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Biomedical subjects

P Irving

Publications and source records attributed to P Irving.

18 recordsLinked to original sources
PubMed2001

A genome-wide analysis of immune responses in Drosophila.

Oligonucleotide DNA microarrays were used for a genome-wide analysis of immune-challenged Drosophila infected with Gram-positive or Gram-negative bacteria, or with fungi. Aside from the expression of an established set of immune defense genes, a significant number of previously unseen immune-induced genes were found. Genes of particular interest include corin- and Stubble-like genes, both of which have a type II transmembrane domain; easter- and snake-like genes, which may fulfil the roles of easter and snake in the Toll pathway; and a masquerade-like gene, potentially involved in enzyme regulation. The microarray data has also helped to greatly reduce the number of target genes in large gene groups, such as the proteases, helping to direct the choices for future mutant studies. Many of the up-regulated genes fit into the current conceptual framework of host defense, whereas others, including the substantial number of genes with unknown functions, offer new avenues for research.

Animals↗
PubMed2001

Critical incident stress debriefing following traumatic life experiences.

This study was designed to explore the use of critical incident stress debriefing as a therapeutic intervention following traumatic life events. A case study approach was used to allow the researchers to adopt a more flexible and overtly involved stance. Initial contact took place 24 h following the traumatic life experiences of three women. Critical incident stress debriefing was provided and data were collected and recorded within an ethical framework. Six months following the traumatic life experiences the women were interviewed again to explore their perceptions of the intervention that was provided. The results demonstrated positive outcomes. The women concluded that the debriefing intervention provided a safe forum for them to explore their needs, process their experiences and create constructive narratives. A carefully constructed critical incident stress debriefing intervention was used within the context of its objectives and acknowledged limitations. The study was small and generalizations cannot be made to other individuals who experience similar tragedies. Nevertheless, evidence from previous research coupled with the findings from this study suggests that mental health nurses might benefit from being educated and trained in critical incident stress debriefing. Further research needs to be carried out to explore the use of different models of stress debriefing applied to special circumstances. The goal of such interventions should be to alleviate symptoms and to prevent the development of a full-blown post-traumatic stress disorder.

Crisis Intervention↗
PubMed2000

The use of stimulus-biased assay systems to detect agonist-specific receptor active states: implications for the trafficking of receptor stimulus by agonists.

The quantitative comparison of the relative potency of agonists is a standard method of receptor and agonist classification. If agonist potency ratios do not correspond in two given tissues, this is used as presumptive data to conclude that the receptors in those two tissues are different. This article presents data to show that a single receptor can demonstrate varying agonist potency ratios in different host cells. These data are described in terms of the production of more than one agonist-selective receptor active state and the interaction of these different active states with multiple G proteins in the membrane to produce cellular response. Stable host human embryonic kidney 293 cells with enhanced quantities of the respective Galpha-protein were created. Wild-type and Galpha-subunit enriched cells were then transiently transfected with human calcitonin receptor type 2 (hCTR2). Binding did not detect differences in the G protein-enriched cells versus wild-type cells. In contrast, functional studies did show differences between the host cell lines and Galpha-subunit enriched cell lines. The relative potency of eight calcitonin agonists was measured in studies of calcium fluorescence in transfected cells containing human calcitonin receptor type 2 by comparing pEC(50) (-log molar concentration producing half-maximal response) values. In Galphas-enriched cells, the relative order of potency of the agonists changed. The host-cell dependent differences in potency ratios ranged from 2-fold to more than 46-fold. This finding is not consistent with the idea that all of the agonists produce response in the same manner (i.e., through a common active state of the receptor). These data are consistent with the idea that these different agonists produce arrays of active states that differentially use G proteins. This idea is discussed in terms of the design of stimulus-bias assay systems to detect agonist-selective receptor active states with resulting potential for increased selectivity of agonists.

Binding, Competitive↗
PubMed1999

An audit of admissions of patients with epilepsy to a district general hospital.

The results of an audit of the admission of epilepsy sufferers in a UK District General Hospital are presented. The results strongly suggest that most admissions were due to potentially mutable problems including poor compliance with medication rather than to difficult epilepsy per se. It is suggested that consistent support of these patients, for example by an epilepsy nurse specialist, would have perhaps prevented many of these admissions. Care of these patients in hospital failed to achieve standards set by various guidelines for epilepsy management.

Anticonvulsants↗
PubMed1997

Expression cloning and receptor pharmacology of human calcitonin receptors from MCF-7 cells and their relationship to amylin receptors.

Human breast cell carcinoma MCF-7 cells were found to bind 125I-labeled rat amylin (rAmylin) and the peptide amylin antagonist radioligand 125I-AC512 with high affinity. This high affinity binding possessed characteristics unique to the already defined high affinity binding site for amylin in the rat nucleus accumbens [Mol. Pharmacol. 44:493-497 (1993); J. Pharmacol. Exp. Ther. 270:779-787 (1994); Eur. J. Pharmacol. 262:133-141 (1994)]. To further define this receptor, we report results of expression cloning studies from an MCF-7 cell library. We isolated two variants of a seven-transmembrane receptor that were identical to two previously described human calcitonin receptors (hCTR1 and hCTR2). These receptors were characterized by expression in different surrogate host cell systems. Transient expression of hCTR1 in COS cells yielded membranes that bound 125I-AC512 and 125I-salmon calcitonin with high affinity, but no high affinity binding was observed with 125I-human calcitonin (hCAL) or 125I-rAmylin. Stable expression of hCTR1 in HEK 293 cells produced similar data. In contrast, expression of hCTR2 in COS cells yielded membranes that bound 125I-AC512, 125I-hCAL, and 125I-rAmylin with high affinity. The agonists 125I-hCAL and 125I-rAmylin bound 65% and 1.5%, respectively, of the sites bound by the antagonist radioligand 125I-AC512 in this expression system. This pattern of binding was repeated in HEK 293 cells stably transfected with hCTR2 (125I-hCAL = 24.8% Bmax, 125I-rAmylin = 8% Bmax). In both expression systems, the agonists hCAL and rAmylin were much more potent in displacing their radioligand counterparts than was the antagonist radioligand 125I-AC512. For example, the pKi value for displacement of 125I-AC512 by rAmylin was 7.2 in HEK 293 cells but rose to 9.1 when displacing 125I-rAmylin. Finally, hCTR2 was expressed in baculovirus-infected Ti ni cells. In this system, only specific binding to the antagonist 125I-AC512 and agonist 125I-hCAL was observed; no binding to 125I-rAmylin could be detected. These data are discussed in terms of two working hypotheses. The first is that amylin is a weak agonist for hCTR2 and that this receptor is unrelated to the amylin receptor found in this cell line. The second is that hCTR2 couples to different G proteins for calcitonin and amylin function in different cells. At present, these data cannot be used to disprove conclusively either hypothesis.

Amino Acid Sequence↗
PubMed1996

A mathematical model for analysis of pharmacologically induced changes in the kinetics of cardiac muscle.

A mathematical model of the isometric contraction of cardiac muscle is developed and utilized to characterize the inotropic and lusitropic effects of cardioactive compounds in isolated guinea pig left atria. In contrast to metrics that are based on minima and maxima of an isometric twitch and its derivative function, the entire time course of the twitch is used to quantify the kinetics of the contraction-relaxation cycle. The model relates observed tension to a time-dependent activation function that describes generation of internal force and a coupling function that determines mechanical response to the activation function. The model is structured so that it is suitable for nonlinear curve fitting to observed data. Results obtained using the model for fitting experimental data from tissues treated with different classes of cardioactive compounds agree with more qualitative results presented by other authors. Experiments using the model to fit data over an extended (90 min) time course revealed differences in the kinetic profiles of milrinone and forskolin. Computer simulations that demonstrate the effect of each model parameter on twitch kinetics are presented, and the relationships between the model and other theoretical and empirical models of cardiac muscle are discussed. The mathematical model is useful to enable a more quantitative understanding of the kinetics of cardiac muscle contraction and relaxation and identify compounds that may be selective for inotropic or lusitropic effects.

Animals↗
PubMed1995

Integrated communications perspectives and the practice of total quality management.

Communication is becoming increasingly identified as a significant factor influencing the ability of the NHS to achieve high-quality outcomes. Typically, organizations have tended to conceptualize communication as a process dealing with external relationships. Emphasizes the importance of both internal and external communications, and argues that the NHS now needs to integrate both these dimensions of the communication function. Proposes a strategic framework which suggests how this can be accomplished. Proposes and discusses a communications-centred model of the management process in the light of this approach. This model integrates perspectives which have hitherto dichotomized management as either a science or an art. It also locates communication at the heart of effective management. Finally, suggests the NHS is uniquely well placed to provide data on the impact and costs of total communication programmes.

Communication↗
PubMed1994

An integrated communication strategy for health service managers.

Highlights the importance of communication as a management activity. In particular, examines ways in which internal and external communication strategies can be integrated. To this end, proposes a communication strategy sequence which provides a robust methodology for gathering data and informing decision making regarding communication needs. Details the four key steps in the sequence and provides examples from work done in Northern Ireland. Discusses the principles and practices of data collection and emphasizes the importance of securing the commitment of senior managers. Examines the costs and benefits of introducing comprehensive communication programmes and points out organizational advantages.

Administrative Personnel↗
PubMed1993

Evaluation of urea and albumen as endogenous markers of dilution of equine bronchoalveolar lavage fluid.

The urea and albumen dilution techniques for standardising the variable concentrations of pulmonary epithelial lining fluid (PELF) in bronchoalveolar lavage fluid (BALF) samples were evaluated in horses. Both techniques proved satisfactory and were of equal accuracy. Albumen adjusted BALF cell counts were significantly higher than PELF cell counts. BALF from normal horses contained, on average, 0.4 per cent PELF (range 0.1 to 1.0 per cent), as determined by the urea dilution technique.

Animals↗
PubMed1993

Comparison of cellular and molecular components of bronchoalveolar lavage fluid harvested from different segments of the equine lung.

A comparison was made of the cellular and molecular components of bronchoalveolar lavage fluid (BALF) harvested from the left and right diaphragmatic lobes, the accessory lobe of the right lung and the apical lobe of the left lung, of seven control horses and six horses with symptomatic chronic obstructive pulmonary disease (COPD). Neither control nor symptomatic COPD affected horses showed significant regional differences in BALF recovery volumes, total and differential BALF cell counts, albumen adjusted total and absolute BALF cell counts, total and absolute pulmonary epithelial lining fluid (PELF) cell counts, and BALF albumen and urea concentrations. This suggests that the composition of PELF is uniform throughout the lungs of normal horses and horses with symptomatic COPD and that a single BALF sample is representative of the entire lung in these horses.

Animals↗
PubMed1993

Local and systemic antibody production in horses affected with chronic obstructive pulmonary disease.

An enzyme-linked immunosorbent assay (ELISA) was used to quantify isotype-specific antibody to Micropolyspora faeni and to Aspergillus fumigatus in the sera and bronchoalveolar lavage fluid (BALF) of normal horses, horses with chronic obstructive pulmonary disease (COPD) and horses with other chronic respiratory diseases. Elevated antibody levels were not detected in the sera of affected horses. However, both IgE and IgA antibody to both allergens was significantly elevated in BALF in COPD affected horses sampled both when symptomatic and asymptomatic. Elevated levels were also found in animals that developed a chronic cough after an acute onset with symptoms compatible with a respiratory virus infection. In one animal a ten fold increase in IgE antibody to the two allergens developed after an interval of 7 weeks. These findings are supportive of a central role of local IgE antibody to mould allergens in the immunopathogenesis of COPD, and also suggest that respiratory viral infection may predispose to the development of COPD in some horses.

Animals↗