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Biomedical subjects

P Beckett

Publications and source records attributed to P Beckett.

16 recordsLinked to original sources
PubMed2006

A comparative linkage map of oilseed rape and its use for QTL analysis of seed oil and erucic acid content.

We have developed a new DH mapping population for oilseed rape, named TNDH, using genetically and phenotypically diverse parental lines. We used the population in the construction of a high stringency genetic linkage map, consisting of 277 loci, for use in quantitative genetic analysis. A proportion of the markers had been used previously in the construction of linkage maps for Brassica species, thus permitting the alignment of maps. The map includes 68 newly developed Sequence Tagged Site (STS) markers targeted to the homologues of defined genes of A. thaliana. The use of these markers permits the alignment of our linkage map with the A. thaliana genome sequence. An additional 74 loci (31 newly developed STS markers and 43 loci defined by SSR and RFLP markers that had previously been used in published linkage maps) were added to the map. These markers increased the resolution of alignment of the newly constructed linkage map with existing Brassica linkage maps and the A. thaliana genome sequence. We conducted field trials with the TNDH population at two sites, and over 2 years, and identified reproducible QTL for seed oil content and erucic acid content. The results provide new insights into the genetic control of seed oil and erucic acid content in oilseed rape, and demonstrate the utility of the linkage map and population.

Brassica napus↗
PubMed2005

Tumour necrosis factor (TNFalpha) as a novel therapeutic target in symptomatic corticosteroid dependent asthma.

BACKGROUND: Tumour necrosis factor alpha (TNFalpha) is a major therapeutic target in a range of chronic inflammatory disorders characterised by a Th1 type immune response in which TNFalpha is generated in excess. By contrast, asthma is regarded as a Th2 type disorder, especially when associated with atopy. However, as asthma becomes more severe and chronic, it adopts additional characteristics including corticosteroid refractoriness and involvement of neutrophils suggestive of an altered inflammatory profile towards a Th1 type response, incriminating cytokines such as TNFalpha. METHODS: TNFalpha levels in bronchoalveolar lavage (BAL) fluid of 26 healthy controls, 42 subjects with mild asthma and 20 with severe asthma were measured by immunoassay, and TNFalpha gene expression was determined in endobronchial biopsy specimens from 14 patients with mild asthma and 14 with severe asthma. The cellular localisation of TNFalpha was assessed by immunohistochemistry. An open label uncontrolled clinical study was then undertaken in 17 subjects with severe asthma to evaluate the effect of 12 weeks of treatment with the soluble TNFalpha receptor-IgG1Fc fusion protein, etanercept. RESULTS: TNFalpha levels in BAL fluid, TNFalpha gene expression and TNFalpha immunoreative cells were increased in subjects with severe corticosteroid dependent asthma. Etanercept treatment was associated with improvement in asthma symptoms, lung function, and bronchial hyperresponsiveness. CONCLUSIONS: These findings may be of clinical significance in identifying TNFalpha as a new therapeutic target in subjects with severe asthma. The effects of anti-TNF treatment now require confirmation in placebo controlled studies.

Adult↗
PubMed2002

Monocyte CD14 response following endotoxin exposure in cotton spinners and office workers.

BACKGROUND: Monocyte cell surface CD14 acts as the major lipopolysaccharide (LPS) binding structure, and as such is of interest in the etiology of LPS induced disease. METHODS: The objective was to assess change in monocyte cell surface CD14 and CD4+ CD25+ lymphocytes in a group of cotton workers exposed to LPS over a working week, and to compare this to changes in office workers. Twenty-five cotton workers and nine office workers were studied. Monocyte CD14 fluorescence was measured by flow cytometry, on samples taken pre-shift on a Monday morning (baseline/pre-exposure), and subsequently after 6 and 72 hr. The majority of cotton workers were exposed to at least 1 EU/m(3) of endotoxin over a working shift, and some highly exposed (between 100 and 400 EU/m(3)). RESULTS: After 6 hr of work in the mill, cotton workers developed a significant upregulation in CD14 in comparison to office workers (P = 0.016), whereas CD14 expression had returned to levels not significantly differing from the office workers at 72 hr after first work exposure (P = 0.426). CONCLUSIONS: We propose that CD14 expression on monocytes may help to determine the mechanism of action of lipopolysaccharide in producing respiratory ill health, and may ultimately play a role in monitoring the health effect associated with LPS exposure in the workplace.

Adult↗
PubMed2001

The development of an antibody to trimellitic anhydride.

Acid anhydrides are a group of highly reactive chemicals used widely in the formulation of paints and plastics. Exposure to acid anhydrides causes several occupational lung diseases such as pneumonititis and asthma. Whilst anhydrides, specifically trimellitic anhydride (TMA), have been shown to bind to lung tissue in an animal model, further investigation has been hampered by the lack of a reagent which would enable the identification of primary target proteins for the binding of TMA. Our objective was to develop an antibody to TMA which would enable in vitro studies of TMA interactions with lung epithelial proteins. We developed a monoclonal antibody which binds solely to TMA. We have demonstrated that the antibody can be used to detect TMA bound to different human proteins with little non-specific binding to unconjugated proteins. We then exposed cells of the A549 lung epithelial cell line to TMA in vitro and have shown by western blotting that binding occurs in the 20-35 Kd weight range. We have developed a specific and sensitive reagent to detect TMA bound to proteins. We have used this to show that when TMA is incubated with a lung epithelial cell line, that the TMA binds to proteins with a restricted molecular weight range. These results suggest that the current paradigm for the detection of IgE to small molecular weight reactive chemicals, which presupposes that the chemical binds to serum albumin, may need further investigation.

Animals↗
PubMed2001

Runway width effects in the visual approach to landing.

The effect of changes in runway width on the perception of glide-slope has been the subject of extensive investigations. Despite considerable research, an explanation of this effect has been elusive. A mathematical model for glide-slope perception was published recently based on the premise that a desirable goal of perception is to form a perception with minimal uncertainty. One of the qualitative predictions of that model was that changes in the aspect ratio of the runway would affect the perceived glide-slope. In this article, the predictions of the model are quantified and are shown to be in close agreement with experimental results in the literature.

Aerospace Medicine↗
PubMed2000

The effect of long-acting beta2-agonists on airway inflammation in asthmatic patients.

Early observations suggested that the inhibition by long-acting beta2-agonists (LABAs) of non-specific bronchial hyperresponsiveness following allergen challenge was unrelated to bronchodilation or functional antagonism and might be a reflection of anti-inflammatory activity. Investigation of the effect of LABAs on airway inflammatory responses has demonstrated an inhibition of eosinophil recruitment in allergen challenge studies. Nevertheless, results from biopsy and other studies suggest that the chronic inflammatory process in asthma patients is unaffected by these drugs. There is no evidence from biopsy studies that LABAs are pro-inflammatory or that they mask existing inflammation. The beneficial effects of LABAs in allergen challenge are probably mediated through stabilization of mast cells. Recent evidence suggests that LABAs may reduce numbers of neutrophils and their associated markers; this observation needs to be confirmed in future studies and its relevance to the treatment of asthma determined.

Adrenergic beta-Agonists↗
PubMed1999

Preclinical and clinical studies of MMP inhibitors in cancer.

The role of matrix metalloproteinases in tumor angiogenesis and growth is now well recognized for models of both human and animal cancer. Clinical studies currently under way with the prototype matrix metalloproteinase inhibitor, marimastat, will establish whether inhibitors of these enzymes are of benefit in the treatment of different types of human cancer. On chronic therapy in humans, marimastat induces a reversible tendinitis that can also be detected in certain animal species. This paper compares the ability of broad-spectrum and various types of selective matrix metalloproteinase inhibitors to induce tendinitis and to exhibit anticancer effects in an animal cancer model. Under conditions in which both systemic exposure and inhibitor potency are controlled, selective inhibitors are less pro-tendinitic, but are weaker anticancer agents than broad-spectrum agents such as marimastat. The clinical relevance of these findings is discussed.

Animals↗
PubMed1995

Matrix metalloproteinases and processing of pro-TNF-alpha.

Tumor necrosis factor-alpha (TNF-alpha) is released from a cell membrane-anchored precursor by proteolytic cleavage. We have shown that broad spectrum synthetic inhibitors of matrix metalloproteinases (MMPs) prevent the processing of the TNF precursor but do not inhibit the release of other cytokines. Purified MMPs, stromelysin, matrilysin, collagenase, and the gelatinases can all cleave a recombinant pro-TNF substrate to yield mature TNF. MMP inhibitors prevent the rise in blood levels of TNF after endotoxin administration in rats and are effective in animal models of inflammatory disease such as adjuvant arthritis. Drugs that inhibit MMP action and TNF release show great promise for the treatment of autoimmune inflammatory diseases.

Amino Acid Sequence↗
PubMed1994

Processing of tumour necrosis factor-alpha precursor by metalloproteinases.

Tumour necrosis factor-alpha (TNF-alpha) is a potent pro-inflammatory and immunomodulatory cytokine implicated in inflammatory conditions such as rheumatoid arthritis, Crohn's disease, multiple sclerosis and the cachexia associated with cancer or human immunodeficiency virus infection. TNF-alpha is initially expressed as a 233-amino-acid membrane-anchored precursor which is proteolytically processed to yield the mature, 157-amino-acid cytokine. The processing enzyme(s) which cleave TNF-alpha are unknown. Here we show that the release of mature TNF-alpha from leukocytes cultured in vitro is specifically prevented by synthetic hydroxamic acid-based metalloproteinase inhibitors, which also prevent the release of TNF-alpha into the circulation of endotoxin challenged rats. A recombinant, truncated TNF-alpha precursor is cleaved to biologically active, mature TNF-alpha by several matrix metalloproteinase enzymes. These results indicate that processing of the TNF-alpha precursor is dependent on at least one matrix metalloproteinase-like enzyme, inhibition of which represents a novel therapeutic mechanism for interfering with TNF-alpha production.

Animals↗
PubMed1987

Campylobacter jejuni in dairy cows and raw milk.

Twelve herds of dairy cows were examined by rectal swabbing for the presence of Campylobacter jejuni. Ten herds were positive with the incidence of colonized animals ranging from 10 to 72% of those tested. With the exception of the two negative herds where mains water only was consumed, all animals drank from rivers or streams when grazing. There was no relationship between total and coliform counts and the presence of C. jejuni in raw milk. However, milk from one farm that consistently gave positive results had significantly higher Escherichia coli counts than other samples.

Animals↗