Immunocytochemical localization of β1,4 galactosyltransferase in epithelial cells from bovine tissues using monoclonal antibodies

Post-embedding immunocytochemistry was employed to investigate the distribution of UDP-galactose:N-acetylglucosamine galactosyltransferase (β1,4-GT) in epithelial cells from various bovine organs. Several well characterized monoclonal antibodies previously demonstrated to recognize distinct polypeptide epitopes within the primary structure of β1,4-GT were applied to thin sections from tissues embedded in Lowicryl K4M, followed by the protein A-gold technique. Immunoreactivity was observed in the Golgi apparatus of epithelial cells from intestine, thymus and trachea. No immunoreactivity was observed in other intracellular structures, including rough endoplasmic reticulum, nuclear envelope and goblet cell mucus droplets. Within the Golgi apparatus, the staining was restricted to several cisternae in the trans region, with most portions of the trans-Golgi network appearing unlabelled. However, in thymic epithelial-reticular cells trans-Golgi network portions resembling classical GERL elements were stained by the antibodies. Thus, although immunoreactivity was subcompartmentalized within the Golgi apparatus in all epithelial cell types examined, the extent of staining within the trans-Golgi network was variable. Immunoreactivity was not detected at the plasma membrane (ecto-galactosyltransferase), except in the case of a subpopulation of tracheal cells that resemble brush cells. These results suggest that in the epithelial cells examined, the subcompartmental distribution of β1,4-GT within the Golgi apparatus is maintained across different types of epithelial cell organization. Moreover, no evidence for a general epithelial cell ecto-galactosyltransferase could be discerned with these reagent

Applying economic evaluation to public health interventions: The case of interventions to promote physical activity

Copyright @ 2012 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.BACKGROUND: This paper explores the application of alternative approaches to economic evaluation of public health interventions, using a worked example of exercise referral schemes (ERSs). METHODS: Cost-utility (CUA) and cost-consequence analyses (CCA) were used to assess the cost-effectiveness of ERSs. For the CUA, evidence was synthesized using a decision analytic model that adopts a lifetime horizon and NHS/Personal Social Services perspective. Outcomes were expressed as incremental cost per quality-adjusted life-year (QALY). CCA was conducted from a partial-societal perspective, including health and non-healthcare costs and benefits. Outcomes were reported in natural units, such as cases of strokes or CHD avoided. RESULTS: Compared with usual care, the incremental cost per QALY of ERS is £20 876. Based on a cohort of 100 000 individuals, CCA estimates cost of ERS at £22 million to the healthcare provider and £12 million to participants. The benefits of ERS include additional 3900 people becoming physically active, 51 cases of CHD avoided, 16 cases of stroke avoided, 86 cases of diabetes avoided and a gain of ∼800 QALYs. CONCLUSIONS: CCA might provide greater transparency than CUA in reporting the outcomes of public health interventions and have greater resonance with stakeholders involved in commissioning these interventions.This work was supported by the NIHR Health Technology Assessment programme (project number 08/72/01). This article is made available through the Brunel Open Access Publishing Fund

Circulating inflammatory and hemostatic biomarkers are associated with risk of myocardial infarction and coronary death, but not angina pectoris, in older men

Aims: The extent to which hemostatic and inflammatory biomarkers are related to angina pectoris as compared with myocardial infarction (MI) remains uncertain. We examined the relationship between a wide range of inflammatory and hemostatic biomarkers, including markers of activated coagulation, fibrinolysis and endothelial dysfunction and viscosity, with incident myocardial infarction (MI) or coronary heart disease (CHD) death and incident angina pectoris uncomplicated by MI or CHD death in older men. Methods: A prospective study of 3217 men aged 60-79 years with no baseline CHD (angina or MI) and who were not on warfarin, followed up for 7 years during which there were 198 MI/CHD death cases and 220 incident uncomplicated angina cases. Results: Inflammatory biomarkers [C-reactive protein (CRP), interleukin-6, fibrinogen], plasma viscosity and hemostatic biomarkers [von Willebrand factor (VWF) and fibrin D-dimer] were associated with a significant increased risk of MI/CHD death but not with uncomplicated angina even after adjustment for age and conventional risk factors. Adjustment for CRP attenuated the relationships between VWF, fibrin D-dimer and plasma viscosity with MI/CHD death. Comparisons of differing associations with risk of MI/CHD deaths and uncomplicated angina were significant for the inflammatory markers (P < 0.05) and marginally significant for fibrin D-dimer (P = 0.05). In contrast, established risk factors including blood pressure and high-density lipoprotein (HDL)-cholesterol were associated with both MI/CHD death and uncomplicated angina. Conclusion: Circulating biomarkers of inflammation and hemostasis are associated with incident MI/CHD death but not incident angina uncomplicated by MI or CHD death in older men

The effects of different alcoholic drinks on lipids, insulin and haemostatic and inflammatory markers in older men

Light to moderate drinking is associated with lower risk of coronary heart (CHD) than non-drinkers. We have examined the relationships between total alcohol intake and type of alcoholic beverage and several potential biological mechanisms. We carried out the study in 3158 men aged 60-79 years drawn from general practices in 24 British towns with no history of myocardial infarction, stroke or diabetes and who were not on warfarin. Total alcohol consumption showed a significant positive dose-response relationship with high density lipoprotein cholesterol (HDL-C), coagulation factor IX, haematocrit, blood viscosity, and tissue plasminogen (t-PA) antigen, and an inverse dose-response relationship with insulin, fibrinogen, von Wille- brand factor (vWF) and triglycerides after adjustment for possible confounders. Total alcohol consumption showed weak associations with plasma viscosity and fibrin D-dimer, and no association with factors VII,VIII, or C-reactive protein (CRP). Wine was specifically associated with lower CRP, plasma viscosity, factor VIII and triglycerides. The findings are consistent with the suggestion that HDL-C in particular but also insulin and haemostatic factors may contribute to the beneficial effect of light to moderate drinking on risk of CHD. Wine has effects that may confer greater protection than other alcoholic beverages

Alcohol consumption and risk of incident heart failure in older men: a prospective cohort study

Light-to-moderate drinking has been associated with reduced risk of heart failure (HF). We have examined the association between alcohol consumption and incident HF in older British men

Resonance-thrombography indices of the haemostatic process in relation to risk of incident coronary heart disease: 9 years follow-up in the Caerphilly Prospective Heart Disease Study

Global assays, such as resonance-thrombography (RTG), which measure the interaction between platelets, coagulation and fibrinolysis have been used as summary measures of risk for over two decades but have not been evaluated in epidemiological studies. We examined whether RTG indices are risk indicators for incident coronary heart disease (CHD). RTG indices, related haematological variables and other risk factors were measured between 1984 and 1988 in a cohort of 2398 British men. Reaction time (r) and amplitude of fibrin leg (AF) were associated with lifestyle risk factors. During 9 years of follow-up, 282 (12%) men developed a major new CHD event, as classified by World Health Organization criteria. On adjustment for age, only r and AF measured at baseline were related to risk of incident CHD. On multivariate adjustment in a multiple logistic regression model that included age, diastolic blood pressure, body mass index, total and high-density lipoprotein cholesterol, lifestyle risk factors and use of prescribed medicine, these associations weakened but remained significant. Additional adjustment for fibrinogen, viscosity, white cell count and fibrin D-dimer either reduced these associations to non- significance (AF) or to borderline significance(r)

Student help seeking from pastoral care in UK high schools: a qualitative study

Background Little is known about high school students' perceptions of school-based pastoral support. This study aimed to explore this in the context of a high school–based emotional support project. Methods Qualitative interviews explored perspectives on help seeking of students (N = 23) and staff (N = 27) in three UK high schools where a pastoral project was introduced. Data were analysed thematically. Results Student peer groups perceived help seeking as a sign of weakness. However, students valued learning skills in managing emotions and friendships. Staff expressed concerns about students' ability to help seek proactively, and highlighted organisational influences on pastoral support. Conclusions Increasing student control over the process, and involving trusted staff, could encourage help seeking in high school. It is possible to access the views of students who do not help seek, to improve understanding of help-seeking behaviour

Carboxyhaemoglobin levels and their determinants in older British men

Background: Although there has been concern about the levels of carbon monoxide exposure, particularly among older people, little is known about COHb levels and their determinants in the general population. We examined these issues in a study of older British men.Methods: Cross-sectional study of 4252 men aged 60-79 years selected from one socially representative general practice in each of 24 British towns and who attended for examination between 1998 and 2000. Blood samples were measured for COHb and information on social, household and individual factors assessed by questionnaire. Analyses were based on 3603 men measured in or close to (< 10 miles) their place of residence.Results: The COHb distribution was positively skewed. Geometric mean COHb level was 0.46% and the median 0.50%; 9.2% of men had a COHb level of 2.5% or more and 0.1% of subjects had a level of 7.5% or more. Factors which were independently related to mean COHb level included season (highest in autumn and winter), region (highest in Northern England), gas cooking (slight increase) and central heating (slight decrease) and active smoking, the strongest determinant. Mean COHb levels were more than ten times greater in men smoking more than 20 cigarettes a day (3.29%) compared with non-smokers (0.32%); almost all subjects with COHb levels of 2.5% and above were smokers (93%). Pipe and cigar smoking was associated with more modest increases in COHb level. Passive cigarette smoking exposure had no independent association with COHb after adjustment for other factors. Active smoking accounted for 41% of variance in COHb level and all factors together for 47%.Conclusion: An appreciable proportion of men have COHb levels of 2.5% or more at which symptomatic effects may occur, though very high levels are uncommon. The results confirm that smoking (particularly cigarette smoking) is the dominant influence on COHb levels