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Biomedical subjects

P J Henry

Publications and source records attributed to P J Henry.

At least 19 recordsLinked to original sources

Examining the principles in principled conservatism: the role of responsibility stereotypes as cues for deservingness in racial policy decisions.

Why do educated conservatives oppose affirmative action? Those in the "principled conservatism" camp say opposition is based on principled judgments of fairness about the policies. Others, however, argue that opposition is based on racism. The present article offers an alternative perspective that may reconcile these contradictory points of view. In 2 studies, the authors show 2 major findings: (a) that conservatives oppose affirmative action more for Blacks than for other groups, in this case women, and (b) that the relationship between conservatism and affirmative action attitudes is mediated best by group-based stereotypes that offer deservingness information and not by other potential mediators like old-fashioned racism or the perceived threat that affirmative action poses to oneself. The authors conclude that educated conservatives are indeed principled in their opposition to affirmative action, but those principles are group based not policy based.

Adult↗

The contact hypothesis revisited: status bias in the reduction of implicit prejudice in the United States and Lebanon.

Although 50 years of research demonstrate that friendly intergroup contact reduces intergroup prejudice, the findings are based solely on self-reported, explicit prejudice. In two parallel experiments examining intergroup contact and prejudice-between Whites and Blacks in the United States (Experiment 1) and between Christians and Muslims in Lebanon (Experiment 2)-we examined whether intergroup status differences moderate contact effects on implicit prejudice, as well as explicit prejudice. Both experiments replicated the standard effect of contact on explicit prejudice. They also demonstrated that intergroup contact reduces implicit prejudice among low-status groups. In Experiment 1, the implicit prejudice of Blacks toward Whites (but not Whites toward Blacks) was reduced as a function of friendly contact. In Experiment 2, the implicit prejudice of Muslims toward Christians (but not Christians toward Muslims) was reduced as a function of friendly contact.

Adult↗

Protease-activated receptors (PARs) are partly pro-inflammatory and partly anti-inflammatory: will PAR agonists or antagonists participate in future drug therapies?

Protease-activated receptors (PARs) are characterised by a unique mechanism of activation, which enables them to act as cellular sensors for protease activity. PARs are expressed throughout the cardiovascular, gastrointestinal and pulmonary systems, where they are potential drug targets for the treatment of disease. However, there are currently very few selective PAR antagonists or potent PAR agonists available as effective research tools, and moreover, there is considerable evidence to suggest that PARs can promote both pro-inflammatory and anti-inflammatory responses in a wide range of disease models. These confounding issues have, to date, prevented us from developing a clear understanding of the role of PARs in disease. Nevertheless, this review provides an overview of the distribution and function of PARs in the cardiovascular, gastrointestinal and pulmonary systems, and attempts to evaluate whether PAR agonists or antagonists have a place in future drug therapy.

Animals↗

The origins of symbolic racism.

The theory of symbolic racism places its origins in a blend of anti-Black affect and conservative values, particularly individualism. We clarify that hypothesis, test it directly, and report several findings consistent with it. Study 1 shows that racial prejudice and general political conservatism fall into 2 separate factors, with symbolic racism loading about equally on both. Study 2 found that the anti-Black affect and individualism significantly explain symbolic racism. The best-fitting model both fuses those 2 elements into a single construct (Black individualism) and includes them separately. The effects of Black individualism on racial policy preferences are mostly mediated by symbolic racism. Study 3 shows that Black individualism is distinctively racial, with effects distinctly different from either an analogous gender individualism or race-neutral individualism.

Attitude↗

The impact of inflammation on bronchial neuronal networks.

It is well-recognized that the activities of airway neuronal systems can be modulated by various agonist molecules. This brief review examines some of the evidence that inflammation and some of the mediators relevant to the expression of inflammatory processes can also significantly alter the function and activities of airway nerves. The concept of neuronal plasticity and phenotype switching induced by inflammation is also examined, with particular emphasis on sensory airway nerves.

Animals↗

Role of PGE(2) in protease-activated receptor-1, -2 and -4 mediated relaxation in the mouse isolated trachea.

1. The potential mediator role of the prostanoid PGE(2) in airway smooth muscle relaxations induced by peptidic and proteolytic activators of PAR-1, PAR-2, PAR-3 and PAR-4 was investigated in carbachol-precontracted mouse isolated tracheal segments. 2. The tethered ligand domain sequences of murine PAR-1 (SFFLRN-NH(2)), PAR-2 (SLIGRL-NH(2)) and PAR-4 (GYPGKF-NH(2)), but not PAR-3 (SFNGGP-NH(2)), induced smooth muscle relaxation that was abolished by the non-selective cyclo-oxygenase (COX) inhibitor, indomethacin. The relative order for mean peak relaxation was SLIGRL-NH(2)>GYPGKF-NH(2) approximately amp; SFFLRN-NH(2)>SFNGGP-NH(2). 3. SFFLRN-NH(2), SLIGRL-NH(2) and GYPGKF-NH(2), but not SFNGGP-NH(2), induced significant PGE(2) release that was abolished by indomethacin. Like that for relaxation, the relative order for mean PGE(2) release was SLIGRL-NH(2)>GYPGKF-NH(2)>SFFLRN-NH(2)>SFNGGP-NH(2). 4. In dose-response studies, SLIGRL-NH(2) induced concentration-dependent increases in PGE(2) release (EC(50)=20.4 microM) and smooth muscle relaxation (EC(50)=15.8 microM). 5. The selective COX-2 inhibitor, nimesulide, but not the COX-1 inhibitor valeryl salicylate, significantly attenuated SLIGRL-NH(2)-induced smooth muscle relaxation and PGE(2) release. 6. Exogenously applied PGE(2) induced potent smooth muscle relaxation (EC(50)=60.3 nM) that was inhibited by the mixed DP/EP(1)/EP(2) prostanoid receptor antagonist, AH6809. SLIGRL-NH(2)-induced relaxation was also significantly inhibited by AH6809. 7. In summary, the results of this study strongly suggest that PAR-mediated relaxation in murine tracheal smooth muscle is dependent on the generation of the spasmolytic prostanoid, PGE(2). PAR-stimulated PGE(2) release appears to be generated preferentially by COX-2 rather than COX-1, and induces relaxation via activation of the EP(2) receptor.

Animals↗

Interleukin-13 mediates airways hyperreactivity through the IL-4 receptor-alpha chain and STAT-6 independently of IL-5 and eotaxin.

Interleukin (IL)-13 is a central mediator of the processes underlying the induction of airways hyperreactivity (AHR) in the allergic lung. However, the mechanisms by which IL-13 induces AHR and the associated role of inflammatory infiltrates as effector cells has not been fully elucidated. In this investigation, we show that intratracheal administration of IL-13 induces AHR in the presence and absence of inflammation. The initial AHR response (peak, 6 to 24 h; preinflammatory phase [PIP]) was dissociated from inflammation (eosinophilia) and mucus hypersecretion but was critically regulated by signaling through the IL-4 receptor alpha chain (IL-4Ralpha) and signal transducers and activators of transcription (STAT)-6. The second response (> 24 h, inflammatory phase [IP]) was characterized by an amplified AHR, eosinophil accumulation, and mucus hypersecretion. These features of the IP were not observed in IL-4Ralpha- or STAT-6-deficient mice. To determine the role of eosinophils in the induction of IP AHR and mucus hypersecretion, we administered IL-13 to IL-5-, eotaxin-, and IL-5/eotaxin- deficient mice. IL-13-mediated eosinophil accumulation was significantly attenuated (but not ablated) in IL-5-, eotaxin-, or IL-5/eotaxin-deficient mice. However, IL-13-induced AHR and mucus secretion occurred independently of IL-5 and/or eotaxin. These findings demonstrate that IL-13 can induce AHR independently of these eosinophil regulatory cytokines and mucus hypersecretion. Furthermore, IL-13-induced AHR, eosinophilia, and mucus production are critically dependent on the IL-4Ralpha chain and STAT-6.

Animals↗

Modulation of airway smooth muscle tone by protease activated receptor-1,-2,-3 and -4 in trachea isolated from influenza A virus-infected mice.

Relaxant and contractile effects of the tethered ligand domain sequences of murine PAR-1, PAR-2, PAR-3 and PAR-4, and of the proteases thrombin and trypsin were examined in mouse isolated tracheal preparations. The epithelium- and cyclo-oxygenase-dependence of these effects and the potential modulatory effects of respiratory tract viral infection were also investigated. In carbachol-contracted preparations, trypsin, thrombin, and the tethered ligand domain sequences of murine PAR-1 (SFFLRN-NH(2)), PAR-2 (SLIGRL-NH(2)) and PAR-4 (GYPGKF-NH(2)), but not PAR-3 (SFNGGP-NH(2)), induced transient, relaxant responses that were abolished by the cyclo-oxygenase inhibitor indomethacin. Repeated administration of SFFLRN-NH(2), SLIGRL-NH(2) or GYPGKF-NH(2) (30 microM) was associated with markedly diminished relaxation responses (homologous desensitization), although there was no evidence of cross-desensitization between these peptides. The tethered ligand domain sequences for PAR-1 and PAR-4 induced a rapid, transient contractile response that preceded the relaxant response. Contractions were not inhibited by indomethacin and were not induced by either thrombin or trypsin. Influenza A virus infection did not significantly affect the responses induced by either the proteases or peptides. Furthermore, epithelial disruption caused by mechanical rubbing had no significant effect on responses to these PAR activators in preparations from either virus- or sham-infected mice. In summary, the proteases trypsin and thrombin, and peptide activators of PAR-1, PAR-2 and PAR-4 induced relaxant responses of mouse isolated tracheal smooth muscle preparations, which were mediated by a prostanoid, probably PGE(2). Interestingly, PAR-mediated relaxations were not significantly diminished following acute damage to the epithelium caused by mechanical rubbing and/or the respiratory tract viral pathogen, influenza A. British Journal of Pharmacology (2000) 129, 63 - 70.

Animals↗

Osseointegrated implants as an adjunct to facemask therapy: a case report.

Branemark Implants were placed in the zygomatic buttresses of the maxilla in a 12-year and 1-month-old female patient with a Class III malocclusion caused by maxillary growth retardation secondary to repair of a unilateral cleft lip and palate defect. The implants were left to integrate for 6 months followed by placement of customized abutments that projected into the buccal sulcus. Elastic traction (400 g per side) was applied from a facemask to the implants at 30 degrees to the occlusal plane for 14 hours per day for 8 months (ages 12 years and 10 months to 13 years and 6 months). The maxilla moved downward and forward 4 mm rotating anteriorly as it was displaced. The change in the maxillary occlusal plane resulted in a secondary opening of the mandible. There was a 2 degrees increase in the SN-mandibular plane angle and an increase in nasion to menton distance of 9 mm. Clinically, this resulted in an increase in fullness of the infraorbital region and correction of the pretreatment mandibular prognathism. There was an increase in nasal prominence as the maxilla advanced. This contributed to the increase in facial convexity. The secondary dental change frequently seen in standard facemask therapy was avoided. The displacement of the maxilla was stable 1 year beyond cessation of facemask therapy. The patient's midface profile was improved by age of 13 years and 6 months. Details of the clinical procedure and treatment changes are presented.

Cephalometry↗

Influence of endothelin-1(1-31) on smooth muscle tone and cholinergic nerve-mediated contraction in rat isolated trachea.

Endothelin-1(1-21) (ET-1(1-21)) is a strong candidate as a significant mediator in asthma, in part because of its powerful spasmogenic actions and its ability to enhance cholinergic nerve-mediated contraction in human and animal airway smooth muscle. In the study reported here, we have demonstrated that [125I]ET-1(1-31) binds specifically to BQ-123-sensitive sites (presumably ET(A)-receptors) and to sarafotoxin S6c (S6c)-sensitive sites (presumably ET(B)-receptors) in rat tracheal and pulmonary airways, as well as in lung alveoli. These sites coexist in tracheal airway smooth muscle and in alveolar tissue in approximately equal proportions. ET-1(1-21) and ET-1(1-31) were equipotent and approximately equally active as spasmogens in rat tracheal smooth muscle. Importantly, both peptides were shown to potentiate cholinergic nerve-mediated rat tracheal contraction, although ET-1(1-31) was less active in this regard. These data are consistent with the idea that ET-1(1-31) could play a significant mediator role in obstructive airway diseases such as asthma.

Animals↗

Tooth loss and implant replacement.

Osseointegrated dental implants are increasingly used to replace missing teeth in a variety of situations ranging from the missing single tooth to complete edentulism. The implant possibility must be carefully considered because treatment involves extended time frames, considerable expense and is not without risk. Accordingly, treatment-planning decisions should have an evidence-based strategy with appropriate risk assessment. Implant systems need to be adequately tested before they are released for general use and success rates should be assessed from peer review scientific publication data and not commercial promotional literature. It is the responsibility of the dentist to ensure the patient is educated so an informed decision can be made on difficult treatment alternatives. The clinical decision making process must respect the issues to assure quality of care and reduction of liability for negligent care. Today, the three-unit fixed bridge can no longer be considered as the standard of care for restoration of a single missing tooth. The evidence has accumulated that the single tooth implant supported replacement is more conservative, more cost-effective and more predictable with respect to long-term outcome in uncomplicated cases.

Dental Implantation, Endosseous↗

HeartSaver VAD: a totally implantable ventricular assist device. Results of in vivo studies.

Currently, the most widely utilized ventricular assist devices (VADs) require percutaneous connections and are located either externally (e.g., Thoratec, Abiomed) or intra-abdominally (e.g., Novacor, TCI). These attributes have been implicated in a variety of complications (infection, thromboembolic, gastrointestinal, etc.). To address these concerns, a totally implantable VAD that requires no percutaneous connections and can be implanted in the left hemi-thorax has been developed. The developed device has undergone in vivo evaluation as part of the design and development process. A total of 43 implants in the bovine model, with 5 device versions, have been conducted between July 1992 and February 2000. These studies successfully have demonstrated several important aspects of the developed device, including 1) feasibility of a totally implantable system; 2) capability of the device to support a dysfunctional heart; and 3) ability of the device to provide flows up to 10 L/min in a physiological setting. The studies to date have played a vital role in the design and development process as well as demonstrating the feasibility of a totally implantable intrathoracic VAD. Based on these studies, design optimization was conducted, resulting in the development of the pre-clinical version of the device in preparation for clinical trials.

Animals↗

A protective role for protease-activated receptors in the airways.

The protection of cells in the upper intestine against digestion by pancreatic trypsin depends on the prostanoid prostaglandin E2 (PGE2) and is mediated by protease-activated receptors in the epithelium. As the airway epithelium is morphologically similar and also expresses one of these receptors, PAR2, and is a major source of PGE2, we reasoned that bronchial epithelial PAR2 might also participate in prostanoid-dependent cytoprotection in the airways. Here we show that activation of PAR2, which co-localizes immunohistochemically with trypsin(ogen) in airway epithelium, causes the relaxation of airway preparations from mouse, rat, guinea-pig and humans by the release of a cyclooxygenase product from the epithelium. This physiological protective response in isolated airways also occurred in anaesthetized rats, where activation of PAR2 caused a marked and prolonged inhibition of bronchoconstriction. After desensitization of PAR2, the response to trypsin recovered rapidly by mechanisms dependent on de novo synthesis and trafficking of proteins. Our results indicate that trypsin released from the epithelium can initiate powerful bronchoprotection in the airways by activation of epithelial PAR2.

Animals↗

Detection of endothelin receptors in rat and guinea-pig airway nerves by immunohistochemistry.

We investigated the existence of endothelin (ET) receptor subtypes in airway neurones from the rat and guinea-pig and determined the ability of these receptors to modulate contractile function. Rat tracheal neuron cultures as well as rat and guinea-pig whole mount preparations were labelled with antibodies to the cholinergic nerve marker choline acetyltransferase (ChAT), the neuron specific marker protein gene product 9.5 (PGP 9.5) and to ET(A)and ET(B)receptors. Following incubation with fluorescent secondary antibodies, fluorescence was detected using confocal microscopy with dual emission protocols. Specific fluorescence was detected both in whole mount preparations and neuron cultures, in association with the primary antibodies. Specific fluorescence associated with either ET(A)and ET(B)receptors was colocalized with that for PGP 9.5. Despite the presence of ET(A)and ET(B)receptors on airway nerves, ET-1 failed to significantly alter cholinergic, excitatory or inhibitory non-adrenergic-non-cholinergic nerve-mediated responses in guinea-pig airways. This is in sharp contrast to ET-1-induced potentiation of responses to cholinergic nerve-evoked contraction in rat trachea. Thus, although ET(A)and ET(B)receptors exist in airway cholinergic neurons in whole mount preparations and in primary neuron cultures from rat and guinea-pig trachea, the influence of these receptors on contractile function appears to be species-dependent.

Animals↗

Endothelins and asthma.

In the decade since endothelin-1 (ET-1) and related endogenous peptides were first identified as vascular endothelium-derived spasmogens, with potential pathophysiological roles in vascular diseases, there has been a significant accumulation of evidence pointing to mediator roles in obstructive respiratory diseases such as asthma. Critical pieces of evidence for this concept include the fact that ET-1 is an extremely potent spasmogen in human and animal airway smooth muscle and that it is synthesised in and released from the bronchial epithelium. Importantly, symptomatic asthma involves a marked enhancement of these processes, whereas asthmatics treated with anti-inflammatory glucocorticoids exhibit reductions in these previously elevated indices. Despite this profile, a causal link between ET-1 and asthma has not been definitively established. This review attempts to bring together some of the evidence suggesting the potential mediator roles for ET-1 in this disease.

Animals↗

The role of endothelin in mediating virus-induced changes in endothelinB receptor density in mouse airways.

Emerging evidence supports a mediator role for endothelin (ET)-1 in airway diseases including asthma. Respiratory tract viral infections, are associated with increased levels of ET and altered ET receptor density and function in murine airways. To determine whether these virus-induced effects are causally linked, perhaps involving ET-1-induced ET(B) receptor downregulation, the current study investigated the influence of in vivo administration of CGS 26303, an ET-converting enzyme inhibitor, on virus-induced changes in ET-content and ET(B) receptor density. CGS 26303 (5 mg x kg(-1) x day(-1)) or placebo was administered to mice via osmotic minipumps implanted subcutaneously. Two days after implantation, mice were inoculated with influenza A/PR-8/34 virus or sham-infected, and all measurements were performed on tissue obtained on the fourth day post-inoculation. Viral infection was associated with elevated levels of immunoreactive ET and decreased densities of ET(B) receptors in murine airways. Both of these effects were attenuated in virus-infected mice that had received CGS 26303. Virus-induced increases in wet lung weight were also inhibited by CGS 26303. Importantly, administration of CGS 26303 had no effect on the titres of infectious virus in the lungs and similarly, viral infection had no effect on the plasma levels of free CGS 26303. In summary, CGS 26303 inhibited the virus-induced changes in both immunoreactive endothelin content and endothelinB receptor density. These findings are consistent with the postulate that the elevated epithelial expression of endothelin-1 during respiratory tract viral infection is a contributing factor in the downregulation of endothelinB receptors in airway smooth muscle. Whether inhibitors of endothelin synthesis attenuate virus-induced exacerbations of asthma or airways hyperresponsiveness remains to be established.

Animals↗

Endothelin-1 potentiates cholinergic nerve-mediated contraction in human isolated bronchus.

That endothelin-1(ET-1) plays a mediator role in asthma is consistent with reports of ET-1-induced potentiation of cholinergic nerve-mediated contraction in airways from various animal species. This study examined the effect of ET-1 on cholinergic contractions in human isolated bronchus. Macroscopically nondiseased human bronchial tissue was obtained from 23 patients with respiratory tumours. An electrical field stimulation (EFS) frequency that produced one third of the contraction at 30 Hz (EFS30) was estimated. The effect of ET-1 on these EFS-evoked contractions was assessed. EFS-evoked contractions were frequency-dependent and abolished by either atropine or tetrodotoxin. Thus, EFS-induced contractions were mediated by acetylcholine from cholinergic nerves. ET-1 (3 nM) potentiated EFS-evoked contractions by 10+/-2% EFS30 (p<0.05) without any significant effect on contractions induced by exogenous acetylcholine. Neither the ET(A) receptor-selective antagonist BQ-123 (3 microM) nor the ET(B) receptor-selective antagonist BQ-788 (10 microM) alone significantly altered ET-1-induced potentiation of EFS-evoked contractions. However, in the combined presence of both BQ-123 and BQ-788, ET-1-induced potentiation of EFS-evoked contractions was abolished. Thus, prejunctional endothelinA and endothelinB receptors appear to mediate endothelin-1-induced potentiation of electrical field stimulation-evoked cholinergic contractions in human bronchus. This suggests another potentially important mechanism through which endothelin-1 could increase bronchial tone in asthma.

Adult↗

Endothelin receptor distribution and function in the airways.

1. Within the lung, endothelin (ET)-1 is synthesized and released by airway epithelial and vascular endothelial cells, as well as by inflammatory cells, such as macrophages. Following release, ET-1 can modulate the activities of a wide range of different cell types within the lung through the stimulation of specific endothelin ETA and ETB receptors. The present review focuses on recent advances in our understanding of the distribution and function of endothelin receptors within the airway wall and peripheral lung and, where possible, particular attention is given to studies using human cells, tissues and subjects. 2. The highest densities of endothelin receptors within the lung appear to be associated with airway smooth muscle and the alveolar septae. The relative proportions of ETA and ETB receptors present within these tissues display marked interspecies differences, although ETB receptors predominate at both sites in human lung. 3. The effects induced by ET-1 within the lung include contraction and proliferation of airway smooth muscle, facilitation of cholinergic neurotransmission, mucous gland hypersecretion, microvascular leakage and inflammatory cell influx and activation. There is also evidence that a proportion of ETB receptors in the pulmonary microvasculature act as clearance receptors for endothelin-1. 4. Evidence to date suggests that changes in the endothelin content within the airway wall, conceivably associated with lung pathology, are likely to have profound effects on the function of many cells within the lung.

Animals↗