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Universiẗat, Diss., 2006--Giessen.

Dissertation (Ph.D.)--Auburn University, 2006. / Abstract. Vita. Includes bibliographic references.

Zugl.: Giessen, Univ., Diss., 2006

Thesis (doctoral)--Universiteit van Amsterdam, 1989. / Summary in Dutch. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Background: The clinical and pathological presentation of COPD is heterogeneous. ‘Chronic bronchitis’ is a phenotype of COPD, which is a clinical diagnosis of a productive cough of ≥ 3 months for ≥ 2 consecutive years. Chronic bronchitis is associated with worse lung function, frequent exacerbations, recurrent hospitalisations and premature death in patients with COPD. Chronic bronchitis sufferers can be further subphenotyped into those who produce sputum during exacerbation or during winter months only and those who are ‘persistent sputum producers,’ who experience mucous hypersecretion throughout the year. An improved understanding of persistent sputum producers is the object of this thesis. Aims: 1) To compare the clinical characteristics and airway inflammatory biomarker profile of COPD persistent sputum producers to that of COPD sputum non-producers 2) To investigate the short term repeatability of sputum parameters in COPD persistent sputum producers 3) To study the expression and relationship of mucins, hypoxia inducible factor (HIF-1α) and carbonic anhydrase IX (CAIX) in COPD persistent sputum producers. Methods: 1) Lung physiology, health status, sputum inflammatory biomarkers and sputum culture results were compared between COPD persistent sputum producers and sputum non-producers 2) Repeatability of spontaneous and induced sputum parameters at 8 weeks was assessed in COPD persistent sputum producers 3) Immunohistochemistry was performed on bronchial biopsies of COPD persistent sputum producers and control groups (COPD sputum non-producers, smokers with normal lung function and lifelong healthy non-smokers with normal lung function) to study the expression of MUC5AC, MUC5B, HIF-1α and CAIX 4) The association between HIF-1α and MUC5B expression was investigated in vitro. Results and Conclusions: The findings suggest that 1) COPD persistent sputum producers have clinically more severe disease, increased airway inflammation, increased impact on health status, increased rate of bacterial colonization and higher number of exacerbations compared to COPD sputum non-producers 2) Induced sputum is repeatable over short term in COPD persistent sputum producers 3) Expression of MUC5B, HIF-1α and CAIX is increased in COPD persistent sputum producers compared to COPD sputum non-producers, smokers with normal lung function and healthy non-smokers 4) HIF-1α can potentially cause increased MUC5B expression. This work reveals potential targets for the development of novel therapies to limit mucous hypersecretion in COPD.

A bronquite infecciosa das galinhas (BIG) é uma doença altamente contagiosa causada por múltiplos genotipos/sorotipos do vírus da bronquite infecciosa das galinhas (IBV), um coronavirus do grupo 3. Embora classicamente associado ao trato respiratório, alguns tipos de IBV têm sido descritos com tropismo pelos rins e pelos tratos reprodutivos e entéricos, o IBV pode ser detectado em diversos tipos de tecidos, e também pode acometer aves de todas as idades. Este estudo tem como objetivo verificar a freqüência do IBV em amostras de diversos órgãos e conteúdo entérico de avós, matrizes, poedeiras comerciais e frangos de corte, genotipar as amostras detectadas e estudar a diversidade molecular entre as amostras brasileiras de IBV. Um total de 844 pools de diversos órgãos e conteúdos entéricos provenientes de 200 lotes de avós, matrizes, poedeiras comerciais e frangos de corte, das regiões Sul, Sudeste, Centro-oeste e Nordeste do Brasil, colhidas durante o período de 2007 a 2009 foram testadas para a presença de IBV com um RT-PCR dirigido à região não traduzida 3′(3′UTR). As aves amostradas apresentaram sinais clínicos compatíveis com a BIG. Todas as amostras de IBV detectadas foram tipificadas utilizando uma RT-PCR dirigida ao gene de espícula do vírus. Dezenove amostras tipificadas como variante foram submetidas ao seqüenciamento parcial da região codificadora da subunidade S1 e à análise genealógica. Considerando os pools de órgãos e de conteúdo entérico, 45,50% foram positivos para a presença de IBV, dos quais, 84,63% pertencem ao genotipo Variante e 9,89% ao sorotipo/genotipo Massachusetts. Considerando os lotes, 73,50% foram positivos para IBV, sendo 77,55% variantes e 6,12% Massachusetts. A análise genealógica revelou quatro linhagens virais, todas agrupadas em um exclusivo grupamento de genotipo brasileiro. Estes resultados demonstram que o IBV está disseminado em todas as regiões avícolas brasileiras, com um predomínio massivo de genotipos não Massachusetts e uma elevada diversidade molecular, que deve ser levada em consideração para desenvolver medidas preventivas contra o IBV. / Infectious bronchitis (IB) is a highly contagious disease of poultry caused by multiple geno/serotypes of avian infectious bronchitis virus (IBV), a group 3 coronavirus. Though classically associated to the respiratory tract, IBV strains also have been described which harbor tropism for the kidneys and the reproductive and enteric tracts, and might be detected in multiple tissues and can also affect birds of all ages. This survey aimed to assess the frequency of in multiple organs and enteric content samples from grandparents, breeders, layers and broilers, to genotype the IBV strains detected and to study the molecular diversity amongst Brazilian IBV strains. A total of 844 pools of multiple organs and enteric contents from 200 flocks of grandparents, breeders, layers and broilers from the Southern, Southeastern, Central-Western and Northeastern Brazilian regions collected between 2007 and 2009 was screened for the presence of IBV with an RT-PCR target to the 3 untranslated region (UTR). The sampled birds presented symptoms compatible with IB. All IBV strains detected were then typed using an RT-PCR target to the spike gene of the virus. Nineteen strains type as variants were submitted to partial sequencing of the S1 coding region and genealogic analysis. Regarding the organs and enteric content pools, 45.50% were positive for the presence of IBV, from which 84.63% were variant and 9.89% Massachusetts. Taking into account the flocks, 73.50% were positive for IBV, being 77.55% variants and 6.12% Massachusetts. Genealogic analysis revealed four viral lineages, all grouped in an exclusive Brazilian genotype cluster. This results shown that IBV is widespread in all Brazilian poultry regions, with a massive predominance of non-Massachusetts genotypes and a high molecular diversity, which must be taken into account in order to develop preventive measures against IB.

In der vorliegenden Studie wurde die Hypothese geprüft, daß Asthmatiker die Aufmerksamkeit von eigenen Körperprozessen ablenken und eine Ungenauigkeit bei der Interozeption relevanter Atemwegsobstruktionen aufweisen. Weiterhin prüften wir die Frage, inwieweit die postulierte Aufmerksamkeitsabwendung generalisiert ist und sich auch auf die nicht atemwegsbezogene Symptomwahrnehmung und die private Selbstaufmerksamkeit bezieht. Die Interozeptionsgenauigkeit wurde als Diskrepanz zwischen subjektivem Urteil und objektiver Atemfunktion bei spirometrischen Messungen berechnet, die anderen Variablen mittels Fragebögen operationalisiert. Es wurden insgesamt 91 Patienten einer Rehabilitationseinrichtung untersucht: 30 Asthmatiker, 30 Patienten mit chronisch obstruktiver Bronchitis (COB) und 31 Kontrollpatienten ohne Atemwegserkrankung. Die Ergebnisse deuten auf eine spezifisch atemwegsbezogene Aufmerksamkeitsablenkung sowie eine Überschätzung von Obstruktionen bei Asthmatikern hin. Überraschend zeigen auch die COB-Patienten auffällige Ergebnismuster in Richtung einer Unterschätzung von Obstruktionen sowie verminderter Selbstaufmerksamkeit. Die Ergebnisse lassen sich im Rahmen verhaltensmedizinischer Überlegungen interpretieren. / The hypothesis that asthmatic patients draw their attention away from bodily processes and show inaccurate interoception with regard to relevant airway obstructions was tested in this study. Additionally, we examined whether this postulated withdrawal of attention can also be generalized for the perception of non-airway related symptoms as well as for private self-consciousness. Accuracy of interoception was measured as the discrepancy between subjective judgement of obstruction and objective obstruction as shown in spirometric tests. Other variables were operationalized by self-reports. Ninetyone patients in a rehabilitation hospital were tested: 30 asthmatic patients, 30 patients with chronic obstructive bronchitis (COB), and 31 control subjects without any airway disease. Asthmatic patients showed attention withdrawal only with regard to bronchial airways. However, they also indicated an overestimation of airway obstruction. Surprisingly, deviant results were also found for the COB patients including underestimation of obstructions and lower self awareness. All results were interpreted from the perspective of behavioral medicine. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

A bronquite infecciosa das galinhas (BIG) é uma doença altamente contagiosa causada por múltiplos genotipos/sorotipos do vírus da bronquite infecciosa das galinhas (IBV), um coronavirus do grupo 3. Embora classicamente associado ao trato respiratório, alguns tipos de IBV têm sido descritos com tropismo pelos rins e pelos tratos reprodutivos e entéricos, o IBV pode ser detectado em diversos tipos de tecidos, e também pode acometer aves de todas as idades. Este estudo tem como objetivo verificar a freqüência do IBV em amostras de diversos órgãos e conteúdo entérico de avós, matrizes, poedeiras comerciais e frangos de corte, genotipar as amostras detectadas e estudar a diversidade molecular entre as amostras brasileiras de IBV. Um total de 844 pools de diversos órgãos e conteúdos entéricos provenientes de 200 lotes de avós, matrizes, poedeiras comerciais e frangos de corte, das regiões Sul, Sudeste, Centro-oeste e Nordeste do Brasil, colhidas durante o período de 2007 a 2009 foram testadas para a presença de IBV com um RT-PCR dirigido à região não traduzida 3′(3′UTR). As aves amostradas apresentaram sinais clínicos compatíveis com a BIG. Todas as amostras de IBV detectadas foram tipificadas utilizando uma RT-PCR dirigida ao gene de espícula do vírus. Dezenove amostras tipificadas como variante foram submetidas ao seqüenciamento parcial da região codificadora da subunidade S1 e à análise genealógica. Considerando os pools de órgãos e de conteúdo entérico, 45,50% foram positivos para a presença de IBV, dos quais, 84,63% pertencem ao genotipo Variante e 9,89% ao sorotipo/genotipo Massachusetts. Considerando os lotes, 73,50% foram positivos para IBV, sendo 77,55% variantes e 6,12% Massachusetts. A análise genealógica revelou quatro linhagens virais, todas agrupadas em um exclusivo grupamento de genotipo brasileiro. Estes resultados demonstram que o IBV está disseminado em todas as regiões avícolas brasileiras, com um predomínio massivo de genotipos não Massachusetts e uma elevada diversidade molecular, que deve ser levada em consideração para desenvolver medidas preventivas contra o IBV. / Infectious bronchitis (IB) is a highly contagious disease of poultry caused by multiple geno/serotypes of avian infectious bronchitis virus (IBV), a group 3 coronavirus. Though classically associated to the respiratory tract, IBV strains also have been described which harbor tropism for the kidneys and the reproductive and enteric tracts, and might be detected in multiple tissues and can also affect birds of all ages. This survey aimed to assess the frequency of in multiple organs and enteric content samples from grandparents, breeders, layers and broilers, to genotype the IBV strains detected and to study the molecular diversity amongst Brazilian IBV strains. A total of 844 pools of multiple organs and enteric contents from 200 flocks of grandparents, breeders, layers and broilers from the Southern, Southeastern, Central-Western and Northeastern Brazilian regions collected between 2007 and 2009 was screened for the presence of IBV with an RT-PCR target to the 3 untranslated region (UTR). The sampled birds presented symptoms compatible with IB. All IBV strains detected were then typed using an RT-PCR target to the spike gene of the virus. Nineteen strains type as variants were submitted to partial sequencing of the S1 coding region and genealogic analysis. Regarding the organs and enteric content pools, 45.50% were positive for the presence of IBV, from which 84.63% were variant and 9.89% Massachusetts. Taking into account the flocks, 73.50% were positive for IBV, being 77.55% variants and 6.12% Massachusetts. Genealogic analysis revealed four viral lineages, all grouped in an exclusive Brazilian genotype cluster. This results shown that IBV is widespread in all Brazilian poultry regions, with a massive predominance of non-Massachusetts genotypes and a high molecular diversity, which must be taken into account in order to develop preventive measures against IB.

In der vorliegenden Studie wurde die Hypothese geprüft, daß Asthmatiker die Aufmerksamkeit von eigenen Körperprozessen ablenken und eine Ungenauigkeit bei der Interozeption relevanter Atemwegsobstruktionen aufweisen. Weiterhin prüften wir die Frage, inwieweit die postulierte Aufmerksamkeitsabwendung generalisiert ist und sich auch auf die nicht atemwegsbezogene Symptomwahrnehmung und die private Selbstaufmerksamkeit bezieht. Die Interozeptionsgenauigkeit wurde als Diskrepanz zwischen subjektivem Urteil und objektiver Atemfunktion bei spirometrischen Messungen berechnet, die anderen Variablen mittels Fragebögen operationalisiert. Es wurden insgesamt 91 Patienten einer Rehabilitationseinrichtung untersucht: 30 Asthmatiker, 30 Patienten mit chronisch obstruktiver Bronchitis (COB) und 31 Kontrollpatienten ohne Atemwegserkrankung. Die Ergebnisse deuten auf eine spezifisch atemwegsbezogene Aufmerksamkeitsablenkung sowie eine Überschätzung von Obstruktionen bei Asthmatikern hin. Überraschend zeigen auch die COB-Patienten auffällige Ergebnismuster in Richtung einer Unterschätzung von Obstruktionen sowie verminderter Selbstaufmerksamkeit. Die Ergebnisse lassen sich im Rahmen verhaltensmedizinischer Überlegungen interpretieren. / The hypothesis that asthmatic patients draw their attention away from bodily processes and show inaccurate interoception with regard to relevant airway obstructions was tested in this study. Additionally, we examined whether this postulated withdrawal of attention can also be generalized for the perception of non-airway related symptoms as well as for private self-consciousness. Accuracy of interoception was measured as the discrepancy between subjective judgement of obstruction and objective obstruction as shown in spirometric tests. Other variables were operationalized by self-reports. Ninetyone patients in a rehabilitation hospital were tested: 30 asthmatic patients, 30 patients with chronic obstructive bronchitis (COB), and 31 control subjects without any airway disease. Asthmatic patients showed attention withdrawal only with regard to bronchial airways. However, they also indicated an overestimation of airway obstruction. Surprisingly, deviant results were also found for the COB patients including underestimation of obstructions and lower self awareness. All results were interpreted from the perspective of behavioral medicine. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.