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Biomedical subjects

C McEwan

Publications and source records attributed to C McEwan.

17 recordsLinked to original sources
PubMed2003

Lack of involvement of nucleotide excision repair gene polymorphisms in colorectal cancer.

DNA repair has an essential role in protecting the genome from damage by endogenous and environmental agents. Polymorphisms in DNA repair genes and differences in repair capacity between individuals have been widely documented. For colorectal cancer, the loss of mismatch repair gene activity is a key genetic determinant. Nucleotide excision repair (NER), recombination repair (RR) and base excision repair (BER) pathways have critical roles in protection against other cancers, and we wished to investigate their role in colorectal cancer. We have compared the frequency of polymorphisms in the NER genes, XPD, XPF, XPG, ERCC1; in the BER gene, XRCC1; and in the RR gene, XRCC3; in colorectal cancer patients and in a control group. No significant associations were found for any of the NER gene polymorphisms or for the XRCC1 polymorphism. The C allele (position 18067) of the XRCC3 gene was weakly but significantly associated with colorectal cancer (odds ratio 1.52, 95% confidence interval 1.04-2.22, P=0.03). For all patients who were heterozygous for any of the repair genes studied, tumour tissue was investigated for loss of heterozygosity (LOH). Only one example of LOH was found for all the genes examined. From the association and LOH data, we conclude that these genes do not have an important role in protection against colorectal carcinogenesis.

Cell Transformation, Neoplastic↗
PubMed2001

A one-step gene amplification system for use in cultured mammalian cells and transgenic animals.

Gene amplification is widely used for the production of pharmaceuticals and therapeutics in situations where a mammalian system is essential to synthesise a fully active product. Current gene amplification systems require multiple rounds of selection, often with high concentrations of toxic chemicals, to achieve the highest levels of gene amplification. The use of these systems has not been demonstrated in specialised mammalian cells, such as embryonic-stem cells, which can be used to generate transgenic animals. Thus, it has not yet proved possible to produce transgenic animals containing amplified copies of a gene of interest, with the potential to synthesise large amounts of a valuable gene product. We have developed a new amplification system, based around vectors encoding a partially disabled hypoxanthine phosphoribosyltransferase (HPRT) minigene, which can achieve greater than 1000-fold amplification of HPRT and the human growth hormone gene in a single step in Chinese hamster-lung cells. The amplification system also works in mouse embryonic-stem cells and we have used it to produce mice which express 30-fold higher levels of human protein C in milk than obtained with conventional transgenesis using the same protein C construct. This system should also be applicable to large animal transgenics produced by nuclear transfer from cultured cell lines.

Animals↗
PubMed1997

How to involve hard to reach groups: a consumer-led project with lay carers of people with advanced HIV infection.

The identification and provision of support to lay carers is crucial if Health Authorities are to meet the identified health care needs of their populations. This paper outlines in Part One the process for recruiting a defined but potentially hard to reach group, namely lay carers of people with advanced HIV infection, into a project designed as part of an ongoing development in HIV/AIDS education, the specific difficulties encountered, and how these were overcome. Part Two describes how to make a video, highlighting the involvement of carers in all stages of the research and development of a health education video-based resource package. Crucial to overcoming many of the difficulties and in winning the confidence and trust of the carers was the overview throughout of a committed multi-disciplinary Steering Group, the emphasis on confidentiality, the support of colleagues in the six UK centres, and the sensitivity and skills of the university research and production facilitators. This process ensured that the carers as consumers were involved in a continuing and active dialogue through the project.

Caregivers↗
PubMed1997

Job sharing at the managerial level.

Job sharing restructures a full-time position-two individuals share the responsibilities and the benefits of the position. If nurses are committed to making it work, this arrangement can succeed at the managerial level.

Humans↗
PubMed1995

'Video, health education and the General Practitioner Contract'.

The 1990 General Practitioner Contract and the 1993 Contract Revision emphasised the role of health education/health promotion within primary care. In this paper, the authors suggest that a highly cost-effective approach is necessary given the premium on time available for general practitioners and members of the primary health care team to undertake such work. The views of general practitioners and the primary health care team in a random sample of general practices within all 15 Health Board areas in Scotland were sought between 1991 and 1993 regarding current experience and future potential in using video-based health education materials, with particular emphasis on the content, structure and parameters appropriate to running effective health education/health promotion programmes. This study has indicated the potential demand for high quality, appropriately targeted video-based materials for use by primary health care workers within a range of practice, community and home settings. Central to this is the need for a better system of information and dissemination of materials and a firmer evaluation framework for health education/health promotion programmes within primary care. The progress of several policy, management and research issues which arose from the findings of the study have been raised by the authors. These include implications for the NHS such as infrastructure resourcing and priority setting, programme development, information and dissemination, research and evaluation, and mechanism(s) whereby general practitioners can be better involved in this process.

Adult↗
PubMed1992

A position- and orientation-dependent element in the first intron is required for expression of the mouse hprt gene in embryonic stem cells.

The gene (hprt) coding for mouse HPRT (hypoxanthine phosphoribosyltransferase) is transcribed from a promoter lacking CAAT and TATAA boxes. It is expressed ubiquitously, albeit at different levels, in all tissues and cultured cells. During investigations to characterise hprt transcription control elements required in embryonic stem (ES) cells and to develop compact hprt minigenes for gene-targeting strategies, we discovered a requirement for intron-1 sequences for expression in ES cells. The essential intron-1 element, which is 420 bp long, is located 230 bp downstream from the transcription start point and is shown to increase transcription from the hprt promoter in a position- and orientation-dependent manner. We propose that this element is an integral downstream part of the hprt promoter.

Animals↗
PubMed1988

Characterization, evolutionary relationships, and chromosome location of processed mouse HPRT pseudogene.

Studies on a cell line with amplified copies of the mouse hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene and HPRT gene transfer experiments revealed the existence of a nonfunctional HPRT-related sequence in the mouse genome. This sequence was isolated and found to be a processed HPRT pseudogene. With the exception of a small internal deletion, the pseudogene is believed to comprise a complete reverse transcript of HPRT mRNA, although the 3' end of the pseudogene was lost in the cloning process. A probe from a region flanking the mouse pseudogene was used to investigate the evolutionary relationships of mammalian HPRT pseudogenes. The pseudogenes in mouse and Chinese hamster appear to have a common origin, but no homology to any of the four known human HPRT pseudogenes was detected. A pseudogene-linked restriction fragment length polymorphism was used to map the pseudogene to the distal end of mouse chromosome 17.

Animals↗
PubMed1986

Expression of the mouse HPRT gene: deletional analysis of the promoter region of an X-chromosome linked housekeeping gene.

The mouse hypoxanthine phosphoribosyltransferase gene, like several other housekeeping genes, lacks many of the features associated with promoters of RNA polymerase II-transcribed genes. HPRT transcripts have multiple initiation sites and an HPRT minigene was used to show that only 49 bases of 5' flanking sequence was necessary for normal expression in cultured cells. The essential region, which occurs within a complex series of direct repeats, is homologous to sequences upstream of other housekeeping genes. When this sequence was deleted, cryptic upstream initiation sites were revealed. Similar aberrant patterns of initiation were seen with all minigenes assayed in Xenopus oocytes. We speculate that this region of the HPRT promoter is involved in a different interaction with the transcriptional machinery to that occurring at more conventional promoters.

Animals↗
PubMed1986

Malignant melanoma of the conjunctiva.

The clinicopathological features of 37 patients with invasive melanoma of the conjunctiva have been studied. Prognosis was closely related to the subsite and size of the primary tumour. Twenty of 21 patients with small localized bulbar neoplasms (95%) and four of six patients with diffuse bulbar melanomas (67%) have survived with no evidence of secondary spread. By contrast, only one of six patients with neoplasms involving the fornix (17%) and two of four (50%) with caruncular melanomas have survived. Metastatic spread was very uncommon in patients with melanomas less than 1.5 mm in maximum thickness, but the outcome of the disease in patients with tumours greater than 1.5 mm was not always bad. Treatment by local excision biopsy was followed by a high rate of conjunctival recurrence (59%). Exenteration of the affected eye guarded against the development of further orbital disease, but was not infrequently followed by the appearance of metastases. Many (62%) of the tumours appeared to have arisen in a pre-existing melanotic lesion or pigmented naevus of long-standing. Histologically, the tumours could be divided into those with an adjacent intra-epithelial component, manifest as atypical melanocytic hyperplasia in the conjunctival epithelium adjacent to the invasive melanoma, and those without (nodular melanoma). However, clear separation of the former group into the subtypes described for cutaneous melanomas proved impossible. Prognosis was not related to the type of melanoma, mitotic rate, cell type or degree of pigmentation.

Adult↗
PubMed1981

A complex Ph1 translocation in a patient with primary thrombocythaemia.

Routine blood examination of a 27-year-old female revealed a platelet count of 2000 X 10(9)/l. Bone marrow cells showed the Philadelphia chromosome which was one product of a complex rearrangement of chromosomes 9, 22 and X. Her platelet count was lowered by plateletphoresis and chemotherapy. She remains in good health 19 months later, but her thrombocythaemia is considered to be an early manifestation of chronic myeloid leukaemia.

Adult↗