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Biomedical subjects

D G Woodside

Publications and source records attributed to D G Woodside.

At least 37 records · Page 2Linked to original sources

Activated lymphocytes reduce adherence of Aspergillus fumigatus.

Lymphocytes comprise up to 30% of the cells present in human bronchoalveolar lavage fluid and thus could participate in host response to infectious Aspergillus fumigatus conidia. We have examined the possibility that lymphocytes might play a role during early infection by either damaging the fungus or interfering with adherence. When incubated with A. fumigatus conidia for 20 h, highly purified 5-day-old lymphocytes activated with either IL-2 or phytohaemagglutinin, but not untreated lymphocytes, were consistently able to reduce residual fungal biomass as estimated by a metabolic assay. T lymphocytes, but not NK cells, appeared to be responsible for this activity. Lymphocytes bound both A. fumigatus conidia and hyphae, and the antifungal activity of the lymphocytes required direct lymphocyte fungus contact. In a separate set of experiments using release of 51Cr from 51Cr-loaded fungi as an estimate of fungal damage, lymphocyte-induced loss of fungal biomass was found to be due to loss of fungal adherence rather than to direct fungal damage. The detached hyphae were also found to be metabolically intact and to have normal morphology by electron microscopy. These data demonstrate that IL-2- and phytohaemagglutinin-activated lymphocytes exhibit a contact-dependent ability to reduce adherence of germinating conidia of A. fumigatus to a surface.

Aspergillus fumigatus↗

Regulation of human T lymphocyte coactivation with an alpha4 integrin antagonist peptide.

The cyclic hexapeptide CWLDVC (TBC 772) is an antagonist of alpha4 integrins and a potent inhibitor of lymphocyte interactions with fibronectin, vascular cell adhesion molecule-1, and muscosal vascular addressin cell adhesion molecule-1 (MAdCAM-1). As such, peptide TBC 772 effectively inhibits the activation of freshly isolated human T lymphocytes stimulated with purified vascular cell adhesion molecule-1 coimmobilized with anti-CD3 mAb. The influence of peptide binding on distinct sites of the alpha4beta1 complex was determined by flow cytometry and cellular adhesion assays employing a panel of mAbs. Binding of the alpha4-specific mAb L25 and the beta1-specific mAb 33B6 was not altered by the peptide; however, binding of mAb 19H8, which is specific for a combinatorial epitope of alpha4beta1, was dramatically inhibited. Treatment of lymphocytes with the peptide caused an increase in a ligand-induced epitope on beta1 integrin defined by mAb 15/7. In T cell activation studies using coimmobilized anti-CD3 mAb and the anti-integrin mAbs, the peptide had broader inhibitory activity, suppressing costimulation induced by all the integrin mAbs. The peptide was not generally toxic and was integrin selective in its suppressive activity, as coactivation by ligation of CD3 in conjunction with CD28 or CD26 was not affected. These results suggest that the antagonist peptide CWLDVC can effectively neutralize integrin coactivation systems by a mechanism independent of competitive binding.

Antibodies, Monoclonal↗

The action of three types of functional appliances on the activity of the masticatory muscles.

Three commonly used functional appliances; namely, the Herbst, Frankel, and a simulation of the Clark twin block appliances were used to test the lateral pterygoid muscle hypothesis. This hypothesis states that postural and functional activity of the superior and inferior heads of the lateral pterygoid muscle increases after the insertion of a functional appliance. This increased activity, especially in the superior head of the lateral pterygoid muscle then acts to stimulate increased condylar growth. The electromyographic (EMG) activity of the masseter, digastric, superior, and inferior heads of the lateral pterygoid muscles was monitored with chronically inserted EMG electrodes, in nonhuman primates, to determine whether functional appliances actually produce a change in functional activity of these muscles. The involuntary swallow was used to represent functional activity. Thus swallow-related EMG activity levels were monitored longitudinally and compared before and after the insertion of each appliance type. The insertion of these three appliances was associated with a decrease in functional EMG activity of the four muscles. This decrease was statistically significant in all muscles 3 and 6 weeks after appliance insertion. This is consistent with our previous findings that functional appliances are associated with a decrease in the postural activity of the above muscles in nonhuman primates. In view of the fact that the animals showed large skeletal changes in the temporomandibular facial area, this study could not support the lateral pterygoid muscle hypothesis.

Analysis of Variance↗

Alpha 4 beta 1 (CD49d/CD29) integrin costimulation of human T cells enhances transcription factor and cytokine induction in the absence of altered sensitivity to anti-CD3 stimulation.

The integrin alpha 4 beta 1 can provide a costimulus to induce IL-2 secretion and IL-2R expression leading to enhanced proliferation of purified, peripheral blood T cells. Similar to expression of IL-2, we demonstrated that recombinant vascular-cell adhesion molecule-1, when co-immobilized with anti-CD3 mAb, significantly enhanced the induction of transcription factors NF-AT, AP-1, and NF-kappa B as determined by electromobility shift assays. alpha 4 beta 1 ligation alone had no effect on transcription factor binding. The requirements for induction of transcription factors reflected the requirements for the secretion of multiple cytokines, including IL-2, TNF-alpha, IFN-gamma, and granulocyte macrophage-CSF. In contrast to freshly isolated T cells, in vitro-cultured T cells did not require costimulation for cytokine secretion in response to anti-CD3 alone. Comparison of the dose response to anti-CD3 stimulation demonstrated that half-maximal induction of IL-2 was achieved using the same dose of anti-CD3 for both freshly isolated and cultured T cells. Furthermore, the dose of OKT3 required to achieve half-maximal activation was the same using PMA or different concentrations of alpha 4 beta 1 ligands. Therefore, costimulation by alpha 4 beta 1 ligands was not due to stabilization of the interaction of the cells with its substrate. We conclude, rather, that alpha 4 beta 1 in freshly isolated T cells delivers a distinct signal that synergizes early with signals initiated by TCR/CD3 ligation to induce DNA binding of multiple transcription factors required for cytokine gene induction.

CD3 Complex↗

Specific inhibition of T lymphocyte coactivation by triggering integrin beta 1 reveals convergence of beta 1, beta 2, and beta 7 signaling pathways.

T cell coactivation is a dynamic process subject to integrin-dependent positive and negative regulation. Costimulation of human peripheral blood T cells by CD3 mAb OKT3 in conjunction with anti-alpha 4 has been shown to be down-regulated by the anti-beta 1.1 epitope-specific mAb 18D3. As expected, maximal costimulation induced by alpha 4-specific mAb L25 was inhibited (70%) by the addition of soluble mAb 18D3. Surprisingly, soluble mAb 18D3 inhibited maximal proliferation induced by the costimulatory alpha 4 beta 7-specific mAb ACT-1 by 40%, thus demonstrating that one integrin subfamily can regulate the activity of another. To determine whether mAb 18D3 could regulate more than alpha 4-associated integrin-mediated costimulation, non-alpha 4 integrins were tested. mAb 18D3 inhibited maximal proliferation induced by alpha 4-specific mAb 3D6, and an alpha 4-specific mAb 16. This clearly demonstrates that a variety of integrin costimulatory molecules (of the beta 1, beta 2, and beta 7 subfamilies) can be regulated negatively by mAb 18D3. To analyze the specificity of this negative regulation, other cell surface costimulatory molecules were tested for susceptibility to mAb 18D3. Although Abs specific for CD4, CD26, CD28, CD44, CD45RA, or CD45RO were sufficient to activate T cells when co-immobilized with anti-CD3 mAb, all were refractory to the inhibitory effects of mAb 18D3. Inhibition of T cell activation directly correlated with diminished IL-2 production. This suggests that mAb 18D3 selectively regulates integrin-dependent T cell activation by delivering a negative effect at some common point utilized by various integrin subfamilies.

Antibodies, Monoclonal↗

A radiographic comparison of apical root resorption after orthodontic treatment with the edgewise and Speed appliances.

Apical root resorption is a serious iatrogenic problem sometimes associated with orthodontic treatment. The Speed appliance (Strite Industries, Ltd., Ontario, Canada) provides a continuous rotatory and torque action through its spring clip mechanism, in contrast with the edgewise appliance that may provide an interrupted force. The effect of continuous action on root resorption compared with the interrupted action of the edgewise system has not been investigated previously. The purpose of the present investigation is to test the null hypothesis that there is no difference in the apical root resorption seen after orthodontic treatment with the edgewise straight wire and the Speed appliance systems. Pretreatment and posttreatment periapical radiographs of 63 patients, (30 treated with the Speed 0.018 bracket and 33 with the 0.018 edgewise bracket) were studied. The long cone paralleling technique was used for all the radiographs. Any image distortion between the pretreatment and posttreatment radiograph was calculated and compensated for by using the crown length measurements, on the assumption that the crown length remains unaltered during the treatment period. Quantitative measurements of crown and root lengths for the maxillary and the mandibular central and lateral incisors were compared. Means and standard deviations for the percentage root resorption per tooth group were calculated. A three-factor analysis for variance (ANOVA test) was performed to determine whether there was an appliance, treatment, or gender effect on the amount of root resorption seen after treatment. No statistically significant difference in root resorption between the two appliance systems was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Variation in maxillary and mandibular molar and incisor vertical dimension in 12-year-old subjects with excess, normal, and short lower anterior face height.

Maxillary and mandibular molar and incisor vertical dimensions were evaluated in subjects who had excessive, normal, and short lower anterior face height in relation to upper face height. Sexual dimorphism was also investigated. The dentoalveolar heights were compared between Class I and Class II, dental and skeletal malocclusions. The sample was drawn from the Burlington Growth Centre sample and consisted of 188 male and 156 female subjects at age 12 years, for whom lateral head films were available. This sample was classified into excessive, normal, and short lower anterior face height, using the ratio upper anterior face height/lower anterior face height (UAFH/LAFH). The results showed that the dentoalveolar heights are significantly different between faces with excessive, normal, and short lower anterior face heights, except for the lower posterior dental height, which showed no difference between short and normal lower anterior face height subjects. All dentoalveolar heights are larger for male subjects except for the upper posterior dental height. Dentoalveolar heights are similar between Class I and Class II dental and skeletal malocclusions. The upper teeth present a higher correlation to the UAFH/LAFH ratio than the lower teeth. Stepwise regression analysis shows that 22% of the variation in the ratio is explained by the maxillary and mandibular molars and 41% is explained by the maxillary and mandibular incisors.

Cephalometry↗

Normalization of incisor position after adenoidectomy.

Changes in incisor inclination and position in both jaws of children during the first 5 years after adenoidectomy were studied. The main change is a significant increased labial inclination of the incisors for the adenoidectomy groups. All variables that measure the labiolingual position of the mandibular incisors confirm a significant labial incisor positioning for both sexes. Stepwise regression analysis shows that 41% to 44% of the incisor proclination after adenoidectomy is accounted for by two regressors--sex (female) and increase in the sagittal size of the nasopharynx. The study supports the hypothesis that a changed mode of breathing after adenoidectomy is associated with significant labial positioning of the incisor teeth.

Adenoidectomy↗

Mandibular and maxillary growth after changed mode of breathing.

The amount of maxillary and mandibular growth and the direction of maxillary growth were studied in 38 children during the 5 years after adenoidectomy for correction of severe nasopharyngeal obstruction. The amount of mandibular growth measured between successive gnathion points on superimposed radiographs was significantly greater in the group who had an adenoidectomy than in the matched controls. In the boys the difference was 3.8 mm (p less than 0.001), and in the girls the difference was 2.5 mm (p less than 0.01). The boys also showed a tendency toward greater growth in the maxilla as measured between successive subnasal points (1.2 mm, p less than 0.05). We detected no difference in the direction of maxillary growth between who had undergone adenoidectomy and the controls.

Adenoidectomy↗

Relationship between mandibular incisor crowding and nasal mucosal swelling.

In this study, cephalometric and dental cast variables relating to 30 male and 20 female children, 8 to 13 years old with chronic nasal mucosal swelling, were compared with those relating to age- and sex-method controls. These controls were orthodontically untreated subjects with no histories of airway obstruction. The children with chronic nasal mucosal swelling had been referred because of chronic difficulties with nasal breathing to the Department of Otolaryngology Airflow Laboratory at the Hospital for Sick Children in Toronto. Previously active posterior rhinomanometry with a head-out volume displacement plethysmograph had been used to measure nasal resistance in 1000 consecutive subjects. Participants in the study reported here were selected from subjects whose nasal resistance fell markedly following administration of a decongestant spray. The subjects selected were found to have significantly (p less than 0.001) more mandibular incisor crowding, significantly (p less than 0.01) smaller mandibular arch widths than the controls, and significantly (p less than 0.001) smaller maxillary arch widths than the controls. The male subjects had significantly (p less than 0.01) smaller mandibular arch widths than the male controls.

Adolescent↗

Effect of functional appliances on jaw muscle activity.

The electromyographic (EMG) activity of masticatory muscles was monitored longitudinally with chronically implanted EMG electrodes to determine whether functional appliances produce a change in postural EMG activity of the muscles. Preappliance and postappliance EMG levels in four experimentals that had been fitted with functional appliances were compared against the background of EMG levels in controls without appliances. The insertion of two types of functional appliance to induce mandibular protrusion was associated with a decrease in postural EMG activity of the superior and inferior heads of the lateral pterygoid, superficial masseter, and anterior digastric muscles; the decrease in the first three muscles was statistically significant. This decreased postural EMG activity persisted for approximately 6 weeks, with a gradual return toward preappliance levels during a subsequent 6-week period of observation. Progressive mandibular advancement of 1.5 to 2 mm every 10 to 15 days did not prevent the decrease in postural EMG activity.

Activator Appliances↗

Panel assessments of the facial frontal view as related to mandibular growth direction.

This paper describes study No. 6 in a series dealing with mandibular growth direction (Lundström and Woodside, 1980). Study No. 5. (Lundström, Woodside and Popovich 1987) investigated facial harmony and disharmony of the facial profile. The present paper describes a study of the frontal views of the same children as paper No. 5. A mixed panel of 17 individuals (four categories of three, four and six people in each) made an aesthetic evaluation of the frontal facial view of 64 subjects (32 of each sex) from the Burlington serial experimental group. The sample consisted of equal numbers of individuals who displayed vertical, average or horizontal mandibular growth between the ages 6-20 years. We calculated correlations between the four assessor groups and found these to be acceptable. On average the panel found no change in frontal appearance between 12 and 18 years because of the balance between individuals improving and deteriorating. Our earlier work showed systematic differences in profile view between those with vertical growth on the one hand and average o horizontal on the other. The vertical cases were more disharmonious than the other categories. Corresponding findings were made also in the frontal view. Mean overall evaluations by all assessors showed a positive correlation between profile and front view assessments.

Adolescent↗

The effect of rapid maxillary expansion on nasal airway resistance.

The purpose of this investigation was to provide quantitative data describing the effects of rapid palatal expansion on nasal airway resistance. Rapid palatal expansion is an orthodontic procedure which is commonly used to widen the maxilla to correct maxillary narrowing resulting in the orthodontic abnormality of crossbite and to provide more space for alignment of crowded teeth. Recordings of nasal airway resistance were taken prior to expansion, immediately after expansion (approximately one month), after a retention period of approximately 4 months and approximately one year after initiation of treatment. Findings indicate an average reduction in nasal airway resistance of 48.7 per cent which was statistically significant at the 0.005 level. The reduction also appeared stable throughout the post treatment observation period (maximum one year) as each series of readings was statistically significantly lower than the initial reading, but not significantly different from each other. Reduction of nasal airway resistance was highly correlated to the initial nasal resistance level prior to rapid maxillary expansion. Those individuals with the greater initial resistance tended to have greater reductions in airway resistance following the expansion.

Adolescent↗

The influence of functional appliance therapy on glenoid fossa remodeling.

This study investigates the remodeling changes in the condyle and glenoid fossa following a period of progressively activated and continuously maintained mandibular advancement using the Herbst appliance. Progressive mandibular advancement was achieved by adding stops to the telescopic arms of the appliance, with the total activation reaching 7.0 to 10.0 mm, dependent upon the length of the treatment phase. This mandibular advancement produced extensive remodeling and anterior relocation of the glenoid fossa, which contributed to anterior mandibular positioning and altered jaw relationships.

Activator Appliances↗

Mandibular growth direction following adenoidectomy.

The purpose of this article is to test the hypothesis that the establishment of nasal respiration in children with severe nasopharyngeal obstruction can be eliminated as a factor in determining mandibular growth direction. The article describes the changes in mandibular growth direction (MGD) in a 5-year period after adenoidectomies and the establishment of nasal breathing in a population of Swedish children. Measurements of mandibular growth directions were obtained from serial cephalometric radiographs after adenoidectomies in 38 Swedish children aged 7 to 12 years with previous nasopharyngeal obstructions. These were compared with the growth directions in a control sample of 37 Swedish children with clear airways and matched for age and sex. The adenoidectomy sample initially showed significantly longer lower face heights, steeper mandibular plane angles, and more retrognathic mandibles than the matched controls. Analysis showed that during the 5 years after adenoidectomies, the girls had a more horizontal MGD (P less than 0.02) than did the female controls. A corresponding but not significant trend was found for the boys. The individual growth directions that were obtained following adenoidectomies were more variable than those found in the controls.

Adenoidectomy↗