide probes in eosinophil-containing tissues, such as bowel and nasal polyps.

Antisense Elements (Genetics)↗