Cell adhesion molecules and the bronchial epithelium

We thank Professor David Garrod, Dr.Tom Fleming, Dr. Dorian Haskard, and Professor Tak Lee for supplying some of the antibodies used in our studies.The bronchial epithelium is the major barrier between the host and the provoking antigens in bronchial asthma. Recent studies have indicated that the epithelium is a truly stratified structure, with the superficial columnar cells depending on the underlying basal cells for anchorage. Only columnar cells are shed into bronchial lavage fluid. The epithelium is more fragile in asthma and more cells are lost in clusters. Desmosomes appear to be the major structural adhesion mechanism at the plane of cleavage between the columnar cells and the basal cells. The as- and 134-integrins, which contribute to hemidesmosomes and anchor cells to the underlying basement membrane, are expressed solely by basal cells. The apical aspects of the columnar cells are sealed by tight and intermediate junctions. There is constitutive expression of ICAM-1 and E-selectin in the vasculature of the bronchial mucosa, and ICAM is also present within the epithelium. These findings indicate that the bronchial epithelium is a complex structure that, as a mucosal surface, has constitutive expression of inflammatory cell adhesion molecules to serve normal leukocyte traffic.peer-reviewe

The site of disruption of the bronchial epithelium in asthmatic and non-asthmatic subjects

Attention has recently been focused on the basal cells of the tracheobronchial epithelium as the mechanism of anchorage of the tall columnar cells, which themselves do not appear to form hemidesmosomes with the basement membrane of the epithelium. Residual basal cells have been described as remaining attached to the basement membrane after epithelial denudation. This led this group to formulate the hypothesis that there may be a potential plane of cleavage between the basal cells and the overlying columnar cell layer within the bronchial epithelium, which becomes disrupted in asthma.peer-reviewe

Diabetes, Obesity, and Hypertension May Enhance Associations between Air Pollution and Markers of Systemic Inflammation

Airborne particulate matter (PM) may lead to increased cardiac risk through an inflammatory pathway. Therefore, we investigated associations between ambient PM and markers of systemic inflammation among repeated measures from 44 senior citizens (≥ 60 years of age) and examined susceptibility by conditions linked to chronic inflammation. Mixed models were used to identify associations between concentrations of fine PM [aerodynamic diameter ≤ 2.5 μm (PM(2.5))] averaged over 1–7 days and measures of C-reactive protein (CRP), interleukin-6 (IL-6), and white blood cells (WBCs). Effect modification was investigated for diabetes, obesity, hypertension, and elevated mean inflammatory markers. We found positive associations between longer moving averages of PM(2.5) and WBCs across all participants, with a 5.5% [95% confidence interval (CI), 0.10 to 11%] increase per interquartile increase (5.4 μg/m(3)) of PM(2.5) averaged over the previous week. PM(2.5) and CRP also exhibited positive associations among all individuals for averages longer than 1 day, with the largest associations for persons with diabetes, obesity, and hypertension. For example, an interquartile increase in the 5-day mean PM(2.5) (6.1 μg/m(3)) was associated with a 14% increase in CRP (95% CI, −5.4 to 37%) for all individuals and an 81% (95% CI, 21 to 172%) increase for persons with diabetes, obesity, and hypertension. Persons with diabetes, obesity, and hypertension also exhibited positive associations between PM(2.5) and IL-6. Individuals with elevated mean inflammatory markers exhibited enhanced associations with CRP, IL-6, and WBCs. We found modest positive associations between PM(2.5) and indicators of systemic inflammation, with larger associations suggested for individuals with diabetes, obesity, hypertension, and elevated mean inflammatory markers

Young pregnancy and motherhood : a discourse analysis of context and expertise

Progressing into the 21st century young pregnancy and parenthood in the United Kingdom is a focus of political, media and public attention. The country is described as experiencing an epidemic, with the highest rates of young pregnancy and parenthood recorded in Western Europe. Statistics demonstrate that in 2000 38,690 under 18 year-olds in England became pregnant, of which 44.8% ended in legal termination. In light of this data, and within their remit to address the issue of Social Exclusion, New Labour commissioned a report into young pregnancy resulting in the development and implementation of the Teenage Pregnancy Strategy. The Strategy has two main aims; namely reducing the rates of young conceptions and providing better support and education for young parents. This thesis argues from a conceptual framework that questions the contested assumption that young pregnancy and parenthood is a problem. A literature review demonstrates a lack of representation of the voices and experiences of young mothers. This directs the research question to ask what is the experience of young mothers in their own words and placed within context? Critical Discourse Analysis is used to examine three examples of context shaping data that includes government policy, a newspaper article and a radio talk show programme. The analysis reveals discourses that suggest there is a right time and framework for motherhood. These discourses form a dialectical relationship with voices and experiences of young mothers that are analysed using Discourse Analysis. This analysis elicits two key central discourses permeating the experiences of young mothers that are the Good- Bad mother binary that informs and exacerbates experiences of maternal ambivalence. Moreover, these discourses inform the practice of discrimination against young mothers. The thesis concludes with a call to listen to the experiences of young mothers in order that their needs might be more fully understood. It suggests that discrimination against young mothers be incorporated into Equal Opportunity and Anti- Discrimination policy.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The temporal relationship between the neural and vascular actions of kallidin within the nose

The time course of effect of the B2-receptor agonist kallidin (K) on induced changes of nasal airflow, rhinorrhoea, nasal pain, sneezing and nasal microvascular leakage has been examined and compared with its B2 metabolite agonist bradykinin (B) and the B1-agonist [des-arg9]-bradykinin (D). When administered as a single dose K and B induced an immediate sensation of pain, rhinorrhoea, elevations in lavage albumin and protein levels and a sustained increase in nasal airways resistance (NAR) for 5–40 min post-challenge. [des-arg9]-Bradykinin and vehicle placebo (V) were without effect on any of these indices. These studies identify the action of K and B within the nose and differentiate the neural and vascular effects of these kinins in addition to suggesting the potential that nasal blockage and nasal microvascular leakage represent alterations in differing vascular compartments. These findings have implications for the understanding and therapeutic manipulation of rhinitis

Determinants of voluntary audit and voluntary full accounts in micro- and non-micro small companies in the UK

This is an Author's Accepted Manuscript of an article published in Accounting and Business Research, 42(4), 441 - 468, 2012, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/00014788.2012.667969.This study investigates the link between the auditing and filing choices made by a sample of 592 small private companies, which includes 419 micro-companies. It examines decisions made in connection with the 2006 accounts following UK's adoption of the maximum EU size thresholds in 2004, and the impact of the proposed Directive on the annual accounts of micro-companies. The research extends the model of cost, management and agency factors associated with voluntary audit, and develops a complementary model for voluntary full accounts. The results show the benefits of placing full audited accounts on public record that outweigh the costs for a significant proportion of companies. In non-micro small companies, voluntary audit is determined by cost and agency factors, whereas in micro-companies it is driven by cost, management and agency factors. In both groups, the predictors of voluntary full accounts include management and agency factors, and choosing voluntary audit is one of the key factors. The study provides models that can be tested in other jurisdictions to provide evidence of the needs of micro-companies, and the discussion of the methodological challenges for small company researchers in the UK makes further contribution to the literature

Smoking in asthma is associated with elevated levels of corticosteroid resistant sputum cytokines—an exploratory study

<p>Background: Current cigarette smoking is associated with reduced acute responses to corticosteroids and worse clinical outcomes in stable chronic asthma. The mechanism by which current smoking promotes this altered behavior is currently unclear. Whilst cytokines can induce corticosteroid insensitivity in-vitro, how current and former smoking affects airway cytokine concentrations and their responses to oral corticosteroids in stable chronic asthma is unclear.</p> <p>Objectives: To examine blood and sputum cytokine concentrations in never, ex and current smokers with asthma before and after oral corticosteroids.</p> <p>Methods: Exploratory study utilizing two weeks of oral dexamethasone (equivalent to 40 mg/day prednisolone) in 22 current, 21 never and 10 ex-smokers with asthma. Induced sputum supernatant and plasma was obtained before and after oral dexamethasone. 25 cytokines were measured by multiplex microbead system (Invitrogen, UK) on a Luminex platform.</p> <p>Results: Smokers with asthma had elevated sputum cytokine interleukin (IL) -6, -7, and -12 concentrations compared to never smokers with asthma. Few sputum cytokine concentrations changed in response to dexamethasone IL-17 and IFNα increased in smokers, CCL4 increased in never smokers and CCL5 and CXCL10 reduced in ex-smokers with asthma. Ex-smokers with asthma appeared to have evidence of an ongoing corticosteroid resistant elevation of cytokines despite smoking cessation. Several plasma cytokines were lower in smokers wi</p> <p>Conclusion: Cigarette smoking in asthma is associated with a corticosteroid insensitive increase in multiple airway cytokines. Distinct airway cytokine profiles are present in current smokers and never smokers with asthma and could provide an explanatory mechanism for the altered clinical behavior observed in smokers with asthma.</p&gt