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Biomedical subjects

E J Gray

Publications and source records attributed to E J Gray.

15 recordsLinked to original sources

A novel bacteriocin, thuricin 17, produced by plant growth promoting rhizobacteria strain Bacillus thuringiensis NEB17: isolation and classification.

AIMS: The aim of this study was to identify and characterize a compound produced by the plant growth promoting bacterium, Bacillus thuringiensis non-Bradyrhizobium Endophytic Bacterium 17. METHODS AND RESULTS: The bacterial peptide was analysed and purified via HPLC. Using the disk diffusion assay this peptide inhibited the growth of 16/19 B. thuringiensis strains, 4/4 Bacillus cereus strains, among others, as well as a Gram-negative strain Escherichia coli MM294 (pBS42). Both bactericidal and bacteristatic effects were observed on B. cereus ATCC 14579 and bactericidal effects were observed on B. thuringiensis ssp. thuringiensis Bt1267. The molecular weight of the peptide was estimated via SDS-PAGE and confirmed with Matrix Assisted Laser Desorption Ionization Quadrapole Time of Flight mass spectrometry; its weight is 3162 Da. The peptide is biologically active after exposure to 100 degrees C for 15 min, and within the pH range 1.00-9.25. Its activity disappeared when treated with proteinase K and protease, but not with alpha-amylase or catalase. CONCLUSIONS: We conclude that this is the first report of a bacteriocin produced by a plant growth promoting rhizobacteria (B. thuringiensis) species and have named the bacteriocin thuricin 17. SIGNIFICANCE AND IMPACT OF THE STUDY: Our work has characterized a bacteriocin produced by a plant growth promoting bacterium. This strain is previously reported to increase soya bean nodulation.

Anti-Bacterial Agents↗

Perception of airway narrowing in a general population sample.

In epidemiological studies, defining asthma as the presence of airway hyperresponsiveness (AHR) plus recent symptoms leaves two groups of subjects whose clinical significance is unclear: those with asymptomatic AHR, and those with symptoms only. The aim of the study was to determine whether subjects with symptoms only differ from the normal and asthmatic groups in the perception of airway obstruction. Six hundred and ninety seven adults completed a questionnaire of symptoms and underwent bronchial challenge with histamine to induce airway obstruction. Recent symptoms included wheeze and morning chest tightness in the last 12 months. AHR was defined as a provoking dose of histamine causing > or = 20% fall in forced expiratory volume in one second (PD20FEV1) <3.9 micromol. At the end of the challenge test, subjects who felt wheezy or tight in the chest marked a value from 0 to 10 on a modified Borg scale, to describe the severity of the sensation. Subjects with asymptomatic AHR did not differ significantly from subjects with AHR plus recent symptoms (current asthma) either in the mean fall in FEV1 or in the median Borg score. In subjects with symptoms only, the mean Borg score was not significantly different from that of the asthmatic subjects, although mean fall in FEV1 differed significantly (p<0.0001). In subjects with symptoms only, chest tightness correlated significantly with the fall in forced vital capacity (FVC) (p= 0.011), but not with the fall in FEV1. Subjects with asymptomatic airways hyperresponsiveness were not poor perceivers of airway narrowing, but may underreport their symptoms. Subjects with symptoms only may have enhanced perception of small changes in lung function, particularly in forced vital capacity.

Adult↗

Designer DNA-binding drugs: the crystal structure of a meta-hydroxy analogue of Hoechst 33258 bound to d(CGCGAATTCGCG)2.

An analogue of the DNA binding compound Hoechst 33258, which has the para hydroxyl group altered to be at the meta position, together with the replacement of one benzimidazole group by pyridylimidazole, has been cocrystallized with the dodecanucleotide sequence d(CGCGAATTCGCG)2. The X-ray structure has been determined at 2.2 A resolution and refined to an R factor of 20.1%. The ligand binds in the minor groove at the sequence 5'-AATTC with the bulky piperazine group extending over the CxG base pair. This binding is stabilised by hydrogen bonding and numerous close van der Waals contacts to the surface of the groove walls. The meta-hydroxyl group was found in two distinct orientations, neither of which participates in direct hydrogen bonds to the exocyclic amino group of a guanine base. The conformation of the drug differs from that found previously in other X-ray structures of Hoechst 33258-DNA complexes. There is significant variation between the minor groove widths in the complexes of Hoechst 33258 and the meta-hydroxyl derivative as a result of these conformational differences. Reasons are discussed for the inability of this derivative to actively recognise guanine.

Binding Sites↗

Isohelicity and phasing in drug--DNA sequence recognition: crystal structure of a tris(benzimidazole)--oligonucleotide complex.

The crystal structure is reported of a tris(benzimidazole) analogue of the minor-groove drug Hoechst 33258 bound to the sequence d(CGCAAATTTGCG)2. The structure has been refined to an R factor of 17.4% at a resolution of 2.2 A. The ligand covers approximately 7 1/2 base pairs, including the 5'-AAATTT central sequence. This has an exceptionally narrow minor-groove width, together with high propeller twists for individual base pairs. The ligand has a highly twisted structure, with an overall twist of 50 degrees between aromatic rings. All three benzimidazole subunits are in register with the DNA, and there is a symmetric group of six hydrogen bonds between ligand and A.T base-pair edges. By contrast, the ligand does not show an optimal isohelical fit to the DNA. The correct phasing of drug and DNA base pairs is ensured by a number of changes to the DNA such that the central 5'-AAATTT region is slightly unwound relative to the structures of other noncovalent minor-groove drug complexes.

Benzimidazoles↗

House dust mite allergens. A major risk factor for childhood asthma in Australia.

If house dust mite allergen (Der p I) is an important cause of asthma, there should be a direct relationship between level of exposure to this allergen and asthma severity. To examine this, we studied six large random samples of children in different regions of New South Wales, Australia. We measured recent wheeze by questionnaire, airway hyperresponsiveness (AHR) by histamine inhalation test and sensitization to house dust mites by skin prick tests. Current asthma was defined as the presence of recent wheeze and AHR. We measured Der p I levels in the beds of approximately 80 children in each region. In regions where Der p I levels were high, more children were sensitized to house dust mites, and these children had significantly more AHR and recent wheeze. After adjusting for sensitization to other allergens, we found that the risk of house dust mite-sensitized children having current asthma doubled with every doubling of Der p I level. There was a modest correlation between AHR and Der p I exposure in individuals (r = 0.23, p < 0.03). These data suggest that house dust mite allergens are an important cause of childhood asthma and that reducing exposure to these allergens could have a large public health benefit in terms of asthma prevention.

Administration, Inhalation↗

Examining the exam.

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Clinical Competence↗

Prevalence and severity of childhood asthma and allergic sensitisation in seven climatic regions of New South Wales.

OBJECTIVE: To compare the prevalence and severity of asthma and of allergic sensitisation in children in different regions. We hypothesised that regions with different standardised hospital admission rates would have different prevalences of childhood asthma and that diverse climates would result in a range of sensitisations to different allergens. DESIGN AND SETTING: We studied large random population samples of children in seven regions in New South Wales (NSW) in 1991-1993. Hospitalisation rates were obtained from NSW Department of Health data. PARTICIPANTS: 6394 children aged 8-11 years. OUTCOME MEASURES: History of respiratory symptoms by self-administered questionnaire; airway hyperresponsiveness by histamine inhalation test; and sensitisation to allergens by skin-prick tests. RESULTS: Children in all regions had a high prevalence of recent wheeze (22%-27%), of diagnosed asthma (24%-38%) and of use of asthma medications (22%-30%), but no region was consistently higher or lower for all measurements. The prevalence of current asthma in children living in three coastal regions (where sensitisation to house-dust mites was high) and in the far west (where sensitisation to alternaria was high) was 12%-13%, which was significantly higher than the prevalence of 7%-10% in children living in three inland regions (where sensitisation to these allergens was lower) (P < 0.01). CONCLUSIONS: We found significant variations in the prevalence and severity of childhood asthma in NSW. The prevalence of hospitalisations, diagnosed asthma, recent symptoms and medication use may relate to different regional diagnostic patterns, whereas current asthma prevalence may relate to different levels of allergic sensitisation.

Asthma↗

Asthma severity and morbidity in a population sample of Sydney school children: Part I--Prevalence and effect of air pollutants in coastal regions.

BACKGROUND: In two regions of Sydney where sewage treatment facilities with high temperature sludge burning incinerators are installed, there was concern that the resultant emissions were causing a local increase in symptoms of asthma and other allergic diseases. AIM: To investigate whether living in a region with high temperature sludge burning incinerators was associated with an increased prevalence of childhood asthma or allergy. METHODS: We studied 713 children aged eight-12 years in two regions close to incinerators and 626 children in a control region with no sludge burning incinerator. We measured respiratory illness in the previous year by questionnaire, airway hyper-responsiveness (AHR) by histamine inhalation test, and atopy by skin prick tests. 'Current asthma' was defined as AHR and recent wheeze. RESULTS: Recordings of oxides of nitrogen and sulphur, hydrogen sulphide, ozone and particulates during the study period showed that the level of pollutants did not vary in any major way between the study regions and the control region. The prevalence of current asthma, atopy, symptom frequency or any category of severity of asthma illness was not significantly different between the control and study regions. CONCLUSIONS: This suggests that factors other than intermittent or industrial air pollutants are responsible for the high prevalence of asthma symptoms, asthma medication use, asthma morbidity and AHR in the study of children.

Air Pollutants↗

Asthma severity and morbidity in a population sample of Sydney schoolchildren: Part II--Importance of house dust mite allergens.

BACKGROUND: Despite an increasing prevalence of childhood asthma, few studies have quantified the strength of associations between asthma and its aetiological factors. AIMS: To quantify the risk factors associated with childhood asthma and to investigate the characteristics of children most at risk. METHODS: We studied a population sample of 1339 schoolchildren aged eight-11 years living in Sydney, NSW. Questionnaires were used to measure respiratory illness, histamine inhalation test to measure airway hyperresponsiveness (AHR), skin prick tests to measure atopy and ELISA assay to measure house dust mite allergen (Der p I) levels. 'Current asthma' was defined as the presence of wheeze in the previous year and AHR. RESULTS: The mean Der p I level in 72 homes was 22.5 micrograms/gm dust which is high compared to suggested thresholds of 2 microgram/gm for sensitisation and 10 micrograms/gm for exacerbation of symptoms. Sensitisation to house dust mites was the most important risk factor for current asthma (odds ratio 7.0, 95% CI 9.4, 22.2). Sensitisation to ryegrass was of minor importance (odds ratio 2.0, 95% CI 1.4, 3.1). The presence of AHR was strongly related to the degree of sensitisation to house dust mite allergen and children with skin wheals greater than 4 mm had frequent morbidity caused by asthma. CONCLUSIONS: To reduce the high prevalence of childhood asthma in NSW, it is imperative that we design interventions which recognise that house dust mite allergens are a dominant risk factor and that children with large skin wheal reactions to this allergen are most at risk for severe illness including disturbed sleep, days missed from school and urgent medical attention.

Airway Resistance↗

Differences in airway responsiveness between children and adults living in the same environment: an epidemiological study in two regions of New South Wales.

The aim of the present study was to compare the severity of asthma in children and adults living in the same home environments. In winter 1991 and 1992, we studied two large random samples of children living in two different regions; and, three months later, we conducted a study of adults who lived with enrolled children. A total of 805 children and 814 adults attended in Lismore, and 850 children and 711 adults in Wagga Wagga. Questionnaires were used to measure symptom history, histamine inhalation challenge to measure airway hyperresponsiveness (AHR) and skin-prick tests to measure allergy. There was a higher prevalence of asthma in children than in adults: recent wheeze was 1.5 times higher; asthma medication use was 1.5 times higher; diagnosed asthma was 1.6 times higher; and AHR was two times higher. Current asthma (AHR and recent wheeze) was 9.5-11.3% in children and 5.4-5.6% in adults. These differences were statistically significant. In both regions, airway responsiveness was more severe in children who were sensitized to common allergens than in similarly sensitized adults. These results suggests that airways can develop protective mechanisms with age, or that recent environmental changes in factors such as allergen levels, diet or treatment practices have led to immunological changes and to increased airway responsiveness in this generation of children.

Adolescent↗

Efficacy of systemic heparinization in maintaining patency of the incised and cannulated brachial artery.

Alternate members of a group of 100 cardiac patients subjected to right and left heart catheterization studies and angiography received 5000 units of heparin intravenously prior to arterial cannulation. There was no instance of arterial occlusion among these 50 patients, while in 6 of the control group the incised brachial artery became occluded. No complications of heparinization were observed. It is recommended that, where no contra- indications exist, all patients subjected to brachial artery incision and cannulation receive systemic anticoagulation.

Adolescent↗