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Biomedical subjects

D Haskard

Publications and source records attributed to D Haskard.

At least 19 recordsLinked to original sources
PubMed2001

Soluble adhesion molecules and prediction of coronary heart disease: a prospective study and meta-analysis.

BACKGROUND: Previous studies have suggested that circulating concentrations of soluble adhesion molecules are useful predictors of risk of coronary heart disease (CHD). Larger studies are needed, however, to test this hypothesis. METHODS: We measured serum concentrations of four soluble cell adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], E-selectin, and P-selectin) in the stored baseline serum samples of 643 men with coronary heart disease and 1278 controls nested in a prospective sutdy of 5661 men who were monitored for 16 years. We also did a meta-analysis of previous relevant studies to place our findings in context. RESULTS: Concentrations of soluble adhesion molecules were significantly associated with one another, with other markers of inflammation, and with some classic coronary risk factors. For ICAM-1, the odds ratio for CHD was 1.68 (95% CI 1.32-2.14) in a comparison of men in the top third with those in the bottom third of baseline measurements after adjustments for age and town. This decreased to 1.11 (0.75-1.64) after adjustment for some classic coronary risk factors and indicators of socioeconomic status. For the three other cell adhesion molecules, the odds ratios for CHD, first adjusted for age and town only, and then additionally adjusted for other risk factors, were: VCAM-1: 1.26 (0.99-1.61) and 0.96 (0.66-1.40); E-selectin: 1.27 (1.00-1.61) and 1.13 (0.78-1.62); and P-selectin: 1.23 (0.96-1.56) and 1.20 (0.81-1.76). INTERPRETATION: The measurement of these adhesion molecules is unlikely to add much predictive information to that provided by more established risk factors.

Adult↗
PubMed1998

Visualising E-selectin in the detection and evaluation of inflammatory bowel disease.

BACKGROUND: Vascular endothelial E-selectin expression is induced by proinflammatory cytokines and contributes to accumulation of leucocytes in tissues. AIMS: To investigate the role of E-selectin in inflammatory bowel disease (IBD). METHODS: E-selectin expression was assessed in patients with ulcerative colitis and Crohn's disease by measuring the concentration of circulating soluble E-selectin (sE-selectin) using ELISA, by immunohistochemistry of colonic biopsy specimens, and by abdominal immunoscintigraphy after injecting radiolabelled F(ab')2 fragment of a monoclonal anti-E-selectin antibody. The value of scintigraphy using anti-E-selectin was judged by a prospective comparative study of autologous leucocyte scanning and E-selectin antibody scanning in 17 patients with IBD. RESULTS: Circulating sE-selectin was elevated in patients with clinically active disease. Tissue expression of E-selectin was enhanced in patients with active inflammation, with weak or absent expression in inactive disease and healthy controls. In-111 labelled anti-E-selectin scintiscans were compared with Tc-99m labelled leucocyte scans performed 24 hours earlier. Twelve patients had areas of active inflammation on leucocyte scan while 11 patients had positive E-selectin scans. The results of the two scans were concordant in 14 patients, with those positive for both (10/17) showing similar disease localisation and extent. CONCLUSIONS: Tissue E-selectin and circulating sE-selectin are increased during active inflammatory bowel disease. Anti-E-selectin imaging with radiolabelled monoclonal antibody identified areas of inflammation in Crohn's disease and ulcerative colitis. The technique should prove useful clinically for identifying the site and extent of disease.

Acute Disease↗
PubMed1998

Monte Carlo simulation of electron cones used in electron beam therapy.

A Siemens Mevatron KV2 accelerator installed at the Royal Adelaide Hospital employs cylindrical solid-walled electron cones for some electron collimation. The cones being used at present result in treatment fields that do not always conform with the International Electrotechnical Commission (IEC) Standards (particularly at high energies). The aim of this project was to simulate the existing cones using Monte Carlo methods in order to evaluate potential cone modifications required to overcome the field irregularities. Simulations were performed using the EGS4 (Electron Gamma Shower version 4, distribution II) Monte Carlo code installed on a DEC Alpha workstation at the University of South Australia. To rigorously simulate the existing electron cones it was necessary to also simulate various components within the treatment head of the linear accelerator. Results of simulations for existing cones were found to be consistent with experimental data. (obtained from Royal Adelaide Hospital beam quality assurance measurements). Two proposed changes to the cones were then simulated and the effects of these alterations were assessed. This study has shown how treatment head simulation techniques can be used to assess the changes in dose distribution that result from alterations to the treatment head and accessories. Within practical engineering constraints modifications to an existing electron collimation system were proposed and theoretically evaluated.

Biophysical Phenomena↗
PubMed1997

Improving wedged field dose distributions.

Dose profiles produced by wedge filters in the non-wedged direction can exhibit a 7% or greater dose reduction at the outer ends of the field compared with open field profiles. However, many planning systems use open field profiles to model wedged dose distributions. In the present work, wedges have been modified to reproduce open field profile shapes. This modification involved removing varying thicknesses of the wedge using a simple milling machine. The wedge thickness was calculated using the assumption that dose is proportional to primary collision kerma. The discrepancies in dose between wedged field and open field profile shapes of up to 7% were reduced to less than 3% with the modifications, even for varying depths and off-axis distances. The necessary measurements are simple to perform, and hence this technique could be applied to improve wedged field dose distributions in other radiotherapy departments.

Biophysical Phenomena↗
PubMed1994

Expression and shedding of intercellular adhesion molecule 1 and lymphocyte function-associated antigen 3 by normal and scleroderma fibroblasts. Effects of interferon-gamma, tumor necrosis factor alpha, and estrogen.

OBJECTIVE: To examine intercellular adhesion molecule 1 (ICAM-1) and lymphocyte function-associated antigen 3 (LFA-3) in cultures of normal and systemic sclerosis (SSc) dermal fibroblasts. METHODS: The surface and soluble forms of ICAM-1 and LFA-3 were measured by flow cytometry and capture enzyme-linked immunosorbent assay, respectively. RESULTS: Surface ICAM-1 was significantly higher on SSc fibroblasts compared with normal controls. Beta-estradiol did not directly enhance ICAM-1 or LFA-3 expression in either normal or SSc cells, but significantly augmented the cytokine-induced increase in ICAM-1. Soluble ICAM-1 (sICAM-1) and sLFA-3 were detected in fibroblast cultures. While no difference was found in the level of sLFA-3, the shedding of sICAM-1 was significantly increased (P < 0.001) in cells from SSc patients. CONCLUSION: SSc fibroblasts express intrinsically elevated levels of surface ICAM-1 and release higher levels of sICAM-1 in vitro. Increased expression of ICAM-1 by interferon-gamma and tumor necrosis factor alpha alone, and the further induction in combination with beta-estradiol may underlie an aspect of fibroblast dysfunction in SSc and the female predisposition to the disease.

Antigens, CD↗
PubMed1994

Circulating adhesion molecules in sarcoidosis.

Sarcoidosis is a disease of unknown etiology characterized by non-caseating granulomata together with a number of systemic abnormalities. We have recently shown these include increased expression of the integrins CD11/CD18 on peripheral blood leucocytes. Here we have measured serum levels of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) in 23 patients and 14 normal controls using antigen capture sandwich ELISAs. Median circulating E-selectin levels in the patients were nearly three times those of the controls (P < 0.0001, Mann-Whitney U-test), whilst ICAM-1 but not VCAM-1 levels were only slightly elevated. These results show that endothelial cell activation and shedding of E-selectin into the circulation are additional features of the pathology of sarcoidosis.

Adult↗
PubMed1993

Intercellular adhesion molecules in normal synovium.

The vasculature of normal synovium and skin has been examined for the presence of molecules believed to be involved in intercellular adhesion and whose expression on endothelial cells in vitro is known to be upregulated by cytokines. Synovium was obtained from clinically and histologically normal joints removed during amputations for proximal sarcomata. Skin was obtained from healthy volunteers. Cryostat sections of tissues were assessed by immunohistochemistry and microdensitometry for the presence of E-selectin using monoclonal antibody 1.2B6, intercellular adhesion molecule-1 (ICAM-1) using monoclonal antibody 6.5B5 and vascular cell adhesion molecule (VCAM-1) using monoclonal antibody 1.4C3. Both E-selectin and ICAM-1 were present on a proportion of normal synovial venules but at a level comparable to or lower than that found on dermal vessels. (Staining intensities given as mean absorption indices: superficial synovium 1.2B6: 9.9 +/- 11.4, 6.5B5: 10.2 +/- 12.0, deep synovium 1.2B6: 6.6 +/- 9.9, 6.5B5: 24.6 +/- 15.7, skin 1.2B6: 13.1 +/- 16.6, 6.5B5: 36.4 +/- 12.9.) E-selectin expression was most prominent on small superficial venules in synovium and ICAM-1 most strongly expressed on larger, deep venules. VCAM-1 was found at low levels on cells associated with vessel walls but no significant endothelial staining was seen in either type of tissue. VCAM-1 was also present on cells of the synovial lining layer. Some of the findings in synovium could have been attributable to tumour related cytokine release, but the consistency of findings and comparability to skin suggest that this is relatively unlikely.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Detection of cytokines at the site of tuberculin-induced delayed-type hypersensitivity in man.

Cytokines are chiefly local mediators which play an important role in the regulation of the cell-cell interactions which may be involved in the development of the delayed-type hypersensitivity (DTH) reaction. Using immunohistochemical techniques, the presence of IL-1 alpha, IL-1 beta, IL-6, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) in the skin in tuberculin-purified protein derivative (PPD)-induced DTH reactions was investigated in six normal individuals. Cells staining for these cytokines were first observed 6 h after PPD challenge, and they were detected throughout the duration of the 7-day experiment. The number of cells staining for IFN-gamma reached a peak at 48 h, where 33% of the total aggregate cells were positive, but declined thereafter to 3% at day 7. On the other hand, the number of cells staining for TNF-alpha and IL-1 persisted at high levels throughout the observation period of 7 days (e.g. at 48 h and thereafter, about 40% cells positive for TNF-alpha and 20% for IL-1 alpha and IL-1 beta). Double immunofluorescence and staining on sequential sections showed that IFN-gamma-staining cells were CD3+ T cells; TNF-alpha, IL-1 and IL-6 staining cells were mainly of the CD68+ macrophages/monocytes and that 80% of the CD1a+ cells (Langerhans-like cells) in the dermis contained TNF-alpha and IL-1. The presence of these cytokines at the site of inflammation suggests that they may be locally produced by the inflammatory cells. Their persistence during the reaction suggests that they are intimately associated with this response, and are involved in the development of the reaction.

B-Lymphocytes↗
PubMed1992

Intercellular adhesion molecule-1 (ICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) expression in the bronchial mucosa of normal and asthmatic subjects.

Bronchial lavage and biopsy studies suggest the involvement of eosinophils and T-lymphocytes in allergic inflammation in asthma. There is evidence suggesting that the expression of adhesion molecules on endothelial cells and of their receptors on leucocytes is involved in this process. To investigate these mechanisms we have obtained bronchial mucosal biopsies from 10 normal subjects and from 10 symptomatic atopic asthmatics. Six of the asthmatics were re-biopsied after 6 weeks of inhaled beclomethasone dipropionate (BDP) during which time their clinical response was monitored. Frozen sections were stained by the immunoperoxidase method using monoclonal antibody (MoAb) 6.5B5 to identify expression of intercellular adhesion molecule (ICAM-1) and MoAb 1.2B6 for endothelial leucocyte adhesion molecule (ELAM-1). Araldite-embedded sections were also stained for eosinophils using MoAb EG2 to identify eosinophilic cationic protein (ECP). A significant mucosal eosinophilia was apparent in the asthmatic but not in the normal biopsies. Immunostaining for ICAM-1 was observed in both the epithelium and endothelium and ELAM-1 in endothelium, with no significant differences being apparent between the asthmatic and normal subjects. Topical BDP markedly reduced the mucosal eosinophilia without affecting the expression of either adhesion molecule. Using this method, we conclude that there is basal expression of ICAM-1 and ELAM-1 in normal human bronchial mucosa, which is not significantly different from that in asthmatics, and that it is insensitive to suppression with corticosteroids at an inhaled dose that causes clinical improvement.

Adult↗
PubMed1990

Novel antibodies associated with unexplained loss of renal allografts.

Using an endothelial/epithelial hybrid cell line, three different non-HLA antibody types have been identified by flow cytometry in patients who have rapidly rejected multiple renal allografts. These antibodies may be classified as anti-endothelial-monocyte, anti-activated endothelial cell, or anti-epithelial cell.

Antibodies↗