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P Gill

Publications and source records attributed to P Gill.

At least 73 records · Page 4Linked to original sources

Learning to value ethnic diversity--what, why and how?

INTRODUCTION: Learning to value ethnic diversity is the appreciation of how variations in culture and background may affect health care. It involves acknowledging and responding to an individual's culture in its broadest sense. This requires learning the skills to negotiate effective communication, a heightened awareness of one's own attitudes, and sensitivity, to issues of stereotyping, prejudice and racism. This paper aims to contribute to debate about some of the key issues that learning to value ethnic diversity creates. CONTEXT: Although some medical training is beginning to prepare doctors to work in an ethnically diverse society, there is a long way to go. Promoting 'valuing ethnic diversity' in curricula raises challenges and the need to manage change, but there are increasing opportunities within the changing context of medical education. Appropriate training can inform attitudes and yield refinement of learners' core skills that are generic and transferable to most health encounters. CURRICULUM DEVELOPMENT: Care must be taken to avoid a narrow focus upon cultural differences alone. Learning should also promote examination of learners' own attitudes and their appreciation of structural influences upon health and health care, such as racism and socio-economic disadvantage. Appropriate training and support for teachers are required and learning must be explicitly linked to assessment and professional accreditation. CONCLUSION: Greater debate about theoretical approaches, and much further experience of developing, implementing and evaluating effective training in this area are needed. Medical educators may need to overcome discomfort in developing such approaches and learn from experience.

Culture↗

Report of the European DNA Profiling Group (EDNAP)--an investigation of the hypervariable STR loci ACTBP2, APOAI1 and D11S554 and the compound loci D12S391 and D1S1656.

This paper describes the results of three collaborative exercises which continues the EDNAP theme to explore whether uniformity of DNA profiling results could be achieved between European laboratories using STRs. In an earlier exercise, complex hypervariable AAAG-repeat STR loci were investigated, but reproducibility was found to be poor because of the variation of techniques used by participating laboratories. In the exercise reported here, an internal allelic ladder composed of ACTBP2 and D11S554 fragments was distributed. This ladder was used to size ACTBP2 analysed by a "singleplex" PCR amplification and D11S554 combined with APOAI1 in a separate "duplex" reaction. Laboratories were asked to test 7 blood stains, one of which was a known control, and to report the results to the co-ordinating laboratory. The exercise demonstrated that ACTBP2 showed good reproducibility between laboratories, whereas further testing would be needed to validate APOAI1 and D11S554 for interlaboratory comparisons. In separate exercises, the simple loci D12S391 and D1S1656 were tested; both of these showed excellent reproducibility between laboratories.

Alleles↗

Primer specific and mispair extension analysis (PSMEA) as a simple approach to fast genotyping.

A simple method, primer specific and mispair extension analysis (PSMEA) with pfu DNA polymerase was developed for genotyping. PSMEA is based on the unique properties of 3'-->5' exonuclease proofreading activity. In the presence of an incomplete set of dNTPs, pfu was found to be extremely discriminative in nucleotide incorporation and proofreading at the initiation step of DNA synthesis, completely preventing primer extension when mispair(s) are found adjacent to the 3'-end of the primer. This has allowed us to accurately detect nucleotide variations, deletions and insertions for fast genotyping.

Base Pair Mismatch↗

Interpreting simple STR mixtures using allele peak areas.

Although existing statistical models can interpret mixtures qualitatively based upon the alleles present, the use of automated sequencers opens the opportunity to take account of quantitative aspects embodied by the peak area. One step in understanding simple mixtures consisting of just two donors is to estimate the mixture ratio. This is relatively easy to do when four-allele mixtures are evident at a given locus. However, if the mixture consists of three or fewer alleles, the process it is not straightforward. We demonstrate that mixture estimates are consistent across all loci in a multiplex system. Once the mixture ratio is known, then the expected peak areas for any given combination of alleles can be estimated using a simple spreadsheet analysis.

Alleles↗

Analysis and interpretation of mixed forensic stains using DNA STR profiling.

The use of multiplex PCR and fluorescent dye technology in the automated detection and analysis of short tandem repeat loci provides not only qualitative information about the profile--i.e. which alleles are present--but can also provide quantitative information on the relative intensities of the bands, and is therefore a measure of the amount of amplified DNA. The availability of this quantitative information allows for the interpretation of mixtures in a detailed way which has not been previously possible with many other human identification systems. In this paper we present a simple approach to the resolution and analysis of mixed STR profiles resulting from the testing of mixed biological stains in forensic casework and highlight factors which can affect it. This approach requires a detailed knowledge--gained through a mixture of experiments and validation studies--of the behaviour of each locus within the multiplex systems described. We summarise the available data from previously published experimental work and validation studies to examine the general principles underlying this approach.

Alleles↗

New reference allelic ladders to improve allelic designation in a multiplex STR system.

This paper reports the composition of a new reference allelic ladder mixture for use with a multiplex DNA profiling system consisting of six short tandem repeat loci. The loci included in this mixture are HUMTH01, D21S11, D18S51, D8S1179, HUMVWAF31/A, HUMFIBRA/FGA and an amelogenin sex test. Sequence analysis of individual ladder alleles was carried out and allelic designations made in accordance with the recommendations of the International Society of Forensic Haemogenetics (1992; 1994). A series of rare alleles which increase the range of alleles previously reported were identified. By including some of the rare alleles into the ladder marker system, we have significantly improved the ability to identify new alleles in unknown samples.

Alleles↗

Effects of a urinary factor from women in early pregnancy on HIV-1, SIV and associated disease.

The effects of clinical grade crude preparations of human chorionic gonadotropin (hCG) on Kaposi's sarcoma, HIV, SIV and hematopoiesis were examined in vitro and in vivo. In contrast to previous studies, we report that the antiviral activity of hCG associated factors is not due to the native hCG heterodimer, including its purified subunits or its major degradation product, the beta-core. Using gel permeation chromatography of the clinical grade hCG and urine concentrates from pregnant women, we demonstrate that an as yet unidentified hCG associated factor (HAF) with anti-HIV, anti-SIV, anti-KS and pro-hematopoietic activities elutes as two peaks corresponding to 15-30 kDa and 2-4 kDa.

Animals↗

Identification and sequencing of a putative variant of proopiomelanocortin in human epidermis and epidermal cells in culture.

Proopiomelanocortin (POMC) is a precursor polypeptide for various bioactive peptides, including adrenocorticotropic hormone, alpha-, beta-, and gamma-melanotropin, beta-endorphin, and beta-lipotropin. Although the classical source of POMC is the pituitary, various studies indicate the expression of POMC in several nonpituitary tissues. In this study, in situ hybridization with anti-sense cRNA riboprobe was used to show expression of POMC mRNA in human epidermis and cultured human epidermal cells (melanocytes and keratinocytes). POMC mRNA was amplified by reverse transcriptase-polymerase chain reaction using anti-sense and sense primers designed from Exons 2 and 3 of POMC gene. A approximately 300 bp product was present in normal human skin, grafted human skin, and cultured normal human melanocytes and keratinocytes. By Southern analysis this product was hybridized specifically to the POMC cDNA. Sequence analysis of the reverse transcriptase polymerase chain reaction product from tissues or cells showed 85% homology to POMC cDNA from human, bovine, pig, and monkey sources. This suggests the existence of a putative isoform or variant of POMC mRNA in human epidermis.

Animals↗

Human immunodeficiency virus tat modulates the Flk-1/KDR receptor, mitogen-activated protein kinases, and components of focal adhesion in Kaposi's sarcoma cells.

Kaposi's sarcoma (KS) spindle cell growth and spread have been reported to be modulated by various cytokines as well as the human immunodeficiency virus (HIV) gene product Tat. Recently, HIV-1 Tat has been shown to act like a cytokine and bind to the Flk-1/KDR receptor for the vascular endothelial growth factor A (VEGF-A), which is expressed by KS cells. We have characterized signal transduction pathways stimulated by HIV-1 Tat upon its binding to surface receptors on KS cells. We observed that stimulation in KS 38 spindle cells resulted in tyrosine phosphorylation and activation of the Flk-1/KDR receptor. We also report that HIV-1 Tat treatment enhanced the phosphorylation and association of proteins found in focal adhesions, such as the related adhesion focal tyrosine kinase RAFTK, paxillin, and p130(cas). Further characterization revealed the activation of mitogen-activated protein kinase, c-Jun amino-terminal kinase (JNK), and Src kinase. HIV-1 Tat contains a basic domain which can interact with growth factor tyrosine kinase receptors and a classical RGD sequence which may bind to and activate the surface integrin receptors for fibronectin and vitronectin. We observed that stimulation of KS cells with basic as well as RGD sequence-containing Tat peptides resulted in enhanced phosphorylation of RAFTK and activation of MAP kinase. These studies reveal that Tat stimulation activates a number of signal transduction pathways that are associated with cell growth and migration.

Calcium-Calmodulin-Dependent Protein Kinases↗

DNA recommendations 1997 of the International Society for Forensic Genetics.

The DNA commission of the International Society for Forensic Haemogenetics (ISFH) has over the years published a series of documents providing guidelines and recommendations concerning the application of DNA polymorphisms to problems of identification. This latest report provides recommendations relating to the nomenclature of short tandem repeat system (STR) typing systems which are at the forefront of systems used at present by forensic scientists and are likely to remain so for the immediate future.

Alleles↗

Open-label phase I study of combination therapy with zidovudine and interferon-beta in patients with AIDS-related Kaposi's sarcoma: AIDS Clinical Trials Group Protocol 057.

The aim of this study was to identify a safe and tolerable dose of recombinant interferon-beta (IFN-beta) used in conjunction with a fixed dose of zidovudine in patients with early-stage, good-prognosis AIDS-related Kaposi's sarcoma. We conducted a phase I, dose-escalation controlled trial of 22.5, 45 of 90 million units of IFN-beta given by daily subcutaneous injection with 500 mg per day of oral zidovudine. At the time of this study, this was standard of care for HIV infection. Patients were sequentially enrolled at three medical centers. Tumor response, drug tolerance, antiviral studies and CD4 changes were assessed. Four patients were enrolled at each dose level, and escalation proceeded when at least four patients had tolerated two weeks of therapy without dose-limiting toxicity. ACTG Kaposi's sarcoma tumor response criteria were used to assess response. Fifteen patients were enrolled. The combination of IFN-beta and zidovudine was well tolerated, and the dose-limiting toxicities were local skin necrosis and systemic symptoms. Despite generally good prognostic characteristics, only two patients achieved a clinical complete response and three addition patients had stable disease for a prolonged period of time (range 24-44 weeks). There was no correlation between baseline CD4 cell counts and tumor response, nor between the antiviral effect of IFN-beta as measured by decreases in immune-complex dissociated p24 antigen and tumor response. Higher doses of IFN-beta did not result in more tumor responses or in greater antiviral activity. The maximum tolerated dose of IFN-beta in combination with 500 mg per day of zidovudine was 45 million units by subcutaneous injection per day. IFN-beta is well tolerated in patients with AIDS-related Kaposi's sarcoma when used in conjunction with zidovudine. However, the antitumor response rate in good-prognosis patients is low. Further studies of this agent should be in the context of four-drug antiretroviral regimens where viral suppression is greatest and any antitumor activity of IFN-beta may be observed.

Anti-HIV Agents↗