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M O'Neill

Publications and source records attributed to M O'Neill.

At least 37 records · Page 2Linked to original sources
PubMed1998

Experimental assessment of the influence of atmospheric pollutants on respiratory disease.

Asthma is a chronic respiratory disease characterized by inflammation, episodes of usually reversible airways obstruction, and bronchial hyperresponsiveness. The disease has significant health, societal and economic consequences. Experimental assessment methods, including controlled human exposure studies, human and animal dosimetry, as well as animal and in vitro toxicology, can shed light on how air pollutants may cause and/or worsen asthma. A brief summary background on selected classes of air pollutants is provided and selected experimental studies that exemplify novel approaches or suggest new hypotheses are highlighted. Possible directions for future research about the effects of particles, pesticides, ambient air toxicants, and pollutant mixtures on asthma, are also outlined.

Air Pollutants↗
PubMed1998

Localization of a protein-DNA interface by random mutagenesis.

The type I restriction and modification enzymes do not possess obvious DNA-binding motifs within their target recognition domains (TRDs) of 150-180 amino acids. To identify residues involved in DNA recognition, changes were made in the amino-TRD of EcoKI by random mutagenesis. Most of the 101 substitutions affecting 79 residues had no effect on the phenotype. Changes at only seven positions caused the loss of restriction and modification activities. The seven residues identified by mutation are not randomly distributed throughout the primary sequence of the TRD: five are within the interval between residues 80 and 110. Sequence analyses have led to the suggestion that the TRDs of type I restriction enzymes include a tertiary structure similar to the TRD of the HhaI methyltransferase, and to a model for a DNA-protein interface in EcoKI. In this model, the residues within the interval identified by the five mutations are close to the protein-DNA interface. Three additional residues close to the DNA in the model were changed; each substitution impaired both activities. Proteins from twelve mutants were purified: six from mutants with partial or wild-type activity and six from mutants lacking activity. There is a strong correlation between phenotype and DNA-binding affinity, as determined by fluorescence anisotropy.

Amino Acid Sequence↗
PubMed1998

An immunochemical analysis of mdm2 expression in human breast cancer and the identification of a growth-regulated cross-reacting species p170.

mdm2 is a 491 amino acid nuclear protein which is involved in complex interactions with important cell-cycle and stress-response regulators including p53, Rb and E2F. Recent data implicate mdm2 in the regulation of both p53 activity and level, and burgeoning data suggest that mdm2 may be involved in human epithelial tumourigenesis, including breast cancer. In this study the expression of mdm2 protein has been investigated in a series of 54 human breast carcinomas using immunoblotting methods. Overexpression of the predominant p90 mdm2 isoform is common in breast cancer (54 per cent) and this is not frequently a consequence of gene amplification. There is no relationship between p90 expression and either p53 protein expression or p53 mutational status. Additional mdm2 immunoreactive species of differing mobilities are identifiable, greatly complicating the analysis. For example, a p170 form is seen in many breast cancer samples (44 per cent) using 2A10 but is not identified by 3G5. This 2A10 immunoreactive species, which is almost certainly not an mdm2 isoform, is a growth-regulated protein, being undetectable in resting peripheral blood lymphocytes and rising to high levels after PHA stimulation. In contrast to mdm2 (p90), p170 is not induced by DNA damage caused by UV light. p170 is identifiable in mdm2 null cells by immunoblotting and is detected as a nuclear protein. While mdm2 immunostaining studies are increasing, this report highlights the complexity of mdm2 analysis in vivo and emphasizes the need to correlate immunohistological and biochemical assays since, in some mdm2 (p90) negative tumours, nuclear immunoreactivity may be identified as a consequence of cross-reacting species such as p170.

Adenocarcinoma↗
PubMed1998

Structural characterization of the galactoxylomannan of Cryptococcus neoformans Cap67.

The galactoxylomannan (GalXM) obtained from the culture supernatant of an acapsular mutant of Cryptococcus neoformans Cap67 was purified by Concanavalin A affinity, ion-exchange, and gel-filtration chromatographies. The structure of GalXM was determined by methylation analysis and by 1D and 2D NMR spectroscopic studies of the intact polysaccharide and of the oligosaccharide fragments generated by Smith degradation and by acetolysis. GalXM is a complex polysaccharide with an alpha-(1-->6) -galactan backbone. The polysaccharide is branched at c-3 of alternate Gal units of the backbone. C-3 is the point of attachment of the oligosaccharide side chains comprised of alpha-D-Man- (1-->3)-alpha-D-Man-(1-->4)- beta-D-Gal-substituted with zero to three terminal beta-Xyl residues as shown in the following structure: [formula: see text].

Carbohydrate Sequence↗
PubMed1998

Health risk profile of prostitutes in Dublin.

This study examined the health risk profile of prostitutes in Dublin. Clinical records of all 150 new prostitutes who attended a drop-in clinic for prostitutes in Dublin city during the period 1991-1997 were reviewed. Variables examined included: age, use of injectable drugs, human immunodeficiency virus (HIV) status, hepatitis B and C status, presence of sexually transmitted disease (STD), cervical cytology. Results showed the mean age of the women was 32 years. Among those tested, 2.5% were HIV positive, 5% were hepatitis B positive, 8% were hepatitis C positive and 25% had an STD. Almost 8% were injecting drug users (IDU) with higher prevalences of HIV, hepatitis B and C compared with non-IDU (P < 0.001). The clinic has been successful in providing a health-care facility for the specific health needs of this patient cohort.

Adult↗
PubMed1997

The restriction-modification genes of Escherichia coli K-12 may not be selfish: they do not resist loss and are readily replaced by alleles conferring different specificities.

Type II restriction and modification (R-M) genes have been described as selfish because they have been shown to impose selection for the maintenance of the plasmid that encodes them. In our experiments, the type I R-M system EcoKI does not behave in the same way. The genes specifying EcoKI are, however, normally residents of the chromosome and therefore our analyses were extended to monitor the deletion of chromosomal genes rather than loss of plasmid vector. If EcoKI were to behave in the same way as the plasmid-encoded type II R-M systems, the loss of the relevant chromosomal genes by mutation or recombination should lead to cell death because the cell would become deficient in modification enzyme and the bacterial chromosome would be vulnerable to the restriction endonuclease. Our data contradict this prediction; they reveal that functional type I R-M genes in the chromosome are readily replaced by mutant alleles and by alleles encoding a type I R-M system of different specificity. The acquisition of allelic genes conferring a new sequence specificity, but not the loss of the resident genes, is dependent on the product of an unlinked gene, one predicted [Prakash-Cheng, A., Chung, S. S. & Ryu, J. (1993) Mol. Gen. Genet. 241, 491-496] to be relevant to control of expression of the genes that encode EcoKI. Our evidence suggests that not all R-M systems are evolving as "selfish" units; rather, the diversity and distribution of the family of type I enzymes we have investigated require an alternative selective pressure.

Alleles↗
PubMed1997

Sensory-perceptual abnormalities in autism: a case for more research?

Sensory-perceptual abnormalities in people with autism are discussed from two perspectives: published firsthand accounts and existing psychological research evidence. A range of abnormalities, including hyper- and hyposensitivity, sensory distortion and overload, and multichannel receptivity and processing difficulties, are described in firsthand accounts and frequently portrayed as central to the autistic experience. A number of dangers are inherent in uncritically accepting these accounts at face value and in any wider generalization to the autistic population as a whole. Evidence from clinical studies suggests that unusual sensory responses are present in a majority of autistic children, that they are manifested very early in development, and that they may be linked with other aspects of autistic behavior. In addition, experimental studies using a range of indices have found evidence of unusual responses to sensory stimuli in autistic subjects. However the clinical and experimental research to date suffers from serious methodological limitations and more systematic investigation is warranted. Key issues for future psychological research in the area are identified.

Arousal↗
PubMed1997

Interactive effects of K+, acid, norepinephrine, and ischemia on the heart: implications for exercise.

We tested the hypothesis that cardiac ischemia uncouples the beneficial interaction among hyperkalemia, acidosis, and raised plasma catecholamines when these chemicals are changed to mimic their exercise levels. Potassium chloride, lactic acid, and norepinephrine (NE) were infused intravenously for 2 min into anesthetized, artificially ventilated, thoracotomized rabbits during either occlusion of the left circumflex artery (3 min; n = 10) or after a period of prolonged ischemia (20 min; n = 7) that led to a small infarction. NE (1 microg x kg(-1) x min(-1) iv) offset the negative cardiac effects of hyperkalemia (up to 8.7 +/- 0.7 mM) and acidosis (arterial pH 7.09 +/- 0.03) in normal hearts. Cardiac performance was not significantly depressed by either acute or chronic ischemia before any infusions. However, the protective effect of NE during acute ischemia or after prolonged ischemia with hyperkalemia and acidosis was substantially reduced. These results show that cardiac ischemia attenuates the protective action of NE and increases the depressive effects of hyperkalemia and acidosis. Whether myocardial ischemia amplifies the cardiotoxic effects of hyperkalemia and acidosis during vigorous exercise by attenuating the beneficial effect of catecholamines remains to be determined.

Acidosis↗
PubMed1997

Time course of hypoxic pulmonary vasoconstriction: a rabbit model of regional hypoxia.

There is disagreement in the literature about the time required for hypoxic constriction of pulmonary vessels to reach its full intensity. Some studies suggest that only minutes are required, others that several hours are needed. We examined the time course over 6 h of changes in pulmonary shunt (as a fraction of cardiac output) following induction of unilateral hypoxia by collapse or liquid filling of the left lung in 47 anesthetized rabbits. The time course was examined at four degrees of lung inflation: during collapse and at airway pressures of 0.3 kPa, 0.6 kPa, and 0.9 kPa. The respective volumes (mean +/- SD) of the liquid-filled lung were estimated to be 6.4 +/- 1.0, 12.8 +/- 2.5, and 15.8 +/- 1.6 ml/kg body weight (BW). During sustained hypoxia (the period from 150 to 360 min after inducing hypoxia), shunt declined at a slow linear rate of 2.37 x 10(-4)/min, which was independent of lung inflation (p = 0.65 analysis of variance [ANOVA]) and significantly different from zero (p < 0.001). The stability of cardiac output in this animal model, as measured sequentially by thermodilution, was confirmed in a further 20 animals. The experiments provide evidence for a slow intensification of blood-flow diversion at a rate that does not depend upon the degree of lung inflation. Whether this change is a feature of hypoxic constriction itself, or some modulation of it, remains unclear.

Animals↗
PubMed1997

Clinical application of the Ottawa ankle rules for the use of radiography in acute ankle injuries: an independent site assessment.

OBJECTIVE: Previous studies show that the clinical criteria known as the Ottawa ankle rules (OAR), used for determining the need for radiographs of the ankle when a fracture is suspected, have a sensitivity of 100%, a specificity of 50%, and an overall reduction in radiographs of the ankle of 28%. The purpose of this study was to further assess the clinical usefulness of the OAR when implemented in an emergency department of a level 1 trauma center. SUBJECTS AND METHODS: Over a 1-year period, all patients who were between 18 and 55 years old and who presented to the emergency department with blunt ankle trauma were examined by emergency department clinicians who used the OAR to determine the need for ordering ankle radiographs. RESULTS: Of 926 patients with blunt ankle trauma, 759 met OAR criteria for ordering radiographs of the ankle. Of these patients, 152 were found to have a fracture. Another 167 of the patients were determined not to need ankle radiographs. Through either telephone contact or medical records review. 152 (91%) of these 167 patients were successfully followed up for the purpose of detecting any missed fractures. Two missed fractures were discovered, but only one required plaster immobilization. Based on these numbers, overall sensitivity using the OAR was 99% (confidence interval, 95-100%), and specificity was 22%. We found an overall 16% reduction in the number of ankle films ordered. CONCLUSION: When implemented at a level 1 trauma center, the OAR can adequately screen for ankle fractures.

Acute Disease↗
PubMed1996

The novel sigma ligand JO 1994 protects against ischaemia-induced behavioural changes, cell death and receptor dysfunction in the gerbil.

To assess the effects of the novel sigma ligand JO 1994 on behavioural, histological and autoradiographical changes following global ischaemia, the Mongolian gerbil was used. Three experiments were carried out and in each case ischaemia was induced by bilateral carotid occlusion (BCO) for 5 min. In the first experiment we examined the effects of JO 1994 administered at doses of 0.25, 0.5 and 1 mg/kg i.p. 1 h before 5 min BCO on histological parameters 96 h after surgery. In the second experiment the effects of JO 1994 administered at doses of 2.5, 5, 10 and 20 mg/kg i.p. 1 h before 5 min BCO on locomotor activity 24, 48 and 72 h after surgery and on histological parameters 96 h after surgery was examined. In the third experiment the effects of JO 1994 (2.5 and 5 mg/kg i.p.), BMY 14802 (1 and 10 mg/kg i.p.) and MK-801 (2.5 mg/kg i.p.) administered 30 min, 6, 24, 48, 72, 96 and 120 h post-surgery on the densities of M1 and M2 muscarinic receptors in 35 brain regions, 7 days after surgery was examined. Results indicated that 5 min bilateral carotid occluded animals were hyperactive 24, 48 and 72 h after surgery. JO 1994 attenuated this hyperactivity. Extensive neuronal death was observed in the CA1 layer of the hippocampus in 5 min BCO animals 96 h after surgery. The low doses of JO 1994 (0.25, 0.5 and 1 mg/kg) had no effect on the ischaemia-induced cell death. However JO 1994 (2.5, 5, 10 and 20 mg/kg i.p.) protected against the neuronal death of cells in the CA1 layer (P < 0.01-0.03). There was a large loss of M1 and M2 receptors in the CA1 regions of the hippocampus. MK-801, BMY 14802 and JO 1994 provided significant (P < 0.01) protection against this ischaemia-induced receptor loss.

Animals↗