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D McAvoy

Publications and source records attributed to D McAvoy.

8 recordsLinked to original sources

Circulating neutrophil CD18 receptor expression and ischemic flap neutrophil infiltration in a guinea pig model.

This article demonstrates a correlation between circulating neutrophil CD18 expression, neutrophil infiltration, and varying periods of ischemia induced in guinea pig island skin flaps. Fifty adult female Hartley guinea pigs were equally separated into a control group, a sham group, and ischemic groups of 2, 4, and 10 hours. All, except those in the control group, had single guinea pig island flank skin flaps raised. Systemic neutrophil surface receptor (CD18) expression was analyzed with monoclonal antibodies, and flap skin biopsy specimens were analyzed for neutrophil infiltration. The results show that neutrophil counts and receptor detection increase as flap ischemia increases. However, a trend toward declining receptor expression was observed in the 10-hour ischemic group. In conclusion, systemic neutrophil adhesion receptor upregulation is correlated with cutaneous flap neutrophil infiltration and ischemia-reperfusion injury in a guinea pig model. A trend toward declining receptor expression with advanced ischemia was observed.

Animals↗

In vivo correlation of neutrophil receptor expression, ischemia-reperfusion injury, and selective 5-lipoxygenase inhibition in guinea pigs.

OBJECTIVE: To determine whether selective 5-lipoxygenase (5-LO) inhibition decreases expression of adhesion molecules (beta2 integrins) on systemic neutrophils, decreases neutrophil infiltration in ischemic flap tissue, and improves flap survival. DESIGN: A randomized, controlled study of 91 adult female Hartley guinea pigs divided into 3 survival groups, 4 neutrophil assay groups, 1 sham group, and 1 control group. Ischemia of varying duration and reperfusion was induced in island flank skin flaps. The treated groups received zileuton, a 5-LO inhibitor, orally during flap ischemia. After reperfusion, systemic neutrophil receptor expression, neutrophil infiltration, and flap survival were measured. Surface receptor molecules on neutrophils from whole blood samples obtained via transcardiac puncture were analyzed using monoclonal antibodies and cell-associated fluorescence. Neutrophil infiltration into a distal 1 cm2 of flap tissue was assessed using myeloperoxidase antibodies. Flap survival was determined within 7 days of surgery. RESULTS: Untreated flaps with 10 hours of ischemia underwent total necrosis. Treated 2- and 10-hour ischemic flaps survived intact. A significant main effect of the drug treatment was detected using analysis of variance (P<.001). Neutrophil receptor detection in the untreated groups undergoing 2 and 10 hours of ischemia was significantly increased compared with that in the treated groups with the same ischemia times. Skin neutrophil infiltration was significantly decreased in the treated groups. CONCLUSIONS: Systemic administration of a 5-LO inhibitor is effective in reducing ischemia-reperfusion injury in flap tissue. Our data indicate that there is a significant reduction in neutrophil receptor expression with administration of 5-LO, reducing the priming of systemic neutrophils from circulating cytokines.

Animals↗

Systemic neutrophil intrinsic 5-lipoxygenase activity and CD18 receptor expression linked to reperfusion injury.

OBJECTIVE: To determine if systemic neutrophil intrinsic 5-lipoxygenase (5-LO) inhibition correlates with decreased expression of surface adhesion molecules and attenuation of ischemia-reperfusion (i/r) injury in guinea pig island skin flaps. METHODS: Eighty-one adult female Hartley guinea pigs were divided into one control group, three 2-hour ischemia groups, and four 10-hour ischemia groups. Island dorsal skin flaps were developed (except in the control group), and 2 hours before reperfusion, zileutin (a 5-LO inhibitor) or vehicle was administered orally. Postreperfusion systemic neutrophil receptor expression, neutrophil flap infiltration, and flap survival were measured. Neutrophils from whole blood were analyzed for CD18 containing surface receptor expression using monoclonal antibodies and cell associated fluorescence. Neutrophil infiltration into a distal centimeter squared of flap tissue was assessed using myeloperoxidase antibodies, and flap survival was determined within 7 days postoperatively. RESULTS: Flaps in the treated 2- and 10-hour ischemic groups survived totally intact, while the untreated 10-hour ischemic flaps underwent total necrosis. A significant main effect of the drug was detected using analysis of variance (ANOVA) (P =.0001). Surface receptor detection and neutrophil infiltration were significantly increased in the untreated animals. CONCLUSIONS: Zileuton, a 5-LO inhibitor, reduces adhesion receptor expression on systemic neutrophils and attenuates i/r injury. Systemic neutrophil intrinsic 5-LO activity and CD18 receptor expression are linked to reperfusion injury and may be fundamental events in its pathogenesis.

Analysis of Variance↗

Grain dust contains a tannin-like material which fixes complement.

Grain dust extract has been found to activate complement. We investigated the possibility that this activity was due to tannin by comparing the characteristics of grain dust extract with those of tannic acid. The properties that were studied were the interaction with albumin and immunoglobulin G, the stability to heat, and the adsorption to polyvinylpolypyrrolidone and hide powder. Grain dust extract was found to show similarities with tannic acid which were consistent with the presence of tannin accounting for most of its complement fixing activity.

Complement Fixation Tests↗

Phenol amplifies complement-fixing activity and induces IgG-precipitating activity in grain-dust extract.

The use of phenol as a preservative in extracts of grain dust was found to be associated with an amplification of complement-fixing activity and the appearance of IgG-precipitating activity. Both activities were absorbed by IgG, suggesting that they were due to a single material. Phenol itself neither fixed complement nor formed a precipitate with IgG. 14C-labeled phenol was incorporated into the IgG precipitating material. Both the amplification of complement-fixing activity and the appearance of IgG-precipitating activity in phenol-containing grain-dust extract were dependent on the presence of air and were inhibited by heating the extract before phenol addition. One interpretation of these results is that a component of grain-dust extract, possibly an enzyme, oxidatively modifies phenol to a form that fixes complement and precipitates IgG. The modified material demonstrates properties of a polyphenol (tannin).

Chemical Precipitation↗

Time course of morphometric changes after acute allergic bronchoconstriction in the guinea pig.

Experimental allergic bronchoconstriction was induced in guinea pigs by passive sensitization with a standard dose of homologous antiserum followed by challenge with aerosolized antigen. Lungs were removed from animals at intervals of up to 6 days thereafter, and several parameters of the reaction were assessed morphometrically by comparison with lungs from unsensitized guinea pigs. We determined all changes in volume of the lung tissue resulting from fixation through to the preparation of histologic sections, but no significant differences were observed between the time course subgroups. The size of both large and small airways was assessed by a point-counting technique, as well as by measurement of the percentage of the diameter of the airways contributed by the mean thickness of the muscular layer. Maximal bronchoconstriction was observed morphometrically to correspond with the peak of a response as determined clinically by the use of a strain gauge around the chest. This was followed by a return to normal of the airway size. The number of mast cells and eosinophils around large and small airways, around branches of the pulmonary artery and in random fields of the lung parenchyma was tabulated. The maximal decrease in mast cells was seen in animals which died immediately following challenge, but the numbers were not restored to the control level even in animals which had survived for 6 days. The greatest increase in eosinophil response occurred in lungs obtained 10 min following challenge. This model will be of value in determining the effects at the tissue level of pharmacological inhibitors of this reaction.

Acute Disease↗

Studies into the occurrence of soluble antigen-antibody complexes in disease. VIII. Fractionation of rheumatoid samples containing immune complex-like material.

Fractionation studies were performed of an immune complex-like material measured in rheumatoid synovial fluid using a biological assay based on histamine release from guinea pig lung. This material was eluted from Sepharose 6B in the excluded fraction, from DEAE cellulose predominantly in the third buffer, and from polyacrylamide electrophoresis in a cathodal position. Heterogeneity of the complexes was evident on iso-electric focussing, with one peak of activity at a pH of 4.2--5.6 and the other at pH 6.8--8.6. Purification of the material was limited by a loss of activity which occurred on using three fractionation procedure in sequence. This instability was avoided in the case of Sepharose 6B by adding 0.1% bovine or rabbit albumin to the elution buffer.

Animals↗