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Biomedical subjects

Peter Frank

Publications and source records attributed to Peter Frank.

6 recordsLinked to original sources

Smoking, respiratory symptoms and likely asthma in young people: evidence from postal questionnaire surveys in the Wythenshawe Community Asthma Project (WYCAP).

BACKGROUND: Although it is recognised that smoking is a major risk factor for subjects with chronic obstructive pulmonary disease and is associated with respiratory symptoms, there is less agreement concerning the relationship between asthma and smoking. This study aims to examine the relationship between cigarette smoking and asthma prevalence. METHOD: Data were used from two postal questionnaire surveys (1999 and 2001) in two general practice populations, using a respiratory questionnaire based on the ECRHQ and a generic quality of life questionnaire (EQ-5D). Only subjects less than 45 years old were included in the survey. An empirical definition of likely asthma was used based on respiratory questionnaire responses. Smoking was examined according to three categories, current smoker, ex smoker and never smoker. RESULTS: Almost 3500 subjects were included in the analyses. Current smokers had a higher prevalence of likely asthma compared to never smokers, odds ratio (OR) 1.59 (95% confidence interval (CI) 1.24 to 2.04). and also compared to ex smokers OR 1.79 (CI 1.25 to 2.56), but there was no difference between ex smokers and never smokers (OR 1.00 (0.75-1.35)). Current smoking was also positively associated with all symptoms but not with a history of hayfever/eczema. CONCLUSION: Although the positive association found between current smoking and obstructive airways disease is likely to be due to the effect of cigarettes on asthma, it could reflect an association with early COPD (GOLD stages 0 or 1). Smoking cessation has a beneficial effect on the prevalence of respiratory symptoms and is therefore of paramount importance among these young adults.

Adolescent↗

IPEADAM study: indoor endotoxin exposure, family status, and some housing characteristics in English children.

BACKGROUND: Many environmental factors have been investigated to determine their involvement in the asthma epidemic. OBJECTIVE: We sought to investigate the indoor environment of English children. METHOD: The Indoor Pollutants, Endotoxin, Allergens, Damp and Asthma in Manchester (IPEADAM) study recruited 200 asthmatic and age-, sex-, and sibship size-matched nonasthmatic children after a questionnaire-based community screening epidemiology survey. Their homes were sampled for several indoor air factors, and reservoir dust samples were obtained. Endotoxin, Der p 1, and dampness levels were assayed. Questionnaires were administered to record housing characteristics. Indoor pollutants, including environmental tobacco smoke, volatile organic compounds, nitrogen dioxide, formaldehyde, temperature, and relative humidity, were investigated. STATA univariate and multivariate analyses were used to compare the indoor environments of the children. RESULTS: The levels of endotoxin (adjusted odds ratio, 1.88; 95% CI, 1.11-3.18; P=.018), living in a single-parent family (adjusted odds ratio, 3.89; 95% CI, 1.25-12.1; P=.019), redecoration in the living room (adjusted odds ratio, 3.15; 95% CI, 1.36-7.33; P=.008), and self-reported absence of dampness (adjusted odds ratio, 0.36; 95% CI, 0.14-0.91; P=.030) were all independent predictive factors of asthma. There was no difference between asthmatic and healthy children in their exposure to Der p 1, objective measurements of dampness, guardian's smoking habits, pet ownership, house type or age, time in residence, central heating systems, insulation types, glazing systems, floor types, and age and measurements of several indoor pollutants. CONCLUSION: The IPEADAM study has shown that there were very few differences in the indoor environments of English asthmatic and nonasthmatic children. However, once asthma has been established, the presence of endotoxin is positively associated with an asthmatic child's living room carpet reservoir dust. CLINICAL IMPLICATIONS: There are no direct clinical implications of this research, although it needs interpreting with other clinical data on endotoxin exposure in epidemiologic settings.

Adolescent↗

Evaluation of macrocyclic Grb2 SH2 domain-binding peptide mimetics prepared by ring-closing metathesis of C-terminal allylglycines with an N-terminal beta-vinyl-substituted phosphotyrosyl mimetic.

Preferential binding of ligands to Grb2 SH2 domains in beta-bend conformations has made peptide cyclization a logical means of effecting affinity enhancement. This is based on the concept that constraint of open-chain sequences to bend geometries may reduce entropy penalties of binding. The current study extends this approach by undertaking ring-closing metathesis (RCM) macrocyclization between i and i+3 residues through a process involving allylglycines and beta-vinyl-functionalized residues. Ring closure in this fashion results in minimal macrocyclic tetrapeptide mimetics. The predominant effects of such macrocyclization on Grb2 SH2 domain binding affinity were increases in rates of association (from 7- to 16-fold) relative to an open-chain congener, while decreases in dissociation rates were less pronounced (approximately 2-fold). The significant increases in association rates were consistent with pre-ordering of solution conformations to near those required for binding. Data from NMR experiments and molecular modeling simulations were used to interpret the binding results. An understanding of the conformational consequences of such i to i+3 ring closure may facilitate its application to other systems where bend geometries are desired.

Adaptor Proteins, Signal Transducing↗

Health related quality of life in individuals with asthma related symptoms.

BACKGROUND: Where evidence is required for disease-area prioritisation (e.g. by national policymakers), impact on health related quality of life (HRQoL) can be considered equitably across diseases using quantitative data from generic HRQoL instruments. Before this can take place, it must be shown that the instrument captures HRQoL impairment associated with each disease area. AIM: To ascertain whether the HRQoL impairment associated with respiratory disease can be represented by responses to EQ-5D, a generic HRQoL questionnaire. METHOD: EQ-5D and a respiratory health questionnaire were sent to 10,471 adults registered with two general practices in Manchester, UK. EQ-5D examines 5 domains (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and includes an overall rating via visual analogue scale. Societal valuations of domain responses were also considered. RESULTS: HRQoL was substantially reduced in respondents who were likely to have obstructive airways disease (mean EQ-5D(index) 0.63 compared to 0.82, t-test P < 0.001; mean EQ-5D(vas) 62.7 compared to 77.6, t-test P < 0.001) and was negatively associated with respiratory symptoms, older age and female gender. The association with respiratory problems remained following stratification by age and gender. The deficit in HRQoL associated with increasing age was more pronounced in those likely to have obstructive airways disease. CONCLUSION: HRQoL measured using EQ-5D is substantially reduced in respondents with respiratory symptoms enabling use of the instrument in inter-disease comparisons.

Adolescent↗

Structural studies of an eukaryotic cambialistic superoxide dismutase purified from the mature seeds of camphor tree.

An iron-superoxide dismutase (SOD) was purified and characterized from the mature seeds of camphor tree (Cinnamomum camphora). The ultraviolet and visible absorption spectra of camphor Fe-SOD showed patterns typical of cambialistic Fe-SODs. The inductively coupled plasma assay indicated that there was 0.5-1 atom of Fe(2+) per camphor Fe-SOD subunit. The cDNA of camphor Fe-SOD, including the coding region and the 3' noncoding region, was obtained by reverse transcription polymerase chain reaction using the total RNA from immature seeds of C. camphora as template and then sequenced. The complete amino acid sequence of camphor Fe-SOD was deduced from the cDNA sequence. The correctness of the amino acid sequence was confirmed by directly sequencing five peptide fragments of the enzyme. The molecular mass calculated for the camphor Fe-SOD subunit from its 204 amino acid residues was 22,930.6 Da, The cDNA of camphor Fe-SOD was cloned into the expression vector PMFT7-5 and then expressed in Escherichia coli strain BL21. The reconstructed Fe- or Mn-SOD was purified to homogeneity through column chromatography. Activity of the Fe- or Mn-SOD was found to be almost equal to that of natural camphor Fe-SOD, which is the first cambialistic SOD isolated from eukaryotic cells.

Base Sequence↗