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Biomedical subjects

M O'Neill

Publications and source records attributed to M O'Neill.

At least 55 records · Page 3Linked to original sources

Effectiveness of an abdominal obesity reduction programme in men: the GutBuster "waist loss' programme.

OBJECTIVE: To examine the long term (1-2 year), as well as immediate effectiveness of a "waist loss' programme for men. DESIGN: Two preliminary studies are reported; one following a small group of 42 men over two years after a 6 week "GutBuster' course, the second following men for 1 year after having completed the initial 6 week programme (n = 83), or the initial course plus an additional six fortnightly "advanced' course (n = 37). MEASUREMENTS: Waist, hip and weight measures were reported for the 2 year group; waist and hip only in study 2. Dietary fat, exercise and alcohol intake were also recorded in study 2 through the use of questionnaires. The goal for the initial course was a 1% waist loss per week. RESULTS: All groups achieved an average waist loss > 1%/week during the initial programme. Waist sizes reported in study 1 were significantly less after 2 years (t = 8.28, p < 0.001) averaging a 6% loss in the group. This equated with an average weight loss of 5.5 kg. A repeated measures ANOVA also showed a significant main effect (F = 85.35; p < 0.0001) for waist losses and an interaction effect (F = 16.53; p < 0.0001) between initial and advanced groups after 1 year in study 2. Average waist losses were 4% and 10% respectively. There were also significant changes in dietary fat intake, exercise and alcohol consumption. CONCLUSION: Reductions in waist size in men appear to be more feasible than weight losses in women. "Waist loss' may also be a more valid measure of fat loss in men that body mass measures.

Abdomen↗

NG-nitro-L-arginine methyl ester protects against lipid peroxidation in the gerbil following cerebral ischaemia.

The aim of this study was to assess the role of nitric oxide (NO) in lipid peroxidation following 5 min of bilateral carotid occlusion in the Mongolian gerbil. The study consisted of 4 experimental groups (n = 10). Animals were either sham operated, subjected to bilateral carotid occlusion or administered the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg i.p.) 30 min, 6, 24 and 48 h following sham operation or 5 min bilateral carotid occlusion. Animals were killed 96 h post surgery and changes in the concentrations of malonaldehyde and 4 hydroxyalkenals (the main decomposition products of peroxides derived from polyunsaturated fatty acids and related esters) were measured in the hippocampus and cortex using the LPO-586 colorimetric method. The results showed a significant increase in the concentrations of both decomposition products following 5 min of bilateral carotid occlusion. L-NAME administered to sham operated controls had no effect, but in those animals subjected to 5 min of bilateral carotid occlusion L-NAME significantly decreased the levels of both decomposition products. These results suggest that inhibition of NO synthase activity decreases lipid peroxidation in the gerbil model of cerebral ischaemia.

Animals↗

The sigma receptor ligand JO 1784 (igmesine hydrochloride) is neuroprotective in the gerbil model of global cerebral ischaemia.

To assess the effects of the novel sigma receptor ligand JO 1784 ((+)-N-cyclopropyl-methyl-N-methyl-1,4-diphenyl-1-yl-but-3-en-1-ylami ne, hydrochloride or igmesine hydrochloride) on behavioural and histological changes following cerebral ischaemia, the gerbil model of cerebral ischaemia was used. Two experiments were carried out. In the first animals were either sham operated, subjected to 5 min of bilateral carotid occlusion or administered JO 1784 (25, 50, 75 or 100 mg/kg p.o.) 1, 24 and 48 h after 5 min bilateral carotid occlusion and histological evaluation carried out 96 h after surgery. In the second experiment the effects of JO 1784 administered at a dose of 100 mg/kg i.p. 30 min, 6, 24 and 48 h post-surgery on home cage activity and nitric oxide (NO) synthase activity in the cortex, hippocampus, cerebellum and brain stem 4 days after surgery was examined. Extensive neuronal death was observed in the CA1 region of 5 min occluded animals. JO 1784 (50, 75 and 100 mg/kg) provided significant protection against this ischaemia-induced cell death (P < 0.03-0.005). In the second experiment a large increase in home cage activity was observed for 5 min occluded animals for 12 h after surgery (P = 0.0018-0.02). A large increase in NO synthase activity was observed in all brain regions for 5 min occluded animals. Post-administration of JO 1784 attenuated the ischaemia-induced hyperactivity and increased NO synthase activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Tandem mass spectrometry and structural elucidation of glycopeptides from a hydroxyproline-rich plant cell wall glycoprotein indicate that contiguous hydroxyproline residues are the major sites of hydroxyproline O-arabinosylation.

Hydroxyproline-rich glycoproteins (HRGPs) occur in the extracellular matrix of land plants and green algae. HRGPs contain from 2 to 95% of their dry weight as carbohydrate, predominantly as oligoarabinosides and/or as heteropolysaccharides which are O-linked to the hydroxyproline residues. A glycosylation code that determines the presence or absence and extent of arabinosylation at each hydroxyproline residue is likely, as each HRGP has a unique arabinosylation profile. Previously we noted a positive correlation between the contiguity of hydroxyproline residues and the extent of HRGP O-arabinosylation (Kieliszewski, M., deZacks, R., Leykam, J.F., and Lamport, D.T.A. (1992) Plant Physiol. 98, 919-926); most arabinosylated hydroxyproline residues and the longer arabinofuranoside chains occur in HRGPs where Hyp residues occur as blocks of tetrahydroxyproline, while those with little or no contiguous Hyp exhibit very little Hyp arabinosylation. In order to test this Hyp contiguity hypothesis, we have for the first time determined the arabinosylation site specifics of an HRGP, namely the proline and hydroxyproline-rich glycoprotein (PHRGP) isolated from Douglas fir (Pseudotsuga menziesii). Pronase digests of PHRGP yielded a major peptide and three glycopeptides whose structures were determined directly from the unfractionated underivatized Pronase digest by tandem mass spectrometry using collisionally induced dissociation. We corroborated the peptide and glycopeptide structures by Edman degradation, neutral sugar analyses, hydroxyproline arabinoside profiles, and further mass spectrometric analyses after purification of the major peptide and glycopeptides by a combination of hydrophilic interaction and reverse phase column chromatography. Consistent with the Hyp contiguity hypothesis, the structural analyses indicate that while the sequence Ile-Pro-Pro-Hyp is never arabinosylated and Lys-Pro-Hyp-Val-Hyp is only occasionally monoarabinosylated at Hyp-5, the peptide containing contiguous Hyp, Lys-Pro-Hyp-Hyp-Val, is always arabinosylated at Hyp-3, mainly by a triarabinoside. We also obtained precise molecular masses for both intact and anhydrous hydrogen fluoride-deglycosylated PHRGPs (73.113 and 53.834 kDa) via matrix-assisted laser desorption/ionization time of flight mass spectrometry, representing the first HRGP to be analyzed by this method.

Amino Acid Sequence↗

Characterization of a cDNA encoding the 55 kDa B regulatory subunit of Arabidopsis protein phosphatase 2A.

Type 2A serine/threonine protein phosphatases (PP2A) are key components in the regulation of signal transduction and control of cell metabolism. The activity of these protein phosphatases is modulated by regulatory subunits. While PP2A activity has been characterized in plants, little is known about its regulation. We used the polymerase chain reaction to amplify a segment of a cDNA encoding the B regulatory subunit of PP2A from Arabidopsis. The amplified DNA fragment of 372 nucleotides was used as a probe to screen an Arabidopsis cDNA library and a full-length clone (AtB alpha) of 2.1 kbp was isolated. The predicted protein encoded by AtB alpha is 43 to 46% identical and 53 to 56% similar to its yeast and mammalian counterparts, and contains three unique regions of amino acid insertions not present in the animal B regulatory subunit. Genomic Southern blots indicate the Arabidopsis genome contains at least two genes encoding the B regulatory subunit. In addition, other plant species also contain DNA sequences homologous to the B regulatory subunit, indicating that regulation of PP2A activity by the 55 kDa B regulatory subunit is probably ubiquitous in plants. Northern blots indicate the AtB alpha mRNA accumulates in all Arabidopsis tissues examined, suggesting the protein product of the AtB alpha gene performs a basic housekeeping function in plant cells.

Amino Acid Sequence↗

Correlations between periovulatory serum and follicular fluid CA-125 and granulosa cell hormones after controlled ovarian hyperstimulation.

OBJECTIVE: To determine the presence and concentration of CA-125 in periovulatory follicular fluid (FF) and serum after controlled ovarian hyperstimulation and to determine if the CA-125 in these two compartments could be related to granulosa cell markers such as inhibin or estradiol. STUDY DESIGN: Fifteen women undergoing controlled ovarian hyperstimulation for in-vitro fertilization-embryo transfer were studied. A transvaginal, ultrasound-guided follicular aspiration was performed. CA-125, inhibin, estradiol and FSH were measured in FF and serum. Pearson and Spearman's Rank Correlation tests were performed. RESULTS: CA-125 was measurable in 59% of follicles. Values ranged from undetectable to 3630 U/ml. Serum CA-125 ranged from undetectable to 126 U/ml. CA-125 and inhibin correlated negatively in FF and positively in serum. CONCLUSION: CA-125 was present in significant but variable concentrations in 59% of periovulatory follicles. A negative correlation was noted between CA-125 and inhibin or estradiol in the FF and a positive correlation with serum inhibin. No correlations were noted to oocyte retrieval or fertilization.

Adult↗

The effect of intermittent steroid therapy on anti-sperm antibody levels.

Sperm-bound antisperm antibody levels were measured in 10 males in subfertile partnerships who were treated with high dose intermittent prednisolone therapy over a period up to 9 months. Antibody levels fell in all patients during therapy, although a transient rise occurred after 2-4 months. There were low treatment complication rates. Four pregnancies occurred during the treatment of the 10 patients. There was no correlation between pregnancy and change in antibody.

Adult↗

Dependence of pulmonary venous admixture on inspired oxygen fraction and time during regional hypoxia in the rabbit.

In order to examine the value of assuming constant pulmonary venous admixture with respect to changes in inspired oxygen fraction (FIO2) and time during sustained unilateral hypoxia, we studied venous admixture for 6 h in 27 anaesthetized rabbits in which the left lung was filled with liquid, isosmotic with plasma. In one group of 10 rabbits the right lung was ventilated for 6 h with FIO2 = 1; in a second group of 10 the right lung was ventilated with FIO2 = 1 for 2.5 h and then with FIO2 = 0.3 for 3.5 h. A third group was similarly studied by changing from FIO2 = 1 to FIO2 = 0.5. We found that hypoxic pulmonary vasoconstriction continued to intensify over 3 h. At 3-6 h, with FIO2 = 0.3, venous admixture (0.32 (SEM 0.03)) was higher than baseline (0.13 (0.01), t = 0 min during bilateral oxygenation) by twice the elevation above baseline of the venous admixture (0.22 (0.01)) in the group with FIO2 = 1. The finding of a marked increase in venous admixture with decreasing FIO2 is discussed in relation to current models of hypoxic pulmonary vasoconstriction.

Animals↗

Linkage of a gene for dominant non-syndromic deafness to chromosome 19.

Inherited hearing impairment can occur either in the presence of other clinical features (syndromic hearing loss, SHL) or in isolation (non-syndromic hearing loss, NSHL). The latter is more common and is highly heterogeneous. To date, six NSHL loci have been mapped. We report the identification of a seventh locus (DFNA4) on chromosome 19q13 and suggest DM kinase as a possible candidate gene.

Chromosome Mapping↗

Consanguineous nuclear families used to identify a new locus for recessive non-syndromic hearing loss on 14q.

Hearing impairment is inherited most frequently as an autosomal recessive isolated clinical finding (non-syndromic hearing loss, NSHL). Extreme heterogeneity and phenotypic variability in the audiometric profile preclude pooling of affected families and severely hamper gene mapping by conventional linkage analysis. However, in instances of consanguinity, homozygosity mapping can be used to identify disease loci in small nuclear families. This report demonstrates the power of this technique by identifying a locus for recessive NSHL on 14q (DFNB4).

Chromosome Mapping↗

Role of the sympathetic nervous system in cardiac performance during hyperkalaemia in the anaesthetized pig.

Cardiovascular performance was studied in 18 alpha-chloralose anaesthetized pigs when arterial potassium ([K+]a) was raised to levels observed in heavy exercise. The effects of hyperkalaemia were then studied during cardiac sympathetic nerve stimulation or during an infusion of noradrenaline. Elevation of [K+]a up to ca. 10 mM caused a progressive decline in cardiovascular performance. However, right cardiac sympathetic nerve stimulation elevated all cardiovascular parameters in the presence of raised [K+]a and offset the negative cardiac effects of hyperkalaemia. Electrical pacing of the right atrium to heart rates (HRs) equivalent to those observed during right cardiac sympathetic nerve stimulation did not offset the depressive effects of hyperkalaemia and, indeed, hastened the decline in cardiovascular performance. Infusion of noradrenaline (1 microgram kg min-1 i.v.) during hyperkalaemia caused an increase in all cardiovascular parameters similar to that seen during sympathetic nerve stimulation. After propranolol (0.5 mg kg-1 i.v.), sympathetic nerve stimulation slightly increased HR, systolic blood pressure (SBP) and dP/dtmax. Elevation of [K+]a occurred more rapidly after propranolol, but the heart was still protected from hyperkalaemia during cardiac sympathetic stimulation. Infusion of noradrenaline elicited arrhythmias in six pigs. Infusion of KCl reduced the incidence of arrhythmias and in some cases abolished them. These findings may be related to how the heart is protected from exercise-induced changes in potassium and catecholamines.

Adrenergic Fibers↗

Effect of verapamil on restoration of cardiac performance in raised [K+]o by adrenergic stimulation in the rabbit.

Modulation of the L-type calcium channel by catecholamines improves action potential parameters in single ventricular myocytes depolarized by high [K+]o Tyrode. Whether this modulation is important in offsetting the negative effects of hyperkalaemia in the whole heart is not known. We tested the effects of the calcium channel antagonist, verapamil, on restoration of cardiac performance by adrenergic stimulation in high [K+]o in anaesthetized rabbits and isolated perfused working rabbit hearts. Raised [K+]o decreased SBP, LVP and LVdP/dtmax in vivo ([K+]a 8.6 +/- 0.2 mM; n = 10) and aortic flow (AF) in the isolated heart (8 mM [K+]o Tyrode; n = 25). However, the negative effects of raised [K+]a were offset by isoprenaline (Iso, 1 microgram kg-1 min-1 i.v.) in vivo and by noradrenaline (NA, 80 nM) in the isolated heart. Verapamil (0.15 mg kg-1 i.v.; 15 nM isolated heart) markedly potentiated the negative inotropic effects of raised [K+]o in both preparations. Verapamil attenuated the effect of isoprenaline in vivo but in the isolated heart, the protective effect of NA in 8 mM [K+] Tyrode (AF 97 +/- 10 mL min-1 in 8 mM [K+]o compared with AF 141 +/- 8.5 mL min-1 in 8 mM [K+]o + NA) was offset by the drug (90 +/- 8 mL min-1 in 8 mM [K+]o + NA + V). Furthermore, verapamil abolished aortic flow in 8 mM [K+]o alone. These findings suggest that the heart may be critically dependent on modulation of intracellular calcium in order to tolerate concentrations of K+ similar to those seen during a short burst of intensive exercise ([K+]a 8.6 mM).

Action Potentials↗

NG-Nitro-L-arginine protects against ischaemia-induced increases in nitric oxide and hippocampal neuro-degeneration in the gerbil.

To assess the effects of the nitric oxide synthase inhibitor NG-Nitro-L-arginine on behavioural, biochemical and histological changes following global ischaemia, the Mongolian gerbil was used. Ischaemia was induced by bilateral carotid occlusion for 5 min. NG-Nitro-L-arginine was administered i.p. at either 1 or 10 mg/kg 30 min, 6, 24, and 48 h after surgery. 5 min bilateral carotid occluded animals were hyperactive 24, 48 and 72 h after surgery. NG-Nitro-L-arginine caused some attenuation in this hyperactivity. The activity of nitric oxide synthase was increased in the cerebellum, brain stem, striatum, cerebral cortex and hippocampus of 5 min bilateral carotid occluded animals. NG-Nitro-L-arginine reversed the increase in nitric oxide synthase activity in all brain regions. Extensive neuronal death was observed in the CA1 layer of the hippocampus in 5 min bilateral carotid occluded animals 96 h after surgery. NG-Nitro-L-arginine significantly protected against the neuronal death of cells in the CA1 layer.

Amino Acid Oxidoreductases↗

The role of bone scintigraphy with pinhole collimation in the evaluation of symptomatic paediatric hips.

Sixty-two children with signs and symptoms of hip pathology underwent bone scintigraphy with pinhole collimation of the hip joints. Three distinct patterns of isotope uptake were observed: a normal uptake of isotope, a focal increase or decrease of isotope uptake and a mild diffuse increase of isotope uptake. Forty-four children had normal isotope scans, an average hospital stay of 6.8 days and no significant pathology on follow-up. Ten children had a focal increase or decrease of isotope uptake, an average hospital stay of 21 days and on follow-up all had significant pathology. Eight children had a mild diffuse increase of isotope uptake, an average hospital stay of 8.75 days and no significant pathology on follow-up. We conclude: (1) Normal isotope hip scintigrams with pinhole collimation indicate an excellent prognosis in symptomatic paediatric hips; (2) Focal scintigraphic abnormalities are indicative of significant pathology; (3) A mild diffuse increase in isotope uptake on both sides of the joint is not associated with significant pathology; (4) There is a good correlation between scintigrams and the length of hospital stay; (5) Scintigraphy is at least twice as sensitive at the time of presentation as plain radiographs in the detection of pathology.

Adolescent↗