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Biomedical subjects

J Ashton

Publications and source records attributed to J Ashton.

At least 19 recordsLinked to original sources
PubMed2002

Placental nutrient transfer capacity and fetal growth.

The objective of this study was to determine whether the ability of the human placenta to transfer glucose and fatty acids is related to normal fetal growth. The intrinsic nutrient transport capacity of the placenta was measured under standardized conditions during in vitro perfusion of 30 human term placentas and related to birth weight (range 2640-4640g), birth weight centile (8th-99th), ponderal index (2.43-3.69), placental weight (418-1030g) and placental:fetal weight (0.14-0.31). There was no statistically significant change in the rate of nutrient transfer per placenta or per kg fetal weight, with birth weight, birth weight centile, ponderal index, placental weight and placental:fetal weight. There was a weak but significant relationship (P=0.020, r(2)=9 per cent) between the ratio of glucose to fatty acid transport and birth weight centile, largely due to the high ratio found in the lowest birth weight quartile where the babies are thinnest. This study provides no evidence that placental nutrient transport capacity limits fetal growth across a wide range of birth weights in normal pregnancies. It is proposed that the fetus itself may regulate placental nutrient transport in vivo via the fetal cardiac output and the rate of fetal nutrient utilization.

Adult↗
PubMed2000

Free and esterified fatty acid and cholesterol synthesis in adult males and its effect on the doubly-labelled water method.

The purpose of the present study was to estimate whole-body fatty acid and cholesterol synthesis in weight-stable adults and to determine the likely effect on the doubly-labelled water (DLW) method for measuring energy expenditure. Synthesis was measured by 2H incorporation over 14 d in six adult males in approximate energy balance following noradrenaline infusion to maximize mobilization of free fatty acid from adipose tissue. The inter-individual variation in synthesis rates was large and in one subject the proportion of free fatty acid synthesized was ten times that of the mean of the rest of the group; the fasting concentration of esterified fatty acid in this subject was five times that of the rest of the group indicating likely violation of the assumptions underlying the calculation of whole-body synthesis. After 14 d of labelling in the other five subjects, 0.9 (SEM 0.3)% of the circulating free fatty acid, 9.3 (SEM 3.0)% of the esterified fatty acid, 14.6 (SEM 2.4)% of the free cholesterol and 28.3 (SEM 3.7)% of esterified cholesterol had been synthesized de novo. A high rate of synthesis correlated with a low pre-dose 2H abundance both within and between lipid classes suggesting that natural 2H abundance variations in some lipid classes may be used to determine their metabolic origin. Whole-body synthetic rates were 8 g/d for fatty acid and 0.3-0.5 g/d for cholesterol. These values correspond to very small errors on DLW-derived estimates of CO2 production; -2.5 litres/d for fatty acid and -0.1 to -0.2 litres/d for cholesterol. These results, obtained in subjects typically consuming a diet with a lower fat and cholesterol content that the typical Western diet, suggest that the DLW method is unlikely to be affected by fatty acid and cholesterol synthesis in subjects in energy balance consuming a typical Western diet.

Adipose Tissue↗
PubMed2000

Dendritic cells loaded with MART-1 peptide or infected with adenoviral construct are functionally equivalent in the induction of tumor-specific cytotoxic T lymphocyte responses in patients with melanoma.

Immunization with tumor-specific-associated antigen--pulsed dendritic cells has proved to be efficacious in various animal models and is being evaluated for the treatment of cancer in humans. Use of dendritic cells pulsed with specific peptides or transfected with tumor-associated antigen genes has been a focused area of investigation for inducing potent tumor and viral immune responses. In this study, the authors demonstrate transgene expression, including the lacZ and MART-1 genes, in dendritic cells infected with adenoviral constructs. These transiently transduced dendritic cells, derived from melanoma patients' monocytes cultured with granulocyte-macrophage colony-stimulating factor and interleukin-4, express the transgene and can stimulate patients' CD8+ T cells to elicit an antitumor immune response comparable to dendritic cells loaded with a defined peptide. These cytotoxic T lymphocytes were able to recognize both known and unknown tumor-associated antigen epitopes and exhibited cytolytic activity against HLA-matched tumor cells expressing the antigen. The ability to induce tumor-specific cytotoxic T lymphocytes in vitro using gene-modified dendritic cells that transiently express tumor-associated antigens demonstrates the potential use of these antigen-presenting cells for developing in vivo cancer vaccines.

Adenoviruses, Human↗
PubMed2000

Cages criticised.

Explore the source record for details and available documents.

Animal Welfare↗
PubMed1999

Effect of maternal polyunsaturated fatty acid concentration on transport by the human placenta.

The role of the placenta in controlling the supply of fatty acids to the fetus was investigated in term placentas (n = 5) from normal pregnancies. The maternal side was perfused ex vivo for 90 min with a modified Krebs Ringer solution containing a physiological mixture of fatty acids - designed to mimic the composition of non-esterified fatty acids (NEFA) measured in the last trimester of pregnancy (n = 10) - and ratio of fatty acid to human albumin. The selectivity for alpha-linolenic acid (alphaLN) transfer to the fetal circulation was not significantly different from that observed when using the triglyceride (TG) composition (1.21 +/- 0.04), but significantly different for AA (1.43 +/- 0.12; p < 0.001) and docosahexaenoic acid (DHA; 2.02 +/- 0.09; p = 0.048). The absolute rate of transfer (nmol. ml-1) compared to that using the TG maternal perfusate composition was significantly different for LA (0.562 +/- 0.038; p = 0.50), alphaLN (0.130 +/- 0.009; p < 0.001), arachidonic acid (AA; 0.218 +/- 0.022; p = 0.001) and DHA (0.383 +/- 0.04; p < 0.001). Thus, placental selectivity for alphaLN and DHA appears to be relatively unresponsive to changes in the mixture of fatty acids in the maternal circulation but the selectivity for AA increased with the increase in the maternal AA concentration. For an 8-fold increase in the concentration of DHA in the maternal circulation there was a 13-fold increase in the transfer of DHA to the fetal circulation. For a 2-fold increase in the concentration of AA, transfer was increased 8-fold. For a 1.3-fold increase in the concentration of alphaLN, transfer was increased 2.1-fold. These results suggest that the maternal concentration of individual fatty acids, and hence the composition of the maternal diet, can have large effects on polyunsaturated/long-chain polyunsaturated fatty acids delivery to the fetus.

Adult↗
PubMed1998

Dietary intake and tissue concentration of fatty acids in omnivore, vegetarian and diabetic pregnancy.

The aim of this study was to determine the effect of fatty acid intake and insulin dependent diabetes on the fatty acid composition of maternal erythrocytes, the placenta and cord. Fatty acid intake (from food frequency questionnaire) and the fatty acid composition of maternal erythrocytes, the placenta and cord from pregnant vegetarians (n = 4) and insulin dependent diabetics (n = 5) was compared with pregnant omnivores (n = 10). There was a significantly lower intake of n-6 long chain polyunsaturated fatty acid (LCPUFA) (-75% P < 0.01) and n-3 LCPUFA (-92% P < 0.01) and increased ratio of n-6/n-3 LCPUFA in the vegetarians (103%; P < 0.001). The concentrations of 22:4 n-6 (+28%; P < 0.05) and 22:5 n-3 (+40%; P < 0.05) were higher in vegetarian erythrocytes. Placental 18:2 n-6 (+26.9%; P < 0.05) 18:3 n-3 (+139%; P < 0.05) and 22:5 n-3 (+24%; P < 0.05) were increased while 20:5 n-3 (-36%; P < 0.05), 22:6 n-3 (-16%; P = 0.059), and the ratios of 20:4 n-6/18:2 n-6 (P < 0.01) and 22:6 n-3/18:3 n-3 were reduced. 22:6 n-6 (-49%; P < 0.05) and total n-3 LCPUFA (-11%; P < 0.01) were reduced in vegetarian cord. For the diabetic mothers, all of the n-6 LCPUFA and n-3 LCPUFA were reduced in the maternal erythrocytes; 22:4 n-6 (-42%; P < 0.05), 22:5 n-6 (-46%; P < 0.05) and 22:6 n-3 (-41%; P < 0.05). For the diabetic placenta and cord the general pattern of n-3 LCPUFA was the same as that in the vegetarians. In the vegetarian mothers, the PUFA profiles in the maternal erythrocytes, placenta and cord are consistent with an elevation in the rate of LCPUFA synthesis in order to make up the relative deficit in LCPUFA intake. However, it may be that the higher level of desaturase activity is not able to overcome the dietary deficit of 22-6 n-3 and 22:6 n-6. Despite the fact that the dietary LCPUFA intake in the pregnant diabetic was comparable with that in the pregnant 'normal' omnivore mothers, the pattern of PUFA in the tissues resembled that of the vegetarian mothers.

Diabetes Mellitus, Type 1↗
PubMed1998

The hospital and the public health: changing needs and new visions.

The practice of medicine and other clinical areas cannot take place in isolation from the society of which it is a part. Changes in demography, public expectations, patterns of health and disease and the capacity of interventions to make a difference indicate that dramatic changes in health care are inevitable, which will need health-care professionals to understand the public health context of their work.

Humans↗
PubMed1998

Estimation of energy expenditure in free-living red deer (Cervus elaphus) with the doubly-labelled water method.

Energy expenditure was estimated using the doubly-labelled water (DLW) method in summer in five free-living adult, non-pregnant, non-lactating, red deer (Cervus elaphus) hinds (weight 107.3 (SE 0.9) kg; age 6 (SE 1) years) on lowland pasture under typical farming conditions. Climatic conditions were monitored throughout the experiment. Errors due to 2H losses in CH4 and faeces were calculated from previous estimates of stoichiometries. CH4 production, fractionated water loss, urinary N and O2 consumption were estimated using an iterative approach. The water flux (rH2O) in these animals consuming only fresh grass was 12 (SE 0.5) kg/d, the CO2 production (rCO2) was 1271 (SE 40) litres/d and the mean energy expenditure was 25 (SE 0.8) MJ/d. There were no significant differences in the isotope distribution spaces and flux rates, rH2O, rCO2 or energy expenditure using the multi-point or two-point approaches to calculation. The DLW-derived energy expenditure of 25 MJ/d is approximately 20% higher than the recommended intake of 21 MJ/d for adult hinds kept outdoors (Adam, 1986) and, at 757 kJ/kg0.75 per d, one third higher than the value of 570 kJ/kg0.75 per d for stags penned indoors (Key et al. 1984).

Animals↗
PubMed1998

A review of induced abortion rates in England and Wales, 1969-1994.

This study examines trends in induced abortion rates in England and Wales, from 1969 to 1994. A comparison of the trends between the different age groups shows contrasting changes and interesting features. The only age group to show a continuous increase since 1969 has been females aged 11 to 14 years. This may be due to birth cohort effect, as younger women begin sexual activity in a social environment of higher risk than previous cohorts. These considerations have important implications for the organisation of preventive services particularly health education. In spite of the availability of improved and better contraceptive services and sex education, the cohort analysis suggests that induced abortion rates in each successive cohort was higher than the preceding cohort.

Abortion, Induced↗
PubMed1997

Long-chain polyunsaturated fatty acid transport across the perfused human placenta.

The role of the placenta in controlling the supply of fatty acids to the fetus was investigated in term placentae (n = 9) from normal pregnancies. The maternal side was perfused ex vivo for 90 min with a modified Krebs Ringer solution containing a physiological mixture of fatty acids and ratio of fatty acid to human albumin. There was no evidence of chain elongation and desaturation of the essential fatty acids. Relative to the value for oleic acid, the rate of transfer to the fetal circulation was: 1.30 +/- 0.02 (P < 0.001) for linoleic acid, 1.61 +/- 0.09 (P = 0.002) for alpha-linolenic acid, 0.67 +/- 0.10 (P = 0.033) for arachidonic acid and 2.10 +/- 0.16 (P = 0.003) for docosahexaenoic acid. For tissue accumulation the values were 1.47 +/- 0.39 (P < 0.001) for linoleic acid, 2.24 +/- 0.37 (P = 0.027) for alpha-linolenic acid, 9.84 +/- 1.03 (P = 0.001) for arachidonic acid, and 3.01 +/- 0.79 (P = 0.064) for docosahexaenoic acid. The order of selectivity for transfer from the maternal to the fetal circulation was docosahexaenoic > alpha-linolenic > linoleic > oleic > arachidonic acid. Such a mechanism would allow the preferential transfer of docosahexaenoic acid and the essential fatty acids to the fetal circulation, thereby protecting the polyunsaturated fatty acid supply to the fetus during a critical period of development.

Adult↗
PubMed1996

Industrial atmospheric pollution, historical land use patterns and mortality.

BACKGROUND: The measurement of atmospheric pollution for epidemiological studies is problematic. This study presents a new proxy measure of atmospheric pollution of industrial origin and uses it to determine, at electoral ward level, the relationship between atmospheric pollution and all-cause mortality. METHODS: All-cause Standardized Mortality Ratios (SMR), all ages, and for persons under 65 years for the period 1984-1988, proportions of land in each ward utilized by industrial works (the proxy for atmospheric pollution) and levels of socioeconomic deprivation of the ward residents were compared in 104 electoral wards. RESULTS: The all-age SMR in the 22 wards containing the largest proportions of industrial land (113) was 9.7 per cent higher than the SMR (103) in the 60 wards with no industrial land. The under 65 years SMR in the 22 highly industrialized wards (120) was 22.4 per cent higher than the SMR (98) in the wards with no industrial land. After matching the levels of deprivation, the all-age SMR in the 15 wards containing over 10 per cent industrial land (116) was significantly higher than the SMR in 15 wards containing no industrial land (108); corresponding figures for the under 65 years SMR were 135 and 118. CONCLUSIONS: A greater proportion of industrial land in a ward is associated with a higher mortality of the ward residents, even after controlling for the level of socio-economic deprivation of the residents. The association between deprivation and mortality is stronger than the association between atmospheric pollution and mortality. There is an urgent need for better measures of atmospheric pollution which are usable in epidemiological studies.

Adolescent↗