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Biomedical subjects

A A Jackson

Publications and source records attributed to A A Jackson.

At least 19 recordsLinked to original sources
PubMed2006

L-serine uptake by human placental microvillous membrane vesicles.

The human fetus requires more glycine than any other amino acid but placental glycine transfer to the fetus is insufficient to meet fetal demand. L-Serine could represent a major metabolic source of glycine for the human fetus but little is known about the kinetics and physiology of L-serine uptake by the human placenta. We have characterised the amino acid transport systems involved in the uptake of L-serine by the microvillous membrane of the human placental syncytiotrophoblast and compared the uptake rates to those of glycine. L-Serine uptake into microvillous membrane (MVM) vesicles was primarily mediated by system A (MeAIB inhibitable) and system L (BCH inhibitable). Further characterisation using specific substrates of LAT1 and LAT2 found the pattern of L-serine uptake was consistent with that expected for uptake mediated by LAT2. Uptakes were performed with tracer levels of (14)C-L-serine, physiological levels of L-serine, or with physiological levels of amino acids. As amino acid concentrations rose, the proportion of uptake by System L decreased while uptake by uncharacterised Na(+)-independent systems increased. Uptake of Lserine into MVM vesicles had a V(max) of 2.1+/-0.4 nmol/mg protein/min, which was significantly higher than for glycine (V(max) 1.0+/-0.2 nmol/mg protein/min). This indicates that MVM vesicles have a higher uptake capacity for L-serine than glycine, despite a greater demand for glycine over serine for fetal protein synthesis. Further studies are now required to define the fate of L-serine taken up by the placenta and its importance for the fetus.

Amino Acid Transport System A↗
PubMed2006

Relationship between birth weight and urea kinetics in children.

OBJECTIVE: To explore the effect of birth weight on urea kinetics in young healthy children. DESIGN: Observational study. SETTING: Tertiary center for treatment of malnutrition. SUBJECTS: A total of 17 male children, 6-24 months old, who had recovered from malnutrition. INTERVENTIONS: Urea kinetics were measured using stable isotope methodology with [(15)N(15)N]-urea over 36 h. RESULTS: Birth weight was negatively related to urea hydrolysis after controlling for the intake of protein (adjusted R (2 ) = 0.91, P = 0.001) and separately for energy intake (adjusted R (2) = 0.95, P = 0.001), age (adjusted R (2) = 0.90, P = 0.001) and rate of weight gain (adjusted R (2) = 0.91, P = 0.001). There was a tendency for higher urea production in the children with lower birth weight after controlling for nitrogen intake (adjusted R (2) = 0.93, P = 0.099), and separately for age (adjusted R (2) = 0.94, P = 0.06) and rate of weight gain (adjusted (R (2) = 0.92, P = 0.096). Urea excretion was not significantly related to birth weight. CONCLUSIONS: The salvaging of urea nitrogen following urea hydrolysis contributed significantly more to the nitrogen economy in children with lower birth weight compared to those with higher birth weight. This may be as a result of reductive adaptation in the children with lower birth weight as a consequence of inappropriate prenatal nutrition and growth.

Adaptation, Physiological↗
PubMed2006

Improving child survival: Malnutrition Task Force and the paediatrician's responsibility.

Malnutrition (underweight) contributes to approximately 60% of all child deaths, yet health professionals, policy makers, and donor agencies often fail to recognise its relevance to child survival. There is a need for the paediatric community to champion the importance of adequate nutrition for normal growth and development, and of placing sufficient emphasis on the prevention and treatment of malnutrition. Many severely malnourished children die from inappropriate treatment. Case fatality rates of 25-30% are commonly found and in some hospitals as many as 50-70% will die. Many of these deaths are avoidable. Weaknesses in health systems, inappropriate training of doctors and nurses, inadequate supervision, and lack of support for staff all contribute to compromised quality of care. The International Union of Nutritional Sciences, with support from the International Pediatric Association, Launched a global Malnutrition Task Force in 2005. The main objective is to ensure that an integrated system of prevention and treatment of malnutrition is actively supported as a fundamental aspect of care, and becomes an integral part of all training programmes.

Case Management↗
PubMed2005

Training does not affect protein turnover in pre- and early pubertal female gymnasts.

This study compared protein turnover in ten young female gymnasts [10.3 (0.5) years] engaged in regular intense physical training with ten age-matched controls [9.4 (0.6) years)]. Nitrogen flux ( Q), protein synthesis (PS), protein degradation (PD) and net protein turnover (NPB = PS-PD) were measured following a single oral dose of [(15)N]-glycine. The habitual dietary intake of each subject was assessed using a 7-day food record, with food portions being weighed before ingestion. The gymnasts had a low total energy intake which was unbalanced in the proportions of lipid, carbohydrate and protein. Protein flux was 7.19 (0.35) g.kg(-1).day(-1) in the gymnasts and 7.53 (0.81) g.kg(-1).day(-1) in the controls; protein synthesis was 6.06 (0.27) g.kg(-1).day(-1 )in the gymnasts and 6.53 (0.74) g.kg(-1).day(-1) in the controls; protein degradation was 5.45 (0.38) g.kg(-1).day(-1) in the gymnasts and 5.27 (0.74) g.kg(-1).day(-1) in the controls. All data are presented as means and standard errors of the mean (SEM). There were no statistical differences for protein flux, protein synthesis or protein degradation between the two groups. However, NPB was lower (-14%) in the trained gymnasts than in the control group ( P <0.05), which might be explained by a greater protein ingestion in the control group on the day of the protocol ( P <0.05). These results show that in pre- and early pubertal female gymnasts intense training does not exert a demonstrable effect on protein turnover.

Child↗
PubMed2003

Glycine rectifies vascular dysfunction induced by dietary protein imbalance during pregnancy.

Protein restriction in rat pregnancy programmes the development of elevated systolic blood pressure and vascular dysfunction in the offspring. A recent study has shown that hypertension is reversed by maternal glycine supplementation. Whether this protective effect is exerted directly on the embryo and fetus, or indirectly via effects on the mother, is unknown although we have previously shown abnormalities in the maternal vasculature. We tested the hypothesis that dietary glycine repletion would reverse endothelial dysfunction in protein-restricted pregnant rat dams using wire myography. Impaired acetylcholine- (P < 0.01) and isoprenaline-induced (P < 0.05) vasodilatation in isolated mesenteric arteries (MA) from protein-restricted pregnant dams was accompanied by reduced vascular nitric oxide (NO) release (P < 0.05). Dietary glycine supplementation reversed vascular dysfunction in MA (P < 0.05) and improved NO release thus potentially protecting the maternal circulation. The impaired NO release in the MA of low protein diet dams was not accompanied by reduced eNOS mRNA expression, suggesting that eNOS activity was altered. Protein restriction did not alter the vascular function of a conduit artery, the thoracic aorta. These results provide evidence that adequate provision of glycine, a conditionally essential amino acid in pregnancy, may play a role in the vascular adaptations to pregnancy, protecting the fetus from abnormal programming of the cardiovascular system.

Animals↗
PubMed2003

Prevalence of risk of undernutrition is associated with poor health status in older people in the UK.

OBJECTIVES: To establish the prevalence of the risk of undernutrition, using criteria similar to those used by the Malnutrition Advisory Group (MAG), in people aged 65 y and over, and to identify relationships between risk of undernutrition and health and demographic characteristics. DESIGN: A cross-sectional nationally representative sample of free-living and institutionalized older people in the UK (65 y of age and over). Secondary analysis of the National Diet and Nutrition Survey based on 1368 people aged 65 y and over. RESULTS: About 14% (21% in those living in institutions) were at medium or high risk of undernutrition based on a composite measure of low body mass index and recent reported weight loss. Having a long-standing illness was associated with a statistically significantly increased risk of undernutrition (odds ratio: men 2.34, 95% CI 1.20-4.58; women 2.98; 1.58-5.62). The risk of undernutrition increased: in women reporting bad or very bad health status; in men living in northern England and Scotland; for those aged 85 y and older; for those hospitalized in the last year, and those living in an institution. Lower consumption of energy, meat products or fruit and vegetables and lower blood measures of zinc, vitamins A, D, E and C were associated with statistically significantly increased risk of undernutrition. CONCLUSIONS: A substantial proportion of the older population of the UK is at risk of undernutrition. High-risk subjects are more likely to have poorer health status. It is unlikely that the individuals at high risk are being detected currently, and therefore effective care is not being provided, either in the community or in institutions.

Aged↗
PubMed2003

ARP1 interacts with the 5' flanking region of the coagulation factor VII gene.

Factor (F)VII plays a critical role in initiation of coagulation. Several segments within the 5' flanking region of the FVII gene were previously demonstrated to recognize hepatic nuclear proteins, but few have been identified. To identify a regulatory protein binding the nuclear hormone response region (-237 to -200) of the FVII 5' flanking region and demonstrate that the interaction is functional. Electrophoretic mobility shift assays and mutation analysis showed that ARP1, an orphan nuclear hormone receptor, interacted with two regions of the FVII 5' flanking region, the hepatic nuclear factor 4 binding region (-77 to -47) and the nuclear hormone response region (-237 to -200). Transfection experiments demonstrated that reporter gene expression was decreased from vectors including the nuclear hormone response segment compared with that containing only the minimal promoter between positions -109 and +1, and that ARP1 also repressed expression through an interaction with the minimal promoter. These data indicate a role for ARP1 in transcriptional modulation of the FVII gene.

5' Flanking Region↗
PubMed2003

A functional haplotype in the 5' flanking region of the factor VII gene is associated with an increased risk of coronary heart disease.

AIMS: The aim of this study was to investigate associations between coronary heart disease risk and polymorphisms in the coagulation factor (F)VII gene in participants of a large prospective study. METHODS: One thousand nine hundred and fifty-seven men were genotyped for four FVII polymorphisms, -670A-->C, -402G-->A, a 10 base pair insertion at -323 (0 > 10) in the promoter, and R353Q in the structural gene. Associations among genotypes and estimated haplotypes, plasma FVII levels, and coronary heart disease risk were evaluated, and the function of the promoter polymorphisms was assessed in reporter gene assays. RESULTS: The -670A-->C and -402G-->A polymorphisms were in complete allelic association. The haplotype containing -670C and -402A (frequency =0.23) was associated with significantly increased plasma FVII coagulant activity and increased risk of an initial coronary event, particularly acute myocardial infarction, which remained after correction for conventional risk factors. In contrast, the -323 insertion and Q353 alleles (frequency =0.11 and 0.10, respectively) were associated with decreased plasma FVII levels, but hazard ratios for coronary events in carriers of these alleles were not significantly different from unity. In transiently transfected hepatoma cells, increased basal expression of the reporter gene was directed by a promoter fragment with rare haplotype -670C/-630G/-402A rather than by a promoter fragment with common haplotype -670A/-630A/-402G; -402A was not responsible for this effect. CONCLUSIONS: The promoter haplotype, -670C/-630G/402A, was associated with significantly increased plasma FVII coagulant activity, risk of an initial coronary event, particularly acute myocardial infarction, and reporter gene expression.

Alleles↗
PubMed2002

The paradox of improved antiretroviral therapy in HIV: potential for nutritional modulation?

Chronic infection with HIV type 1 is associated with alterations in macronutrient metabolism, specifically elevated plasma lipids, glucose and reduced insulin sensitivity. These alterations are most severe in patients at the later stages of AIDS, indicating a relationship with disease progression. Recently, a metabolic syndrome, termed lipodystrophy, has been described in successfully-treated HIV patients in whom the altered macronutrient metabolism of HIV infection appears to be amplified markedly, with concurrent alterations in adipose tissue patterning. This syndrome presents a paradox, as before the development of highly-active antiretroviral therapy (HAART) the most severe perturbations in metabolism were observed in the sickest patients. Now, the patients that respond well to therapy are showing metabolic perturbations much greater than those seen before. The implications of this syndrome are that, whilst life expectancy may be increased by reducing viral load, there are concomitant increases in the risk of cardiovascular disease, diabetes and pancreatitis within this patient population. The aetiology of the syndrome remains unclear. In a collaborative trial with the Chelsea and Westminster Hospital in London we have used stable-isotope-labelled fatty acids to examine the hypothesis that treatment with HAART causes a delayed clearance of dietary lipid from the circulation, resulting in the retention of lipid within plasma and the downstream changes in insulin and glucose homeostasis. This hypothesis would indicate a role for low-fat diets, exercise and drugs that reduce plasma lipid or insulin resistance, in modulating the response to antiretroviral therapy in HIV infection.

Antiretroviral Therapy, Highly Active↗
PubMed2002

Maldigestion and malabsorption of dietary lipid during severe childhood malnutrition.

BACKGROUND: Diets rich in lipid are used to provide energy density in treating children with severe malnutrition, but the extent to which their digestion and absorption can cope with the load effectively is uncertain. AIM: To determine the extent of impaired digestion or absorption, in three groups of eight malnourished children (aged 5-23 months) using isotopic probes of the predominant fatty acids in coconut and corn oil used to fortify the diet. METHODS: Each child received oral doses of one of three (13)C labelled triglycerides (trilaurin, triolein, or trilinolein). The recovery of (13)C label in stool either as triglyceride (TAG) or fatty acid (FA), was used to assess digestion and absorption. In a separate test, the recovery of label in stool following an oral dose of [(13)C]-glycocholate was measured to assess bile salt malabsorption. RESULTS: The median recovery of label in stool was 9% (range 1-29%) of administered dose. Following treatment there was a reduction in stool (13)C excretion for the labelled TAG (<1%). In half the subjects, label was recovered as TAG in stool (median 0.6%, range 0-44%). Most label in stool was recovered as FA (median 30%, range 0-100%). Following [(13)C]-glycocholate, label was recovered in excess in about one third of studies. CONCLUSION: Abnormalities in the gastrointestinal handling of lipid were observed in over 50% of children with severe malnutrition, reflecting problems in absorption, although impaired solubilisation or hydrolysis could also be contributory factors. The underlying lesion improves as treatment progresses, leading to concomitant improvement in function.

Carbon Isotopes↗
PubMed2002

Persistence of lower birth weight in second generation South Asian babies born in the United Kingdom.

OBJECTIVE: To assess differences in birth weight between all first and second generation South Asian babies born in Southampton, and trends since 1957. DESIGN: Retrospective, cohort study. SETTING: Birth records for babies born in Southampton from 1957 to 1996 were searched to identify all babies born of South Asian origin (including from the Indian subcontinent, East Africa, and elsewhere). MAIN OUTCOME MEASURES: All information recorded in the birth record about the mother and baby was extracted. RESULTS: 2395 full term (>37 weeks; mean birth weight 3110; 95%CI 3092 to 3129) singleton births were identified. Detailed analysis was restricted to mothers either born in the Indian subcontinent (India, Pakistan, or Bangladesh (1435)) or United Kingdom (283). Mean birth weight and % low birth weight (<2500 g) were 3133 g (95%CI 3108 to 3157) and 7.5%, for first generation babies and 3046 g (2992 to 3099) and 11.7% for second generation babies. There was no trend over time to increased average birth weight in either first or second generation babies. Adjusting for other factors that were statistically significantly related to birth weight (gender, gestational age, mother's age, maternal weight at 15 weeks, parity, and mother's ethnic group) did not alter the trends. CONCLUSIONS: For that group in the UK who derive from the Indian subcontinent, average birth weight is significantly less than the national average. There has not been any increase in the average birth weight over the past 40 years, and the birth weight of babies of women who were born in the UK are no greater. The persistence of lower than desirable birth weight may result long term in higher than average rates of diabetes and heart disease in these groups.

Adult↗
PubMed2001

Dietary guidelines for pregnancy: a review of current evidence.

In a successful pregnancy maternal health is maintained, a healthy baby is delivered and the mother is able to nurture her newborn adequately. Despite continued interest in the role and importance of maternal diet in this process, we do not have a clear understanding of how the nutritional status of the mother influences fetal growth and development. Recent epidemiological evidence of an association between poor fetal growth and adult disease highlights the need to reconsider the influences which act on the fetus, and the role maternal nutrition may play. Nutrient needs are increased in pregnancy. For the mother to be solely dependent upon her dietary intake to meet these demands, would represent a very high risk strategy. Hence adequate reserves are important for a successful outcome. Whilst there are numerous observational studies of diet during pregnancy, there are only limited data from well-controlled, randomised supplementation studies. A recent systematic review showed only dietary supplements balanced in energy and protein content to result consistently in improved fetal growth. There is no strong evidence that nutrient supplements confer benefit in women without overt deficiency. To interpret future dietary studies in pregnancy we need to consider metabolic differences between women which may influence their ability to meet fetal nutrient demand, to allow for nutrient-nutrient interactions, and to take account of differences in timing in gestation. Consideration of these factors in studies of pregnancy, will lead to a clearer understanding of the links between maternal diet and fetal growth and development. Until we have this understanding, it is reasonable to expect that women entering pregnancy are provided with a diet which is adequate, based upon our normal understanding of requirements, and it is not acceptable for women to be expected to carry a pregnancy with an obvious or overt nutritional deficiency.

Dietary Supplements↗
PubMed2001

Human nutrition in medical practice: the training of doctors.

Nutritional advice from doctors and other health workers is held in high regard by the general public. It is important, therefore, to ensure that the advice given is sound and safe. Historically, the training in nutrition for the health professions has been piecemeal and selective. As a first step in the development of national standards, a core curiculum on nutrition for health professionals was developed as part of the National Nutrition Task Force. Designed for undergraduates, the curriculum sought to provide a standard for training which would ensure safe practice. The curriculum, which has been accepted by all undergraduate medical schools, identifies eighteen bullet points covering: the principles of nutritional science; public health nutrition; clinical nutrition and nutritional support. Postgraduate training for doctors is the responsibility of the Royal Colleges, who have formed an Intercollegiate Group on nutrition. This group has developed an intercollegiate foundation course in nutrition which lasts for I week and is offered at different centres around the country. Using the Intercollegiate Course as a base, individual Colleges are exploring how they might best develop the next level of training by identifying the educational needs for nutrition in different sub-specialities. There is some discussion as to whether it is timely to develop a defined clinical speciality in human nutrition. Within these developments, nutritionists and dietitians are identified as a resource to be called upon by other health professionals, and therefore it is important that in their own training they are suitably equipped to take on this challenge.

Clinical Competence↗
PubMed2001

Concomitant supplemental vitamin A enhances the response to weekly supplemental iron and folic acid in anemic teenagers in urban Bangladesh.

BACKGROUND: Iron deficiency is the most common micronutrient deficiency and affects >2 billion persons worldwide, leading to anemia in >40% of women of reproductive age in the developing world. OBJECTIVE: The objective was to determine whether weekly supplementation with iron and folate would reduce the frequency of anemia in teenage women in urban Bangladesh before they became pregnant. DESIGN: Participants with a hemoglobin concentration of 80-120 g/L were entered into a randomized, double-blind, placebo-controlled trial and received supplements of placebo, vitamin A, iron + folic acid, or iron + folic acid + vitamin A weekly for 12 wk. The supplements contained 2.42 mg vitamin A (retinol) as retinyl palmitate, 120 mg elemental Fe as ferrous sulfate, and 3.5 mg folic acid. RESULTS: Hemoglobin concentrations increased significantly more after supplementation with iron + folic acid or iron + folic acid + vitamin A than after either the placebo or vitamin A alone. There was a significantly greater increase in hemoglobin after iron + folic acid + vitamin A than after iron + folic acid, but the additional effect disappeared after adjustment for baseline hemoglobin, serum vitamin A, and ferritin and the number of supplements taken. Those with the lowest baseline hemoglobin had the greatest increase in hemoglobin. Compared with the placebo, iron + folic acid + vitamin A reduced anemia by 92%, iron deficiency by 90%, and vitamin A deficiency by 76%. CONCLUSION: There may be significant health benefits from a program that enhances the nutritional status of iron, folate, and vitamin A in poor urban young women before they become pregnant.

Adolescent↗
PubMed2001

Intake of micronutrient-rich foods in rural Indian mothers is associated with the size of their babies at birth: Pune Maternal Nutrition Study.

One third of the Indian babies are of low birth weight (<2.5 kg), and this is attributed to maternal undernutrition. We therefore examined the relationship between maternal nutrition and birth size in a prospective study of 797 rural Indian women, focusing on macronutrient intakes, dietary quality and micronutrient status. Maternal intakes (24-h recall and food frequency questionnaire) and erythrocyte folate, serum ferritin and vitamin C concentrations were measured at 18 +/- 2 and 28 +/- 2 wk gestation. Mothers were short (151.9 +/- 5.1 cm) and underweight (41.7 +/- 5.1 kg) and had low energy and protein intakes at 18 wk (7.4 +/- 2.1 MJ and 45.4 +/- 14.1 g) and 28 wk (7.0 +/- 2.0 MJ and 43.5 +/- 13.5 g) of gestation. Mean birth weight and length of term babies were also low (2665 +/- 358 g and 47.8 +/- 2.0 cm, respectively). Energy and protein intakes were not associated with birth size, but higher fat intake at wk 18 was associated with neonatal length (P < 0.001), birth weight (P < 0.05) and triceps skinfold thickness (P < 0.05) when adjusted for sex, parity and gestation. However, birth size was strongly associated with the consumption of milk at wk 18 (P < 0.05) and of green leafy vegetables (P < 0.001) and fruits (P < 0.01) at wk 28 of gestation even after adjustment for potentially confounding variables. Erythrocyte folate at 28 wk gestation was positively associated with birth weight (P < 0.001). The lack of association between size at birth and maternal energy and protein intake but strong associations with folate status and with intakes of foods rich in micronutrients suggest that micronutrients may be important limiting factors for fetal growth in this undernourished community.

Adolescent↗
PubMed2001

Synthesis of hepatic secretory proteins in normal adults consuming a diet marginally adequate in protein.

The plasma concentration and hepatic synthesis rates of albumin, transthyretin, very low-density lipoprotein apolipoprotein B-100 (VLDL-apoB-100), high-density lipoprotein apolipoprotein A-1, fibrinogen, alpha1-antitrypsin, and haptoglobin were measured in six normal adults before and after consuming a protein intake of 0.6 g. kg body wt(-1). day(-1) for 7 days. The synthesis of hepatic proteins was measured from the incorporation of [(2)H(5)]- phenylalanine, following prime/continuous infusion, using plasma VLDL-apoB-100 isotopic enrichment to represent the precursor pool. Synthesis of albumin declined by 50% (P < 0.001) following the lower-protein diet, VLDL-apoB-100 declined by 20% (P < 0.001), and apoA-1 declined by 16% (P < 0.05). By contrast, synthesis increased for fibrinogen (50%, P < 0.05) and haptoglobin (90%, P < 0.001). This pattern of change, with decreased synthesis of nutrient transport proteins and increased formation of acute-phase proteins, suggestive of a low-grade inflammatory response, was accompanied by increased plasma concentration of the inflammatory cytokine interleukin 6 (30%, P < 0.05). The pattern of change in the synthesis of hepatic secretory proteins following 7 days on the low-protein diet may be of functional relevance for lipid transport and the capacity to cope with stress.

Acute-Phase Proteins↗