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Biomedical subjects

A McElroy

Publications and source records attributed to A McElroy.

At least 19 recordsLinked to original sources

Coexpression of CCR5 and IL-2 in human genital but not blood T cells: implications for the ontogeny of the CCR5+ Th1 phenotype.

Memory T cells that home to inflamed tissues typically express the beta-chemokine receptor CCR5 and exhibit a Th1 cytokine profile. The migration of these cells into the genital tract following antigenic exposure has particular relevance to acquisition of HIV-1 infection, because CCR5 functions as the coreceptor for most sexually transmitted HIV-1 strains. We recently established methodology to purify and culture mononuclear cells from the female reproductive tract, and here we analyzed the phenotype, CCR5 expression, and cytokine production of cervicovaginal T cells in up to 16 donors. The proportion of mucosal T cells expressing CCR5 was markedly expanded as compared with peripheral blood (mean 88% vs 24% in 13 donors), but the receptor density on individual CCR5+ T cells was only slightly increased (mean 5837 vs 4191 MEPE (molecules of equivalent PE) units in 6 of 7 donors). Intracellular costaining for IL-2, IFN-gamma, IL-4, and IL-5 revealed a Th1-type pattern in cervical T cells, with significantly higher percentages of IL-2- and IFN-gamma-producing T cells in the mucosa than in blood (mean 67% vs 29%). Coexpression of surface CCR5 with intracellular IL-2 and IFN-gamma was observed only among T cells in the mucosa, but not among those in circulation. Thus, we postulate that T cell homing to the genital mucosa leads to differentiation into the combined CCR5+ Th1 phenotype. Moreover, the predominance of CCR5+ Th1-type T cells in normal cervical mucosa provides targets accessible for the efficient transmission of macrophage-tropic HIV-1 variants in women following sexual exposure.

Antigens, CD↗

The assessment and management of self-harming patients in an accident and emergency department: an action research project.

The Government, in Health of the Nation (DoH, 1992), set targets for health authorities to introduce specific interventions intended to reduce the rates of suicide in the districts for which they are responsible. Those who deliberately harm themselves are an important group for interventions aimed at suicide prevention. Self-harming individuals are known to seek help from a range of care providers, not just those specifically intended to meet their needs. Individuals with problems of self-poisoning and self-injury have placed increasing pressure on general hospital staff involved in their care. There should therefore be adequate services for suicide attempters in every general hospital. Policies and protocols must be introduced and evaluated, to ensure that the self-harmer's experience during crisis is not a catalogue of unhelpful encounters. This paper is an account of an action research project concerned with the assessment and management of self-harming patients in one accident and emergency department. The project aimed to enhance departmental policies and procedures for managing this group of patients. Practical problems can inhibit the introduction of even the most desirable of innovations. Action research provides a way of overcoming these problems whilst doing research at the same time.

Emergency Nursing↗

Dendritic cell-T-cell interactions support coreceptor-independent human immunodeficiency virus type 1 transmission in the human genital tract.

Worldwide, human immunodeficiency virus (HIV) is transmitted predominantly by heterosexual contact. Here, we investigate for the first time, by examining mononuclear cells obtained from cervicovaginal tissue, the mechanisms whereby HIV type 1 (HIV-1) directly targets cells from the human genital tract. In contrast to earlier findings in mucosal models such as human skin, we demonstrate that the majority of T cells and macrophages but none or few dendritic cells (DC) express the HIV-1 coreceptor CCR5 in normal human cervicovaginal mucosa, whereas all three cell types express the coreceptor CXCR4. To understand the role of coreceptor expression on infectivity, mucosal mononuclear cells were infected with various HIV-1 isolates, using either CCR5 or CXCR4. Unstimulated T cells become rapidly, albeit nonproductively, infected with R5- and X4-tropic variants. However, DC and T cells form stable conjugates which permit productive infection by viruses of both coreceptor specificities. These results indicate that HIV-1 can exploit T-cell-DC synergism in the human genital tract to overcome potential coreceptor restrictions on DC and postentry blocks of viral replication in unactivated T cells. Thus, mononuclear cells infiltrating the genital mucosa are permissive for transmission of both R5- and X4-tropic HIV-1 variants, and selection of virus variants does not occur by differential expression of HIV-1 coreceptors on genital mononuclear cells.

Cervix Uteri↗

Developing the nurse teacher's role: the use of multiple focus groups to ensure grassroots involvement.

Strategies for teacher development must ultimately recognize that the only constant is likely to be change, and acknowledge the importance of social interaction as a component of organizational development. The process of development must therefore begin with the implementation of structures which enable an ongoing exploration of the role of the nurse teacher whilst at the same time creating an empowering, collectivist culture. This article describes a project undertaken by a number of nurse teachers to achieve this through the use of focus groups allied to the principles of action research. In total 10 groups were facilitated, involving 52 teachers. The data collected enabled the identification of dominant themes around which to cluster teacher activity and focus role development.

Education, Nursing, Baccalaureate↗

Effect of matrix metalloproteinase inhibitors on tumor growth and spontaneous metastasis.

Four potent, synthetic inhibitors of matrix metalloproteinases (MMPs) were assessed as inhibitors of tumor growth and spontaneous metastasis to the lung. Mat Ly Lu rat prostate tumor, LOX human melanoma and M27 murine Lewis lung tumor were implanted subcutaneously (s.c.) in mice and allowed to grow for 3-12 days. The lungs of the tumor-bearing mice were then removed and implanted s.c. into untreated mice, and the outgrowth of secondary tumors from the implanted lungs measured. The incidence and rate of outgrowth of secondary tumors increased with the length of primary tumor growth, validating these measurements as indices of spontaneous metastasis to the lung. Compounds were tested by s.c. implantation of minipumps which delivered compound throughout the period of primary tumor growth and spontaneous metastasis to the lung at steady-state drug concentrations orders of magnitude greater than the concentrations needed to either inhibit collagenase, gelatinase or stromelysin in vitro. Inhibitor treatment slowed the growth of primary s.c. Mat Ly Lu and LOX tumors by 40-60% but had no significant effect on the growth of primary M27 tumors. Surprisingly, inhibitor treatment had no significant effect on the ability of the lung to generate secondary tumors when reimplanted s.c. in untreated mice. Because of the possible importance of cathepsins B, H and L in tumor growth and metastasis, the irreversible inhibitor E-64 was also infused by s.c. minipump. E-64 had no effect on the growth or spontaneous metastasis of Mat Ly Lu or M27 tumors.

Animals↗

Fix the skill mix.

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Activities of Daily Living↗

Inhibition of cartilage and bone destruction in adjuvant arthritis in the rat by a matrix metalloproteinase inhibitor.

Considerable evidence has associated the expression of matrix metalloproteinases (MMPs) with the degradation of cartilage and bone in chronic conditions such as arthritis. Direct evaluation of MMPs' role in vivo has awaited the development of MMP inhibitors with appropriate pharmacological properties. We have identified butanediamide, N4-hydroxy-2-(2-methylpropyl)-N1-[2-[[2-(morpholinyl)ethyl]-,[S- (R*,S*)] (GI168) as a potent MMP inhibitor with sufficient solubility and stability to permit evaluation in an experimental model of chronic destructive arthritis (adjuvant-induced arthritis) in rats. In this model, pronounced acute and chronic synovial inflammation, distal tibia and metatarsal marrow hyperplasia associated with osteoclasia, severe bone and cartilage destruction, and ectopic new bone growth are well developed by 3 wk after adjuvant injection. Rats were injected with Freund's adjuvant on day 0. GI168 was was administered systemically from days 8 to 21 by osmotic minipumps implanted subcutaneously. GI168 at 6, 12, and 25 mg/kg per d reduced ankle swelling in a dose-related fashion. Radiological and histological ankle joint evaluation on day 22 revealed a profound dose related inhibition of bone and cartilage destruction in treated rats relative to rats receiving vehicle alone. A significant reduction in edema, pannus formation, periosteal new bone growth and the numbers of adherent marrow osteoclasts was also noted. However, no significant decrease in polymorphonuclear and mononuclear leukocyte infiltration of synovium and marrow hematopoietic cellularity was seen. This unique profile of antiarthritic activity indicates that GI168 is osteo- and chondro-protective, and it supports a direct role for MMP in cartilage and bone damage and pannus formation in adjuvant-induced arthritis.

Animals↗

Pick and mix.

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Curriculum↗

Spread the word and reach a wider audience. Writing for publication.

1. The advancement of nursing depends on sharing ideas through submitting articles for publication. 2. Nurses are often reluctant to write up their ideas for publication. 3. A review of the literature is essential in understanding the principles of writing for publication. 4. A system of peer review should be developed in the workplace to encourage and support nurses in the publication process.

Diffusion of Innovation↗

Toward an ecology of women's reproductive health.

Medical ecology has been one of the dominant theoretical strands in medical anthropology since the 1960s. It has come to be identified with a rather narrow range of research issues, concerning such matters as adaptation to climate and infectious disease, and has dealt with small-scale foraging societies. An ecological model has potential for dealing broadly with other health issues, in the case explored here, women's reproductive health, a topic that has frequently been approached from either a cultural or biological standpoint rather than the integrated one advocated here.

Anthropology↗

Boundaries and breakdowns: applying Agar's concept of ethnography to observations in a pediatric clinic.

This paper discusses a methodology for observing and describing interactions between clinicians and patients in an inner-city pediatric clinic serving families of diverse ethnicity. The framework is derived from Michael Agar's concept of ethnography as an interpretive, problem-resolving method. In Agar's model, the participant-observer moves cognitively and analytically from focusing on breakdown (awareness of a problem in understanding) to resolution (applying knowledge structures or schemas to bounded phenomena or strips) and ultimately to coherence. This framework applies not only to describing what the ethnographer does, but also stages in the clinician's efforts to communicate. Awareness of repeated breakdowns allows the ethnographer to document fundamental differences in expectations and premises that affect communication between clinician and patient. Two major types of breakdowns are discussed: those occurring between clinic staff and families, and those occurring between staff and ethnographer. Terminological and analytical modifications of Agar's method are recommended to reflect more accurately the ethnographer's degree of involvement in the communication breakdown (active resolution versus passive resolution). The paper concludes that Agar's model provides a useful structure for developing a systematic ethnographic language that can readily be demonstrated and communicated to clinicians.

Anthropology, Cultural↗

A survey of in vivo benzo[alpha]pyrene metabolism in small benthic marine invertebrates.

A micro-extraction technique was used to examine in vivo polycyclic aromatic hydrocarbon (PAH) metabolism in 10 small invertebrate species exposed to sediments amended with 3H-benzo[alpha]pyrene (BaP). Phyla examined included Mollusca (Hydrobia totteni, Ilyanassa obsoleta, Yoldia limatula, and Gemma gemma), Annelida (Nereis succinea, Pectinaria gouldii, Haploscolopolous sp., and Capitella sp. 1) and Arthropoda (Edotea triloba, and Gammarus mucronatus). Organisms were exposed to BaP-labeled sediments, harvested, and parent BaP separated from all polar metabolites by liquid extraction The percent of BaP-derived radio-activity present as polar metabolites ranged from 96% for N. succinea to 7% for P. gouldii. Wide ranges in metabolic capability were also observed between species in the other two phyla examined. Reverse-phase HPLC analysis of extracts of representative species from each phyla indicated that all these organisms form bay region metabolites, with two species forming the 7,8-dihydrodiol (N. succinea and G. mucronatus). In light of the high variability in metabolic capability observed within each phylum, species-specific information on metabolic ability should be obtained before assessing bioaccumulation, critical body burdens, or trophic transfer of PAHs in invertebrates.

Animals↗