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Biomedical subjects

A Coyle

Publications and source records attributed to A Coyle.

17 recordsLinked to original sources

Expression of the Th1 chemokine IFN-gamma-inducible protein 10 in the airway alters mucosal allergic sensitization in mice.

Although the preliminary characterization of chemokines and their receptors has been prolific, comparatively little is known about the role of chemokines in the evolution of immune responses. We speculate that the preferential recruitment of a particular immune cell population has implications for the short- and long-term features of an adaptive response. To test this hypothesis, we employed adenovirus-mediated gene transfer to express the Th1-affiliated, CXC chemokine IFN-gamma-inducible protein (IP) 10 in the airways of mice undergoing a mucosal sensitization regimen known to result in a Th2-polarized allergic response. This resulted in a approximately 60-75% inhibition of eosinophils in the bronchoalveolar lavage (BAL); these inflammatory changes were accompanied by enhanced IFN-gamma, ablated IL-4, and, peculiarly, unaltered IL-5 and eotaxin levels in the BAL. The effect of IP-10 expression was shown to be dependent on IFN-gamma, as there was no statistically significant reduction in BAL eosinophilia in IFN-gamma knockout mice subjected to the IP-10 intervention. Flow cytometric analysis of mononuclear cells in the lung revealed a approximately 60% reduction in the fraction of CD4(+) cells expressing T1/ST2, a putative Th2 marker, and a parallel increase in the proportion expressing intracellular IFN-gamma following IP-10 treatment. The effect of IP-10 expression at the time of initial Ag encounter is persistent, as mice rechallenged with OVA following the resolution of acute inflammation exhibited reduced eosinophilia and IL-4 in the BAL. Collectively, these data illustrate that local expression of the chemokine IP-10 can introduce Th1 phenomena to a Th2-predisposed context and subvert the development of a Th2 response.

Adenoviruses, Human↗

IL-15 and IL-2: a matter of life and death for T cells in vivo.

Interleukin (IL)-2 and IL-15 are redundant in stimulating T-cell proliferation in vitro. Their precise role in vivo in governing T-cell expansion and T-cell homeostasis is less clear. Each may have distinct functions and regulate distinct aspects of T-cell activation. The functional receptors for IL-2 and IL-15 consist of a private alpha-chain, which defines the binding specificity for IL-2 or IL-15, and shared IL-2 receptor beta- and gamma-chains. The gamma-chain is also a critical signaling component of IL-4, IL-7 and IL-9 receptors. Thus, the gamma-chain is called the common gamma or gamma-c. As these receptor subunits can be expressed individually or in various combinations resulting in the formation of receptors with different affinities, distinct signaling capabilities or both, we hypothesized that differential expression of IL-2 and IL-15 receptor subunits on cycling T cells in vivo may direct activated T cells to respond to IL-2 or IL-15, thereby regulating the homeostasis of T-cell response in vivo. By observing in vivo T-cell divisions and expression of IL-2 and IL-15 receptor subunits, we demonstrate that IL-15 is a critical growth factor in initiating T cell divisions in vivo, whereas IL-2 limits continued T-cell expansion via downregulation of the gamma-c expression. Decreased gamma-c expression on cycling T cells reduced sustained Bcl-2 expression and rendered cells susceptible to apoptotic cell death. Our study provides data that IL-2 and IL-15 regulate distinct aspects of primary T-cell expansion in vivo.

Animals↗

Genomic organization and characterization of mouse SAP, the gene that is altered in X-linked lymphoproliferative disease.

X-linked lymphoproliferative (XLP) disease is a fatal immunological disorder that renders the immune system unable to respond effectively to Epstein-Barr virus (EBV) infection. The gene that encodes a protein termed SAP or SH2D1A is either deleted or mutated in XLP patients, resulting in uncontrolled B- and T-cell proliferation upon EBV infection. Here, we report the cloning and characterization of the mouse SAP gene. It is localized on the mouse X chromosome and comprises four exons spanning approximately 25 kb. Its expression appears to be restricted to T lymphocytes. Whereas a high level of SAP expression is observed in Thl cells, only small amounts are detectable in Th2 cells. Moreover, SAP expression is down-regulated upon in vitro activation of T cells, including CD4+, CD8+ single-positive T cells, and Thl and Th2 cells. This study provides valuable information for in-depth genetic and biochemical analysis of the function of SAP in the immune system.

Alternative Splicing↗

What does it mean to be a donor offspring? The identity experiences of adults conceived by donor insemination and the implications for counselling and therapy.

In the absence of research with adult donor offspring, this study begins to bridge that gap by asking individuals about their experiences as donor offspring and considering the implications for psychotherapeutic and counselling practice. Sixteen participants (13 male, three female, age range 26-55 years) recruited through donor insemination support networks in the UK, USA, Canada and Australia, were sent semi-structured questionnaires by E-mail and post. Using identity process theory as a framework for understanding participants' accounts, the data were qualitatively analysed using interpretative phenomenological analysis. Participants consistently reported mistrust within the family, negative distinctiveness, lack of genetic continuity, frustration in being thwarted in the search for their biological fathers and a need to talk to a significant other (i.e. someone who would understand). These experiences could be postulated as being indicative of a struggle to assimilate, accommodate and evaluate information about their new identities as donor offspring. Psychotherapists and counsellors need to be aware of these identity issues if they are to meet the needs of donor offspring within therapeutic practice.

Adult↗

How counselling psychologists view their personal therapy.

A survey of UK chartered counselling psychologists (N = 192) was carried out to investigate how they viewed their personal therapy. Eighty-four respondents completed questionnaires about their reasons and motivations for therapy, as well as its outcome and process. The results indicated that the majority (88%) were in favour of personal therapy as a training requirement. Most respondents rated the outcome and process of their personal therapy as positive, however 27% also reported some negative effects. A factor analysis of various components of personal therapy indicated that counselling psychologists made a distinction between three factors, i.e. learning about therapy itself, issues arising out of training and dealing with personal issues. Analyses of the data suggested that aims and motivation for therapy were related to dealing with personal issues, whereas these were not important for the other factors. Learning about therapy itself was related to the number of sessions: more specifically, those who had more than the mandatory 40 sessions rated contributions of their personal therapy to understanding therapeutic relationships and processes more highly than those who had less. Initial sessions may be used by trainees to explore personal issues, leading to a preoccupation with the self, and learning about therapy per se may only occur once this has been dealt with.

Adult↗

A review of research on the nature and quality of HIV testing services: a proposal for process-based studies.

Considerable research has been conducted on various issues associated with HIV testing. However, rather than conceptualizing HIV testing as a dynamic process which consists of interrelated elements, this body of work has focused on discrete aspects of the HIV testing process. As an example of such research, studies which have examined HIV testing in terms of various behavioural and psychological outcomes are critically reviewed. Their limitations are attributed to their failure to account for all the elements involved in the HIV testing process that-singly and in dynamic combination-could have produced the measured outcomes. It is contended that if research on HIV testing is to be of use in the development and improvement of HIV testing services, it should be able to identify and describe in detail the factors that might lead to various outcomes of testing. This requires an in-depth examination of all aspects of the HIV testing process and their interrelationships from the perspectives of those undergoing testing and those providing testing services. The principal process elements in HIV testing are described; existing research on these topics is critically reviewed; and recommendations are made for future research. The process elements of HIV testing are identified as making a decision to be tested; accessing testing services; test counseling; and waiting for the test result. Of these, most consideration is accorded to the HIV test counselling process. It is contended that research is needed which examines both clients' and counsellors' expectations, experiences of and satisfaction with HIV test counselling. Specific issues that could usefully be addressed by future research include the process of obtaining clients' informed consent for testing; the ways in which test results are conveyed to clients; the strategies used in HIV counselling to help clients avoid or reduce behaviours in the future; partner notification; and which professional groups are best placed to conduct HIV test counselling. Finally, the question of which research methods might be suitable for process-based studies is considered. It is concluded that qualitative methods could be particularly appropriate as they are well-placed to chart in detail the varied aspects of the HIV testing process and their interrelationships.

AIDS Serodiagnosis↗

Blood-flow augmentation of intermittent pneumatic compression systems used for prevention of deep vein thrombosis prior to surgery.

PURPOSE: To compare, using Duplex ultrasonography, different intermittent pneumatic compression (IPC) systems to augment venous blood flow for deep venous thrombosis (DVT) prevention during and after surgery and during periods of immobility. METHODS: This cross-over study randomly assigned 26 young, healthy, adult subjects, without history of DVT, hypertension, diabetes, stroke. vascular or cardiac pathologies, to an order of knee-high, foam, single-pulse IPC device and thigh-high, vinyl, sequential-pulse pneumatic compression systems. Prior to making the flow measurement, the girth of the calf and thigh and length of the leg of each subject were determined. The right leg was used in this evaluation. RESULTS: The average flow augmentation, which is a direct measure of the amount of femoral vein blood flow velocity increase over the base, was 107%+/-49% with the knee-high system, and 77%+/-35% with the thigh-high IPC system (P<0.002). Augmentation was higher for 62% of the subjects with knee-high IPC, and for 23% of the subjects with the thigh-high system. Overall, the blood was actively moving through the vein during the decompression phase. On occasion, the velocity during the decompression phase would fall to zero for short intervals with both systems, indicating complete emptying of the vessel. Variation in limb anatomy did not significantly affect blood-flow augmentation with the knee-high IPC, but augmentation decreased with increase in girth with the thigh-high IPC. CONCLUSIONS: The study indicates that the knee-high, foam, single-pulse IPC device produces a significantly higher venous blood-flow augmentation than the thigh-high, vinyl, sequential-pulse system.

Adult↗

Decision making in HIV testing among a group with low HIV risk.

Relatively little is known about how individuals (apart from gay and bisexual men) decide to have an HIV test and how, once they have presented for testing, they make decisions about proceeding through the testing trajectory. This paper reports on a qualitative study in which 55 mainly heterosexual respondents with low HIV risk were interviewed about their experiences of decision making around HIV testing. Reasons for deciding to be tested centred on a desire for reassurance and the circumstances of the respondents' current relationship. The most common relationship reason focused on a desire to confirm HIV status before beginning sexual relations or engaging in unprotected sex with a partner. Although some respondents recognized that other individuals had influenced their decision to be tested, few said that pre-test counselling had been influential in this respect. Instead, it was said to have promoted feelings of 'ownership' of a decision which had already been taken prior to counselling. The potential effects of HIV testing on HIV risk behaviour were also examined and a non-significant increase in unprotected sex was reported between the month before the test and the month after. The implications of these findings for the provision of HIV testing services are explored.

AIDS Serodiagnosis↗

Strategies for dealing with problems associated with use of services for HIV infection and AIDS out of region: views of providers and users.

OBJECTIVES: To identify reasons why people with HIV infection and AIDS living within the former South West Thames Regional Health Authority use HIV and AIDS services outside the region, and to identify strategies for dealing with the problems associated with such use. DESIGN: Qualitative study consisting of interviews with individual subjects and focus groups. SETTING: Providers of services for patients with HIV infection and AIDS in South West Thames, central London, and Brighton. Users of such services resident in South West Thames. SUBJECTS: Thirty four South West Thames residents with HIV infection and AIDS who use or used services outside the former region; and 70 providers of services within and beyond South West Thames. RESULTS: Principal reasons for use of services out of the region were accessibility (15) and negative appraisals of local services (14). Three main strategies for dealing with the problems of such use were suggested by providers. These entailed introducing users of services outside the region to services in their locality (16); sharing the responsibility for care between providers in specialist centres and in the person's locality (10); and involving the person's general practitioner in their care (12). These strategies were deemed acceptable by 29, 30, and 20 service users respectively. CONCLUSION: The reasons underlying use of services for patients with HIV infection and AIDS outside the region offer suggestions for developing services in areas with a high incidence of such use. The suggestions advanced by service providers offer an acceptable framework for dealing with the problems.

Acquired Immunodeficiency Syndrome↗

A study of psychological well-being among gay men using the GHQ-30.

This study uses the 30-item General Health Questionnaire (GHQ-30) to examine the psychological well-being of 140 gay men from the London area. These men exhibited a level of psychological well-being comparable to that shown by single men from the general population in a study by Cox et al. (1987) and higher than that of divorced/separated and widowed men. This finding suggests that homosexuality per se is not inimical with psychological well-being.

Adult↗

The effect of cephalothin prophylaxis on postoperative ventriculoperitoneal shunt infections.

Postoperative infection is an important complication after insertion of a ventriculoperitoneal (VP) shunt in children with hydrocephalus. A randomized double-blind placebo-controlled study was performed to determine the efficacy of cephalothin in preventing postoperative shunt infection. Sixty-three children who presented for elective VP shunt insertion between January 1982 and December 1985 and who did not have a history of shunt infections were randomly assigned to receive four doses of prophylactic cephalothin, 25 mg/kg (32 patients), or of a multivitamin placebo (31 patients). Postoperative infection developed in 6% of the treatment group, compared with 10% of the placebo group, a difference that was not statistically significant, although a clinical significance may have been masked by the small sample size. A large multicentre trial is needed to determine the efficacy of antibiotic prophylaxis in reducing the incidence of postoperative VP shunt infections.

Bacterial Infections↗

Demonstration of the therapeutic potential of non-anaphylactogenic anti-IgE antibodies in murine models of skin reaction, lung function and inflammation.

BACKGROUND: Allergies and allergic asthma are believed to be mediated by allergen-specific IgE antibodies. We have investigated the therapeutic potential of inhibiting endogenous IgE by a non-anaphylactogenic anti-mouse IgE antibody 1-5 with respect to its effects on antigen-induced skin reaction, lung function changes and lung inflammation in mice. METHODS: Mice were immunized with benzylpenicillinoyl-KLH or ovalbumin, and antigen-mediated skin reaction, bronchoconstriction, bronchopulmonary hyperresponsiveness (BHR) and lung eosinophilic inflammation determined in anti-IgE 1-5-treated versus untreated animals. RESULTS: Application of anti-IgE 1-5 inhibited (by 90%) the serum IgE and, 3-4 days after onset of treatment, blocked the antigen-induced skin reaction. Furthermore, the antibody also inhibited (by 90%) the antigen-induced infiltration of eosinophils into the lung. This latter effect seems to be mediated by blocking the IgE-CD23 interaction and indicates that lung eosinophilic inflammation also depends on IgE. Moreover, when applied to rats passively sensitized with mouse IgE, antibody 1-5 inhibited the antigen-induced bronchoconstriction. A similar effect could be seen in actively immunized mice, where antibody 1-5 was able to inhibit (by 70%) the ovalbumin-induced bronchoconstriction as well as BHR. CONCLUSIONS: In summary, non-anaphylactogenic anti-IgE antibodies can markedly inhibit IgE levels and IgE-mediated allergic reactions. Since bronchoconstriction, BHR and lung eosinophilic inflammation can be suppressed, such antibodies may be attractive principles for the treatment of allergic asthma.

Animals↗