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Biomedical subjects

M Reid

Publications and source records attributed to M Reid.

At least 127 records · Page 7Linked to original sources
PubMed1995

Human dosimetry and biodistribution of iodine-123-iododexetimide: a SPECT imaging agent for cholinergic muscarinic neuroreceptors.

UNLABELLED: Iodine-123-iododexetimide (IDEX) has recently been used for SPECT imaging of muscarinic cholinergic neuroreceptors (mAChR) in humans. We report the human radiation dosimetry, whole-body and normal cerebral distribution of IDEX. METHODS: Serial whole-body planar and brain SPECT scans were performed over 24 hr in four normal subjects. Organ activity was calculated from attenuation-corrected geometric mean counts from ROIs drawn over visible organs. Thigh activity was used for background subtraction. Organ absorbed doses and effective dose were calculated using the MIRD schema. Brain SPECT was performed 6 hr postinjection in ten normal subjects. ROIs placed over cortical and subcortical structures were used to determine brain distribution. RESULTS: The effective dose was 24.7 microSv/MBq. An average of 54% of IDEX remained in the body background. Decay-corrected brain uptake was 6.9% of injected dose at 1 hr, 8.6% at 6 hr and 8.1% at 24 hr. Regional brain distribution showed high uptake in striatum and cortex with low activity in thalamus and cerebellum. At 6 hr, activity relative to striatum was 70% for frontal and parietal cortex, 102% for occipital cortex, 54% for thalamus and 11% for cerebellum. CONCLUSION: Iodine-123-IDEX produced high quality SPECT images with activity at 6 hr reflecting the known distribution of mAChR receptors. The favorable dosimetry of IDEX and high synthetic yield (50%-70%) suggest it to be a suitable agent for clinical studies.

Aged↗
PubMed1995

High-throughput genotyping using horizontal polyacrylamide gels with wells arranged for microplate array diagonal gel electrophoresis (MADGE).

Genotyping (typing of genetic variation) typically involves PCR followed by an allele-specific oligonucleotide-binding assay, restriction enzyme digest or direct check of the outcome of a PCR designed to distinguish genotype. Electrophoresis can resolve "bound" from "free" oligonucleotide, as well as resolve PCR fragments and digests, but it is traditionally regarded as cumbersome and laborious in comparison with solution assays. Here we describe simple horizontal polyacrylamide gels which can receive a 96-well array of samples directly, which can be stacked in tanks and which are bound to a robust support of glass. The line of electrophoresis is on a 71.6 degree diagonal relative to the columns of the array (microplate array diagonal gel electrophoresis [MADGE]). Several thousand reactions can conveniently be analyzed in a shoebox-sized apparatus in a couple of hours. High resolution is achieved in the range of 20-1000 bp, information processing is simplified and automation is possible.

Electrophoresis, Polyacrylamide Gel↗
PubMed1994

Topology of Kell blood group protein and the expression of multiple antigens by transfected cells.

Kell is one of the major blood group systems in human red blood cells (RBCs). The Kell antigens are carried on a 731 amino acid glycoprotein that is thought to span the erythrocyte membrane once. Rabbit antibodies to three synthetic peptides, derived from different parts of the Kell protein, were used to determine the topology of Kell protein on the RBC. Antibodies to a C-terminal peptide and to a peptide derived from amino acid residues 410 to 439 reacted with RBCs treated with 0.2 mol/L dithiothreitol. An antibody to the N-terminal peptide reacted with inside-out RBC vesicles but not with right-side-out vesicles nor with intact RBCs, showing that Kell is a type II membrane protein and that the extracellular portion of the protein is folded by disulfide bonds. By transfection, Kell protein was expressed on the cell surface of surrogate cells, and the transfected cells expressed similar antigenic properties as native RBCs. Kell protein was expressed in COS-1 and K562 cells and in Sf9 cells infected by the Baculovirus system. Transfected K562 cells expressed several high-incidence antigens but not the low-incidence antigen K1.

Animals↗
PubMed1994

Randomised controlled trial of routine cervical examinations in pregnancy. European Community Collaborative Study Group on Prenatal Screening.

Preterm delivery is strongly associated with neonatal mortality and morbidity. In some European countries, cervical examinations are used routinely during pregnancy to identify women at risk of preterm delivery. We sought to evaluate the efficacy and secondary effects of these routine cervical examinations. We did a randomised controlled trial in seven European countries, comparing two policies--namely, an attempt to do a cervical examination at every prenatal visit (2803 women) and avoidance of cervical examination if possible (2799). The median number of cervical examinations was 6 in the experimental group and 1 in the controls. There were 6.7% preterm (< 37 weeks) deliveries in the experimental group and 6.4% in the control group (risk ratio 1.05 [95% confidence interval 0.85-1.29]; non-significant). The low birthweight rate was 6.6% in the experimental group and 7.7% in the controls (non-significant). Premature rupture of membranes was not significantly more frequent in the experimental group (27.1% vs 26.5%). Our findings do not support the routine use of cervical examinations during pregnancy.

Adult↗
PubMed1994

The effects of sucrose on everyday eating in normal weight men and women.

Energy intake was estimated from the food diaries of 52 overnight-fasted adult volunteers after ingestion of 110 ml of a solution of either 40 g of sucrose or 4.34 g of saccharin administered in blind conditions. Men consumed more calories and carbohydrates than women. Women's eating was unaffected by the preload. The sucrose preload led to 60% of male subjects choosing to consume a calorific beverage soon afterwards; they then delayed eating compared to men who received a saccharin preload. Men who had received sucrose, but consumed no beverage, ate as early as the saccharin preload group. It is concluded that under fasted, blind administration followed by everyday eating, sucrose does not increase hunger, but eating behaviour after a preload varies with eating habits.

Adult↗
PubMed1994

PBDX is the XG blood group gene.

We have identified the Xga antigen, encoded by the XG blood group gene, by employing rabbit polyclonal and mouse monoclonal antibodies raised against a peptide derived from the N-terminal domain of a candidate gene, referred to earlier as PBDX. In indirect haemagglutination assays, these anti-peptide antibodies react with Xg(a+) but not Xg(a-) erythrocytes. In antibody-specific immobilization of antigen (ASIA) and immunoblot assays, the anti-peptide antibodies react with the same molecule as does human anti-Xga. Therefore, by its identity with PBDX, Xga is identified as a cell-surface protein that is 48% homologous to CD99 (previously designated the 12E7 antigen), the product of MIC2 which is tightly linked to XG. PBDX is renamed here XG.

12E7 Antigen↗
PubMed1994

Demonstration by the monoclonal antibody-specific immobilization of erythrocyte antigens assay that a new red cell antigen belongs to the Kell blood group system.

BACKGROUND: The Kell blood group system comprises 21 antigens residing on a red cell membrane glycoprotein of apparent M(r) 93,000. STUDY DESIGN AND METHODS: Serologic techniques were used to identify a new red cell antigen. The monoclonal antibody-specific immobilization of erythrocyte antigens (MAIEA) assay was used to identify the red cell membrane component carrying that antigen. RESULTS: A new high-frequency red cell antigen was identified and provisionally named RAZ. RAZ is absent from K.o red cells and from red cells treated with 2-amino-ethylisothiouronium bromide and is expressed weakly on McLeod phenotype cells. It differs from all other Kell system antigens, and no depression of other Kell system antigens on RAZ+ red cells was noticed. The RAZ antigen was shown by the MAIEA assay to be located on the Kell glycoprotein. CONCLUSION: RAZ is a new high-frequency antigen located on the Kell glycoprotein. The MAIEA assay is a very effective method of demonstrating the membrane structure carrying a red cell antigen.

Antibodies, Monoclonal↗
PubMed1994

Variations in family visiting policies in neonatal intensive care units in eleven EC countries. EC Study Group of Parental Involvement in Neonatal Care.

The paper addresses the lack of information concerning parental visiting in neonatal intensive care units (NICU) across European Community (EC) countries. It reports on a study involving 11 EC countries and 38 units carried out under the auspices of a Concerted Action project. Information gathered from the 38 units yields data on the parental and family visiting policies. The study reveals a wide variation in the policies from considerable parental access to the infant in the NICU to restricted visiting. Policies concerned with unit facilities and unit support staff reflect the orientation of the overall unit policy with regard to visiting.

Attitude of Health Personnel↗
PubMed1994

Counselling following diagnosis of fetal abnormality: a comparison between German, Portuguese and UK geneticists.

The principle of non-directiveness in genetic counselling is embraced by all relevant professional bodies. Little is known about the extent to which it is endorsed by geneticists, or incorporated into their clinical practice. The aim of the current study is to document how geneticists in three European countries, Germany, Portugal and the UK, report counselling women at risk for having children with a range of conditions. While geneticists in all three countries reported counselling in a largely non-directive style, this varied both across genetic conditions and between countries. German and Portuguese geneticists were significantly more directive than UK geneticists, although they differed in the way in which they were directive. German geneticists were more likely to encourage continuation of pregnancies, while Portuguese geneticists were more likely to encourage termination of affected pregnancies. There was no strong consensus on approaches to counselling for any of the genetic conditions, defined as agreement between 70% of all three groups of geneticists. Despite strong professional codes of non-directiveness, geneticists report being somewhat directive in some counselling situations. Future research needs to focus on what geneticists are trying to achieve in genetic counselling, how they actually counsel, and with what effects.

Abortion, Induced↗
PubMed1994

Orange juice enhances aluminium absorption from antacid preparation.

Aluminium absorption from four doses of the antacid preparation 'Aludrox' when taken alone, with orange juice or with milk was compared by measuring the change in urinary aluminium following Aludrox dosage in 15 normal adults. There was an approximately 10-fold increase in 24 h urinary aluminium excretion following the Aludrox plus orange juice (232 micrograms) which was significantly higher than that following Aludrox alone (62 micrograms) (P < 0.001), but milk had no effect on aluminium absorption. The results showed that orange juice greatly enhanced aluminium absorption and should not therefore be taken in conjunction with aluminium-containing antacid preparations.

Absorption↗
PubMed1993

Alteration of splice site selection by an exon mutation in the human glycophorin A gene.

We report the identification in human glycophorin A gene of a novel exon mutation that affects splice site selection. DNA mapping showed that the mutation has abolished a unique MspI site marking the exon III-intron 3 splice junction (ACCG/GT). Genomic sequencing confirmed the occurrence of a single G-->A transition at the terminal nucleotide position of exon III. Analysis of the mRNA composition demonstrated a partial inactivation of the altered 5' splice site as well as skipping of exons involving the alternative use of other constitutive splice sites. The full-length transcript with the cognate A change encodes a variant glycophorin with an arginine replacing a glycine at position 59 and defining the ERIK epitope, whereas the exon III-deleted transcript specifies a shorter glycophorin carrying the Sta antigen. Also identified were the misspliced mRNA species with exon I-IV and exon I-V connections generated by selection of 5' splice sites far distant from the mutated site. Although having a correct translation frame, the predicted polypeptides of such exon-skipping products were not assembled on the erythrocyte membrane probably due to the severe truncation of the signal sequence required for targeting and translocation. These observations reveal a new mechanism for antigenic diversity of human glycophorins.

Alternative Splicing↗
PubMed1993

A point mutation in the GYPC gene results in the expression of the blood group Ana antigen on glycophorin D but not on glycophorin C: further evidence that glycophorin D is a product of the GYPC gene.

Glycophorin C (GPC) and glycophorin D (GPD) are homologous sialoglycoproteins in the human red blood cell membrane. Both are thought to be encoded by the GPC gene (GYPC). We report that the rare blood group antigen, Ana, is expressed on GPD but not on GPC. cDNA was synthesized from total RNA obtained from two unrelated, heterozygous Ana+ blood donors and analyzed by the polymerase chain reaction using primers that spanned sequences encoded by the GYPC gene. The expected 412-bp fragment was generated, and sequencing of the amplified product showed a G-->T substitution at nucleotide 67 of the coding sequence, resulting in the substitution of alanine by serine at amino acid residue 23 of GPC and, presumably, residue 2 of GPD. To explain the expression of Ana on GPD but not on GPC, we postulate that the conformation of the amino acid residues at the N-terminal region of GPD determines the antigenic expression as this conformation would be different from that of the same sequence of amino acids occurring within GPC. Other possible reasons for antigen expression on a shorter protein product but not on the full-length protein product of the same gene are discussed. We extrapolate this reasoning to account for the expression of the common GE2 blood group antigen on GPD but not on GPC.

Amino Acid Sequence↗
PubMed1993

Molecular analysis of glycophorin C deficiency in human erythrocytes.

Human erythrocyte glycophorin C plays a functionally important role in maintaining erythrocyte shape and regulating membrane mechanical stability. We report here the characterization of the glycophorins C and D deficiency in erythrocytes of the Leach phenotype. Glycophorin C gene is encoded by 4 exons. Amplification of reticulocyte cDNA from Leach phenotype and normal individuals generated a 140-bp fragment when using primers spanning exons 1 and 2. However, no polymerase chain reaction (PCR) products were detected in the Leach phenotype using primers flanking either exons 1 and 3 or exons 1 and 4, suggesting that the 3' end of the mRNA was missing or altered. Exon 4 also appeared to be missing from Leach genomic DNA, based on both Southern hybridization and PCR. These results indicate that an absence of glycophorin C and glycophorin D in erythrocytes from these Leach phenotype individuals is a consequence of a deletion or marked alteration of exon 3 and exon 4 of their glycophorin C gene. Surprisingly, the mutant gene encodes an mRNA stable enough to be detected in circulating reticulocytes. Although this mRNA could encode an N-terminal fragment of glycophorin C, these protein isoform(s) would not be expressed in the membrane because they lack the transmembrane and cytoplasmic domains.

Base Sequence↗
PubMed1993

Structure and struggle: implementing a social model of a well woman clinic in Glasgow.

Although the values of the women's health movement are widely shared in the U.K., they are little in evidence in the services providing health care for women. This article makes the distinction between a medical model of health care and a social model. It describes a research project which took place in which a well woman clinic was transformed from one which operated on a medical model to one which reflected those of a social model of health care. The article describes the problems which the project team faced in implementing the changes.

Female↗