PubMed Health⌕ Search

Biomedical subjects

A MacPherson

Publications and source records attributed to A MacPherson.

At least 19 recordsLinked to original sources
PubMed2002

Association between CYP2D6 genotype and tardive dyskinesia in Korean schizophrenics.

The CYP2D6 gene codes for human cytochrome P450 2D6 enzyme, which is responsible for the metabolism of many psychiatric drugs. In schizophrenic patients treated with neuroleptics, decreased or loss of function CYP2D6 alleles may contribute to the development of tardive dyskinesia (TD), a movement disorder that frequently occurs with chronic neuroleptic treatment. The goal of this study was to determine whether the occurrence of TD is associated with CYP2D6 genotype in a cohort of Korean schizophrenics by employing a CYP450 GeneChip((R)) oligonucleotide microarray and PCR assays to screen for 19 CYP2D6 alleles. Our results revealed that males with at least one decreased or loss of function allele have a moderately greater chance of developing TD than males with only wild-type alleles. Female schizophrenics did not have a significantly greater chance of developing TD. Our results demonstrate the utility of CYP2D6 microarrays to assess genotype status in this Korean cohort.

Adolescent↗
PubMed2001

Abnormal fetal growth is not associated with altered chorionic villous expression of vascular endothelial growth factor mRNA.

Altered placental and circulating levels of vascular endothelial growth factor (VEGF) and its receptor (flt-1) may be associated with pre-eclampsia and intrauterine growth restriction (IUGR). The aim of this study was to determine whether chorionic villous VEGF or flt-1 mRNA are altered at early gestation in pregnancies subsequently found to be complicated by abnormal fetal growth. Quantitative reverse transcription-polymerase chain reaction was performed on chorionic villous samples for VEGF and flt-1 using an internal RNA standard. Using the individualized birthweight ratio (IBR), the subjects (n = 51) were divided into three groups; IUGR (IBR <10th centile, n = 6), normal (IBR 10th-90th centiles, n = 41) and macrosomic (IBR >90th centile, n = 4). There was no correlation between the mRNA expression of VEGF(121) or VEGF(165) and gestational age of the normal controls. There was also no difference in the expression of either of the VEGF isoforms between the IUGR or macrosomic groups and the normal controls. Expression of flt-1 was below the detection limit of the assay. In conclusion, we have found that altered chorionic villous expression of VEGF is not associated with the initial stages of development of IUGR or macrosomia.

Actins↗
PubMed2001

Constitutive expression of the steroid sulfatase gene supports the growth of MCF-7 human breast cancer cells in vitro and in vivo.

Many human breast tumors are driven by high intratumor concentrations of 17beta-estradiol that appear to be locally synthesized. The role of aromatase is well established, but the possible contribution of the steroid sulfatase (STS), which liberates estrogens from their biologically inactive sulfates, has been inadequately assessed and remains unclear. To evaluate the role of STS further, we transduced estrogen-dependent MCF-7 human breast cancer cells with a retroviral vector directing the constitutive expression of the human STS gene. Gene integration was confirmed by Southern hybridization, production of the appropriately sized messenger RNA by Northern hybridization, and expression of functional protein by metabolism of [(3)H]estrone sulfate to [(3)H]estrone. Maximum velocity estimates of estrone formation are 64.2 pmol estrone/mg protein.h in STS-transduced cells (STS Clone 20), levels comparable to those seen in some human breast tumors. Lower levels of endogenous activity are seen in MCF-7 cells (13.0 pmol estrone/mg protein.h) and in cells transduced with vector lacking the STS gene (Vector 3 cells; 12.0 pmol estrone/mg protein.h). 17beta-Estradiol sulfate induces expression of the progesterone receptor messenger RNA only in STS Clone 20 cells, whereas estrone sulfate produces the greatest stimulation of anchorage-independent growth in these cells. STS Clone 20 cells retain responsiveness to antiestrogens, which block the ability of estrogen sulfate to increase the proportion of cells in both the S and G(2)/M phases of the cell cycle. Consistent with these in vitro observations, only STS Clone 20 cells exhibit a significant increase in the proportion of proliferating tumors in nude ovariectomized mice supplemented with 17beta-estradiol sulfate. The primary activity in vivo appears to be from intratumor STS, rather than hepatic STS. Surprisingly, 17beta-estradiol sulfate appears more effective than 17beta-estradiol when both are administered at comparable concentrations. This effect, which is seen only in STS Clone 20 cells, may reflect differences in the cellular pharmacology of exogenous estrogens compared with those released by the activity of intracellular STS. These studies directly demonstrate that intratumor STS activity can support estrogen-dependent tumorigenicity in an experimental model and may contribute to the promotion of human breast tumors.

Animals↗
PubMed2000

Relationship of hair calcium concentration to incidence of coronary heart disease.

This study was designed to evaluate whether hair calcium concentration reflects the mortality from coronary heart disease on a UK-wide basis and to determine the effect--if any--of environmental factors which might affect calcium metabolism on this relationship. The study was based on our earlier findings of an inverse relationship between hair calcium concentration and that in the intima of the aorta and the association of high aorta calcium with severe alterations to the vessel walls which was found never to co-exist with hair calcium concentrations greater than 700 ppm. Hair samples were collected from 4393 males in an ethically approved study in 40 different health districts. These covered the range in known prevalence of heart disease as reflected in the published standardised mortality ratios (SMR). Data on water hardness were obtained from the Water Authorities and on mean annual sunshine hours from the Meteorological Office. Statistical analysis was by regression and multivariate regression techniques. Hair calcium was determined by XRF analysis and the accuracy validated by means of certified reference samples. Significant relationships were found between health district and county SMR and their respective mean hair calcium concentrations accounting for 37 and 55% of their respective variances in SMR. Water hardness and sunshine hours accounted for 39 and 49% of the variance in mortality from CHD. In combination they accounted for 54% of the variance and with the inclusion of hair calcium 65%. South-east England had the highest hair calcium, the hardest water and the most sunshine hours and the lowest mortality from CHD. The converse was true of Scotland. Hair calcium concentration did reflect the risk of CHD on a population basis and was strongly influenced by both the hardness of the water supply and the annual sunshine hours which also independently affected the SMR for CHD.

Adult↗
PubMed2000

Analysis of single-nucleotide polymorphisms in the interleukin-4 receptor gene for association with inflammatory bowel disease.

Genetic linkage analysis in families with multiple cases of inflammatory bowel disease (IBD) has mapped a gene which confers susceptibility to IBD to the pericentromeric region of chromosome 16 (IBD1). The linked region includes the interleukin(IL)-4 receptor gene (IL4R). Since IL-4 regulation and expression are abnormal in IBD, the IL4R gene is thus both a positional and functional candidate for IBD1. We screened the gene for single-nucleotide polymorphisms (SNPs) by fluorescent chemical cleavage analysis, and tested a subset of known and novel SNPs for allelic association with IBD in 355 families, which included 435 cases of Crohn's disease and 329 cases of ulcerative colitis. No association was observed between a haplotype of four SNPs (val50ile, gln576arg, A3044G, G3289A) and either the Crohn's disease or ulcerative colitis phenotypes using the transmission disequilibrium test. There was also no evidence for association when the four markers were analyzed individually. The results indicate that these variants are not significant genetic determinants of IBD, and that the IL4R gene is unlikely to be IBD1. Linkage disequilibrium analyses showed that the val50ile and gln576arg variants are in complete equilibrium with each other, although they are separated by only about 21 kilobases of genomic DNA. This suggests that a very dense SNP map may be required to exclude or detect disease associations with some candidate genes.

Alleles↗
PubMed2000

Designer egg evaluation in a controlled trial.

OBJECTIVE: To evaluate the ability of designer eggs enriched in vitamin E, lutein, selenium (Se) and docosahexaenoic acid (DHA) to deliver micronutrients to the human in a palatable and visually acceptable form. DESIGN: Double-blind, placebo-controlled trial, two treatment groups balanced for sex and age. SETTING: Department of Biochemistry and Nutrition, SAC, Scotland. SUBJECTS: Forty healthy adult volunteers completed the study. Volunteers were recruited among staff of the Scottish Agricultural College Interventions: Volunteers consumed, for 8 weeks, either a designer egg or a normal table egg per day. Fasting blood samples were taken before and at the end of the study. RESULTS: Consumption of designer eggs enriched in vitamin E, lutein, Se and DHA significantly increased the levels of alpha-tocopherol, lutein and DHA in plasma as compared to the changes found after consumption of normal table eggs, with the largest increases found in plasma lutein (1.88-fold increase). The proportion of DHA was increased in all the main lipid classes of the plasma including triacylglycerol (2.3-fold), free fatty acids (1. 6-fold), cholesteryl ester (1.4-fold) and phospholipid (1.3-fold). Egg consumption did not change Se concentration in plasma, blood pressure, total plasma lipid concentrations or the concentrations of total cholesterol and HDL-cholesterol in plasma. CONCLUSION: Consumption of designer eggs enriched in vitamin E, lutein, DHA and Se as part of normal diet for 8 weeks effectively increased the blood levels of alpha-tocopherol, lutein and DHA. SPONSORSHIP: Scottish Office Agriculture, Environment, and Fisheries Department.

Adult↗
PubMed1998

The effect of oral selenium supplementation on human sperm motility.

OBJECTIVES: To determine whether the decline in selenium intake and selenium status in men in the West of Scotland might be a contributory factor to male subfertility. PATIENTS AND METHODS: Two semen samples were collected from patients attending a subfertility clinic and those patients with samples showing reduced motility were invited to participate in an ethically approved double-blind clinically controlled trial with informed consent. Sixty-nine patients were recruited and received either placebo, selenium alone or selenium plus vitamins A, C and E daily for 3 months. A further semen sample was collected at the end of the trial. Plasma selenium status was determined at the beginning and end of the trial period, as was total sperm density and motility. RESULTS: Plasma selenium concentrations were significantly (P < 0.001) higher in both selenium-treated groups than in controls. No significant effect of treatment on sperm density was recorded. Sperm motility increased in both selenium-treated groups, in contrast to a slight decline in the placebo group, but the difference was not significant. However, as the provision of additional vitamins had no effect on any variable measured it was considered justified to combine the two selenium-treated groups and compare them with the placebo treatment. On this basis, selenium treatment significantly (P < 0.002) increased plasma selenium concentrations and sperm motility (P = 0.023) but sperm density was again unaffected. Five men (11%) achieved paternity in the treatment group, in contrast to none in the placebo group. CONCLUSION: This trial confirms the result of an earlier study, that selenium supplementation in subfertile men with low selenium status can improve sperm motility and the chance of successful conception. However, not all patients responded; 56% showed a positive response to treatment. The low selenium status of patients not supplemented again highlights the inadequate provision of this essential element in the Scottish diet.

Adult↗
PubMed1998

Effect of supplementing the hen's diet with vitamin A on the accumulation of vitamins A and E, ascorbic acid and carotenoids in the egg yolk and in the embryonic liver.

1. The effect of a range of supplementations of vitamin A to the laying hen on the concentration of vitamins A, E, ascorbic acid and carotenoids in the maternal liver, the egg yolk and the embryonic liver were investigated. 2. Four groups of 25 Rhode Island Red hens were fed on standard layer-breeder diets with concentrations of supplemented vitamin A ranging from 0 to 120 micrograms/g retinol equivalents from 28 weeks of age. After 3 months, the concentration of vitamin A in the maternal liver was found to be greatly enhanced in proportion to the increasing rates of supplementation with the vitamin. However, the concentration of vitamin E in the maternal liver was markedly reduced by high dietary contents of vitamin A. 3. The concentration of vitamin A in the yolk of the hens' eggs was markedly increased by the dietary supplementation. However, the concentration of both vitamin E and carotenoids in the yolks were significantly reduced by high dietary contents of vitamin A. 4. The concentration of vitamin A in the liver of the embryo and the day old chick was greatly increased by the high concentrations of maternal vitamin A provision. However, the concentration of vitamin E, carotenoids and ascorbic acid in the embryonic/neonatal liver were significantly reduced by high contents of vitamin A in the maternal diet. 5. The susceptibility of the embryonic/neonatal liver to lipid peroxidation was significantly increased as a result of high provisions of maternal vitamin A. 6. It is concluded that excessive provision of vitamin A to the laying hen results in an adverse effect on vitamin E, carotenoids and ascorbic acid in the embryonic/neonatal liver and can compromise the antioxidant status of the progeny.

Animal Feed↗
PubMed1996

Effect of supplementation with selenium on whole blood glutathione peroxidase activities and on plasma and tissue selenium concentrations in lambs.

In recent years the selenium (Se) intake of the human population of the UK has shown a marked decline from 60 micrograms/d in 1978 to around 30 micrograms/d in 1990 owing largely to a significant reduction in the importation of North American wheat for bread-making flour. Other countries (Finland, for example) in similar situations have instituted fertilization programs in order to raise cereal Se concentrations and thus boost dietary intakes. An alternative approach would be to increase the Se concentration of carcass meat by supplementation of meat animals for a limited period prior to slaughter. A trial was set up with store lambs to evaluate this approach. Sixteen Scottish Blackface lambs were stratified according to live weight and then randomly allocated to one of four treatments: unsupplemented, or 3.5, 7, or 10.5 mg Se/head/wk. After 14 wk, the lambs were sacrificed and samples of shoulder and thigh muscle, liver, and kidney were obtained for analysis. All three treatments effected an increase in whole blood glutathione peroxidase (GSH-Px) and plasma Se concentrations over controls. Shoulder, thigh, and liver Se exhibited a dose-response relationship to treatment, but kidney Se concentrations were unaffected by treatment. Muscle and some organ meat Se concentrations can therefore be increased by supplementation and could contribute to increased human dietary intakes of the element.

Animal Feed↗
PubMed1995

Intestinal permeability: an overview.

The noninvasive assessment of intestinal permeability in humans has a 20-year history. Because the tests are increasingly used in clinical practice and research and because there is much controversy, we reviewed the literature and outlined the potential and possible shortcomings of these procedures. Data was obtained from personal files and from a systemic search through MEDLINE and EMBASE. The principle of the differential urinary excretion of orally administered test markers is explained with reference to the desired physicochemical properties of the markers and how the principle can be exploited to allow assessment of various other gastrointestinal functions. The use of intestinal permeability tests for diagnostic screen for small bowel disease and assessment of responses to treatment, the pathogenesis of disease, normal intestinal physiology, and the effect of drugs and toxins on the intestine is described and reviewed. The controversy surrounding the anatomic location of the permeation pathways that the markers use is highlighted. Noninvasive tests of intestinal permeability have fulfilled early promises of usefulness in clinical practice and research. There is now a need for integrated research into the basic mechanisms of regulatory control of the intestinal barrier function.

Animals↗
PubMed1995

Beard calcium concentration as a marker for coronary heart disease as affected by supplementation with micronutrients including selenium.

Hair calcium concentration is biologically regulated and inversely correlated to the concentration in the aorta. Populations generally divide into high and low hair calcium groups which differ significantly from each other. It has been found that about 90% of people who suffer an acute myocardial infarction belong to the low hair calcium group. It follows that raising a person's calcium status from the low to the high group should decrease their risk of coronary heart disease. A trial was set up with four groups of 12 people, randomly allocated to one of the following treatments: placebo; vitamin D; antioxidants; and antioxidants plus vitamin D. Beard samples were collected for two months prior to four months of supplementation and for two months afterwards. Blood samples were collected at the end of the supplementation period. All treatments significantly lowered plasma calcium concentrations but did not significantly affect beard calcium concentrations due, primarily, to some large individual fluctuations. Within the limitations of the experiment the combined treatment was the most effective as it was the only one to raise beard calcium levels for the duration of the supplementation period. A higher rate of vitamin D supplementation [i.e., > 50% recommended daily allowance (RDA)] might have established clear differences but larger group sizes would also have been helpful. Of the unsupplemented subjects 80% had plasma selenium concentrations of < 90 micrograms l-1 in contrast to only 10% of supplemented ones.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Selenium content of convenience and fast foods in Ayrshire, Scotland.

Selenium concentrations were determined via hydride generation atomic absorption spectrometry in more than 100 convenience and fast foods including 34 vegetarian dishes. The foods were purchased mainly in Ayrshire, Scotland but some came from other parts of the UK. The results indicate a considerable amount of selenium in certain mushrooms, spinach, fish, offals and chicken-based products. The selenium content of beef- and pork-based products was generally somewhat lower. Vegetarians having a sufficient intake of mushrooms (in particular button and closed cap mushrooms) and spinach do not seem to be at risk of selenium deficiency provided of course that the selenium in mushrooms, in particular, is bioavailable.

Animals↗
PubMed1994

Breast cancer gene therapy: transgenic immunotherapy.

A number of studies have demonstrated that potent anti-tumor immunity can be induced using cytokine gene transfer, a strategy termed transgenic immunotherapy. Our aim is to express cytokine genes in the vicinity of tumor cells, either by transducing tumor cells themselves, or by delivering cytokine-expressing endothelial cells to tumor sites. We compared the ability of cytokine-expressing tumor cells or endothelial cells to inhibit the tumorigenesis of MDA-MB-435 breast cancer cells in athymic nude mice. Retroviral vectors containing either human interleukin 2 (hIL-2) or interleukin 1 (hIL-1 alpha) were used to transduce MDA-MB-435 cells or human umbilical vein endothelial cells (HUVEC). Using a modified MTT bioassay and an ELISA specific for hIL-2, 43 of 70 MDA-MB-435 clones transduced with IL-2 were found to secrete between 100-800 units of IL-2/10(6) cells/24 hr. hIL-2 and hIL-1 alpha-transduced HUVEC secreted 40 ng/IL-2/10(6)/24 hr and 1.8 ng/10(6)/24 hr, respectively. To facilitate in vivo tracking of tumor cells, both nontransduced and IL-2-expressing MDA-MB-435 cells were genetically-marked with the E. coli lacZ gene and selected using flow cytometry. To study in vivo tumorigenicity, cells were injected into the mammary fat pad of athymic nude mice: (1) lacZ/MDA-MB-435 cells injected alone formed tumors in all animals; (2) IL-2-expressing lacZ/MDA-MB-435 cells did not form any tumors; (3) co-inoculation of MDA-MB-435/IL-2, or HUVEC/IL-2, or HUVEC/IL-1 alpha with lacZ/MDA-MB-435 cells prevented or delayed tumor growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

The gene therapy of cancer: transgenic immunotherapy.

Gene therapy can be defined as the insertion of functional genes into cells to treat a disease. Cellular augmentation, whereby gene transfer confers a novel function to the cell, has proved to be useful in designing strategies for the treatment of cancer. In particular, a variety of cell types may be transduced with immune response genes that are intended to elicit a more effective immune attack against tumor cells. This process has been termed transgenic immunotherapy. Preclinical studies involving the transduction of tumor cells, stromal cells, and lymphocytes with a number of immune response genes have demonstrated potent cytotoxic lymphocyte responses against tumor cells, and in some cases the induction of long-lasting immunity against tumor rechallenge. It is hoped that this form of cancer immunotherapy will permit the development of vaccines effective in eradicating minimal residual disease and immunizing individuals at risk for cancer.

Animals↗
PubMed1992

Selenium content of wheat for bread making in Scotland and the relationship between glutathione peroxidase (EC 1.11.1.9) levels in whole blood and bread consumption.

The selenium content of the 1989 harvest of wheat used for bread making in Scotland ranged from 0.028 microgram/g dry weight for home-grown wheat to 0.518 microgram/g for Canadian wheat. The tonnage values indicate that 13.8% of the wheat used in bread making came from Canada. This reflects in a calculated dietary intake of 31 micrograms/d which is well below the recommended levels of 70 and 55 micrograms for adult males and females respectively (National Research Council, 1989). The average glutathione peroxidase (EC 1.11.1.9) level in 478 samples of human whole blood was 6.08 (SE 0.065) units/ml. This increased to 6.65 (SE 0.321) in sixty-two subjects consuming brown or wholemeal bread but was unaffected by oily fish consumption. Analysis of a small number of samples of whole milk, eggs and meat indicated slightly higher concentrations than previously published values but this trend was insufficient to compensate for the lower cereal provision of Se.

Bread↗
PubMed1990

A comparison of serum vitamin B12 and serum methylmalonic acid as diagnostic measures of cobalt status in cattle.

In two trials an assessment was made of serum methylmalonic acid as a diagnostic criterion of cobalt status in housed cattle. Despite the small number of animals used the method showed some promise, and normal concentrations are tentatively suggested as being less than 2 mumole/litre, subclinically cobalt deficient 2 to 4 mumole/litre and cobalt-deficient greater than 4 mumole/litre. However, for assessing how cobalt status is likely to influence the rate of liveweight gain of cattle, measurements of both serum methylmalonic acid and vitamin B12 concentrations would appear to be better.

Animals↗
PubMed1989

Duration of effective benefit from administration of graded oral doses of cobalt to sheep.

The rapidity and duration of the response of sheep to graded oral doses of cobalt, given as the sulphate or as a cobalt-supplemented anthelmintic Panacur SC, was assessed by the determination of serum vitamin B12 and methylmalonic acid concentrations. The rapidity of the response to the treatments, which ranged from 1 to 250 mg cobalt, was unaffected by dose rate but the effective duration was dose related. There was some evidence of a cumulative effect from repeat treatments of the anthelmintic at three weekly intervals. It is suggested that the optimum inclusion rate for cobalt in anthelmintics lies within the range 21 to 100 mg/treatment.

Animals↗