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Regulation of human breast stem cells
RB Clarke
Breast Cancer Research , 2006, DOI: 10.1186/bcr1550
Abstract: We employed several complementary approaches to identify putative stem cell markers, to characterise an isolated stem cell population and to relate these to cells expressing ERα. ERα-positive cells were found to coexpress the putative stem cell markers p21CIP1 and Msi-1. Human breast epithelial cells with Hoechst dye-effluxing 'side population' (SP) properties characteristic of mammary stem cells in mice were demonstrated to be undifferentiated cells by lack of expression of myoepithelial and luminal epithelial membrane markers. These SP cells were sixfold enriched for ERα-positive cells and expressed several-fold higher levels of the ERα, p21CIP1 and Msi1 genes than non-SP cells. In contrast to non-SP cells, SP cells formed branching structures in matrigel which included cells of both luminal and myoepithelial lineages. The data suggest a model where scattered ERα-positive cells are stem cells that self-renew through asymmetric cell division and generate patches of transit amplifying and differentiated cells.In recent studies we have been investigating breast cancers for the presence of a stem cell population. Using a nonadherent culture method analogous to neurosphere culture that enriches for neural stem cells, we have demonstrated that breast cancer cell lines and primary tumours contain a self-renewing population that is highly regulated by the Notch receptor signaling pathway. Inhibitors of this pathway could represent a new therapeutic modality in breast cancer, perhaps through combination with current treatments.In order to discover novel pathways that regulate stem cell self-renewal, we have applied functional genomics using an RNAi library targeting ~8,000 genes involved in cancer. This has revealed the importance of several pathways not previously associated with stem cell self-renewal. These pathways may represent novel targets for breast cancer therapy aimed at the breast cancer stem cells that survive conventional therapies.
Aberrant activation of Notch signalling in human breast cancer
S Stylianou, GM Collu, RB Clarke, K Brennan
Breast Cancer Research , 2006, DOI: 10.1186/bcr1551
Abstract: Activation of the Notch pathway in human breast cancer cell lines and breast carcinoma samples was monitored by western blotting with an antibody that recognises the cleaved Notch1 intracellular domain which is produced during signalling. Regulation of apoptosis by Notch was studied in MCF 10A cells transformed by overexpressing the Notch1 intracellular domain. Apoptosis was triggered by treating cells with the kinase inhibitor staurosporine or the DNA damaging agents melphalan and mitoxantrone, and monitored by nuclear fragmentation or cleavage of caspase 3. Changes in the apoptotic machinery were examined by western blotting using a range of antibodies that recognise both total and phosphospecific forms of different components.We will present data showing that Notch signalling is activated in a wide range of breast cancer cell lines and in a panel of 20 human breast carcinomas of different pathological grade and prognosis. In addition, we will demonstrate that sustained signalling is required to maintain the transformed phenotype of breast cancer cell lines, as its inhibition by expressing Numb, a natural inhibitor of the pathway, causes both MCF7 and MDA-MB-231 cells to adopt a normal phenotype. Our data with the normal breast epithelial cell line MCF 10A indicate that Notch signalling contributes to the transformed phenotype by inhibiting apoptosis. Activation of Notch signalling in these cells by overexpressing the Notch1 intracellular domain prevents apoptosis in response to growth factor withdrawal, removal from the extracellular matrix and DNA damage. Finally, we will provide evidence that the apoptosis resistance seen in Notch transformed MCF 10A cells is through the activation of the Akt survival pathway.Altogether this suggests that targeting Notch signalling may be a novel therapeutic strategy for the treatment of breast cancer.This work was supported by Breast Cancer Campaign. KB was a Wellcome Trust Research Career Development Fellow.
On-demand sedation with propofol for colonoscopy—A prospective pilot study of the influence on short-term memory, psychomotor function and postural stability*  [PDF]
Mogens R?rb?k Madsen
Open Journal of Clinical Diagnostics (OJCD) , 2013, DOI: 10.4236/ojcd.2013.33023
Abstract: Background: After sedated colonoscopy, patients are discharged on the basis of their subjective judgment that they have recovered, corroborated by the nursing staff. The aim of this study was to assess objectively whether patients were in fact fully recovered at the time of discharge, and to demonstrate whether the methods of testing applied could detect any influence of sedation on short-term memory, psychomotor function and postural stability. Methods: Twenty-two patients were investigated. At the beginning of the procedure, a defined bolus of propofol/alfentanil was given intravenously. During the procedure, an additional bolus was injected one or more times as requested by the patient. After colonoscopy, the patients stayed in the recovery room until the patients judged that they had recovered completely, which was also the judgement of the nursing staff at that time. Before colonoscopy and again before discharge, tests were performed of short-term memory, psychomotor function and postural stability (balance). Results: A positive correlation was found between the duration of colonoscopy and the amount of sedative given (p < 0.03). No differences in short-term memory or postural control were found when measurements obtained before and after colonoscopy were compared. Reaction time was prolonged significantly after colonoscopy (p < 0.01), which was mainly due to prolongation of perception time (p < 0.003). No correlation was found between the observed reduction in psychomotor function and the amount of sedative given. Conclusions: The introduction of ultrashort-acting sedative and hypnotic agents has facilitated out-patient colonoscopy. However, although they feel that they have recovered fully, some patients are still affected by the sedative at the time of discharge, as demonstrated by tests of short-term memory, reaction time and postural stability.
Hormonal indicators of reproductive merit
RB Land
Genetics Selection Evolution , 1976, DOI: 10.1186/1297-9686-8-2-293b
Genetic improvement of reproduction: time for deeds
RB Land
Genetics Selection Evolution , 1982, DOI: 10.1186/1297-9686-14-4-579a
The role of foraging (harvester) ants, Messor cephalotes, in land degradation in Meserani area Monduli District, Tanzania
RB Kiunsi
Ethiopian Journal of Environmental Studies and Management , 2010,
Abstract: Meserani is a semi arid area in Monduli District in north east Tanzania that is prone to land degradation in terms of vegetation and soil degradation due to natural and anthropological factors. For a number of years the local community including extension officers had suspected that in certain locations of Meserani area bare lands, apart from grazing and farming activities were also created by grazing insects. The main objective of this paper was firstly, to identify the type of grazing insects that were creating bare lands, hence land degradation. Land degradation in this context is taken to mean the removal of herbaceous vegetation caver. Secondly, to determine the extent in which grazing insects are contributing to land degradation in the area. The harvester ants of species Messor cephalotes, Emmery were identified as the main insects that were foraging herbaceous vegetation cover thus creating bare lands in some of the locations in the study area. Areas with high intensity of human activities in terms of framing and grazing had more bare lands created by ants than the fallow or stony areas. Therefore in the Meserani harvester ants just like grazing or farming activities were contributing to land degradation through the creation of bare lands.
Commentary: How would extracorporeal shockwave therapy possibly promote wound healing in colon anastomosis?
RB Sanda
Annals of African Medicine , 2011,
Abstract: No
Surgical perspectives on inflammatory bowel disease - Commentary
RB Sanda
Annals of African Medicine , 2011,
Abstract: No
Ensuring safe access to medication for palliative care while preventing prescription drug abuse: innovations for American inner cities, rural areas, and communities overwhelmed by addiction
Francoeur RB
Risk Management and Healthcare Policy , 2011, DOI: http://dx.doi.org/10.2147/RMHP.S24068
Abstract: suring safe access to medication for palliative care while preventing prescription drug abuse: innovations for American inner cities, rural areas, and communities overwhelmed by addiction Commentary (3791) Total Article Views Authors: Francoeur RB Published Date September 2011 Volume 2011:4 Pages 97 - 105 DOI: http://dx.doi.org/10.2147/RMHP.S24068 Richard B Francoeur School of Social Work, Adelphi University, Garden City, NY, USA; Center for the Psychosocial Study of Health and Illness, Columbia University, New York, NY, USA Abstract: This article proposes and develops novel components of community-oriented programs for creating and affording access to safe medication dispensing centers in existing retail pharmacies and in permanent or travelling pharmacy clinics that are guarded by assigned or off-duty police officers. Pharmacists at these centers would work with police, medical providers, social workers, hospital administrators, and other professionals in: planning and overseeing the safe storage of controlled substance medications in off-site community safe-deposit boxes; strengthening communication and cooperation with the prescribing medical provider; assisting the prescribing medical provider in patient monitoring (checking the state prescription registry, providing pill counts and urine samples); expanding access to lower-cost, and in some cases, abuse-resistant formulations of controlled substance medications; improving transportation access for underserved patients and caregivers to obtain prescriptions; and integrating community agencies and social networks as resources for patient support and monitoring. Novel components of two related community-oriented programs, which may be hosted outside of safe medication dispensing centers, are also suggested and described: (1) developing medication purchasing cooperatives (ie, to help patients, families, and health institutions afford the costs of medications, including tamper- or abuse-resistant/deterrent drug formulations); and (2) expanding the role of inner-city methadone maintenance treatment programs in palliative care (ie, to provide additional patient monitoring from a second treatment team focusing on narcotics addiction, and potentially, to serve as an untapped source of opioid medication for pain that is less subject to abuse, misuse, or diversion).
How to design education on mental disorders for general practitioners in South Africa
RB Mash
South African Family Practice , 2002,
Abstract: Objective: This study looks at how the WHO programme Mental Disorders in Primary Care should be adapted for GPs in the South African context in order to positively impact the recognition and management of mental disorders. Design: Participatory action research was used to adapt the WHO programme. There were 3 phases to the study. Firstly a co-operative inquiry group of 10 GPs adapted the WHO materials. Secondly the findings of the inquiry were incorporated into the design of a web-based distance education programme. Thirdly the web-based programme was evaluated by means of an action inquiry with the 21 registered GPs. Setting: South African general practitioners working in both public and private practice. Results: The findings of the study are presented as a model of the primary care consultation with a specific focus on the recognition and management of mental disorders. The approach includes the use of one hypothesis for ‘mental problems' and assessment in the ‘lobby' of general practice. Sixgoverning variables for this approach are described: cues, communication skills, continuity of care, confidence, course tools and community resources. Conclusion: This study presents a practical model of the primary care consultation, which focuses on an approach to the recognition and management of mental disorders. This model has been used to adapt the WHO programme for the South African context. The model may be of use to general practitioners, educational designers, teachers of family medicine /primary care as well as district managers who wish to enhance the quality of care for patients with mental disorders. SA Fam Prac Vol.25(5) 2002: 4-10
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