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Biomedical subjects

M Bailey

Publications and source records attributed to M Bailey.

At least 127 records · Page 7Linked to original sources

Activation of T cells from the intestinal lamina propria of the pig.

This study found CD4+ T cells present in leucocyte populations isolated from the lamina propria of the pig to be almost exclusively CD45RC-, consistent with their being highly differentiated by exposure to antigen. Following activation in vitro these cells up-regulated expression of IL-2R with similar kinetics to splenic CD4+ cells. However, while splenic cells progressively secreted IL-2 into cultures during the first 24 h, IL-2 was not detected in supernatants of lamina propria cells after 8 h. Reverse-transcriptase polymerase chain reaction (RT-PCR) confirmed that this reflected a transcriptional difference: IL-2 transcripts were detected in cultures of splenic and lamina propria cells in the first few hours after activation but persisted only in splenic cells. In contrast, IL-4 transcripts were strongly expressed by activated lamina propria cells. Cell-cycle analysis demonstrated that fewer lamina propria CD4+ cells progressed into S-phase than did splenic CD4+ cells (26.0 11.1% and 45.0 11.3% respectively, P=0.011). Our results suggest that CD4+ T cells in these populations are differentiated effector cells whose potential for expansion may be dependent upon local factors. Such cells may be targets for immunoregulation by their local microenvironment.

Animals↗

Genetics of psoriasis: paternal inheritance and a locus on chromosome 6p.

The pathogenesis of psoriasis is not fully understood, but population and twin studies suggest a large heritable component to the etiology. Several large population studies have also suggested a parental sex effect. Since 1994, three main genetic loci (on chromosomes 17q, 4q, and 6p) have been reported in genome scans. With a view to elucidating the genetic basis of psoriasis, we have carried out linkage analysis in a large number of families with well-characterized psoriasis. From a cohort of 1250 probands with psoriasis, 395 individuals (301 affected, 94 unaffected) in 103 families were recruited. Each subject was carefully examined by an experienced dermatologist and stringent diagnostic criteria applied. Genotypes were generated at 11 polymorphic loci on chromosomes 17q, 4q, and 6p and the results were analyzed parametrically and nonparametrically. In the population from which the probands were drawn, there was evidence of a parental sex effect, more probands having an affected father than an affected mother. Genetic anticipation was also apparent and most marked if the disease was inherited from the father. The loci on chromosomes 17 and 4 were not replicated but there was strong evidence for linkage to chromosome 6p (maximum two point LOD score 4.63 at D6S291). The evidence for linkage in sibling pair analysis was greatest when the allele was of paternal origin and was most significant in those families without psoriatic arthritis. These studies confirm the presence of a susceptibility gene on chromosome 6p. The available evidence suggests that a different genetic susceptibility may underlie psoriasis and psoriatic arthritis.

Age of Onset↗

Pharyngeal flap necrosis as a cause of airway obstruction during induction of anesthesia.

Anesthesiologists should approach the airway carefully in the patient with a diagnosis of head and neck carcinoma, particularly if the patient has had previous surgery and reconstruction. Patients with head and neck carcinoma may be difficult intubations due to altered anatomy from the tumor or fibrotic changes because of radiation therapy. Our patient had had pharyngectomy and reconstruction with a pectoralis major skin flap. The patient returned to the operating suite for wide-excision pharyngectomy and had acute airway obstruction after induction of general anesthesia. The pectoralis flap had necrosed, pulling away from the pharyngeal wall and obstructing the patient's glottic opening.

Aged↗

Air pollution in the Latrobe Valley and its impact upon respiratory morbidity.

OBJECTIVE: To assess the relationship between air pollution and respiratory morbidity. DESIGN: An ecological study of the daily hospital admissions abstracted for the 1988 calendar year. Air quality data, including nitrogen dioxide (NO2), sulphur dioxide (SO2), ozone (O3) and particulates, were obtained from the relevant authorities. SETTING: Latrobe Valley, Victoria. SUBJECTS: Hospital admissions for asthma and Chronic Obstructive Airways Disease. (COAD). RESULTS: There were significant associations (r = 0.11 to 0.17) between airborne particles, nitrogen dioxide and respiratory morbidity. There was no significant relationship between any of the pollutants and asthma admissions. However, multi-variate analysis confirmed that NO2 and particulates were associated with admissions for COAD. CONCLUSION: Respiratory morbidity appears to be affected even by the low air pollution levels in the Latrobe Valley.

Air Pollution↗

Biodegradation of metal-EDTA complexes by an enriched microbial population.

A mixed culture utilizing EDTA as the sole carbon source was isolated from a mixed inoculum of water from the River Mersey (United Kingdom) and sludge from an industrial effluent treatment plant. Fourteen component organisms were isolated from the culture, including representatives of the genera Methylobacterium, Variovorax, Enterobacter, Aureobacterium, and Bacillus. The mixed culture biodegraded metal-EDTA complexes slowly; the biodegradability was in the order Fe > Cu > Co > Ni > Cd. By incorporation of inorganic phosphate into the medium as a precipitant ligand, heavy metals were removed in parallel to EDTA degradation. The mixed culture also utilized a number of possible EDTA degradation intermediates as carbon sources.

Biodegradation, Environmental↗

Reported food intolerance and respiratory symptoms in young adults.

The aim of the study was to assess the ability of the European Community Respiratory Health Survey (ECRHS) questionnaire to provide data on the prevalence, type and reported symptoms associated with food intolerance from a group of young adults in Melbourne. Six hundred and sixty nine randomly selected subjects completed the questionnaire with 553 attending the laboratory for skin-prick tests, anthropometry, and ventilatory function tests. A further 207 symptomatic participants completed the questionnaire, with 204 of them attending the laboratory. Seventeen per cent of all respondents reported food intolerance or food allergy. A wide variety of food items was cited as being responsible for food-related illnesses. Those with current asthma did not report food-related illness more frequently than those without asthma. Respondents who reported respiratory symptoms following food ingestion were more likely to be atopic, to have used inhaled respiratory medications in the previous 12 months, reported less exposure to regular passive smoking over the past 12 months and weighed more. These associations between respiratory symptoms and food intolerance require further prospective investigation and verification. The importance of using appropriate dietary methodology in future studies for determining diet-disease relationships was highlighted by this study.

Adult↗

Peptidomimetic inhibitors of the human cytomegalovirus protease.

The development of peptidomimetic inhibitors of the human cytomegalovirus (HCMV) protease showing sub-micromolar potency in an enzymatic assay is described. Selective substitution of the amino acid residues of these inhibitors led to the identification of tripeptide inhibitors showing improvements in inhibitor potency of 27-fold relative to inhibitor 39 based upon the natural tetrapeptide sequence. Small side chains at P1 were well tolerated by this enzyme, a fact consistent with previous observations. The S2 binding pocket of HCMV protease was very permissive, tolerating lipophilic and basic residues. The substitutions tried at P3 indicated that a small increase in inhibitor potency could be realized by the substitution of a tert-leucine residue for valine. Substitutions of the N-terminal capping group did not significantly affect inhibitor potency. Pentafluoroethyl ketones, alpha,alpha-difluoro-beta-keto amides, phosphonates and alpha-keto amides were all effective substitutions for the activated carbonyl component and gave inhibitors which were selective for HCMV protease. A slight increase in potency was observed by lengthening the P1' residue of the alpha-keto amide series of inhibitors. This position also tolerated a variety of groups making this a potential site for future modifications which could modulate the physicochemical properties of these molecules.

Antiviral Agents↗

Wide variation in DNA content among isolates of Trypanosoma brucei ssp.

The DNA contents of 18 Trypanosoma brucei ssp. stocks were compared using flow cytometry, karyotype analysis and quantitation of repetitive DNA by Southern blotting and hybridisation. The DNA contents of Type 1 T. b. gambiense stocks were lower than those of non-gambiense stocks, but both groups showed a wide range of variation in DNA content. Amongst T. b. gambiense stocks. Mabia at the lower end of the range had 14% less DNA than Dal 972 at the top of the range. Similarly, amongst non-gambiense stocks. 117R at the lower end of the range had 14% less DNA than LM55 at the top of the range. The T. b. gambiense stock Mabia had 29% less DNA than non-gambiense stock LM55. The DNA content of Type II T. b. gambiense stocks had minichromosomes albeit fewer than non-gambiense stocks. This result was verified by hybridisation with probes for satellite DNA and a telomere-specific repeat. Hybridisation with the probe for the beta-tubulin genes also revealed an apparent reduction of gene copy number T. b. gambiense relative to non-gambiense stocks. In conclusion, there is a wide range of variation in genome size in T. brucei ssp., with T. b. gambiense stocks at the lower end of the range. The reduction in genome size correlates with loss of repeated genes and non-coding sequences in T. b. gambiense stocks, and is not continued to chromosomes of a particular size.

Animals↗

Effects of molecular crowding on the interaction between DNA and the Escherichia coli regulatory protein TyrR.

Fluorescence quenching has been used to measure quantitatively the effects of sucrose and triethylene glycol on the interaction between the Escherichia coli regulatory protein TyrR and a 30-basepair oligonucleotide containing the strong TyrR box of the TyrR operon. It was observed that the apparent binding constant increased in the presence of co-solutes, the dependence of the logarithm of the apparent binding constant on molar concentration being indistinguishable and essentially linear for both co-solutes. This activation of the TyrR-oligonucleotide interaction is attributed to thermodynamic nonideality arising from molecular crowding, an interpretation which is supported by the reasonable agreement observed between the experimental extent of reaction enhancement and that predicted on the statistical-mechanical basis of excluded volume.

Base Sequence↗

The importance of negative feedback and consequences of actions in the design of processes.

Like many organizations, Continental Rehabilitation Hospital of San Diego designs and communicates templates and targets for desired changes in behaviors and tracks results. It recognizes and celebrates successes and struggles with its failures. A recent case example demonstrates the importance of generating immediate feedback and consequences as a strategy for increasing effectiveness in changing behavioral patterns.

Anti-Anxiety Agents↗

The effects on asthmatics of exposure to a conventional water-based and a volatile organic compound-free paint.

The water-based paints now frequently used for house painting still contain small amounts of volatile organic compounds (VOCs), with the potential to exacerbate symptoms of asthma. Because of these potential problems and environmental concerns, some manufacturers have produced paints with no VOC content. We wished to compare the effects on asthmatics of conventional water-based paint and the new VOC-free paint. Seventeen asthmatics were recruited on the basis of having previously reported exacerbation of symptoms by paint or other odours. Each undertook a standard painting task with identically coloured conventional acrylic and VOC-free paints in a double-blind, crossover study. Respiratory symptoms, lung function, and airway responsiveness were measured at each visit. A significant increase in reported "wheeze" was detected during use of conventional paint (p<0.01), but not with the new paint. There was also a significantly greater increase in reported "breathlessness" whilst using conventional paint than with the new paint (p<0.05). In contrast, lung function measurements showed a small but significant increase during the use of both paints (p<0.05). There was no significant change in airway responsiveness after use of either paint. The new paint appears to be less likely to cause a worsening of respiratory symptoms than conventional acrylic paint, although this difference is not reflected in measurements of lung function or airway responsiveness. Although the benefit conferred in the majority of asthmatics is probably modest, there may be some patients with an increased sensitivity to paint odour, who would derive a useful symptomatic benefit from using the VOC-free paint.

Adult↗

Antigen handling in the gastrointestinal lamina propria.

Enteric infections associated with bacteria, viruses and parasites are a world health problem accounting for at least one billion episodes of diarrhoea and up to 10 million deaths in the Third World each year. The widely held conclusion that responses which are protective in the gastrointestinal tract are best stimulated by mucosal presentation of antigen remains largely unchallenged. Despite this there are but a few effective mucosal vaccines. The mucosal immune system of the gastrointestinal tract is presented with a contrasting array of antigens, ranging from harmless dietary components to highly pathogenic organisms, and has evolved a battery of responses from which an appropriate response may be orchestrated. We have postulated that the microenvironment in which an antigen is processed and presented to the mucosal immune system may profoundly influence the nature of the response and the purpose of this review is discuss a possible role for the lamina propria in this process.

Animals↗

Analysis of voice outcomes in pediatric patients following surgical procedures for laryngotracheal stenosis.

OBJECTIVE: To evaluate long-term (> 2 years) voice function and corresponding anatomical features in children who have undergone augmentation procedures for laryngotracheal stenosis. DESIGN: Follow-up survey assessment. SETTING: Academic pediatric referral center. PATIENTS OR OTHER PARTICIPANTS: The families of 50 patients were contacted by mail, and completed home questionnaires. Of these 50 patients, 33 agreed to participate in a comprehensive hospital-based voice assessment, and 28 of these underwent fiberoptic endoscopy. INTERVENTIONS: Hospital-based evaluation and parental questionnaire. MAIN OUTCOME MEASURES: (1) Perceptual voice assessment from taped samples by using the Vocal Profile Analysis protocol performed by 3 speech and language therapists, (2) fiberoptic laryngeal endoscopy assessment performed by 3 otolaryngologists, and (3) parental assessment of voice by questionnaire. The conditions of the patients were categorized by etiology, the degree of stenosis, coexisting laryngeal lesions, and the type of surgical procedure that was done based on a review of medical records. RESULTS: Eight of 33 patients were judged perceptually by using an amended version of the Vocal Profile Analysis scheme to have "normal" voices. In the remaining 25 patients, abnormalities were demonstrated in the parameters, including harshness (52%), whisper (36%), ventricular band phonation (21%), continuity (27%), mean pitch (27%), and falsetto voice (12%). By using endoscopy, 3 of 25 larynges were judged to be anatomically normal. Abnormalities that were found in the other patients included altered vocal fold mobility (42%), abnormal subglottis (38%), supraglottic vibration (31%), and anterior commissure blunting (31%). Supraglottic vibration corresponded with the perceptual judgment "ventricular band phonation type," and was seen in children with glottic insufficiency. Only 12% of parents indicated by questionnaire that deterioration of voice and dissatisfaction with voice function occurred after surgical procedures were performed. CONCLUSIONS: A substantial proportion of children who have undergone laryngotracheal surgical procedures for stenosis demonstrate chronic voice and endoscopic abnormalities. The effects of these surgical procedures and preexisting laryngeal abnormalities on voice continue to be difficult to establish in the pediatric population. Careful management by speech and language therapists who are familiar with such children is essential for optimal voice function.

Adolescent↗

Measuring cognitive, affective, and behavioral components of homophobic reaction.

Comprehensive, reliable, and valid measurement of prejudicial attitudes and behaviors toward lesbians and gay males has been identified as a priority. A sample of undergraduate (N = 97) and high school students (N = 40) completed three reliable measures of cognitive (Modified Attitudes Toward Homosexuality Scale), affective (Affective Reactions to Homosexuality Scale), and behavioral (Homophobic Behavior of Students Scale) reactions to homosexuals. Undergraduate students' responses confirmed the three-factor structure (homophobic guilt, homophobic anger, delight) of affects in this domain, and supported the concurrent validity of the behavioral measure. Predictive validity of the behavioral scale was demonstrated by findings of the high school study which showed that students subsequently acted in accordance with their responses to this paper-and-pencil test. LISREL confirmatory factor analysis of the overarching model indicated that a tripartite (cognition-affect-behavior) measurement strategy was appropriate. This strategy may be used in future research to provide comprehensive indication of which educational interventions make a difference in improving understanding and acceptance of homosexuality.

Adolescent↗

Antigen presenting cells in the porcine gut.

It has long been known that mucosal responses are most effectively stimulated by local presentation of antigen but the mechanisms whereby the gut immune system is able to distinguish between potential pathogens and harmless dietary antigens are not clear. The gut immune system is capable of mounting both primary and secondary responses to potentially harmful antigens while avoiding the expression of damaging responses to harmless food proteins. Historically, most attention has focused on Peyer's patches and there is evidence of their role in the induction of both primary and secondary responses. Fed antigen can also be detected in the intestinal lamina propria (LP) and it has been shown that murine LP cells can stimulate allogenic mixed lymphocyte responses and present KLH to naive T cells. In contrast to guinea pigs, rodents and humans, pig intestinal epithelial cells do not express MHC Class II molecules, but they are present on a number of other cell types in the subepithelial LP. Amongst these are a significant proportion of non-professional APC including endothelial cells and eosinophils. Phenotypically pig LP T cells are a homogeneous population and the majority of CD4 T cells express the low molecular weight isoform of CD45. This is compatible with the suggestion that they are CD45RO-positive cells. A significant proportion of LP CD4 T cells are CD25 (IL-2R) positive, but following activation they secrete IL-4, with little or no IL-2 production. Based upon these observations, we would conclude that the lamina propria is a unique immunological microenvironment, and suggest that it may be of significance not only in surveillance and the provision of help during rapid responses to recall antigens but also in the down-regulation of local responses to food-derived peptides.

Animals↗

Airway obstruction in children due to plexiform neurofibroma of the larynx.

Plexiform neurofibroma of the larynx is a rare disease. Three cases in children with airway obstruction are presented. After tumour reduction via a lateral pharyngotomy their tracheostomies could be closed. The surgical treatment of plexiform neurofibroma of the superior laryngeal nerve is discussed and conservative, subtotal resection is recommended.

Airway Obstruction↗