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Biomedical subjects

M Cox

Publications and source records attributed to M Cox.

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

Does moderate aerobic activity have a stimulatory effect on 24 h resting energy expenditure: a direct calorimeter study.

This study was designed to establish whether moderate aerobic exercise (2 h at 30-35% VO2 max) in lean non-athletic male adults had a prolonged stimulatory effect on energy expenditure while at rest. Four weight maintaining male adults had their 24 h energy expenditure measured by direct calorimetry on four separate occasions. During the 24 h in the calorimeter each subject received a diet which in total supplied 35 kcal (146 kJ) per kg body weight. All studies in an individual were completed within four to six weeks during which time body weight remained stable. On two of these 24 h periods, individuals rested throughout while on the other two, they also performed the prescribed exercise. This consisted of cycling for two 1 h sessions; the first while they were fasting while the second period was approximately 45 min after consuming a 800 kcal (3.4 MJ) meal. Total 24 h energy expenditure was greater on exercise (8.3 +/- 1.8 MJ/day) than non-exercising days (6.3 +/- 1.4 MJ/day, P < 0.001) In contrast when the acute effects of the cycling where removed 24 h resting energy expenditure on the exercise day (6.8 +/- 1.7 MJ/day) was not significantly different from that of rest days (95% confidence intervals of the difference ranged from -0.36 to 1.27 MJ/day). This study did not demonstrate a prolonged stimulatory influence on non-exercising resting energy expenditure following physical activity likely to be achieved by non-athletes. These data provide no evidence that such exercise is associated with a greater energy deficit than that due to the activity itself.

Adult↗
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↗
PubMed1994

Kringle solution structures via NMR: two-dimensional 1H-NMR analysis of horse plasminogen kringle 4.

The kringle 4 domain of equine plasminogen (ePgn/K4), a close variant of the human homolog (hPgn/K4), contains residues, such as Trp32, which also appear in human apolipoprotein(a) kringle 4-type modules. The ePgn/K4 was investigated as a complex with epsilon-aminocaproic acid, an antifibrinolytic drug, by two-dimensional 1H-NMR spectroscopy at 500 MHz. Secondary structure elements were recognized from sequential medium and long-range dipolar (proton Overhauser) interactions, as well as from the identification of resonances originating from backbone amide protons with slow 1H-2H exchange in 2H2O. Antiparallel beta-sheets, consisting of strands 52-53, 61-65 and 71-75, were identified. Additionally, the segments 14-16 and 20-22 were found to assume characteristic interstrand antiparallel (beta-sheet-like) H-bond pairing. Four type I turns could be identified in strands 6-9, 16-19, 24-27 and 67-70. Ten structures were generated using distance geometry methods, followed by dynamic simulated annealing calculations. The root mean squares deviation of the distances was 2.79 A for all atoms and 1.81 A for backbone atoms only. Hydrogen bridges, involving side chain hydroxyl groups, were identified for Thr16 and Thr65. As observed for the hPgn/K4, the three-dimensional structure of the ePgn/K4 is mainly defined by two antiparallel beta-sheets, 14-16/20-22 and 62-66/71-75, which are oriented perpendicular to each other. Adjacent to these is a hydrophobic pocket, formed by Trp62, Tyr64, Trp72 and Phe74, whose side chains contribute a lipophilic component to the exposed lysine binding site surface. In contrast to the Trp25, Trp62 and Trp72 residues, conserved in the human and equine homologs, the spectrum of the Trp32 side chain reveals an unrestrained, solvent-exposed indole ring.

Amino Acid Sequence↗
PubMed1993

Parvalbumin as an anatomical marker for discrete subregions of the ambiguus complex in the rat.

The topography of parvalbumin-immunoreactive neurons within the ventrolateral medulla of rats was investigated. Parvalbumin is a member of the 'EF-hand' family of Ca-binding proteins and is present in certain cell types within the central nervous system (fast-firing neurons with high metabolic rates). Parvalbumin-immunoreactive neurons were located in discrete rostrocaudal divisions of the ambiguus complex corresponding to regions containing respiratory-related neurons. Based on the location of physiologically characterized respiratory-related neurons reported in the literature, parvalbumin immunoreactivity does not appear to distinguish inspiratory- from expiratory-related neurons.

Animals↗
PubMed1993

NMR studies of the POU-specific DNA-binding domain of Oct-1: sequential 1H and 15N assignments and secondary structure.

The 1H and 15N resonances of the POU-specific DNA-binding domain of transcription factor Oct-1 have been assigned sequentially using two-dimensional homo- and heteronuclear NMR techniques, as well as three-dimensional heteronuclear NMR techniques, including TOCSY, 2D NOE, and NOESY-HMQC experiments. A number of typical short- and medium-range NOE contacts, as well as amide proton exchange data, gave evidence for the presence of four alpha-helices, in the peptide segments 1-19, 23-34, 40-49, and 54-71, which are connected by short loops of irregular structure. Interestingly, the second helix contains three glycine residues and the fourth helix a proline in the middle of the helix. Although the regular pattern of hydrogen bonds in the fourth helix is interrupted, due to the absence of an amide proton in proline, the helix is remarkably stable. All four helices are amphipathic, which suggests a packing of the apolar sides of the helices in the folded structure of the protein.

Amino Acid Sequence↗