No description available.

No description available.

Thesis (M.P.H.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 96-110).

No description available.

The major objective of this project was to examine the potential for mediators of IgE-mediated allergic reactions to alter neural activity. The project was divided into three parts. In Part I, the ability of endogenously released chemical mediators to alter neural activity in vitro was assessed by measuring isometric contractile responses to electrical field stimulation (EFS) (2-128 Hz, 20 V, 0.5 msec. duration) of sensitized rabbit bronchi before and after exposure to the antigen horseradish peroxidase (HRP). Antigen enhanced bronchial responses to EFS with low frequencies: mean log (± S.E.) frequency which produced 20% of maximum response decreased from 1.04 (± 0.05) to 0.90 (± 0.07) Hz (p < 0.05). Responses of unsensitized bronchi were not enhanced by antigen. Chlorpheniramine, an H₁ antagonist, abolished the antigen effect. Antigen did not enhance the responses to exogenous acetylcholine. Hence, the antigen is apparently modulating neural activity and not smooth muscle per se. In Part II, the capacity for histamine to modulate vagally-induced bronchoconstriction in anesthetized, vagotomized, mechanically-ventilated rabbits was examined in vivo. Changes in pulmonary resistance induced by electrically stimulating the cut ends of the vagi (2-32 Hz, 20 V, 0.5 msec. duration) were assessed before and 10 minutes after histamine aerosolization (10 breaths of 10 mg/ml). Histamine inhalation potentiated vagally-induced bronchoconstriction at low frequencies: mean log (± S.E.) frequency producing a 20% change in pulmonary resistance decreased from 0.88 (± 0.09) to 0.56 (± 0.15) (p < 0.05). Chlorpheniramine abolished this effect. In Part III, the dependence on IgE antibodies of the in vitro modulation of neurally-induced contraction of sensitized bronchi was investigated. Rabbits were passively immunized with fractions enriched with HRP-specific IgE, IgG, or IgM antibodies. After 72 hours, rabbits were sacrificed and the responses of bronchi to EFS were assessed before and after antigen challenge. Antigen enhanced the responses to EFS only of bronchi passively sensitized with IgE. Therefore, antigen enhancement of neural activity was dependent on IgE. These studies demonstrate that the interaction between antigen and IgE antibodies can induce the release of chemical mediators which can alter neural activity.

No description available.

Submitted in fulfillment of the requirements for the degree of Master of Technology: Health Sciences, Durban University of Technology, Durban, South Africa, 2013. / Several genes are associated with an increased susceptibility to respiratory diseases, including asthma, which may be exacerbated by ambient air pollution. These genes include the Tumour Necrosis Factor alpha (TNFα) gene and the Cluster of Differentiation 14 (CD14) gene A total of 104 schoolchildren from seven primary schools in a heavily industrialized region of south Durban participated in the study. For the purpose of this study, DNA was extracted from whole blood using the GENTRA Puregene kit. Genotyping for the TNF-308α G/A polymorphism was conducted using restriction fragment length polymorphism (RFLP) polymerase chain reaction (PCR). The CD14 (-159) C/T genotype was determined using real time PCR and Taqman probes (Applied Biosystems). Multiple logistic models and Pearson’s chi-squared tests were used to evaluate the association between any asthma, BHR, atopy, persistent asthma and genotype. Covariate-adjusted generalised estimating equations (Martin et al.) with lags of 1-5 days were used to evaluate genotype effect modification of exposure-response. The TNF-308α variant A allele was quite common in the population, it was detected in more than forty percent of the population and with an allelic frequency of 0.24. Similarly almost 38% of the population carried the variant CD14 (-159) T allele, with an allelic frequency of 0.24. TNF-308α G/A and CD14 (-159) C/T polymorphisms were not associated significantly with asthma, and its related respiratory phenotypes. In addition there was no association detected between any of the gene polymorphisms and the levels of their respective cytokine proteins. Increased TNFα levels were associated with persistent asthma. On the other hand lower sCD14 levels were associated with atopy in children. There was a significant relationship between TNF- α levels and acute asthma (p=0.03) and sCD14 levels and atopy (p=0.04) GEE models showed that the TNF- 308-α A allele carriers had a greater deterioration of lung function post pollution exposure to SO2 (intraday variability FEV1 readings lag 2) β= 2.62, CI (0.51, 4.71) p= 0.02 and p (interaction=0.03). There was a statistically significant gene environment interaction with NO in individuals who were carriers of the TNF- A allele (Nadir of PF readings lag 2: β= -12.3, CI (-22.09, -2.51), p=0.01 p (interaction) =0.03.and 5 day average β= - 42.83, CI (-70.11,-15.55), p≤0.005 and p (interaction) =0.01). With analysis of the CD14 gene polymorphism gene environment interaction, adverse effects of SO2 were limited to individuals carrying the C allele of this polymorphism, β= - 1.50, CI (-0.36, 3.37), p=0.01, p (interaction) =0.01. Carriers of the T allele seemed to have a protective effect with NO2 and NO exposure. Intraday variability of FEV1 improved 5 days post exposure to NO2 β= -4.02, CI (-6.52,- 1.53), p=0, p (interact) =0.05. There was also improvement five days post exposure to NO β= -9.42, CI (-12.45, -6.03), p= p≤0.005, p (interact) ≤0.005 There was no association of co-inheritance of the 2 gene polymorphisms, CD14 (-159) C/T and TNF-308α G/A, and protein expression or respiratory phenotype. The GEE model results were consistent with modification of air pollutant-pulmonary function relationships by proinflammatory cytokine associated genotypes. Results indicate that genetic susceptibility combined with exposure to pollutants causes adverse respiratory effects. This study supports the importance of further investigation on these and other genotype variants involved in inflammation and respiratory linked phenotypes in larger cohorts. / M

published_or_final_version / Community Medicine / Master / Master of Public Health

Thesis (Ph.D.)--Australian National University, 2004.

Thesis (MSc) -- Stellenbosch University, 1995. / ENGLISH ABSTRACT: The aim of this study was to investigate the influence of the allergic reaction on the respiratory system. The influence of parasite infestation (with specific reference to the roundworm, Ascaris lumbricoides) on the normal functioning of the respiratory system was also investigated. Firstly a pilot study was done to determine the normal immunoglobulin E (IgE) levels of coloured newborns in the Western Cape. The cord blood IgE values of a group of coloured newborns were determined by using the RIA technique. Although a mean value was reached, it is important for more controlled studies, that would take into account a variety of factors, to be done before determining separate reference values for this population. The levels of one of the most important effector cells in the allergic reaction, namely eosinphils, were determined in a group of asthma patients by using the counting chamber method. In all the cases the eosinophil levels were elevated The influence of Ascaris lumbricoides on the respiratory system was investigated from two different points of view, namely the possible allergic reactions it could induce in the host and secondly by determing the influence of this parasite on one of the parametres of the respiratory system, namely the peak expiratory flow (PEF) values. In the first case the presence of specific Ascaris allergens in a group of asthma patients was determined by using the RAST technique. The incidence of these specific allergens was however not high. Secondly the PEF values of two groups (the one group was infested with the roundworm and the other not) were compared. Wet stool mounts were investigated under a light microscope to identy parasite ova. There was however no significant difference in PEF values between these two groups. This study underlines the complex interaction between parasites and the respiratory system. Further studies in this regard are needed in order to fully understand the nature of this interaction. / AFRIKAANSE OPSOMMING: Die doel van hierdie studie was om ondersoek in te stel na die invloed wat die allergiese reaksie uitoefen op die respiratoriese sisteem. Daar is verder ook aandag gegee aan die uitwerking van parasiet infestasies (met spesifieke verwysing na die rondewurm, Ascaris lumbricoides) op die normale funksionering van die respiratoriese sisteem. 'n Loodsstudie is eerstens uitgevoer ten einde normale immunoglobulien E (IgE) vlakke vir Kleurling pasgeborenes te bepaal. lgE bepalings is gedoen op die nawelstring bloed van 'n groep Kleurling babas in die Wes-Kaap. Die RIA tegniek is vir hierdie doel gebruik. Hoewel 'n gemiddelde waarde verkry is, is dit egter noodsaaklik dat meer gekontrolleerde studies wat 'n wye verskeidenheid van faktore in ag neem, uitgevoer sal moet word alvorens aparte verwysingswaardes vir hierdie bevolkingsgroep saamgestel kan word. Die voorkoms van een van die belangrikste effektor selle in die allergiese reaksie, naamlik eosinofiele, is bepaal in die bloed van 'n groep asma pasiente. Die eosinofiele is getel deur gebruik te maak van die telkamer metode. In al die gevalle was die eosinofiel vlakke verhoog. Die invloed van Ascaris lumbricoides op die respiratoriese sisteem is vanuit twee oogpunte ondersoek, naamlik die uitlokking van 'n allergiese respons in ~ie gasheer en die invloed van hierdie parasiet op een van die parameters van longfunksie, naamlik "peak expiratory flow" (PEF) vlakke. In die eerste geval is die mate van teenwoordigheid van Ascaris allergene in 'n groep asma pasiente bepaal deur gebruik te maak van die RAST tegniek. Die insidensie van allergie teen hierdie allergene was egter nie hoog nie. Tweedens is die PEF waardes van twee groepe proefpersone (die een groep gei:nfesteer met Ascaris lumbricoides en die ander groep nie) met mekaar vergelyk. Daar was egter nie 'n beduidende verskil tussen die waardes van die twee groepe nie. Parasiet ova is gei:dentifiseer deur die maak van eenvoudige nat stoelgang smere en die ondersoek daarvan onder 'n ligmiroskoop. In hierdie studie word die komplekse aard van die interaksie tussen parasiete en die respiratoriese sisteem duidelik na vore gebring. Verdere studies is nodig ten einde die verband tussen hierdie twee faktore te bepaal. / SNO and Stellenbosch 2000 scholarship