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Biomedical subjects

J E Gallagher

Publications and source records attributed to J E Gallagher.

At least 19 recordsLinked to original sources
PubMed2002

Differential particulate air pollution induced oxidant stress in human granulocytes, monocytes and alveolar macrophages.

It has been proposed that oxidant stress of cells in the lung is one of the underlying mechanisms of particulate pollution-induced exacerbation of lung disease. Individuals who are considered most sensitive to particulate pollution are those with pre-existing airways inflammation, such as chronic obstructive pulmonary disease (COPD), lung infection or asthma. These diseases are characterized by a presence of inflammatory cells in the airways including neutrophils (PMN), eosinophils and monocytes (Mo), and increased numbers of alveolar macrophages (AM). These cells have a high capacity for production of oxygen radicals, as compared to other cell types of the lung. To assess the oxidative response of these various cell types to pollution particles of various sources, luminol-dependent chemiluminescence was employed. Particles including transition metal-rich residual oil fly ashes (ROFAs), coal fly ashes, diesel, SiO2, TiO2 and fugitive dusts were co-cultured with AM, Mo and PMN in a dose range of 10-100 microg/2 x 10(5) cells and chemiluminescence determined following a 20-min interaction. A strong oxidant response of AM was restricted to oil fly ashes, while the PMN were most reactive to the dusts containing aluminium silicate. In general, the Mo response was less vigorous, but overlapped both AM- and PMN-stimulating dusts. However, in response to SiO2 and volcanic ash the Mo chemiluminescence exceeded that of the other cell types. Oxygen radicals generated in response to ROFA by the AM were likely to be dependent on mitochondrial processes, while the response in PMN involved the membrane NADPH oxidase complex, as determined by targeting inhibitors. The response of AM to SiO2 of various sizes and TiO2 in the fine size range obtained from different commercial sources, was highly variable, implying that composition rather than size was responsible for the oxidant response. A strong chemiluminescence response was not consistently associated with cytotoxicity in the responsive cell. Taken together, these results suggest that oxidant activation by various sources of particulate matter is cell specific. Therefore, the inflamed lung is likely to be more susceptible to harm of ambient air particulates because of the oxidant stress posed by a broader range of particles.

Adult↗
PubMed2001

Air pollution particles mediated oxidative DNA base damage in a cell free system and in human airway epithelial cells in relation to particulate metal content and bioreactivity.

Epidemiological studies demonstrate an association between increased human morbidity and mortality with exposure to air pollution particulate matter. We hypothesized that such effects may be associated with the ability of the particles to mediate generation of reactive oxygen species (ROS), either directly, via interaction with ambient oxygen or indirectly through initiation of an oxidative burst in phagocytes. To test this hypothesis, we determined 8-oxo-dG formation as a measure of direct generation of ROS, in response to particulate exposures to 2'-deoxyguanosine (dG), free and in calf thymus DNA in aerated solutions as the target molecule and cell culture, to assess the relationship between induction of oxidative damage, particulate metal content and metal bioreactivity. The HPLC-ECD technique was employed for separation and quantification of 8-oxo-dG, the most widely recognized marker of DNA oxidation. Particles used in this study include: Arizona desert dust (AZDD), coal fly ash (CFA and ECFA), oil fly ash (OFA and ROFA), and ambient air [SRM 1649 and Dusseldorf (DUSS), Germany]. The major difference between these particles is the concentration of water-soluble metals. The fly ash particulates OFA and ROFA showed a significant dose-dependent increase in dG hydroxylation to 8-oxo-dG formation over the control dG (p < 0.05), with yields 0.03 and 1.25% at the highest particulate concentration (1 mg/mL). Metal ion chelators and DMSO, a hydroxyl radical scavenger, inhibited this hydroxylation. In contrast, desert dust, coal fly ash and urban air particles induced 8-oxo-dG with yields ranging from 0.003 to 0.006%, respectively, with levels unaffected by pretreatment of the particles with metal ion chelators or addition of DMSO to the incubation mixture. When calf thymus DNA was used as a substrate, all the particles induced 8-oxo-dG in a pattern similar to that observed for dG hydroxylation, but with relatively less yield. Treatment of the particles with metal ion chelator before reacting with DNA or addition of catalase in the incubation mixture, suppressed 8-oxo-dG formation significantly (p < 0.05) in oil-derived fly ash particles only. To determine whether the oxidative responses of these particulates as shown in cell-free systems were consistent with responses using a more biologically relevant environment, human airway epithelial cells were treated with the particulates and induction of 8-oxo-dG was determined. All particles induced 8-oxo-dG in the DNA of cells above culture control, except CFA. Cells exposed to 10-400 mg/mL of ROFA for 2 h induced a dose-dependent increase in 8-oxo-dG formation. Treatment of ROFA with metal ion chelator attenuated these effects. Overall, damage enhancement by particulates in dG, calf thymus, and cellular DNA as determined by 8-oxo-dG formation under aerobic conditions is consistent with the concentration of water-soluble, not the total metal content of the particle.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Oral health status and dental service use of adults with learning disabilities living in residential institutions and in the community.

OBJECTIVE: To investigate the oral health status of adults on Sheffield's Learning Disability Case Register, and their reported use of dental services. DESIGN: A short questionnaire interview of subjects with learning disabilities or their carers followed by a standardised epidemiological examination, by one trained and calibrated examiner. SETTING: Residential homes, day centres or community homes of people with learning disabilities in Sheffield. SUBJECTS: A 20% random sample of adults (18-65 years) on the register. RESULTS: A response rate of 209 (67%) was achieved, 62% (n=130) of whom were living in the community. People living in residential care were significantly older (43.2 years) than those based in the community (36.3 years) (P<0.05). Both groups had similar mean DMFT scores; however, adults living in the community had significantly more untreated decay (DT = 1.6) and poorer oral hygiene than their counterparts in residential care (DT = 0.7). Adults in residential care had significantly more missing teeth (MT = 10.1) than those in community care (MT = 7.5). General and community dental services were the main providers of dental care. Subjects living in the community were significantly less likely to have a dentist and to use community dental services than their residential counterparts; they were more likely to attend only when having trouble. CONCLUSIONS: Adults with learning disabilities living in the community have greater unmet oral health needs than their residential counterparts and are less likely to have regular contact with dental services. Commissioners and providers of dental services have a responsibility to ensure that the health of adults with learning disabilities is not compromised by 'normalisation'.

Adolescent↗
PubMed2000

Enhancement of 2'-deoxyguanosine hydroxylation and DNA damage by coal and oil fly ash in relation to particulate metal content and availability.

Epidemiologic studies have shown causal relationships between air pollution particles and adverse health effects in susceptible subpopulations. Fly ash particles (containing water-soluble and insoluble metals) are a component of ambient air particulate pollution and may contribute to particulate-induced health effects. Some of the pathological effects after inhalation of the particles may be due to reactive oxygen species (ROS) produced by metal-catalyzed reactions. In this investigation, we analyzed emission source particulates oil fly ash (OFA) and coal fly ash (CFA) for metal content and solubility in relation to their ability to induce 2'-deoxyguanosine (dG) hydroxylation and DNA damage as measured by 8-oxo-dG formation by HPLC/UV-electrochemical detection (ECD). Water-soluble vanadium and nickel were present at the highest concentrations, and iron was present in trace amounts in OFA (5.1% V, 1.0% Ni, and 0.4% Fe by weight). In contrast, CFA comprised mostly of water-insoluble aluminosilicates and iron (9.2% Al, 12.2% Si, and 2.8% Fe by weight). As a first approach to gain insight into the mode of action of these particulates, we examined metal species-catalyzed kinetics of dG hydroxylation. Metal species at a concentration of 0.1 mM in the incubation mixture containing 0.1 mM dG under ambient air at room temperature catalyzed maximum 8-oxo-dG formation at 15 min with yields ranging from 0.05 to 0.17%, decreasing in the following order: vanadium(IV) > iron(II) > vanadium(V) > iron(III) > or = nickel(II). Insoluble Fe(III) oxide (Fe(2)O(3)) under similar conditions had no effect. Consistent with these results, OFA rich in vanadium and nickel concentrations showed a dose-dependent increase in the level of dG hydroxylation to 8-oxo-dG formation at particulate concentrations of 0.1-1 mg/mL (p < 0.05). In contrast, CFA with high concentrations of aluminosilicates and iron did not result in a significant increase in the level of 8-oxo-dG over that of the control, i.e., dG (p > 0.05). DMSO, a (*)OH scavenger, inhibited OFA-induced 8-oxo-dG formation, and metal ion chelators, deferoxamine (DFX), DTPA, and ferrozine blocked OFA-induced 8-oxo-dG formation. OFA and CFA induced 8-oxo-dG formation in a pattern similar to that observed for dG hydroxylation when calf thymus DNA was used as a substrate. Treatment of OFA particles with DFX before reacting with DNA or addition of a catalase in the incubation mixture significantly suppressed 8-oxo-dG formation (p < 0.05). These results suggest that metal availability, but not the concentration of metals present in CFA and OFA, is critical in mediating molecular oxygen-dependent dG hydroxylation and DNA base damage.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

Dental caries prevalence and dental health behaviour in HIV infected children.

OBJECTIVES: To determine dental caries prevalence in a group of HIV positive children and their reported dental health behaviour. DESIGN: Standardized epidemiological dental examination and structured interview. SETTING: Paediatric HIV outpatient department in a South London hospital. STUDY POPULATION: HIV-positive children attending the above outpatient clinic over a 6-month period (30 subjects) and parents (20 informants). METHODS: Epidemiological examination of children was undertaken by one trained and calibrated examiner to determine caries prevalence using dmft/DMFT. Parents were interviewed to obtain information on their children's dental health behaviour: toothbrushing, diet, fluoride; oral medication and dental attendance were explored. RESULTS: Sixty-three per cent (n = 19) of children had dental caries experience, much of it untreated. Mean dmft/DMFT was 4.4. Sixty per cent (n = 18) of all children presented with active or untreated caries and the care index for those at/under age 5 years was low (10%). Unfavourable dental health behaviour included: consumption of nonmilk extrinsic sugars at night, use of sugar-based medications, low fluoride intake, late commencement of toothbrushing and poor dental attendance. Dental health was not considered a priority for many of these children. Parents did not necessarily disclose their child's HIV status on dental attendance. CONCLUSION: Caries prevalence was high, much of the disease untreated, and unfavourable dental health behaviour, including the use of sugar-based medicines was common. HIV infected children should be considered a high caries risk and receive appropriate dental care, in terms of both treatment and preventive services, following confirmation of seropositivity.

Child↗
PubMed1999

Ambient air particles: effects on cellular oxidant radical generation in relation to particulate elemental chemistry.

Epidemiologic studies have reported causal relationships between exposures to high concentrations of ambient air particles (AAP) and increased morbidity in individuals with underlying respiratory problems. Polymorphonuclear leukocytes (PMN) are frequently present in the airways of individuals exposed to particles. Upon particulate stimulation the PMN may release reactive oxygen species (ROS), which can result in tissue damage and injury. In this study a wide range of AAP samples from divergent sources (1, natural dust; 2, oil fly ash; 2, coal fly ash; 5, ambient air; and 1, carbon black) were analyzed for elemental content and solubility in relation to their ability to generate ROS. Elemental analyses were carried out in AAP and dH(2)O-washed AAP using energy dispersive x-ray fluorescence (XRF). Percent of sample mass accounted for by XRF-detectable elements was 1.2% (carbon black); 22-29% (natural dust and ambient air particles); 13-22% (oil fly ash particles); 28-49% (coal fly ash particles). The major proportion of elements in most of these particles were aluminosilicates and insoluble iron, except oil-derived fly ash particles in which soluble vanadium and nickel were in highest concentrations, consistent with particle acidity as measured in the supernatants. Human blood-derived monocytes and PMN were exposed to AAP and dH(2)O-washed particles, and generation of ROS was determined using luminol-enhanced chemiluminescence (LCL) assay. All the particles induced chemiluminescence response in the cells, except carbon black. The oxidant response of monocytes induced by AAP (with the exception of oil fly ash particles) was less than the response elicited by PMN. The LCL response of PMN in general increased with all washed particles, with oil fly ash (OFA) and one urban air particle showing statistically significant (p < 0. 05) differences between dH(2)O-washed and unwashed particles. The LCL activity in PMN induced by both particles and dH(2)O-washed particles was significantly correlated with the insoluble Si, Fe, Mn, Ti, and Co content of particles (p < 0.05). No relationship between LCL activity in PMN and soluble transition metals such as V, Cr, Ni, and Cu was noted. Pretreatment of the particles with a metal ion-chelator, deferoxamine, did not affect LCL in PMN, suggesting that metal ions are not related to the induction of LCL in PMN. Particulate S content and acidity of the particles as measured in the supernatants did not relate to LCL activity in PMN. These results point to the possibility that the insoluble constituents of the particles are related to LCL in PMN. Since some of these dusts are capable of depositing in the lungs and can cause infiltration of PMN, the ability to activate those cells may contribute to particulate toxicity.

Air Pollutants↗
PubMed1996

An education and training initiative on dental care for the HIV-positive patient.

Workshops were established on the theme of 'HIV and the General Dental Team' to meet the expressed needs of dentists working in one family health services authority (FHSA). The workshop's effect with regard to knowledge, attitudes and working practices was assessed. A questionnaire, completed at the beginning of the day by the 29 participants, explored areas of staff knowledge, attitudes, concerns and reported practices regarding treatment of people with HIV. A second questionnaire was completed at the end of the day to enable comparisons to be made before and after the course. After the workshop, there were general improvements in the levels of knowledge about clinical signs and symptoms, oral manifestations of HIV and AIDS and modes of the transmission of HIV. A change of attitude towards the provision of dental care for people with HIV was reported by 39%, 59% were more likely to provide this care and 72% of participants said they would change their working practices, principally with respect to infection control. A follow-up survey one year later reported long term behaviour changes and requests for further support in the form of a newsletter, video or telephone helpline and a confidentiality policy for use in general practice.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Perioperative ketorolac tromethamine and postoperative hemorrhage in cases of tonsillectomy and adenoidectomy.

The charts of 258 patients undergoing tonsillectomy with or without adenoidectomy between June 1991 and June 1993 were reviewed. One hundred sixty-nine of these patients received ketorolac tromethamine during the perioperative period as a nonnarcotic alternative for postoperative pain management. The incidence of postoperative hemorrhage among patients who received ketorolac tromethamine was 10.1%, compared to 2.2% in those patients who received narcotic analgesia only. The average time to adequate oral intake and discharge was evaluated. Ketorolac appeared to moderately decrease the time to adequate oral intake. The use of ketorolac did not significantly alter the time to discharge. The increased incidence of postoperative hemorrhage in patients receiving ketorolac should be considered before this medication is used in the perioperative period. The risk/benefit ratio of ketorolac use as a postoperative analgesic may be better demonstrated in a prospective study.

Adenoidectomy↗
PubMed1994

Comparison of DNA adduct levels in human placenta from polychlorinated biphenyl exposed women and smokers in which CYP 1A1 levels are similarly elevated.

Previous studies demonstrated that cigarette smoking is associated with high elevations in levels of both cytochrome P450 1A1 (CYP1A1) and DNA adducts in human placenta. To date, the identity of the smoking related DNA adducts is not known. The DNA adducts identified in placenta of smokers could result from chemicals present in cigarette smoke, substances formed by CYP 1A1 metabolic activation of endogenous compounds, noncigarette related exposures or a combination of these processes. Exposure to contaminated rice oil containing large doses of polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) also resulted in massive elevation of CYP 1A1 in human placenta but formation of DNA adducts directly from this exposure has not previously been reported. The purpose for comparing the two populations was to test the hypothesis that if CYP 1A1 induction results in the metabolic activation of endogenous compounds, then DNA adducts should also be present in PCB/PCDF exposed tissues exhibiting high CYP 1A1 activity and some of the adducts detected in the placental DNA from smokers may be identified as those derived from the metabolic activation of endogenous compounds. To test this hypothesis, we measured DNA adducts using 32P-postlabeling to analyze placental DNA from women exposed to PCB/PCDF and from cigarette smokers where levels of CYP 1A1 were similarly elevated. There was no evidence of DNA adducts among specimens obtained from PCB/PCDF exposed individuals. These data suggest that CYP 1A1 induction alone (in the absence of cigarette smoking) does not induce the formation of DNA adducts detectable by this approach, and that smoking related adducts are not a consequence of CYP 1A1 induction mediated activation of endogenous compounds or xenobiotics other than cigarette smoke.

Aryl Hydrocarbon Hydroxylases↗
PubMed1993

Genotoxic activity of 1-chloromethylpyrene in stomach epithelium in vivo: insensitivity of the stomach scintillation UDS assay.

An acknowledged weakness of current testing programmes for genotoxic hazard has been the potential insensitivity of the established mouse bone marrow micronucleus test and rat liver unscheduled DNA synthesis (UDS) assays to direct-acting or short-lived mutagens, which may be consumed at the site of initial contact. In such cases, in vivo test systems sampling tissues such as the skin or the stomach would provide valuable data. To test these principles a stomach UDS assay was evaluated using the potent locally active mutagen 1-chloromethylpyrene (1-CMP). Contrary to expectations, no UDS response was observed 16 h following 1-CMP dosage by oral gavage. To confirm the integrity of the 1-CMP used for the stomach UDS assay, a sample of the stored chemical was re-evaluated in vitro and shown to be still strongly positive in the Ames assay and to have alkylating activity at least 15 min after incubation at stomach acid pH. No UDS response was observed when test dose levels were reduced or when earlier sampling times were used. Other genotoxic endpoints were examined in stomach. 32P-Postlabelling analysis revealed high levels of adduct formation in gastric DNA. An assay utilizing electrophoresis of DNA (the comet assay) showed the occurrence of DNA damage following dosing with 1-CMP in vivo. These positive results confirmed that 1-CMP should be regarded as a potential in vivo genotoxin. The failure to detect a UDS response to 1-CMP in stomach was investigated; a strong UDS response was observed in an in vitro hepatocyte UDS assay of 1-CMP indicating that the rat was capable of repairing 1-CMP-derived DNA adducts. Pretreatment of rats with hydroxyurea depressed the level of incorporation of thymidine into DNA both in negative and positive [methyl-N-nitrosoguanidine (MNNG)] controls. The results of these studies indicated that the protease digestion method employed did not selectively or efficiently sample those cells with any UDS response to 1-CMP or MNNG, and the activity seen for the latter was most likely due to the presence of S phase cells within the digests. As a result of the finding that UDS responses were not demonstrated for the potent direct-acting mutagens 1-CMP and MNNG, the protease digestion/scintillation method for stomach UDS does not appear to have general value in a screening programme for locally active genotoxic agents.

Administration, Oral↗