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Biomedical subjects

T Forrester

Publications and source records attributed to T Forrester.

At least 73 records · Page 4Linked to original sources
PubMed1996

Development of food frequency questionnaires in three population samples of African origin from Cameroon, Jamaica and Caribbean migrants to the UK.

OBJECTIVES: To develop the methods for assessment of food and nutrient intake using standardized food frequency questionnaires (FFQ) in three African origin populations from Cameroon, Jamaica and Caribbean migrants to the United Kingdom. DESIGN: Cross-sectional assessment of diet from a representative sample in each site, using either a 2-day food diary or a 24-h recall method to determine foods for inclusion on the food frequency questionnaire. SETTING: A rural and urban site in Cameroon, Evodoula and Cite Verte in Yaounde, respectively; a district in Kingston Jamaica; African-Caribbeans living in central Manchester, UK. SUBJECTS: Aged 25-79 years, 61 from the Cameroonian urban site, 62 from the village site; 102 subjects from Jamaica (additional analysis on a subsample of 20): 29 subjects from Manchester, UK. MAIN OUTCOME MEASURES: Foods contributing to nutrients in each site to allow the development of a FFQ. RESULTS: A high response rate was obtained in each site. Comparison of macronutrient intakes between the sites showed that carbohydrate was the most important contributor to energy intake in Jamaica (55%) and the least in rural Cameroon. In rural Cameroon, fat (mainly palm oil) was the most important contributor to energy intake (44%). Manchester had the highest contribution of protein to energy (17%). Foods contributing to total energy, protein, fat and carbohydrate were determined. In rural Cameroon, the top 10 food items contributed 66% of the total energy intake compared to 37% for the top 10 foods in Manchester. Foods contributing to energy were similar in Jamaica and Manchester. Cassava contributed 44% of the carbohydrate intake in rural Cameroon and only 6% in urban Cameroon. One FFQ has been developed for use in both sites in Cameroon containing 76 food items. The FFQ for Jamaica contains 69 foods and for Manchester 108 food items. CONCLUSION: Considerable variations exist within sites (Cameroon) and between sites in foods which are important contributors to nutrient intakes. With careful exploration of eating habits it has been possible to develop standardized, but locally appropriate FFQs for use in African populations in different countries.

Adult↗
PubMed1995

The erythrocyte as a regulator of vascular tone.

Local regulation of microvascular blood flow is a complex process in which the needs of the tissue must be communicated to the vasculature, enabling the appropriate matching of O2 supply to demand. We hypothesize that the red blood cell is not only the major O2 carrier but also serves as an O2 sensor and affecter of changes in O2 delivery via its release of ATP, which subsequently binds to P2y receptors on the vascular endothelium, altering vessel caliber. Using the hamster as a model, we determined that the efflux of ATP from red blood cells after exposure to low-PO2 (PO2 = 17 +/- 6 mmHg) and low-pH (pH = 7.06 +/- 0.07) solutions was significantly (P < 0.01) greater than that after exposure to normoxic, normal pH (PO2 = 87 +/- 4; pH = 7.38 +/- 0.04) solutions, indicating that two factors that are associated with an impaired O2 supply relative to demand increase the release of ATP from the red blood cell. To ascertain whether ATP alters vascular caliber, we applied 10(-6) M ATP intraluminally to arterioles of the retractor muscle, using a micropressure system. Vessel diameter increased 8 and 10%, 140 +/- 60 microns upstream of the site of infusion after 50- and 500-ms pulses, respectively. Application of ATP to arteriolar and venular capillaries induced a 31 and 81% increase in red blood cell supply rate, respectively. These results support our hypothesis that the red blood cell is more than just an O2 carrier and has a direct role in the regulation of vascular tone.

Adenosine Triphosphate↗
PubMed1995

Segregation and linkage analysis of serum angiotensin I-converting enzyme levels: evidence for two quantitative-trait loci.

Human serum angiotensin I-converting enzyme (ACE) levels vary substantially between individuals and are highly heritable. Segregation analysis in European families has shown that more than half of the total variability in ACE levels is influenced by quantitative-trait loci (QTL). One of these QTLs is located within or close to the ACE locus itself. Combined segregation/linkage analysis in a series of African Caribbean families from Jamaica shows that the ACE insertion-deletion polymorphism is in moderate linkage disequilibrium with an ACE-linked QTL. Linkage analysis with a highly informative polymorphism at the neighboring growth-hormone gene (GH) shows surprisingly little support for linkage (LOD score [Z] = 0.12). An extended analysis with a two-QTL model, where an ACE-linked QTL interacts additively with an unlinked QTL, significantly improves both the fit of the model (P = .002) and the support for linkage between the ACe-linked QTL interacts additively with an unlinked QTL, significantly improves both the fit of the model (P = .002) and the support for linkage between the ACe-linked QTL and GH polymorphism (Z = 5.0). We conclude that two QTLs jointly influence serum ACE levels in this population. One QTL is located within or close to the ACE locus and explains 27% of the total variability; the second QTL is unlinked to the ACE locus and explains 52% of the variability. The identification of the molecular mechanisms underlying both QTLs is necessary in order to interpret the role of ACE in cardiovascular disease.

Analysis of Variance↗
PubMed1994

Urea production and salvage during pregnancy in normal Jamaican women.

The pattern of aggregate nitrogen demand during pregnancy and the fetal and maternal components are unclear. Excess demand enhances efficiency of nitrogen utilization. Urea salvage contributes to enhanced efficiency. Dietary protein intake, urea production, and salvage of urea nitrogen were measured in eight nonpregnant control subjects, and trimesterly in nine pregnant women. Production was measured after prime-intermittent intravenous doses of [15N 15N]-urea by dilution of label in urinary urea. Dietary protein intake was greater in trimester 1 than in nonpregnant women (167 +/- 36 vs 224 +/- 60 mg N.kg-1.d-1), and increased further in trimester 2 (266 +/- 59 mg N.kg-1.d-1). Urea production was not higher during pregnancy. Despite higher protein intake, urea salvage was higher in pregnancy (40 +/- 24 nonpregnant vs 77 +/- 23, 61 +/- 31, and 51 +/- 12 mg N.kg-1.d-1). Therefore, the demand-supply gap for nitrogen was greatest early in pregnancy when fetoplacental growth is slowest, and implies heightened maternal demand.

Adult↗
PubMed1994

Maternal nutritional status in pregnancy and blood pressure in childhood.

OBJECTIVE: To examine the relation between indices of maternal nutrition during pregnancy, including haemoglobin concentration, skinfold thickness and body weight, and the child's blood pressure at 10 to 12 years of age. DESIGN: Follow up study of children whose mothers had haemoglobin estimations, weights and skinfold thicknesses recorded during pregnancy. SETTING: Kingston, Jamaica. SUBJECTS: Seventy-seven children whose mothers took part in a prospective study of nutrition during pregnancy in relation to fetal growth. MAIN OUTCOME MEASURE: Blood pressure at 10 to 12 years of age. RESULTS: The child's mean systolic pressure adjusted for current weight rose by 2.6 mmHg (95% CI 0.5-4.6, P = 0.01) for each 1 g/dl fall in the mother's lowest haemoglobin during pregnancy. Mothers with a lower haemoglobin had thinner skinfold thicknesses, especially over the triceps (P = 0.005). In multiple regression analyses, taking account of the child's sex and current weight, there was a strong association between thin maternal triceps skinfold thickness at 15 weeks of gestation and raised blood pressure in the offspring. Taking account of the mother's triceps skinfold thickness abolished the relation between lower haemoglobin and raised blood pressure in the child. Lower weight gain between 15 and 35 weeks of gestation was independently associated with raised children's blood pressure. Systolic pressure rose by 10.7 mmHg (95% CI 5.7 to 15.6, P = 0.0001) for each log mm decrease in the mother's triceps skinfold thickness, and by 0.6 mmHg (95% CI 0.1 to 1.0, P = 0.02) for each 1 kg decrease in the mother's weight gain during pregnancy. CONCLUSIONS: These results parallel animal experiments suggesting that impaired maternal nutrition may underlie the programming of adult hypertension during fetal life.

Blood Pressure↗
PubMed1994

Parkinsonian-like tremors in the recovery phase of kwashiorkor.

Kwashi shakes is described in a 17-month-old Jamaican male infant. This is the first reported case seen at the Tropical Metabolism Research Unit at the University of the West Indies, Mona, Jamaica and the first documented case in the West Indian literature.

Humans↗
PubMed1992

Release of ATP from human erythrocytes in response to a brief period of hypoxia and hypercapnia.

OBJECTIVE: The aims were, first, to detect and quantify the release of ATP from human erythrocytes in response to a brief exposure to a hypoxic/hypercapnic environment, similar to that found in vigorously exercising skeletal or cardiac muscle; and second, to explore the mechanism of ATP release in response to hypoxia. METHODS: Washed human erythrocytes suspended in Krebs-Henseleit solution were exposed for 50 s to an atmosphere of approximately 8.0 kPa PCO2 and 2.7 kPa PO2; ATP released into the suspension was assayed using the firefly luminescence technique. Samples of human blood were obtained by venepuncture of the median cubital vein from male and female volunteers ranging in age from 21 to 74 years. Anticoagulation was with EDTA. RESULTS: A background of 0.49 x 10(6) (SEM 0.037 x 10(6)) ATP molecules.cell-1 was attributed to spontaneous haemolysis of 1% of the cell population, as estimated by levels of haemoglobin measured in the suspension fluid. When the erythrocytes were exposed to the hypoxic/hypercapnic gas mixture at 37 degrees C the ATP concentration in the suspension fluid rose to 2.67 x 10(6) (0.27 x 10(6)) molecules.cell-1. An efflux rate of 276(37) molecules.mu-2.s-1 was calculated. The hypoxia induced ATP release was blocked in three different ways: first, by application of 50 microM of the specific band 3 anion channel blocking agents niflumic acid (a translocation inhibitor), DIDS (a transport site inhibitor), or dipyridamole (a channel blocker); secondly, by replacement of extracellular chloride and bicarbonate with the impermeant anion methanesulphonate; and thirdly, by application of 5 nM of the nucleoside transport blocker nitrobenzylthioinosine. None of these blocking techniques affected the background levels of ATP attributed to haemolysis. CONCLUSIONS: A situation of hypoxia/hypercapnia, such as would be found in exercising muscle, induces release of ATP from the erythrocyte via the plasma membrane protein moiety known as band 4.5 (a nucleoside transporter) and electrical balance across the erythrocyte membrane is maintained by the simultaneous influx of extracellular chloride and/or bicarbonate via the plasma membrane protein known as band 3 (anion channel). The circulation of erythrocytes into a region of hypoxia in vivo could promote an increase in local blood flow through release of endothelium dependent relaxing factor in response to released ATP.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

Urea kinetics: comparison of oral and intravenous dose regimens.

Urea kinetics were measured on two separate occasions in five adults with normal haemoglobin genotype (HbAA) and in four who were homozygous for sickle cell disease (HbSS). Prime/intermittent doses of [15N15N]urea were given orally on one occasion and intravenously on the other. In three of the nine individuals there appeared to be significant hydrolysis of the oral dose of urea before absorption, leading to spurious results for the urea kinetics. When only the studies in which isotope was given intravenously were considered, there was a difference in the rate at which urea-N was salvaged, with more urea-N being salvaged by HbSS subjects than HbAA. It is concluded that the oral presentation of isotope can be used to measure urea kinetics provided care is taken to exclude those subjects who are likely to display upper intestinal hydrolysis, and that there are differences in aspects of urea kinetics between HbAA and HbSS which may be of metabolic importance.

Absorption↗
PubMed1990

Reduction in vitro of red cell glutathione reproduces defects of cellular sodium transport seen in oedematous malnutrition.

Red cells in oedematous malnutrition (kwashiorkor) have an increased sodium content, 'leakiness' to sodium and enhanced sodium pumping. In non-oedematous malnutrition (marasmus) there is a reduction in the sodium pump activity. The explanation has hitherto been unknown but the glutathione content of red cells is low in kwashiorkor and normal in marasmus. We artificially lowered the glutathione content of normal red cells to values characteristic of mild oedematous malnutrition, using the enzyme inhibitors bischloronitrosourea (BCNU) and buthionine sulfoximine (BSOX). After preincubation, the cells were washed to remove the inhibitors and oxidized glutathione. Cellular content of sodium and potassium, and 86Rb influx were then measured. The reduction in glutathione reproduced the abnormalities of sodium content and flux observed in kwashiorkor. We suggest that oxidant stress in kwashiorkor, by reducing cellular glutathione, may affect cell membrane electrolyte transport. This may act through alterations in membrane sulfhydryl groups. Glutathione depletion may therefore play an important role in the clinical picture and natural history of oedematous malnutrition and may have relevance to other conditions where oxidant stress occurs.

Adult↗
PubMed1989

Relationship between leucocyte sodium content and high blood pressure during development and resolution of pre-eclampsia.

1. One hundred and five primigravidae were followed sequentially at 4-weekly intervals starting at gestational week 31. They were seen again at 6 weeks post partum. 2. At each visit measurements were made of blood pressure as well as of leucocyte and erythrocyte sodium and potassium content. 3. Eighty-five subjects completed the study. Seven developed pre-eclampsia. 4. In both controls and patients who developed pre-eclampsia, leucocyte and erythrocyte sodium content increased with gestational age and fell post partum. These changes were of greater magnitude in the patients with pre-eclampsia. Cell potassium fell in both groups, but to a greater extent in patients with pre-eclampsia. 5. These changes in cell sodium paralleled those in blood pressure in both groups. 6. These data suggest that the excessive blood pressure changes in pre-eclampsia might be related to similar changes in cell sodium content.

Adult↗
PubMed1988

Protective effect of exogenous fructose-1,6-diphosphate in cardiogenic shock.

The effect of intravenous fructose-1,6-diphosphate (FDP) infusion on haemodynamic and biochemical variables was studied in dogs after ligation of the anterior descending branch of the left coronary artery. In the control series cardiogenic shock was present in every case 4 h after ligation. In FDP treated animals 4 h after ligation there was no fall in cardiac output and the systolic blood pressure was restored to pre-ligation values. Levels of serum creatine kinase isoenzyme (CK-MB), a highly specific indicator of myocardial cell damage, rose in the shocked (no FDP given) group, but remained low in the FDP treated group, equalling the levels measured in sham operated (no ligation) dogs. Samples of myocardium were taken from infarcted and adjacent normal regions 4 h after ligation for biochemical analysis. CK-MB concentrations in the infarcted region did not change from normal levels with FDP infusion; in the infarcted region lactate concentration (mumol.g-1 wet weight) fell from 18.48 in the control group to 7.90 in the FDP treated group. ATP levels in the infarcted region remained the same as those in the adjacent normal region with FDP treatment. It is concluded that infusion of FDP improves myocardial performance and metabolism following acute myocardial ischaemia.

Animals↗
PubMed1987

Urinary excretion of 5-oxoproline (pyroglutamic aciduria) as an index of glycine insufficiency in normal man.

1. The evidence is accumulating to suggest that glycine, the simplest amino acid, is conditionally essential in man. Benzoic acid, by conjugation with glycine to form hippuric acid, is known to deplete the free glycine pool of the body. Glycine is one substrate for the enzyme glutathione synthase (EC 6.3.2.3) and in the inborn error of metabolism in which glutathione synthase function is defective, increased quantities of 5-oxoproline are excreted in the urine. 2. An oral dose of 4-10 g sodium benzoate was given to six normal adults to deplete the metabolic pool of glycine, and the urinary excretion of 5-oxoproline was followed for 6 h. In five of the six, a significant increase in the urinary 5-oxoproline was seen within 3 h. 3. These findings show that 5-oxoprolinuria can result from limited glycine availability, and may provide a useful test for assessing glycine sufficiency in a range of physiological and pathological states.

Adult↗
PubMed1985

Appearance of adenosine triphosphate in the perfusate from working frog heart.

Frog hearts (Rana pipiens) were perfused in situ with Ringer's solution and the perfusate tested on firefly extract for the presence of ATP. At a normal perfusion pressure of 8 cm. H2O the rate of release of ATP into the perfusate was 8.8 (+/- S.E.1.7) pmoles.min-1. When the workload was increased by raising the perfusion pressure to 12 cm. H2O the rate of release increased to 28.3 (+/- S.E.4.8) pmoles.min-1. The rate of release was found to be proportional to the amount of workload imposed upon the heart. It is postulated that the trigger for release is hypoxia and that the release of ATP from the cardiac cell will augment contractility of the myocardium through its action upon adjacent cells via the P2 purinergic receptor. cells via the P2 purinergic receptor.

Adenosine Triphosphate↗
PubMed1985

A method for enriching the cadmium content of cigarette smoke and effect of exposure to this smoke on coronary vascular reactivity in the rat.

To study the effect of smoke-borne cadmium on the cardiovascular system, a method was developed to vary the cadmium content in the smoke of Kentucky 2R1 reference cigarettes. 2R1 filler tobacco was sprayed with aqueous solutions of CdSO4; cigarettes were prepared from this tobacco and smoked through Cambridge filters. These treatments increased the cadmium content of the cigarette smoke from 0.23 +/- 0.01 micrograms Cd/2R1 cigarette to 0.317 +/- 0.029, 2.38 +/- 0.092, and 4.9 +/- 0.1 micrograms Cd/cigarette for 500 microM, and 50 mM CdSO4, respectively. Male Sprague-Dawley rats were exposed for 5 or 23 weeks to smoke from 2R1 reference cigarettes and cigarettes prepared from 2R1 tobacco that was treated with 500 microM CdSO4. Following 5 weeks of smoke exposure, neither kidney cadmium amount nor coronary vascular reactivity to angiotensin was altered in either smoke-exposed group compared to cage controls or sham-smoked animals. After 23 weeks of exposure, cadmium amounts in kidneys from animals exposed to cadmium-enriched smoke were significantly greater than quantities observed in any other group. Exposure to either type of cigarette smoke increased coronary vascular reactivity above either control group. Exposure to cadmium-enriched cigarette smoke increased coronary vascular reactivity to angiotensin above the amount observed following exposure to 2R1 cigarette smoke. This finding indicates that smoke-borne cadmium may mediate the observed increases in coronary vascular reactivity following exposure to cigarette smoke.

Analysis of Variance↗
PubMed1983

Possible source of adenosine triphosphate released from rat myocytes in response to hypoxia and acidosis.

Ventricular cells from adult rats were isolated enzymatically and used as a model system for determining what factors affect the release of adenosine triphosphate (ATP) from myocardial cells. The enzyme systems used to isolate cells were trypsin:collagenase; hyaluronidase:collagenase and dispase:collagenase. Adenosine triphosphate was released in greater amounts in response to hypoxia from cells freed by each of the enzymatic procedures. This occurred while the intracellular concentration of ATP remained constant. Experiments were then performed to determine whether the conditions that occur during myocardial ischaemia or hypoxia altered the release of ATP. Cells suspended in either oxygenated or anoxic buffer at a pH of 6.8 released a significantly lower amount of ATP than cells suspended in either condition at pH 7.4. To test the possibility that ATP was released from nucleotide-protein-Ca2+ complexes located in the sarcolemma, artificial disruption of these structures was carried out. Incubation of oxygenated cells with the chelating agent, ethyleneglycol-bis (B-aminoethyl ether)-N, N-tetraacetic acid (EGTA), stimulated the release of ATP in a hyperbolic relationship while incubation of anoxic cells with ethylenediamine tetraacetate (EDTA) stimulated the release of ATP in such a way that the pattern of release followed a sigmoid response with maximal amounts of ATP, 995 +/- 55 pmol.mg-1 protein, occurring in the presence of 0.1 to 2.0 mmol.litre-1 EDTA. By incubating cells with radioactive EDTA, there was no indication that EDTA entered the cells. No release of ATP above control levels occurred when EDTA was chelated with Ca2+ before being applied to isolated cells. These data suggest that the source of ATP found extracellularly may have been nucleotide-protein-Ca2+ complexes located in the sarcolemma, and further support the role of ATP as a coronary vasodilator during hypoxic conditions.

Adenosine Triphosphate↗
PubMed1982

Exacerbation of the calcium paradox with exogenous adenosine triphosphate in isolated working rat heart.

The deleterious effect of calcium withdrawal and restoration on cardiac cell membranes ('Ca-paradox') was studied using isolated, working rat heart. The optical density of the coronary sinus effluent was measured at 260 nm wavelength. The efflux of A260 material upon restoration of calcium was proportional to the duration of calcium-free perfusion, indicating graded membraneous injury. When ATP, 10(-6) to 10(-4) M, was added to the calcium-free perfusate for 30 s of calcium-free perfusion, release of A260 material increased as a logarithmic function of exogenous ATP concentration. That this exacerbating effect is produced by such low concentrations relative to intracellular amounts indicates an action of ATP on the membrane surface. It is suggested that exogenous ATP enhances calcium entry into the cell, thus contributing to calcium influx through membranes already rendered abnormally permeable from the 'Ca-paradox' mechanism.

Adenosine Triphosphate↗