PubMed Health⌕ Search

Biomedical subjects

M Cox

Publications and source records attributed to M Cox.

At least 19 recordsLinked to original sources
PubMed1995

World distribution of factor V Leiden.

We have analysed 3380 chromosomes (1690 unrelated individuals) from twenty-four populations for the presence of factor V Leiden, an important risk factor in venous thromboembolism. The allele frequency in 618 Europeans was 4.4%, with the highest prevalence among Greeks (7%). It was 0.6% in Asia Minor. Factor V Leiden was not found in any of 1600 chromosomes from Africa, Southeast Asia, Australasia, and the Americas. This distribution may partly explain the rarity of thromboembolic disease in these populations. The high prevalence in Europeans suggests that screening for this mutation should be considered in some circumstances.

Africa↗
PubMed1995

Mutation of the Oct-1 POU-specific recognition helix leads to altered DNA binding and influences enhancement of adenovirus DNA replication.

To assess which residues of Oct-1 POU-specific (POUs) are important for DNA recognition and stimulation of adenovirus DNA replication we have mutated 10 residues of the POUs helix-turn-helix motif implicated in DNA contact. Seven of these turned out to have reduced DNA binding affinity. Of these, three alanine substituted proteins were found to have a changed specificity using a binding site selection procedure. Mutation of the first residue in the recognition helix, Gln44, to alanine led to a loss of specificity for the first two bases, TA, of the wild-type recognition site TATGC(A/T)AAT. Instead of the A, a T was selected, suggesting a new contact and a novel specificity. A change in specificity was also observed for the T45A mutant, which could bind to TATAC(A/T)AAT, a site hardly recognized by the wild-type protein. Mutation of residue Arg49 led to a relaxed specificity for three consecutive bases, TGC. This residue, which is critical for high affinity binding, is absent from the structurally homologous lambdoid helix-turn-helix motifs. Employing a reconstituted system all but two mutants could stimulate adenovirus DNA replication upon saturation. Mutation of residues Gln27 and Arg49 impairs the ability of the Oct-1 POU domain protein to enhance replication, with a concomitant loss of DNA contacts. Since the POU domain binds the precursor terminal protein-DNA polymerase complex and guides it to the origin, lack of stimulation may be caused by incorrect targetting of the DNA polymerase due to loss of specificity.

Adenoviridae↗
PubMed1995

Solution structure of the Oct-1 POU homeodomain determined by NMR and restrained molecular dynamics.

The POU homeodomain (POUhd), a divergent member of the well-studied class of homeodomain proteins, is the C-terminal part of the bipartite POU domain, the conserved DNA-binding domain of the POU proteins. In this paper we present the solution structure of POUhd of the human Oct-1 transcription factor. This fragment was overexpressed in Escherichia coli and studied by two- and three-dimensional homo- and heteronuclear NMR techniques, resulting in virtually complete 1H and 15N resonance assignments for residues 2-60. Using distance and dihedral constraints derived from the NMR data, 50 distance geometry structures were calculated, which were refined by means of restrained molecular dynamics. From this set a total of 31 refined structures were selected, having low constraint energy and few constraint violations. The ensemble of 31 structures displays a root-mean-square deviation of the coordinates of 0.59 A with respect to the average structure, calculated over the backbone atoms of residues 6 to 54. The fold of POUhd is very similar to that of the canonical homeodomains. Interestingly, the recognition helix of the free POUhd ends at residue 53, while in the cocrystal structure of the intact POU domain with the DNA octamer motif [Klemm, J.D., Rould, M.A., Aurora, R., Herr, W. and Pabo, C.O. (1994) Cell, 77, 21-32] this helix in the POUhd subdomain is extended as far as residue 60.

Amino Acid Sequence↗
PubMed1995

YAC contig mapping of six expressed sequences encoded by human chromosome 21.

Six cDNA clones from human chromosome 21 have been mapped in a set of complete YAC contig spanning the entire chromosome 21q. The mapping positions between two STSs on the YAC contig and the NotI coordinates starting from the telomere of 21q were determined for the cDNA clones. The YAC contig mapping positions agree well with those using a comprehensive somatic cell hybrid mapping panel.

Animals↗
PubMed1995

Hereditary angioneurotic oedema: current management in pregnancy.

A 20-year-old primiparous woman, with a history of type 1 hereditary angioneurotic oedema, presented for induction of labour. She was hirsute, obese and presented technical difficulties for both general and epidural/spinal anaesthesia. Her management included prophylactic C1 esterase inhibitors and epidural analgesia for pain relief. A spontaneous vaginal delivery was achieved and no adverse complications occurred. Five days after delivery she had abdominal pain which was investigated and resolved spontaneously. The management of this condition is discussed.

Adult↗
PubMed1995

The effects of inhaled beclomethasone dipropionate on lung function and histamine responsiveness in recurrently wheezy infants.

Inhaled steroids improve pulmonary function and bronchial responsiveness in older asthmatics. Data from studies using subjective outcome measures to determine the effectiveness of inhaled steroids in infants with recurrent wheezing are equivocal. Therefore, this study tested the hypothesis that beclomethasone dipropionate improves pulmonary function, including bronchial responsiveness to histamine, in recurrently wheezy infants. The study was double blind, placebo controlled lasting nine weeks. After the first baseline week, pulmonary function was measured using the rapid thoracoabdominal compression technique and bronchial responsiveness assessed with a histamine challenge test. Infants were then randomly allocated to receive doses of placebo or beclomethasone dipropionate (100 micrograms/puff) from metered aerosols. Two puffs of test aerosol were administered twice daily for eight weeks via a large volume spacer fitted with a facemask. Symptoms were recorded daily and pulmonary function and bronchial responsiveness assessed at the end of the treatment period; 50 infants, median age 12 months (range 5 to 18 months), were recruited. Twenty three in the beclomethasone dipropionate group and 15 in the placebo group completed the study and had pairs of pulmonary function measurements. Three were probable treatment failures (one beclomethasone dipropionate, two placebo), three were possible treatment failures (placebo), and others were non-compliant with study protocol. Baseline variables were not significantly different between those infants who completed the study and those who did not. Beclomethasone dipropionate and placebo groups were similar in all respects at baseline. Lung function and symptoms improved for both groups of infants during the study. Bronchial responsiveness increased significantly in the placebo group but there were not statistically significant differences between groups for any of the other outcome measures. It is concluded that beclomethasone dipropionate (400 microgram daily) via a large volume spacer does not significantly improve lung function or symptoms in recurrently wheezy infants but might hav a beneficial effect on bronchial responsiveness.

Administration, Inhalation↗
PubMed1995

Hospital resources for care of acutely ill older persons.

Older patients in acute care hospitals are at high risk for problems. Care of older persons is further jeopardized by a shortage of physicians and nurses interested and prepared in gerontology and geriatrics, as shown in a survey of hospitals and staff in one southwestern state.

Aged↗
PubMed1995

Body composition measurement in elite heavyweight oarswomen: a comparison of five methods.

The study was designed to evaluate the range of body composition in elite heavyweight oarswomen as well as the level of agreement between various methods used to measure this variable. Percent body fat was determined at the start of the competitive season by densitometry, taken to represent the reference standard, and measurement of total body potassium, skinfold thicknesses, bioelectrical impedance analysis and body mass index. The athletes were studied within a two week period with all measurements in any individual taken during one morning. We demonstrated a surprisingly large range of percent fat between these oarswomen, 13.6 to 29.3% by densitometry, which was a feature common to all methods. Percent body fat by total body potassium was lower (p < 0.05) while from body mass index higher (p < 0.01) than the reference value from densitometry. Similar methodologies generated significantly different estimates of % fat (SFT1 versus SFT2, p < 0.01 and BIAv versus BIAB, p < 0.01) highlighting the potential problems that may arise with the use of different regression equations to convert primary measurements into % fat. The limits of agreement between various methods were wide and reflect the large variability about the estimated mean bias. Practically this negates the correction of "non reference" values by adding or subtracting the mean difference or bias between the techniques in individuals. These methodological problems need to be considered when setting specific body composition targets for an athlete.

Adipose Tissue↗
PubMed1992

Evaluation of the obstetric significance of some pelvic characters in an 18th century British sample of known parity status.

The excavations at Christ Church, Spitalfields (1984-86) produced a sample of 968 human skeletons which were interred between 1729 and 1859. Of these, 387 were recovered in association with coffin plates stating name, age at death, and date of death. There are 138 adult females in the named sample and the obstetric histories of 94 have been reconstructed from historical documentation. Such variables as birth spacing, number of children, and age at first and last births are known for the majority of this sample. Any individual about whose history there is any doubt has been excluded from the analysis. A middle-class group, they were largely of high nutritional status and, by the standards of the day, lived in sanitary and comfortable conditions. Both males and females have a mean age at death of 56 years. The presence or absence, the typology, the severity, the width and the length of the preauricular sulcus, the presence or absence and the number of pits on the dorsal aspect of the pubic body, sulci along the anterior sacrum adjacent to the auricular facet, and the extension of the pubic tubercle were evaluated in relation to the obstetric histories of these females. Statistical analysis has demonstrated a relationship between the presence of pubic tubercle extension and parity status and between the degree of extension and the number of children borne (P < .02). Statistically there is no significant relationship (P > .05) between either the preauricular sulcus or pubic pitting and parity status. Sacral scarring is significantly associated (P < .05) with parity status, but as it was evident in only eight females it has little practical application. Sample sizes are small, and it must be considered that statistical evaluation of larger samples might detect associations between variables not demonstrated here. There is no significant relationship between any of the cortical variants under consideration and age at death.

Adult↗
PubMed1992

Improved technique for polytetrafluoroethylene bypass grafting: long-term results using anastomotic vein patches.

Results of peripheral arterial bypass using polytetrafluoroethylene grafts have remained poor in comparison with those using saphenous vein grafts, particularly for anastomoses to tibial and peroneal vessels. A simple modification to the conventional operative technique, involving the incorporation of a vein patch into the distal anastomosis, has enabled considerable improvement. Five-year patency rates of 71 per cent for popliteal and 54 per cent for infrapopliteal grafts have been achieved in a series of 256 patients operated on between 1982 and 1989.

Aged↗
PubMed1992

Evidence that inhibitor(s) are formed which may interfere with the growth of revertant colonies in the Ames Salmonella and the E. coli tryptophan reverse mutation assays when strictly anaerobic conditions are used.

Spontaneous and chemically induced revertant colonies were not observed on plates when a strictly anaerobic environment and anaerobically prepared media were used to perform the Ames histidine reversion assay with each of eight different Salmonella strains. A similar effect was observed when the E. coli tryptophan reverse mutation assay was performed under strictly anaerobic conditions. We provide evidence here that under anaerobic conditions growth inhibitor(s) are formed by the S. typhimurium and E. coli bacteria when the limited histidine and tryptophan, respectively, are depleted from the medium. The inhibitor(s) are nonspecific and inhibit the growth not only of prototrophic bacteria but also of the inhibitor-producing bacteria as measured by neutralized supernatants of growth-limiting minimal liquid cultures. Inhibitor(s) are also formed in stationary phase cultures of Salmonella and E. coli in minimal liquid medium supplemented with excess histidine and tryptophan, respectively. These results suggest that inhibitor formation under anaerobic conditions is a physiological phenomenon which interferes with at least two reverse mutation assays. Whether or not it also interferes with the reverse mutagenesis process remains to be determined.

Anaerobiosis↗
PubMed1992

Spontaneous cessation of umbilical blood flow in the acardiac fetus of a twin pregnancy.

The acardiac fetus is a rare entity found only in monozygotic multiple pregnancy. Although the acardiac fetus is non-viable, the perinatal mortality rate for the normal fetus may be as high as 50 per cent, and is usually associated with fetal heart failure and hydrops fetalis, or as the result of prematurity. In this communication, we describe a case of spontaneous cessation of blood flow to an acardiac fetus and discuss the management of this condition with special reference to optimizing the outcome for the normal fetus.

Abnormalities, Severe Teratoid↗
PubMed1992

Development of a high performance zinc-62/copper-62 radionuclide generator for positron emission tomography.

Clinical utilisation of positron emission tomography could be enhanced by the availability of short-lived radionuclides derived from generator systems. The zinc-62/copper-62 combination is one such system which could be used as a source for a number of copper-62 radiopharmaceuticals. We have developed and optimised a high activity (5.6 GBq, 150 mCi) zinc-62/copper-62 generator to provide 62Cu in a form that is suitable for direct labelling of pyruvaldehyde-bis-(N4-methylthiosemicarbazone)-copper(II), Cu(PTSM). The distribution coefficients of Zn(II) and Cu(II) between anion-exchange resin and various hydrochloric acid/organic solvent mixtures were measured. Based on these measurements a generator eluent of 0.3 M HCl/40% ethanol provided 62Cu in greater than 90% yield in a 3-ml volume. A very low 62Zn breakthrough of less than 3 x 10(-7)% was achieved. Copper-PTSM was successfully labelled with the no-carrier-added 62Cu eluent directly from the generator with 94% radiochemical yield.

Copper↗