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Biomedical subjects

R Dobson

Publications and source records attributed to R Dobson.

At least 19 recordsLinked to original sources
PubMed2001

ZD1839 (Iressa), a novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, potently inhibits the growth of EGFR-positive cancer cell lines with or without erbB2 overexpression.

Overexpression of the growth factor receptors EGFR and erbB2 occurs frequently in several human cancers and is associated with aggressive tumour behaviour and poor patient prognosis. We have investigated the effects of ZD1839 (Iressa), a novel EGFR tyrosine kinase inhibitor, on the growth, in vitro and in vivo, of human cancer cell lines expressing various levels of EGFR and erbB2. Proliferation of EGFR-overexpressing A431 and MDA-MB-231 cells in vitro was potently inhibited (50%-70%) by ZD1839 with half-maximally effective doses in the low nanomolar range. In parallel, ZD1839 blocked autophosphorylation of EGFR and prevented activation of PLC-gamma 1, ERK MAP kinases and PKB/Akt by EGF. It also inhibited proliferation in EGFR(+) cancer cell lines overexpressing erbB2 (SKBr3, SKOV3, BT474) by between 20% and 80%, effects which correlated with inhibition of EGF-dependent erbB2 phosphorylation and activation of ERK MAP kinase and PKB/Akt in SKOV3 cells. Oral administration of ZD1839 inhibited the growth of MDA-MB-231 and SKOV3 tumours, established as xenografts in athymic mice, by 71% and 32%, respectively. Growth inhibition coincided with reduced proliferation but no change in apoptotic index. Collectively, these results show that ZD1839, at the doses studied, is a potent inhibitor of proliferation not only in cells overexpressing EGFR but also in EGFR(+) cells that overexpress erbB2.

Cell Division↗
PubMed2001

Presence of Mycobacterium avium subspecies paratuberculosis in suspensions of ovine trichostrongylid larvae produced in faecal cultures artificially contaminated with the bacterium.

A reference strain of Mycobacterium avium subspecies paratuberculosis was added to faecal larval cultures of Haemonchus contortus, Ostertagia circumcincta and Trichostrongylus colubriformis. Samples of the larvae produced were cultured for the presence of the bacterium in modified BACTEC 12B medium, both before and after exposure to gamma irradiation. The water used to wash the larvae off the faecal cultures was also tested for the presence of the bacterium. Positive growth was confirmed as M. avium subspecies paratuberculosis by IS900 polymerase chain reaction and restriction endonuclease analysis of the product. M. avium subspecies paratuberculosis was detected in the unirradiated larval suspensions and wash waters of all three nematode species, and in the irradiated H. contortus larval suspension.

Animals↗
PubMed2001

Nodal vessels disease as a risk factor for atrial fibrillation after coronary artery bypass graft surgery.

OBJECTIVE: Atrial fibrillation (AF) is common after coronary artery bypass graft (CABG) surgery. Atrial ischaemia due to diseased atrioventricular (AV) and sinoatrial (SA) arteries has been proposed as a cause of AF post-CABG. We examined if the presence of diseased nodal arteries was a significant predictor of the development of AF post-CABG. METHODS: 100 consecutive cases (AF post-CABG) were compared to 100 consecutive controls (No AF post-CABG) with respect to pre-operative angiographic evidence of diseased nodal arteries. Cases and controls identified from the Society of Thoracic Surgeons database underwent detailed chart reviews to obtain data on potential risk factors. Patients were excluded if they were undergoing anything but a routine CABG procedure, were older than 65 years, or had previous AF. All angiograms were reviewed by a single radiologist blinded to outcome. The effect of grafting diseased nodal arteries on the development of AF post-CABG was also measured. A multiple logistic regression model was utilized to measure the effect of disease in each artery on the development of AF post-CABG. RESULTS: Cases and controls were comparable regarding potential risk factors, with the exception that the AF group was older than the non-AF group. Significant AV artery disease was detected in 78 cases compared to 74 controls (adjusted odds ratio (OR) OR=1.04, CI, 0.51-2.12, P=0.82). Significant SA artery disease was detected in 34 cases compared to 21 controls (adjusted OR=2.093, CI: 1.06-4.09, P=0.03). Six of ten patients having revascularization of their SA nodal artery developed AF versus 28 of 45 of those who did not (OR=0.91, CI: 0.18-5.06, P=0.58). Forty-eight of 87 patients having revasacularization of their AV nodal artery developed AF versus 30 of 65 of those who did not (OR=1.44, CI: 0.72-2.88, P=0.27). CONCLUSION: The presence of a diseased SA artery is significantly associated with AF post-CABG. Such association may be used to identify a subset of patients who might be targeted with prophylaxis.

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