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C Burrows

Publications and source records attributed to C Burrows.

At least 19 recordsLinked to original sources
PubMed2006

Insulin-like growth factor binding protein 3 has opposing actions on malignant and nonmalignant breast epithelial cells that are each reversible and dependent upon cholesterol-stabilized integrin receptor complexes.

IGF-binding protein (IGFBP)-3 is generally considered to have actions that counterbalance those of IGFs and is therefore being developed as a cancer treatment. In breast tumors, however, high levels are associated with aggressive tumors and poor prognosis. Consistent with this we have demonstrated that although IGFBP-3 and a non-IGF-binding fragment (serine phosphorylation domain peptide) reduced attachment and enhanced apoptosis of Hs578T breast cancer cells cultured on collagen or laminin, it promoted their attachment and survival on fibronectin, which is abundant in the matrix of aggressive tumors. We have now examined the factors that determine whether IGFBP-3 has positive or negative actions on breast epithelial cells. IGFBP-3 also promoted survival of Hs578T cells in the presence of an antibody to the beta1-integrin subunit or when cholesterol-stabilized complexes were disrupted. These actions were blocked by IGF-I or a MAPK inhibitor. Serine phosphorylation domain peptide had similar actions on MCF-7 cells that were again reversed on fibronectin or with disruption of cholesterol-stabilized complexes and blocked by the beta1-integrin antibody. In contrast, IGFBP-3 promoted growth and survival for nonmalignant MCF-10A cells, but these effects were again reversed on fibronectin and blocked by the beta1 antibody or a MAPK inhibitor or by disruption of cholesterol-stabilized complexes. On Hs578T cells, IGFBP-3 bound to caveolin-1 and beta1-integrins, enhancing their aggregation, the recruitment of focal adhesion kinase, and the activation of MAPK. In summary, with three breast epithelial cell lines, IGFBP-3 had positive or negative effects on growth and survival dependent upon the status of cholesterol-stabilized integrin receptor complexes.

Apoptosis↗
PubMed2002

Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.

Since the sequencing of the first two chromosomes of the malaria parasite, Plasmodium falciparum, there has been a concerted effort to sequence and assemble the entire genome of this organism. Here we report the sequence of chromosomes 1, 3-9 and 13 of P. falciparum clone 3D7--these chromosomes account for approximately 55% of the total genome. We describe the methods used to map, sequence and annotate these chromosomes. By comparing our assemblies with the optical map, we indicate the completeness of the resulting sequence. During annotation, we assign Gene Ontology terms to the predicted gene products, and observe clustering of some malaria-specific terms to specific chromosomes. We identify a highly conserved sequence element found in the intergenic region of internal var genes that is not associated with their telomeric counterparts.

Animals↗
PubMed2001

The physical maps for sequencing human chromosomes 1, 6, 9, 10, 13, 20 and X.

We constructed maps for eight chromosomes (1, 6, 9, 10, 13, 20, X and (previously) 22), representing one-third of the genome, by building landmark maps, isolating bacterial clones and assembling contigs. By this approach, we could establish the long-range organization of the maps early in the project, and all contig extension, gap closure and problem-solving was simplified by containment within local regions. The maps currently represent more than 94% of the euchromatic (gene-containing) regions of these chromosomes in 176 contigs, and contain 96% of the chromosome-specific markers in the human gene map. By measuring the remaining gaps, we can assess chromosome length and coverage in sequenced clones.

Chromosomes, Human, Pair 1↗
PubMed2001

Effects of inducible MEK1 activation on the cytokine dependency of lymphoid cells.

The Raf/MEK/MAP kinase cascade plays a critical role in transducing growth signals from activated cell surface receptors. Using deltaMEK1:ER, a conditionally active form of MEK1, we demonstrate the ability of this dual specificity protein kinase to abrogate the cytokine dependency of the murine lymphoid hematopoietic cell line FL5.12. Cytokine-independent cells were obtained from FL5.12 cells at a frequency of 1 x 10(-7), indicating that a low frequency of cells expressing deltaMEK1:ER were factor-independent. In general, cells that were converted to a cytokine-independent phenotype displayed a higher level of MAP kinase activity in response to deltaMEK1:ER activation than those that remained cytokine-dependent. deltaMEK1:ER-responsive cells could be maintained long-term in the presence of beta-estradiol, as well as the estrogen-receptor antagonist 4-hydroxy-tamoxifen. Removal of hormone led to the rapid cessation of cell growth in a manner similar to that observed when cytokine is withdrawn from the parental cells. GM-CSF mRNA transcripts were detected in the MEK1-responsive cells indicating that activated deltaMEK1:ER may induce a pathway leading to autocrine proliferation. Cytokine-dependent deltaMEK1:ER cells were found to increase the expression of GM-CSF receptor alpha (GM-CSFRalpha) in response to beta-estradiol. In contrast, MEK1-responsive cells were found to express constitutively lower levels of GM-CSFRalpha and beta common (betac) chains indicating that constitutive GM-CSF expression resulted in a decrease in GM-CSFR expression. Treatment of parental cells with supernatant from MEK1-responsive FL5.12 cells was sufficient to promote [3H]-thymidine incorporation. GM-CSF was found to enhance the viability of FL5.12 cells. The cell lines described here will be useful for elaborating the ability of the MAP kinase pathway to regulate cell proliferation in hematopoietic cells.

Cell Cycle↗
PubMed2001

Enhanced ability of daniplestim and myelopoietin-1 to suppress apoptosis in human hematopoietic cells.

Modified and chimeric cytokines have been developed to aid in the recovery of hematopoietic precursor cells after myeloablative chemotherapy. The interleukin-3 (IL-3) receptor agonist, daniplestim, binds to the IL-3 receptor-alpha subunit with 60-fold greater affinity and induces cell proliferation and colony-forming unit formation 10- to 22-fold better than native IL-3. A chimeric cytokine, myelopoietin-1, composed of daniplestim and a G-CSF receptor agonist binds both the IL-3 and G-CSF receptors. While the in vivo effects of daniplestim and myelopoietin-1 are well described, the mechanisms by which they stimulate growth are not well understood. We have investigated the effects of daniplestim and myelopoietin-1 on the prevention of apoptosis in two human hematopoietic cell lines, OCI-AML.5 and AML 193. Daniplestim and myelopoietin-1 prevented apoptosis to a greater degree than native recombinant IL-3 or G-CSF as determined by annexin V/propidium iodide binding and TUNEL assays. Daniplestim and myelopoietin-1 promoted the maintenance of the mitochondrial membrane potential better than native IL-3 or G-CSF. These cytokines promoted a lower redox potential as higher levels of free radicals were detected after cytokine treatment than in cytokine-deprived cells implying increased respiration. These results indicate that daniplestim and myelopoietin-1 are able to prevent apoptosis in hematopoietic cells more effectively than native IL-3 and G-CSF. These effects of daniplestim and myelopoietin-1 may contribute to their effective ability to repopulate hematopoietic precursor cells after chemotherapy.

Apoptosis↗
PubMed2000

Effects of deregulated Raf activation on integrin, cytokine-receptor expression and the induction of apoptosis in hematopoietic cells.

The effects of deregulated Raf activation on the growth and differentiation of hematopoietic cells were investigated. The cytokine-dependent murine myeloid FDC-P1 and human erythroleukemic TF-1 cell lines were transformed to grow in response to deregulated Raf expression in the absence of exogenous cytokines. The conditionally active Raf proteins were regulated by beta-estradiol as cDNAs containing the Raf catalytic, but lacking negative-regulatory domains, were ligated to the hormone binding domain of the estrogen receptor (deltaRaf:ER). Continuous deltaRaf expression prevented apoptosis in the absence of exogenous cytokines and altered the morphology of the FD/deltaRaf:ER cells as they grew in large aggregated masses (>100 cells) whereas the parental cytokine-dependent FDC-P1 cells grew in smaller grape-like clusters (< 10 cells). FD/deltaRaf-1:ER cells growing in response to Raf activation displayed decreased levels of the Mac-2 and Mac-3 molecules on their cell surface. In contrast, when these cells were cultured in IL-3, higher levels of these adhesion molecules were detected. Expression of activated Raf oncoproteins also abrogated cytokine dependency and prevented apoptosis of TF-1 cells. Moreover, the differentiation status of these Raf-responsive cells was more immature upon Raf activation as culture with the differentiation-inducing agent phorbol 12 myristate 13-acetate (PMA) and beta-estradiol resulted in decreased levels of the CD11b and CD18 integrin molecules on the cell surface. In contrast when the Raf-responsive cells were induced to differentiate with PMA and GM-CSF, in the absence of deltaRaf:ER activation, increased levels of the CD11b and CD18 molecules were detected. Retinoic acid (RA) inhibited 3H-thymidine incorporation in response to GM-CSF. Interestingly, Raf activation counterbalanced the inhibition of DNA synthesis caused by RA but not PMA. Thus deregulated Raf expression can alter cytokine dependency, integrin expression and the stage of differentiation. These Raf-responsive cell lines will be useful in elucidating the roles of the MAP kinase cascade on hematopoietic cell differentiation and malignant transformation.

Animals↗
PubMed1999

Do memory clinics improve the quality of life of carers? A randomized pilot trial.

OBJECTIVE: To determine the effects of attendance at a memory clinic on the psychosocial health of carers. DESIGN: Randomized control trial. PARTICIPANTS: Fifty community dwelling subjects with mild to moderate dementia and their carers. MAIN OUTCOME MEASURES: Carer burden, psychological morbidity and psychosocial health related quality of life at 6 and 12 months post intervention. MAIN RESULTS: There was significant improvement in psychosocial health related quality of life of carers as measured by the psychosocial domain of the Functional Limitation Profile (FLP) at 6 months (p < 0.01), including improvement in the subgroups of alertness behaviour (p < 0.05) and social interaction (p < 0.01), after adjustment for age of subject and baseline scores. The improvement in social interaction was maintained at 12 months (p < 0.05). There was no significant difference in carer psychological morbidity (General Health Questionnaire), carer burden (Zarit family interview) or carer knowledge of dementia (Dementia Knowledge Test) at 6 or 12 months, between groups. CONCLUSIONS: These results demonstrate improved psychosocial health related quality of life for carers of those with mild to moderate cognitive impairment attending a memory clinic. Further research in this area is indicated, comparing memory clinic intervention with alternative support.

Aged↗
PubMed1999

Human power output during repeated sprint cycle exercise: the influence of thermal stress.

Thermal stress is known to impair endurance capacity during moderate prolonged exercise. However, there is relatively little available information concerning the effects of thermal stress on the performance of high-intensity short-duration exercise. The present experiment examined human power output during repeated bouts of short-term maximal exercise. On two separate occasions, seven healthy males performed two 30-s bouts of sprint exercise (sprints I and II), with 4 min of passive recovery in between, on a cycle ergometer. The sprints were performed in both a normal environment [18.7 (1.5) degrees C, 40 (7)% relative humidity (RH; mean SD)] and a hot environment [30.1 (0.5) degrees C, 55 (9)% RH]. The order of exercise trials was randomised and separated by a minimum of 4 days. Mean power, peak power and decline in power output were calculated from the flywheel velocity after correction for flywheel acceleration. Peak power output was higher when exercise was performed in the heat compared to the normal environment in both sprint I [910 (172) W vs 656 (58) W; P < 0.01] and sprint II [907 (150) vs 646 (37) W; P < 0.05]. Mean power output was higher in the heat compared to the normal environment in both sprint I [634 (91) W vs 510 (59) W; P < 0.05] and sprint II [589 (70) W vs 482 (47) W; P < 0.05]. There was a faster rate of fatigue (P < 0.05) when exercise was performed in the heat compared to the normal environment. Arterialised-venous blood samples were taken for the determination of acid-base status and blood lactate and blood glucose before exercise, 2 min after sprint I, and at several time points after sprint II. Before exercise there was no difference in resting acid-base status or blood metabolites between environmental conditions. There was a decrease in blood pH, plasma bicarbonate and base excess after sprint I and after sprint II. The degree of post-exercise acidosis was similar when exercise was performed in either of the environmental conditions. The metabolic response to exercise was similar between environmental conditions; the concentration of blood lactate increased (P < 0.01) after sprint I and sprint II but there were no differences in lactate concentration when comparing the exercise bouts performed in a normal and a hot environment. These data demonstrate that when brief intense exercise is performed in the heat, peak power output increases by about 25% and mean power output increases by 15%; this was due to achieving a higher pedal cadence in the heat.

Acid-Base Equilibrium↗
PubMed1998

The psychosocial health status of carers of persons with dementia: a comparison with the chronically ill.

This project aimed to determine overall psychosocial health (measured using the psychosocial dimension of the Functional Limitations Profile) and factors which influence this in a group of carers of those with dementia and to compare their psychosocial health with that of older people attending general practitioners (GPs); arthritis support groups and a pain clinic (out-patients) and a group of community dwellers undergoing renal dialysis. The carer group showed a significant decrease in recreation and pastimes and social interactions compared to older GP attenders. The carers showed similar restrictions in social interactions and recreation to those with chronic arthritis, but the latter were more impaired in the domains of emotional behaviour and sleep and rest. The older people attending a pain clinic did not differ in the areas of alertness and social interactions compared to the carer group. The dialysis group demonstrated the greatest dysfunction overall. These results suggest that the psychosocial health of carers of those with dementia is impaired, the profile of which differs from those suffering with chronic diseases. Social and recreation activities appear most affected in the carers. Commensurate with studies exploring the health status of those suffering from diseases, the measurement of the psychosocial health status of carers should also be considered in the scope of assessment and intervention.

Analysis of Variance↗
PubMed1997

Health care costs of people referred to an aged care assessment team: the effect of cognitive impairment.

The aim of this study was to determine the effect cognitive impairment has on direct and indirect costs to elderly people, their carers and the community over one year, by following prospectively a cohort of elderly people referred to an aged care assessment team. The 78 subjects were drawn from a random sample of people referred to the NorthWest Hospital team, and validated tools were used to assess their cognitive state. Outcome measures included total costs of community services, residential care, hospital bed use, carer burden and psychological morbidity. A comparison of outcome measures was made between those with cognitive impairment and those without. Use of community services and hospital beds was high overall. Those with cognitive impairment were substantially greater users of residential care, accounting for the higher expenditure in this group. Psychological morbidity and burden remain high in carers of those with cognitive impairment despite a high rate of institutionalisation in this group. The total costs for those referred to aged care assessment teams with cognitive impairment are double those seen for those with normal cognition.

Aged↗
PubMed1997

Interstitial myofibroblasts: predictors of progression in membranous nephropathy.

AIMS: To determine the role of interstitial myofibroblasts in the progression of membranous nephropathy; and to assess the predictive value of quantifying myofibroblasts in determining long term renal outcome. METHODS: All cases of membranous nephropathy, diagnosed by renal biopsy at University Hospital of South Manchester between 1984 and 1987, were studied retrospectively. The biopsy specimens (n = 26) were reviewed and analysed morphometrically to measure interstitial volume as a proportion of the total volume of renal cortex, and numbers of interstitial myofibroblasts (cells positive for alpha-smooth muscle actin within the interstitium). Clinical data, with a follow up of seven to eight years, was available for 24 patients, and renal outcome was correlated with pathological changes in the initial diagnostic biopsy specimen. RESULTS: The number of myofibroblasts and interstitial volume were inversely correlated with creatinine clearance at the initial biopsy, and at the end of follow up. Percentage sclerosed glomeruli or stage of glomerular disease, assessed by electron microscopy, did not correlate with renal function at initial biopsy or during follow up. The number of myofibroblasts, but not interstitial volume, correlated with severity of proteinuria at initial biopsy. Of 15 biopsy specimens showing no or mild interstitial fibrosis, four showed a notable increase in the number of interstitial myofibroblasts. All of these patients developed chronic renal failure, compared with three of 11 patients whose specimens showed no or a mild increase in myofibroblast numbers. CONCLUSIONS: Interstitial myofibroblasts play a role in the development of interstitial fibrosis and progressive renal failure in membranous nephropathy. Increased numbers of myofibroblasts in biopsy specimens showing only mild fibrosis may predict subsequent chronic renal failure.

Actins↗
PubMed1997

The role of the nurse in health promotion: an evaluation of a smoking cessation programme in surgical pre-admission clinics.

This paper presents a pilot study evaluating a smoking cessation programme, implemented by a nurse, in surgical pre-admission clinics at The Chesterfield and North Derbyshire Royal Hospital NHS Trust, Chesterfield, England. Using a quasi-experimental design, a convenience sample of 60 subjects who smoked were randomized, 30 to a control and 30 to a treatment group. Those in the treatment group received a variety of educational interventions and self-assessment questionnaires relating to smoking cessation, when attending the clinic. The control group received routine information. Data were collected using the combined interview and questionnaire method. There was a significant increase in positive behaviour on admission to hospital in the treatment group (80% stopped or reduced smoking), compared to a control group (50% stopped or reduced smoking), particularly in subjects who did not intend to reduce or stop before admission. The level of satisfaction with the service and information relating to smoking cessation was also significantly higher in the treatment group. Subjects described the approach of the nurse and a leaflet devised for the study, as the most helpful aspects of the programme. The study highlights how the nurse, using appropriate theory to underpin such a programme, can facilitate smokers' intention to stop or reduce tobacco consumption prior to hospital admission, and help them to prepare for their surgery, anaesthesia, and the hospital's no smoking policy.

England↗
PubMed1994

Integrated specialty and operational system for diabetes management in south west England.

The management and control of diabetes throughout South West England has been assisted by the use of a networked computerised information system which is totally integrated with hospital and community information systems. The objectives of the diabetes system are to produce an aid to diabetes management, which includes the creation of a district diabetes register accessed and maintained by clinicians based in both the hospital and in the community, whilst at the same time providing auditable information.

Delivery of Health Care, Integrated↗
PubMed1993

QALYs for resource allocation: probably not and certainly not now.

Quality-adjusted life years (QALYs) have the attractive characteristic of combining morbidity and mortality into a single index which purports to measure the outcomes of health interventions. Their primary aim, when combined with cost, is to permit comparisons across candidate spending programs and thereby promote economic efficiency in the use of rationed funds. QALYs, in fact, comprise a family of measures with major differences in approach and many variations in construction, process and methods of measurement. A necessary unifying characteristic is the ethical assumption of utilitarianism. The paper examines the state of the art in the development of QALY measures. It concludes that they fall far short of requirements for their advocated use in resource allocation decisions. Furthermore, their demands on measurement for this purpose are such that it is unlikely that methodological problems can be solved.

Australia↗
PubMed1992

Are any numbers better than no numbers? The sorry state of willingness-to-pay and some major methodological shortcomings.

Willingness-to-pay (WTP) is grounded in welfare economics and is used to measure benefits in public decision-making. However, obtained values vary widely, differences between WTP and its obverse, willingness-to-accept, are very large, studies to validate the techniques are almost non-existent and methodologies to elicit values are underdeveloped. Major problems with WTP are discussed with emphasis on cognitive aspects of eliciting preferences and values. It is concluded that until its validity has been established, WTP must be rejected as a measure of economic value.

Attitude to Health↗
PubMed1992

A prospective cost-effectiveness study of alternative work-up strategies in colorectal cancer screening.

Population screening for colorectal cancer has not yet been introduced in Australia, although there is considerable pressure to do so. A significant cost in these programs is the follow-up or confirmatory diagnostic testing for individuals who screened positive and there are many suggested or available strategies with widely differing costs and outcomes. This study is a prospective analysis of diagnostic work-up strategies and two dominant protocols are identified among the twenty-two candidates. The study also discusses extensions to the analysis.

Australia↗