To see the other types of publications on this topic, follow the link: Cystic fibrosis; Genetic diseases.
Dissertations / Theses on the topic 'Cystic fibrosis; Genetic diseases'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Cystic fibrosis; Genetic diseases.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Darrah, Rebecca J. "Genetic Modifiers of Cystic Fibrosis Pulmonary Disease." Case Western Reserve University School of Graduate Studies / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1270133199.
Full text
2
Hedgecoe, Adam Michael. "Narratives of geneticization : cystic fibrosis, diabetes and schizophrenia." Thesis, University College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.324672.
Full text
3
Romano, Pascale Renee. "Cell-specific expression of the multidrug resistance genes." Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.339300.
Full text
4
Walker, Jennifer Harriet. "The production, and characterisation of monoclonal, polyclonal and phage display antibodies to the cystic fibrosis transmembrane regulator." Thesis, University of Bristol, 1994. http://hdl.handle.net/1983/e64704e1-ced9-4cd9-a358-d6cab313ed52.
Full text
5
Limberis, Maria. "A lentiviral gene transfer vector for the treatment of cystic fibrosis airway disease." Title page, synopsis and list of contents only, 2002. http://web4.library.adelaide.edu.au/theses/09PH/09phl735.pdf.
Full textAbstract:
"16th September 2002." Accompanying CD contains 2 MPEG clips with accompanying text, and a copy in PDF format of: Recovery of airway cystic fibrosis transmembrane conductance regulator function in mice with cystic fibrosis after single-dose lentivirus-mediated gene transfer / M. Limberis ... [et al.], published in Human gene therapy vol. 13 (2002). Bibliography: leaves xxix-li. This thesis focuses on modulating the physical barriers of the airway epithelium with mild detergents, so as to enhance gene transfer by a HIV-1 based lentivirus vector in vivo. The efficiency of the gene transfer was evaluated in the nasal airway of C57B1/6 mice using the Lac Z marker gene. This demonstration of lentivirus-mediated in vivo recovery of CFTR function in CF airway epithelium illustrated the potential of combining a pre-conditioning of the airway surface with a simple and brief HIV-1 based gene transfer vector exposure to produce therapeutic gene expression in the intact airway.
6
Gu, Yuanyuan. "Immunobiology of IFRD1, a Novel Genetic Modifier of Cystic Fibrosis Lung Disease." University of Cincinnati / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1247935975.
Full text
7
Hillian, Antoinette D. "Interleukin-8 as a genetic modifier and pharmacologic target for cystic fibrosis pulmonary disease." Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1244177510.
Full text
8
Shao, Jing. "Association of polymorphisms in the glutamate cysteine ligase catalytic subunit gene and glutathione-S-transferase genes with fibrotic lung diseases /." Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/8452.
Full text
9
Frangolias, Despina Daisy. "Candidate genes other than the CFTR gene as possible modifiers of pulmonary disease severity in cystic fibrosis." Thesis, University of British Columbia, 2008. http://hdl.handle.net/2429/527.
Full textAbstract:
Cystic fibrosis (CF) is a single gene Mendelian disorder characterized by pulmonary disease and pancreatic insufficiency. Pulmonary disease is the major cause of death in CF patients. Although some cystic fibrosis transmembrane conductance regulator (CFTR) genotypes are associated with less severe disease, patients possessing the same genotype show great variation in pulmonary disease severity and progression. Genes involved in modulating the inflammatory response and genes increasing susceptibility to infection are proposed as modifiers of pulmonary disease severity. Polymorphisms selected for based on evidence that they affect the function of the gene and prevalence of the putative risk allele: 1) antiprotease gene alpha-1-antitrypsin (alpha-1-AT), 2) innate immunity genes: mannose binding lectin (MBL2) (promoter [G→C] at -221 and codon 52 (Arg52Cys, D allele), 54 (Gly54Asp, B allele), and 57 (Gly57Glu, C allele), and pulmonary surfactant genes SPA-1 (Arg219Trp), SPA-2 (Thr9Asn, Lys223Gln) and SPD (Thr11Met), 3) antioxidant genes GSTM1 and T1 (gene deletion polymorphisms), GSTP1 (Ile105Val) and GCLC repeats, 4) mucin genes (MUC2 and MUC5B). Pulmonary disease progression and survival in patients with chronic Burkholderia cepacia complex (BCC) infection were also investigated controlling for genomovar and RAPD type of the organism. BCC infection was associated with more severe pulmonary disease progression and worse survival. Alpha-1-AT genotype was not a major contributor to variability of pulmonary disease severity, but the results suggest that alpha-1-AT plasma levels during pulmonary infections may be affected by poor nutritional status. We showed similar pulmonary disease progression and MBL2 genotype. Contrary to the previous literature, wild-type MBL2 genotype was associated with steeper decline in pulmonary disease over time following chronic infection with BCC, but genotype was not associated with increased susceptibility to BCC infection. We showed inconsistant results for the pulmonary surfactant gene polymorphisms, GSTM1, T1 and GSTP1 polymorphisms, and number of repeats for GCLC and MUC5B depending on the phenotype investigated. We conclude that some of the variability in pulmonary disease severity and progression in CF is explained by polymorphisms in secondary genes.
10
Castaing, Pauline. "Survenue de grossesses chez les femmes atteintes de mucoviscidose : spécificités démographiques et sanitaires." Thesis, Bordeaux, 2017. http://www.theses.fr/2017BORD0740/document.
Full textAbstract:
Concernant près de 7000 personnes en France, la mucoviscidose est une maladie génétique évolutive dont les atteintes sont multiples. Ces dernières décennies, l’amélioration de la prise en charge des malades a permis de faire évoluer leur durée de vie, et donc d’augmenter la part d’adultes dans la population touchée. Cela a naturellement amené à de nouvelles problématiques concernant la vie des malades, notamment en termes de procréation. A partir des données du Registre Français de la Mucoviscidose récoltées entre 1992 et 2011, ce travail avait d’une part pour objectif d’étudier la fécondité de cette population et de mieux cerner les caractéristiques des femmes atteintes de la maladie, et d’autre part d’identifier les interactions se jouant entre la mucoviscidose et la survenue d’une grossesse. Les résultats ont montré un certain décalage entre la fécondité de la population française générale et celle de la population malade, expliqué en partie par la jeunesse des patientes et leurs comportements conjugaux et scolaires. Une étude de leurs caractéristiques a permis de mettre en évidence l’évolution du nombre de femmes suivies chaque année et leur avancée en âge, mais également l’amélioration de leur état de santé et de l’offre de soin qui leur est proposée. Des analyses multi-variées ont permis par la suite de distinguer les caractéristiques les plus prédictives de la survenue d’une première grossesse : si certaines variables médicales apparaissent significatives, la plupart sont d’ordre sociodémographique. Enfin, ces analyses ont pu mettre en avant le fait que l’effet à court terme de la grossesse sur l’état de santé des patientes n’apparait pas de façon évidente, et lorsqu’il apparaît, reste modeste ; mais également que les modalités du déroulé de la grossesse peuvent avoir un impact sur la santé de la mère.Mots clés : Mucoviscidose, grossesse, fécondité, maladie génétiqueCystic fibrosis is a progressive genetic disease with multiple levels of harm that affects nearly 7000 people in France. Over the last decades, health care improvements has led to an increase in patients’ life expectancy and hence the proportion of adults in the affected population. This has naturally led to new issues relative to the life of patients, notably procreation. Data from the French Cystic Fibrosis Register recorded between 1992 and 2011 were used in this work, firstly to study the fertility of that population and to pinpoint the characteristics of female patients, secondly to identify any interaction between cystic fibrosis and the occurrence of pregnancy. Results showed a discrepancy between the fertility of general French population and that of the patients, which is partly explained when considering the young age of the patients and their conjugal and school behaviour. By studying their characteristics, an increase in both the age and the number of women being followed, as well as an improvement in their health and the treatments provided to them are observed. In the following multivariate analyses single out the most predictive characteristics of the occurrence of first pregnancy: while some medical variables appear to be significant, most of those are socio-demographic. Finally, those analyses showed that the short-term effect of pregnancy on the patients’ state of health does not appear to be evident and remains low when it occurs ; however specific modalities or events throughout the course of the pregnancy could have an impact on the mother’s health
11
Mekus, Frauke. "Cystic fibrosis as a genetically complex disease Cystische Fibrose: eine genetisch komplexe Erkrankung /." [S.l.] : [s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=959242287.
Full text
12
Schwarz, Martin. "The application of genetic analysis in cystic fibrosis." Thesis, Manchester Metropolitan University, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.334244.
Full textAbstract:
Cystic fibrosis (CF) is the most common lethal autosomal recessive disease in Caucasians, with an incidence of approximately 1 in 2,500 newborns and a carrier frequency of 1 in 25. The major symptoms of the disease are due to malfunction of exocrine glands; sweat glands in the skin secrete excessive sodium and chloride, pancreatic ducts become blocked with thickened mucus, giving rise to pancreatic insufficiency, and the lungs also produce a thickened mucus which facilitates bacterial infection, notably with Pseudomonas species. The gene for CF has been isolated and its product, Cystic Fibrosis Transmembrane conductance Regulator (CFTR), has been determined. Over 240 different mutations of the CFTR gene have so far been described, and most of these have been shown to be disease-causing. CFTR protein is itself a chloride channel regulated by cyclic AMP-dependent protein kinase and it is expressed primarily in epithelial cells. The highest level of transcription is found in those tissues involved in the major symptoms of the disease, notably the pancreas, sweat and salivary glands, the intestine and the reproductive tract. Genetic analysis in cystic fibrosis has enabled accurate first-trimester prenatal diagnosis, initially using linked markers and latterly using direct mutation analysis. Since the isolation of the gene in 1989 it has become of considerable importance to identify CF mutations in a population (for the purpose of population screening) and in individuals with CF (to enable carrier detection and prenatal diagnosis within that family). To that end, the CF population of the North-West of England has been extensively studied. A total of 1108 CF chromosomes of the native North-West population have been investigated and 92% of mutations (comprising 20 different mutations of the CFTR gene) in that group have been identified. Two further groups were of interest, namely a small number of Pakistani CF patients in whom 50% of mutations were identified, and a phenotypically variant group with atypical sweat test results, which yielded no mutations. During the course of the investigation, five previously unrecorded mutations were identified: DeltaI507 in a patient from Bath, 300delA in one from Birmingham, 1161de1C in a Pakistani CF patient, and E60X and 1138insG in patients from the North-West of England. Since these comprise a three-base deletion, a stop codon mutation, and three frameshift mutations, they can all be accepted as diseasecausing mutations. While some headway has been made in identifying CF mutations in Pakistani patients, none has been possible in the phenotypically variant group. There remains some doubt, therefore, that individuals in the latter group do in fact have CF or whether a phenocopy disease is present.
13
Parsons, Yasmin Nicole. "Genetic studies of epidemic strains of cystic fibrosis pathogens." Thesis, University of Liverpool, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.400306.
Full text
14
Jenkins, Bradlee A., and L. Lee Glenn. "Morbidity Indicators of Asthma in Cystic Fibrosis." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etsu-works/7555.
Full text
15
Smart, Catherine Helen Mary. "Genetic studies of cystic fibrosis epidemic strains of Pseudomonas aeruginosa." Thesis, University of Liverpool, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.439469.
Full text
16
Jenkins, Bradlee A., and L. Lee Glenn. "Effect of Asthma on Morbidity in Cystic Fibrosis." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etsu-works/7554.
Full text
17
Jenkins, Bradlee A., and L. Lee Glenn. "Cystic Fibrosis Carrier Screening Attitudes and Multiple Hypothesis Testing." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/7466.
Full textAbstract:
The recent study by Cunningham, Lewis, Curnow, Glazner, and Massie [1] on the attitudes of respiratory physicians and clinic coordinators towards cystic fibrosis (CF) carrier screening drew several unsupported conclusions because the α level of 0.05 was not corrected for the large number of hypothesis tests conducted, leading to a Type 2 error and the acceptance of hypotheses that were likely false [2].
18
Liu, Yi-Chia. "Understanding chronic inflammatory diseases in the human lung : the cystic fibrosis and idiopathic pulmonary fibrosis paradigms." Thesis, University of Nottingham, 2014. http://eprints.nottingham.ac.uk/27807/.
Full textAbstract:
The chronic infection of the cystic fibrosis (CF) lung with Pseudomonas aeruginosa strongly correlates with critical outcomes. Pseudomonas alkyl-quinolone signal (PQS) is a diffusible cell-density dependent signal controlling the production of virulence determinants. The PQS amount in the CF lung was proportionate to P. aeruginosa colonisation and PQS molecules have been demonstrated to inhibit pro-inflammatory signalling. However, how PQS influence the recognition of P. aeruginosa by the human lung is unknown. The contribution of PQS to the interaction of P. aeruginosa with human bronchial epithelial cells (HBECs) was characterised using a PQS-deficient mutant ΔpqsA in comparison with its isogenic wild type (WT). Although ΔpqsA appeared attenuated, the pathogenesis of WT and ΔpqsA upon infection of HBEC did not differ in bacterial growth, actin and junctional protein degradation, and pro-inflammatory activation. Despite PQS being highly secreted by a CF isolate LESB58, preliminary data showed that LESB58 was less cytotoxic than the laboratory WT. Our results suggest that PQS does not alter P. aeruginosa pathogenicity on HBECs. Idiopathic pulmonary fibrosis (IPF) is characterised with heterogeneous pathological patterns caused by scarring leading to irreversible destruction of lung architecture. Emerging evidence suggests that dysregulated immunological events could cause the failure of tissue-healing. Systemic immune responses of patients with IPF and age- and sex-matched healthy donors were determined by quantifying cytokines produced by peripheral blood mononuclear cells (PBMCs) upon an array of stimuli. The results showed that PBMCs in patients with IPF were less likely to produce IL-17A, IL-10 and IL-13 than healthy controls (OR 0.14-0.3, 95% CI 0.003-0.03). Patients with lower levels of cytokines had a four to six-fold increased risk of death (HR 4.31-6.13, 95% CI 0.0052-0.0176). This study contributes to a better understanding of the role of PQS in P. aeruginosa pathogenesis and identified cytokine production as a novel biomarker in IPF.
19
Mennie, Moira E. "Prenatal genetic screening for cystic fibrosis carriers : implications for maternity care." Thesis, University of Edinburgh, 1995. http://hdl.handle.net/1842/20687.
Full textAbstract:
The psychological response of 64 women identified as CF carriers and their partners who received a negative test result were assessed together with selected controls on 4 further occasions: 10 on receiving the carrier's positive test result; 2) on receiving the partner's negative test result; 3) six weeks later; 4) six weeks after delivery. Knowledge of the genetics of CF and attitude to having been screened were measured by self-administered questionnaire. Compared to control subjects, carriers showed a significant increase in generalised psychological disturbance attributed specifically to symptoms of anxiety and depression during the period awaiting their partner's test result but returned to control levels on receipt of a partner's negative test result. Although there was no significant difference in generalised psychological disturbance between partners and their selected controls, partners did become significantly more anxious and manifested signs of inadequacy while awaiting their own test result. All four groups were well informed about the genetics of CF and the significance of being a gene carrier, although 23% of carriers felt information given at the booking clinic was insufficient. 20% of carriers felt regret or ambivalence about having been screened. There was a consensus that screening should be routinely offered to pregnant women but should also be made available in family planning clinics and GP centres. Results showed that the implications for midwifery practice focus on 3 areas of care: information giving; counselling; and emotional support.
20
Smith, Eric Earl. "Genetic adaptation by Pseudomonas aeruginosa during chronic cystic fibrosis infections and genetic variation between strains of P. aeruginosa /." Thesis, Connect to this title online; UW restricted, 2006. http://hdl.handle.net/1773/5067.
Full text
21
Brouqueyre, Laurent. "Hydro-acoustic therapy : design, construction and testing." Thesis, Georgia Institute of Technology, 1999. http://hdl.handle.net/1853/18215.
Full text
22
Saferali, Aabida. "Genetic association and gene expression analysis of inflammatory genes in cystic fibrosis." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/59277.
Full textAbstract:
Cystic fibrosis (CF) is characterized by a progressive decline in lung function due to airway obstruction, infection, and inflammation. CF patients are particularly susceptible to respiratory infection by a variety of pathogens, and the inflammatory response in CF is dysregulated and prolonged. This thesis identifies and characterizes BPI fold containing family A, member 1 (BPIFA1) and BPIFB1 as putative anti-inflammatory molecules in CF, and explores the CF inflammatory response to rhinovirus infection.
BPIFA1 and BPIFB1 are proposed innate immune molecules expressed in the upper airways. We interrogated BPIFA1/BPIFB1 single-nucleotide polymorphisms in data from the North American genome-wide association study (GWAS) for lung disease severity in CF and discovered that the G allele of rs1078761 was associated with reduced lung function in CF patients. Microarray and qPCR gene expression analysis implicated rs1078761 G as being associated with reduced BPIFA1 and BPIFB1 gene expression, suggesting that decreased levels of these genes are detrimental in CF.
Functional assays to characterize the role of BPIFA1 and BPIFB1 in CF indicated that these molecules do not have an anti-bacterial role against P. aeruginosa, but do have an immunomodulatory function in CF airway epithelial cells. To further investigate the mechanism of action of BPIFA1 and BPIFB1 during bacterial infection, gene expression was profiled using RNA-Seq in airway epithelial cells stimulated with P. aeruginosa and treated with recombinant BPIFA1 and BPIFB1.
Viral infections are now recognized to play an important role in the short and long term health of CF patients. Rhinovirus is emerging as a lead viral pathogen although little is known about the inflammatory response triggered by rhinovirus in the CF lung. To investigate whether CF patients have a dysregulated response to rhinovirus infection, primary airway epithelial cells from CF and healthy control children were infected with rhinovirus and gene expression profiles were assessed by RNA-Seq. Although rhinovirus stimulation resulted significantly altered gene expression, the response to infection was not different in CF patients compared to healthy controls. However, CF cells had significantly higher rhinovirus levels than controls, indicating that CF patients may have a deficient antiviral response allowing for increased rhinovirus replication.Medicine, Faculty of
Experimental Medicine, Division of
Graduate
23
Gunnell, Sarah. "Percutaneous Endoscopic Gastrostomy Placement Time in People with Cystic Fibrosis." DigitalCommons@USU, 2002. https://digitalcommons.usu.edu/etd/5485.
Full textAbstract:
A retrospective chart review was conducted on pediatric patients at the Intermountain Cystic Fibrosis Center who had a percutaneous endoscopic gastrostomy (PEG) placed between 1993 and 1999. Height velocity improved significantly in the group of patients with a PEG placed; however, pulmonary function declined more significantly over time.
Questionnaires regarding attitude toward PEG placement were sent to patients enrolled in accredited cystic fibrosis centers in the mountain west region and to their parents. The overall response rate was 54.25% for the PEG questionnaire and 24% for the non-PEG questionnaire. Ninety-six percent of the patients with a PEG reported that weight was a problem at time of placement, and 91% reported weight gain after PEG ill placement. Sixty-four percent of the patients with a PEG reported that they would have a PEG placed if they made the decision again. Of the patients without a PEG, 60.7% thought a PEG looked bad, and 59.2% would be embarrassed to have a PEG. Forty-nine percent of patients without a PEG expressed a lack of knowledge of the pros and cons of PEG placement and 35.4% had no opinion about their knowledge of PEGs.
PEG placement can be beneficial in improving nutritional status. Optimal time for PEG placement may be earlier rather than after pulmonary function has declined. People with a PEG have felt positive toward placement, and those without a PEG seem to lack knowledge about the pros and cons of PEG placement.
24
Hazlett, Dee Allen 1942. "EFFECTS OF DIET AND CHRONIC RESERPINE TREATMENT (A MODEL FOR CYSTIC FIBROSIS) ON THE RAT EXOCRINE PANCREAS." Thesis, The University of Arizona, 1986. http://hdl.handle.net/10150/277181.
Full text
25
Jenkins, Bradlee A., and L. Lee Glenn. "Miglustat Effects on the Basal Nasal Potential Differences in Cystic Fibrosis." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etsu-works/7490.
Full textAbstract:
A recent study by Leonard, Lebecque, Dingemanse, and Leal [1] tested the effect of Miglustat, an alpha inhibitor on the cystic fibrosis conductance regulator gene using total chloride secretion in the nasal epithelium as the key variable estimated from basal nasal potential differences. The conclusion was drawn that “There was no evidence of a treatment effect on any nasal potential difference variable.” This conclusion may not be correct because of a slight misinterpretation of their statistical results. There also is a question of whether longer exposure periods than 8 days would have produced a more pronounced effect.
26
Barbato, Eric. "GENETIC VARIATION NEAR CHRXQ22-Q23 IS LINKED TO EMOTIONAL FUNCTIONING IN CYSTIC FIBROSIS." Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1576069523062159.
Full text
27
Moulin, Danielle S. "Regulation of expression of the CFTR gene." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298347.
Full text
28
Vries, Hendrik Gerardus de. "Application of molecular techniques in population genetic studies of cystic fibrosis in the Netherlands." [S.l. : [Groningen] : s.n.] ; [University Library Groningen] [Host], 1996. http://irs.ub.rug.nl/ppn/149413165.
Full text
29
Skrentny, Thomas, and Brittany Traylor. "Influence of Genetic Variation of the β2 Adrenergic Receptor in Patients with Cystic Fibrosis." The University of Arizona, 2010. http://hdl.handle.net/10150/623791.
Full textAbstract:
Class of 2010 AbstractOBJECTIVES: Cystic fibrosis (CF) is a disease that adversely affects the lung resulting in a reduction of lung diffusion. Stimulation of the β2 adrenergic receptors results in mucocilliary clearance, and therefore, lung diffusion. We sought to determine the influence of an inhaled β-‐agonist on the diffusing capacity of the lungs for carbon monoxide (DLCO), alveolar-‐capillary membrane conductance (DM), pulmonary capillary blood volume (Vc), and peripheral oxygen saturation (SaO2) in subjects with CF and compare the data to matched healthy subjects. METHODS: To determine this we recruited 20 healthy subjects and 18 subjects with CF (age=23±7 vs. 24±4years, ht=168±8 vs. 174±12cm. wt=64±16 vs. 70±13kg, BMI= 23±4 vs. 23±3kg/m2, FEV1= 72±27 vs. 92±12%pred., VO2peak = 45±25 vs. 99±24%pred., P<0.05 for FEV1 and VO2peak, mean±SD) for the study and measured DLCO, DM, Vc and SaO2 before and 30, 60, and 90 minutes following the administration of inhaled albuterol. RESULTS: Within the healthy subjects, there were no differences in DLCO, DM, Vc, DM/Vc at baseline or in response to albuterol according to genetic variation of the ADRB2 at amino acid 27. Within the CF group, the Glu27Glu/Gln27Glu group had higher DM/Vc when compared to the Gln27Gln group at baseline. Both genotype groups had a significant decline in Vc and a significant improvement in DM/Vc and SaO2 in response to albuterol, but not in DLCO or DM. CONCLUSIONS: These results suggest that there are differences in lung diffusion and peripheral SaO2 according to genetic variants of the ADRB2 at position 27 and could play a potential role in treatment options.
30
Ghosh, Arkasubhra. "Rational design of split gene vectors to expand the packaging capacity of adeno-associated viral vectors." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/4712.
Full textAbstract:
Thesis (Ph. D.)--University of Missouri-Columbia, 2007.The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "December 2007" Includes bibliographical references.
31
Dawson, Kenneth P., and mikewood@deakin edu au. "Cystic fibrosis in children of the Eastern Arabian Peninsula : A clinical, spatial and genetic study." Deakin University. School of biological and chemical sciences, 2003. http://tux.lib.deakin.edu.au./adt-VDU/public/adt-VDU20050728.091141.
Full textAbstract:
Aim:
The aim of this thesis is to describe the process by which the inherited disease, cystic fibrosis, (CF) was recognised as an important clinical entity in the United Arab Emirates (UAE) and the Sultanate of Oman (Oman). It examines the clinical presentation of the first patients and assesses their degree of severity. Further, it describes the first studies carried out to determine the underlying CF mutations associated with the disease in the UAE and Oman. An estimate is offered of the birth frequency of the condition. Overall, the cultural, geographical and historical aspect of the societies in which the disease occurs is stressed.
Methods:
An initial literature search was carried out using Medline of any literature pertaining to the
Arab World and CF. this was read and classified into the relevance to Arabs in general, the
Middle East and then specifically the Arab (Persian) Gulf societies.
Thereafter, a clinic was established at Tawam Hospital, Al Ain, UAE, for children presenting
With chronic respiratory disease that could serve as a national referral centre. It was run by the
Author as a service of the Paediatric Department of the UAE University Medical School. I sent
a letter to every Paediatrician working in the UAE informing them of our clinic and offering
our services for the diagnosis and management of chronic respiratory disease in children. This
was based on the author's experience as a respiratory paediatrician in Australia and New
Zealand and as the Professor of Paediatrics in the UAE. No such service then existed in the UAE.
Funding was sought to establish a research programme and develop a molecular genetics laboratory in the UAE Medical School. A series of successful research applications provided the grants to commence the investigations. Once a small number of children had been identified as having CF from those referred to the respiratory clinic, the initial project was to assess and report their clinical presentation. Following this an early start was made on the identification of the mutations responsible. Once these were established an attempt was made to estimate the frequency of the condition at birth.
Additional clinical studies revolved around assessing the severity of the condition that was associated with the main mutations that were identified. A clinical comparison was made with those with the mutation AF508 and the other main mutation, despite the obvious limitation of small numbers then available. Radiological assessment was made to evaluate the progression of the disease.
The final aspect of the study was to assess patients from Oman and compare their findings and mutations with the neighbouring UAE. Based on information gained hypotheses are proposed regarding the spread of the gene mutation by population drift.
Thesis outline:
A literature review is presented in the form of a critique on the disease and a resume of the relevant aspects of the genetics of CF. Additionally, facts about the two countries' geography and history are presented. Finally, knowledge about CF mutations and population origins from other areas is presented.
The second main section deals with the clinical features of the disorder as it presents in the UAE. Molecular findings are then presented and details of the common mutation found in Bedouin Arabs. Hypotheses are then presented based on the information gathered.
Results:
CF is not a rare disease in the Arab children of the UAE and Oman. These findings refute previous reports of CF being a rare or non-existent disease in Arabs. The condition presents with a severe clinical picture, with early colonisation of the respiratory tract with staphylococcus, haemophilus and pseudomonas organisms, even with conventional CF management practices in place.
The CF mutation S549R is prevalent in Arabs of Bedouin stock, while AF508 is found in those of Baluch origin. The former may be descendants of Arabs who left southern Arabia and travelled to the Trucial Coast at the time of the destruction of the great dam at Marib. The origins of this mutation may lie in the area that corresponds to the modern Republic of Yemen. The latter groups are descendants of those who came originally from Baluchistan. It is hypothesised also that the ancestral home of the AF508 mutation may be in the geographical area now known as Baluchistan, that spans three separate modern political territories. The evidence presented supports the concept that the S549R mutation may be associated with a severe, if not the severest, clinical pattern recognised. It equates with that seen with the homozygous AF508 genotype. The absence of an additional mutation in the promoter region accounts for the different clinical pattern seen in previously described patients.
Conclusions:
There needs to be a major awareness of the presence of CF as a severe clinical disease in the children of the Gulf States. The clinical presentation and findings support the concept of under recognition of the disease. Climatic conditions put the children at special risk of hyponatraemia and electrolyte imbalance. The absence of surviving adults with the disease suggests premature deaths have occurred, but the high fertility rates have maintained the gene pool for this recessive disorder.
32
Wang, Yunguan. "Data-driven Approaches to Understand Development, Diseases and Identify Therapeutics." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1535704902199176.
Full text
33
Virley, O'Connor Barbara. "Predictive genetic testing for cystic fibrosis carrier status, the role of health beliefs and coping style." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1996. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/mq22060.pdf.
Full text
34
Virley, O'Connor Barbara (Barbara Jeanne) Carleton University Dissertation Psychology. "Predictive genetic testing for Cystic Fibrosis carrier status; the role of health beliefs and coping style." Ottawa, 1996.
Find full text
35
Krepkovich, Katherine Elizabeth. "Transition to Adult Care and Awareness of Genetic Counseling: Perceptions of Cystic Fibrosis Patients and Parents." Cincinnati, Ohio : University of Cincinnati, 2006. http://www.ohiolink.edu/etd/view.cgi?acc_num=ucin1148318614.
Full textAbstract:
Thesis (M.S.)--University of Cincinnati, 2006.Advisor: Martha Walker. Title from electronic thesis title page (viewed June 5, 2009). Includes abstract. Keywords: Cystic fibrosis; transition; adult care; genetic counseling; parent perception. Includes bibliographical references.
36
Schoeman, Mardelle. "An investigation into the level of genetic knowledge and family communication regarding genetic risk in parents of children with cystic fibrosis." Master's thesis, University of Cape Town, 2007. http://hdl.handle.net/11427/3103.
Full textAbstract:
Includes bibliographical references (leaves 94-103).The aims of the present study were to determine the level of genetic knowledge of parents with a child with cystic fibrosis; to determine the impact of the birth of a child with cystic fibrosis upon subsequent reproductive choices and to investigate family communication about genetic risk. A qualitative approach was selected as it aims to understand, attempts to make sense of and provides descriptions that portray the richness and complexity of ordinary events from the perspective of the participants.
37
Smith, Emily M. "The Three-Dimensional Structure of the Cystic Fibrosis Locus: A Dissertation." eScholarship@UMMS, 2011. http://escholarship.umassmed.edu/gsbs_diss/744.
Full textAbstract:
The three dimensional structure of the human genome is known to play a critical role in gene function and expression. I used chromosome conformation capture (3C) and 3C-carbon copy (5C) techniques to investigate the three-dimensional structure of the cystic fibrosis transmembrane conductance regulator (CFTR) locus. This is an important disease gene that, when mutated, causes cystic fibrosis. 3C experiments identified four distinct looping elements that contact the CFTR gene promoter only in CFTR-expressing cells. Using 5C, I expanded the region of study to a 2.8 Mb region surrounding the CFTR gene. The 5C study shows 7 clear topologically associating domains (TADs) present at the locus, identical in all five cell lines tested, regardless of gene expression status. CFTR and all its known regulatory elements are contained within one TAD, suggesting TADs play a role in constraining promoters to a local search space. The four looping elements identified in the 3C experiment and confirmed in the 5C experiment were then tested for enhancer activity using a luciferase assay, which showed that elements III and IV could act as enhancers. These elements were tested against a library of human transcription factors in a yeast one-hybrid assay to identify potential binding proteins. Element III gave two strong candidates, TCF4 and LEF1. A literature search supported these transcription factors as playing a role in CFTR gene expression. Overall, this work represents a model locus that can be used to test important questions regarding the role of three dimensional looping on gene expression.
38
Smith, Emily M. "The Three-Dimensional Structure of the Cystic Fibrosis Locus: A Dissertation." eScholarship@UMMS, 2014. https://escholarship.umassmed.edu/gsbs_diss/744.
Full textAbstract:
The three dimensional structure of the human genome is known to play a critical role in gene function and expression. I used chromosome conformation capture (3C) and 3C-carbon copy (5C) techniques to investigate the three-dimensional structure of the cystic fibrosis transmembrane conductance regulator (CFTR) locus. This is an important disease gene that, when mutated, causes cystic fibrosis. 3C experiments identified four distinct looping elements that contact the CFTR gene promoter only in CFTR-expressing cells. Using 5C, I expanded the region of study to a 2.8 Mb region surrounding the CFTR gene. The 5C study shows 7 clear topologically associating domains (TADs) present at the locus, identical in all five cell lines tested, regardless of gene expression status. CFTR and all its known regulatory elements are contained within one TAD, suggesting TADs play a role in constraining promoters to a local search space. The four looping elements identified in the 3C experiment and confirmed in the 5C experiment were then tested for enhancer activity using a luciferase assay, which showed that elements III and IV could act as enhancers. These elements were tested against a library of human transcription factors in a yeast one-hybrid assay to identify potential binding proteins. Element III gave two strong candidates, TCF4 and LEF1. A literature search supported these transcription factors as playing a role in CFTR gene expression. Overall, this work represents a model locus that can be used to test important questions regarding the role of three dimensional looping on gene expression.
39
Laval, Julie. "Metabolic adaptation of inflammatory neutrophils in human diseases revealed by retroviral envelope-derived ligands : focus on cystic fibrosis." Phd thesis, Université Montpellier II - Sciences et Techniques du Languedoc, 2013. http://tel.archives-ouvertes.fr/tel-01021456.
Full textAbstract:
The present study focuses on adaptive metabolic steps adopted by neutrophils during inflammation, particularly during their recruitment into the cystic fibrosis (CF) airways. In CF, we previously described that airway neutrophils are alive and undergo reprogramming, featuring notably the activation of the anabolic mTOR pathway. The present work is based on specific properties of soluble ligands derived from the receptor-binding domains (RBD) of retroviral glycoprotein envelopes, which can be used for the detection of metabolite transporters at the cell surface. First, we validated the use of this new set of markers for the identification and characterization of the metabolic phenotype of CF leukocytes obtained from distinct compartments (blood and sputum). Second, by studying the metabolite transporter expression on blood neutrophils from CF or rheumatoid arthritis patients and control subjects, we distinguished metabolic phenotypes characteristic of specific inflammatory states. Then, we compared metabolite transporter expression between CF blood and airway neutrophils and showed that neutrophils undergo significant metabolic adaptation upon recruitment into the lungs. Finally, we demonstrated that CF airway neutrophils display significant transcriptional modulation and that despite their metabolic reprogramming, they remain functionally competent, thus adding an additional angle of approach to neutrophil studies with regard to inflammation, notably during CF airway disease.
40
Herko, Kara, Benjamin Guthrie, and Eric Snyder. "Genetic Variation of the BETA-2 Adrenergic Receptor and the Bronchodilatory Response to Albuterol in Patients with Cystic Fibrosis." The University of Arizona, 2012. http://hdl.handle.net/10150/614494.
Full textAbstract:
Class of 2012 AbstractSpecific Aims: We sought to determine the influence of genetic variation of ADRB2 on the airway response to albuterol in patients with CF when compared to matched healthy controls at baseline and at 60 minutes following the administration of albuterol (2.5mg diluted in 3ml normal saline). Methods: Baseline pulmonary function (forced vital capacity, FVC, forced expiratory flow in 1-second, FEV1, mid-maximal expiratory flow, MMF, and forced expiratory flow at 50% of the FVC) was assessed in 17 patients with CF and 31 healthy subjects. Main Results: As expected, the healthy group had higher baseline pulmonary function when compared to the CF group (FVC=97±3 vs. 83±5; FEV1=95±3 vs. 72±6; MMF=90±4 vs. 54±8, % predicted for healthy and CF, respectively, mean±SE, p<0.05 for all. We compared Arg16Arg to Arg16Gly/Gly16Gly subjects. There was no effect of genotype on the response to albuterol in healthy subjects. However, in the CF group, we found that the Arg16Arg group (n=6) had an attenuated response to β-agonist when compared to the Gly-containing group (n=11) (FVC=0±0.9 vs. 6±3: FEV1=3±1 vs. 7±4: MMF=12±3 vs. 12±5 % change, for Arg16Arg and Gly-containing groups, respectively, p<0.05 for FVC, p=0.06 for FEV1). Conclusions: These results demonstrate a differential response to β-agonists according to genetic variation of the ADRB2 at amino acid 16. Due to the differences in FVC and FEV1 but not in MMF, these data suggest that the genetic difference in airway function is primarily in bronchodilation of the larger airways.
41
Damera, Gautam V. "Molecular mechanisms of mucus hypersecretion in chronic airway obstructive diseases." Oklahoma City : [s.n.], 2006.
Find full text
42
Herko, Kara, and Benjamin Guthrie. "Genetic Variation of the BETA-2 Adrenergic Receptor and the Bronchodilatory Response to Albuterol in Patients with Cystic Fibrosis." The University of Arizona, 2012. http://hdl.handle.net/10150/623639.
Full textAbstract:
Class of 2012 AbstractSpecific Aims: We sought to determine the influence of genetic variation of ADRB2 on the airway response to albuterol in patients with CF when compared to matched healthy controls at baseline and at 60 minutes following the administration of albuterol (2.5mg diluted in 3ml normal saline). Methods: Baseline pulmonary function (forced vital capacity, FVC, forced expiratory flow in 1-second, FEV1, mid-maximal expiratory flow, MMF, and forced expiratory flow at 50% of the FVC) was assessed in 17 patients with CF and 31 healthy subjects. Main Results: As expected, the healthy group had higher baseline pulmonary function when compared to the CF group (FVC=97±3 vs. 83±5; FEV1=95±3 vs. 72±6; MMF=90±4 vs. 54±8, % predicted for healthy and CF, respectively, mean±SE, p<0.05 for all. We compared Arg16Arg to Arg16Gly/Gly16Gly subjects. There was no effect of genotype on the response to albuterol in healthy subjects. However, in the CF group, we found that the Arg16Arg group (n=6) had an attenuated response to β-agonist when compared to the Gly-containing group (n=11) (FVC=0±0.9 vs. 6±3: FEV1=3±1 vs. 7±4: MMF=12±3 vs. 12±5 % change, for Arg16Arg and Gly-containing groups, respectively, p<0.05 for FVC, p=0.06 for FEV1). Conclusions: These results demonstrate a differential response to β-agonists according to genetic variation of the ADRB2 at amino acid 16. Due to the differences in FVC and FEV1 but not in MMF, these data suggest that the genetic difference in airway function is primarily in bronchodilation of the larger airways.
43
Barthe, Catherine. "Contribution a l'etude de la cfp (cystic fibrosis protein) proteine serique marqueur de la mucoviscidose." Aix-Marseille 2, 1988. http://www.theses.fr/1988AIX22048.
Full text
44
Jabr, Suha Said Mohammad. "Contribution to the Study of the Role of Arachidonic Acid Metabolism in Airway Inflammatory Diseases (Nasal polyps, Asthma and Cystic Fibrosis)." Doctoral thesis, Universitat de Barcelona, 2013. http://hdl.handle.net/10803/125775.
Full textAbstract:
Eicosanoids are derived from the fatty acids that make up the cell membrane and nuclear membrane. They begin as a single poly unsaturated fatty acid, the arachidonic acid. (AA) is produced from membrane phospholipids and then it can be enzymatically metabolized through the cycloooxygenase pathway into different eicosanoids including prostaglandins. They have various roles in inflammation, and many diseases including asthma, and cystic fibrosis. Fibroblasts from nasal polyps of asthma patients have reduced expression of cyclooxygenase-2 and production of prostaglandin (PG) E2. It is hypothesized that the reported alterations are due to alterations in the availability of AA. So we aimed to determine the fatty acid composition of airway fibroblasts from healthy subjects and from asthma patients with and without aspirin intolerance.
In patients with cystic fibrosis there is a relationship between prostanoid production and cystic fibrosis (CF) genotype severity, and also with the severity of the phenotype expression determined by the presence or absence of pancreatic insufficiency. We aimed to assess the relationship in patients with cystic fibrosis between prostanoid production and lung function values, pancreatic function as a measure of CF severity, and genotype severity. And to assess the relationship between PGE-M and PGD-M urinary metabolites of PGE(2) and PGD(2) and CF severity.
Since eicosanoids and their precursor AA have a crucial role in physiology and
pathology, it is very important to identify and quantify the amount that is produced by the cells and tissues in order to identify better the targets for pharmaceutical intervention. They need a special method for isolating them and a specific and sensitive instrument for identifying, and quantifying them. Gas chromatography was used for the analysis of fatty acids in human nasal fibroblasts culture, and the high performance liquid chromatography tandem mass spectrometry was used for the identification and quantification of prostaglandins metabolites (Tetranor-PGEM and Tetranor-PGDM) in human urine.
45
Marcelino, Aline Roberta Bariani 1985. "Polimorfismos -765G>C e 8473T>C no gene COX2 e 57460C>T no gene IFRD1 como modificadores da gravidade da fibrose cística." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308605.
Full textAbstract:
Orientador: Carmen Sílvia BertuzzoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-22T19:39:30Z (GMT). No. of bitstreams: 1 Marcelino_AlineRobertaBariani_M.pdf: 1077026 bytes, checksum: b7315e705aba4125ea2a4e2574a78b6b (MD5) Previous issue date: 2013
Resumo: A Fibrose Cística (FC) é uma doença autossômica recessiva causada por mutações no gene CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) que acarretam em defeito ou na ausência da proteína por ele sintetizada. A CFTR, produto deste gene é uma proteína canal, localizada na membrana apical das células, responsável pela condução de íons cloreto. As mutações levam à ausência da proteína CFTR ou a alteração qualitativa/quantitativa da proteína, que acarreta no desequilíbrio osmótico entre os meios intra e extracelular. Como consequência há a ocorrência de muco viscoso e de difícil excreção nos pulmões e obstrução dos ductos pancreáticos, afetando desta forma o sistema respiratório e digestório. São conhecidas mais de 1.900 mutações no gene CFTR, sendo que mesmo em pacientes com mutações iguais como a F508del - com alta prevalência na população brasileira - há divergência entre os fenótipos observados. Dessa forma, o genótipo CFTR parece não ser determinante na modulação da gravidade clínica, uma vez que, indivíduos com mesmo genótipo CFTR apresentam manifestações clínicas diferentes. Outros genes, diferentes do CFTR foram associados à gravidade clínica dos pacientes, revelando que os produtos por eles expressos exercem algum tipo de ação modificadora do fenótipo da FC. Tais genes foram denominados modificadores e atuam em fatores secundários relacionados à evolução do quadro clínico, como a articulação do sistema imune. Os genes COX2 e IFRD1, com ação importante no sistema imune e no recrutamento de células de defesa foram identificados como modificadores da FC em estudos prévios realizados em uma população diferente da brasileira. No presente estudo, os polimorfismos -765G>C e 8473T>C no gene COX2 e 57460C>T no gene IFRD1, candidatos a modificadores, foram identificados nos pacientes e um estudo de associação genótipo-fenótipo foi conduzido a fim de verificar a ação moduladora de tais polimorfismos nos pacientes estudados. Nenhuma associação foi encontrada, exceto para o íleo meconial (p=0,028 - em pacientes com duas mutações identificadas no gene CFTR pertencentes à classe I, II e III) e para a polipose nasal (p=0,022 - em pacientes sem considerar o genótipo CFTR) para o polimorfismo 8473T>C no gene COX2
Abstract: Cystic fibrosis (CF) is an autosomal recessive disease caused by CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene mutations that lead to defective polypeptide or lack of the protein CFTR. The CFTR is a channel protein located in the apical cells membrane, responsible for chloride ions conductance. The mutations lead to an osmotic disequilibrium between intra and extracellular mediums, which causes viscous mucus production that is hard to be eliminated from lungs and pancreatic ducts, affecting, this way, respiratory and digestive systems. More than 1,900 CFTR different mutations are known, and even patients that carries identical mutations as F508del - the most common one in Brazilian population - shows a great discrepancy between the phenotypes that are observed. Thus, CFTR genotype seems not to be crucial in disease clinical course modulation, once different subjects carrying the same CFTR mutations reveal distinctive clinical manifestations. Genes besides CFTR were associated to CF patients clinical manifestation, revealing that the molecules they express have some kind of modifier activity in CF phenotype. Such genes were labeled as modifier genes and they act in secondary factors related to clinical course evolution as immune system response. The genes COX2 and IFRD1 have an important role in immune system and defense cell recruitment and they were identified as CF modifiers in previous studies that analyzed different population from the Brazilian one. In this current study, the polymorphisms -765G>C, 8473T>C and 57460C>T located in these genes were identified in our patients and association genotype-phenotype were carried out in order to verify the modulator activity of such variants in the studied casuistic. There was not found association, except for meconium ileus (p=0,028 - in patients with two CFTR mutations from class I, II and III) and for nasal polyposis (p=0,022 - in patients whose CFTR genotype was not considered) to 8473T>C polymorphism in COX2 gene
Mestrado
Ciencias Biomedicas
Mestre em Ciências Médicas
46
Foxx-Lupo, William T., and Eric M. Snyder. "Influence of Genetic Variation of the Alpha-Subunit of the Epithelial Sodium Channel (ENaC) on Baseline Pulmonary Function and Exhaled Sodium Ions (Na+) and Chloride Ions (Cl-) in Healthy Subjects and Patients with Cystic Fibrosis." The University of Arizona, 2012. http://hdl.handle.net/10150/614485.
Full textAbstract:
Class of 2012 AbstractSpecific Aims: The epithelial sodium channels (ENaC) found on the apical membranes of epithelial cells including those lining the respiratory tract are the rate limiting step of the absorption of excess fluid from the airspace of the alveoli. ENaC function is modulated by the effects of various physiologic signals such as the adrenergic and purinergic pathways, in addition to other local channels which control the flow of negatively charged ions such as the cystic fibrosis transmembrane conductance regulator (CFTR). We sought to determine the influence of genetic variation on the alpha subunit of ENaC at amino acid position 663 on baseline exhaled ions and pulmonary function in patients with CF. Methods: We assessed pulmonary function ( forced vital capacity[FVC], forced expiratory volume in one second [FEV1], forced expiratory flow maximum[FEFmax]) using a Medical Graphics cardiopulmonary testing device (Minneapolis, MN). Measures of exhaled sodium (Na+) and chloride (Cl-) were obtained using exhaled breathe condensate collected on a Jaeger Ecoscreen condenser unit (Cardinal Health, Yorba Linda, CA) with Na+ quantification using an atomic absorption spectrophotometer (Analyst 100; Perkin Elmer, Norwalk, CT) and Cl- anion quantification using a Dionex AS11 HC column. Healthy n=31 (n=18[58%], 9[29%], and 4[13%] subjects; Body mass index (BMI)=23±1, 25±2, and 25±2kg/ m2 for AA, AT and TT groups respectively). CF n= 42 (n=33[79%], 7[16%], and 2[5%] subjects; BMI equals 23±7, 19±0.4, and 20±2.2kg/m2 for AA, AT and TT groups respectively). Main Results: We found that the distribution of genotypes in CF differed from healthy subjects, with the AA genotype in 80% of CF and 59% in healthy. No significant difference were demonstrated in healthy subjects between genotype groups for pulmonary function and exhaled chloride while the genotypes did differ in exhaled Na (Na=2.9±0.4, 1.7±0.3, and 3.7±1.1mmol/L for AA, AT, and TT respectively, ANOVA p=0.07). CF subjects with the AA genotype had a higher baseline exhaled Cl-, FEV1, and FEFmax than those in the AA group (Cl=0.125±0.038,0.0 27±0.007, and 0.033±0.02 mmol/L ; FEV1=71±5, 68±11, and 40±22L; FEFmax=86±4, 72±7, and 44±24L/sec; for AA, AT, and TT respectively, ANOVA p<0.05, Tukey [AA vs. TT] p<0.05) while exhaled Na+ and FVC were similar between genotypes. Conclusions: Our results suggest that CF subjects with the AA genotype of the alpha subunit of the ENaC have a higher baseline exhaled Cl- and a resulting increase in pulmonary function when compared to the overactive TT groupCF patients with the TT αENaC genotype are likely candidates for early identification and treatment with inhaled ENaC inhibitors or other modulators of this pathway in order to improve survival.
47
Foxx-Lupo, William T. "Influence of genetic variation of the alpha-subunit of the epithelial sodium channel (ENaC) on baseline pulmonary function and exhaled sodium ions (Na+) and chloride ions (Cl-) in healthy subjects and patients with cystic fibrosis." The University of Arizona, 2012. http://hdl.handle.net/10150/623609.
Full textAbstract:
Class of 2012 AbstractSpecific Aims: The epithelial sodium channels (ENaC) found on the apical membranes of epithelial cells including those lining the respiratory tract are the rate limiting step of the absorption of excess fluid from the airspace of the alveoli. ENaC function is modulated by the effects of various physiologic signals such as the adrenergic and purinergic pathways, in addition to other local channels which control the flow of negatively charged ions such as the cystic fibrosis transmembrane conductance regulator (CFTR). We sought to determine the influence of genetic variation on the alpha subunit of ENaC at amino acid position 663 on baseline exhaled ions and pulmonary function in patients with CF. Methods: We assessed pulmonary function ( forced vital capacity[FVC], forced expiratory volume in one second [FEV1], forced expiratory flow maximum[FEFmax]) using a Medical Graphics cardiopulmonary testing device (Minneapolis, MN). Measures of exhaled sodium (Na+) and chloride (Cl-) were obtained using exhaled breathe condensate collected on a Jaeger Ecoscreen condenser unit (Cardinal Health, Yorba Linda, CA) with Na+ quantification using an atomic absorption spectrophotometer (Analyst 100; Perkin Elmer, Norwalk, CT) and Cl- anion quantification using a Dionex AS11 HC column. Healthy n=31 (n=18[58%], 9[29%], and 4[13%] subjects; Body mass index (BMI)=23±1, 25±2, and 25±2kg/ m2 for AA, AT and TT groups respectively). CF n= 42 (n=33[79%], 7[16%], and 2[5%] subjects; BMI equals 23±7, 19±0.4, and 20±2.2kg/m2 for AA, AT and TT groups respectively). Main Results: We found that the distribution of genotypes in CF differed from healthy subjects, with the AA genotype in 80% of CF and 59% in healthy. No significant difference were demonstrated in healthy subjects between genotype groups for pulmonary function and exhaled chloride while the genotypes did differ in exhaled Na (Na=2.9±0.4, 1.7±0.3, and 3.7±1.1mmol/L for AA, AT, and TT respectively, ANOVA p=0.07). CF subjects with the AA genotype had a higher baseline exhaled Cl-, FEV1, and FEFmax than those in the AA group (Cl=0.125±0.038,0.0 27±0.007, and 0.033±0.02 mmol/L ; FEV1=71±5, 68±11, and 40±22L; FEFmax=86±4, 72±7, and 44±24L/sec; for AA, AT, and TT respectively, ANOVA p<0.05, Tukey [AA vs. TT] p<0.05) while exhaled Na+ and FVC were similar between genotypes. Conclusions: Our results suggest that CF subjects with the AA genotype of the alpha subunit of the ENaC have a higher baseline exhaled Cl- and a resulting increase in pulmonary function when compared to the overactive TT groupCF patients with the TT αENaC genotype are likely candidates for early identification and treatment with inhaled ENaC inhibitors or other modulators of this pathway in order to improve survival.
48
Winfield, Kaye R. "Extraction of desmosines from urine : an indicator for inflammatory lung damage." University of Western Australia. School of Paediatrics and Child Health, 2007. http://theses.library.uwa.edu.au/adt-WU2007.0059.
Full textAbstract:
[Truncated abstract] Urinary desmosines have been proposed as a biomarker for inflammatory lung damage. Desmosine, a breakdown product of elastin, is an effective marker of the degradation of elastin and has been studied in many disease scenarios where there is acute and chronic lung inflammation. Lung matrix degradation has been proven in vitro and in vivo with many experiments showing that the excess proteases degrades lung matrix. The secretion of proteases by neutrophils is an innate response of the body to the invasion by micro organisms and when secreted in excess, the protective anti-protease mechanism is swamped. Chronic inflammation and persistent infection eventually leads to bronchiectasis and respiratory failure. Urinary desmosine has been shown to be elevated in respiratory conditions with acute and chronic inflammation . . . Urinary desmosine levels in a large cohort of healthy children have been established using this method and predictive Z-score formulae have been developed to use in children with lung disease. Exploration of these scores in children with CF have shown that the levels of urinary desmosine appear to be sensitive to the clinical setting, where high urinary desmosine levels were present during exacerbation and significantly reduced when treated for infection with antibiotic therapy and physiotherapy. The study of young children under the age of seven was undertaken to determine if the urinary desmosine levels could indicate when lung damage was occurring and to determine what mechanisms might be involved. Since there appeared to be no apparent relationship between elevated desmosines and proteases in the lung in young children with CF, further studies are required to define the mechanisms behind increased elastin metabolism in those children.
49
Šáchová, Vendula. "Management vzácných nemocí v České republice - Cost of Illness cystické fibrózy." Master's thesis, Vysoká škola ekonomická v Praze, 2011. http://www.nusl.cz/ntk/nusl-125239.
Full textAbstract:
This diploma thesis describes the issue of rare diseases in terms of their essence and the situation in the Czech Republic nowadays. As a disease model was chosen cystic fibrosis. The main goal of this work is to quantify the cost of treatment of cystic fibrosis for three consecutive years and to analyse their structure in the cohorts of patients.
50
Veronez, Liliani de Fátima 1980. "A capnografia volumétrica na avaliação da doença pulmonar em pacientes adultos com fibrose cística e pacientes bronquectásicos não fibrocísticos." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/309663.
Full textAbstract:
Orientador: Ilma Aparecida PaschoalDissertação (mestrado) - Universidade Estadual de Campinas. Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-16T07:57:21Z (GMT). No. of bitstreams: 1 Veronez_LilianideFatima_M.pdf: 1419140 bytes, checksum: 5e1cf61453007024c5cfed1c82bd88b0 (MD5) Previous issue date: 2010
Resumo: Objetivos: O objetivo geral deste trabalho foi estudar o uso da capnogragfia volumétrica na avaliação de pacientes portadores de bronquectasias, relacionadas ou não à fibrose cística, para verificar o comportamento de algumas medidas fornecidas pelo aparelho, mais especificamente, analisar a variável "Slope da fase 3" (Slp3) e aquelas relacionadas à caracterização do padrão ventilatório (frequência e tempo expiratório), nos pacientes bronquectásicos, em comparação aos valores obtidos em pacientes normais. Métodos: Foram estudados 24 (vinte e quatro) pacientes com Fibrose Cística e 21 (vinte e um) pacientes não fibrocísticos com bronquectasias idiopáticas, que frequentam o ambulatório de Pneumologia do Hospital de Clínicas da Unicamp. O diagnóstico de Fibrose Cística (FC) foi baseado em 02 (dois) testes de suor, com concentrações de cloro (Cl) alteradas, pelo método de iontoforese por pilocarpina. Os pacientes com bronquectasias foram assim diagnosticados por apresentarem produção crônica de secreção e tomografia computadorizada de alta resolução do tórax (TCAR) com bronquectasias em pelo menos dois segmentos pulmonares. Testes Espirométricos e Capnografia Volumétrica foram feitos. O Grupo Controle foi composto por 114 (cento e quatorze) pacientes não fumantes, sem sintomas e antecedentes de doença respiratória. Resultados: Como resultados, quando comparados o grupo de pacientes com FC com o Grupo Controle, aquele apresentou valores significativos (p<0,05) para Saturação de Oxigênio (SpO2); Frequencia Respiratória (FR); volume expiratório normalizado pelo peso menor (VE/Kg); tempo expiratório (Te) menor e aumento do Slope 3 normalizado pelo volume expirado (P3Slp/Ve). Comparados o grupo de pacientes com Bronquectasias (BQ) com o grupo controle, os resultados significativos (p<0,05) obtidos foram SpO2 menor nos pacientes; FR maior; Ve/Kg menor; Te menor; P3Slop/Ve maior; VCO2 menor. Reunidos os grupos de pacientes (FC e BQ) para comparação com os controles, os pacientes apresentaram valores significativos (p<0,05) para as variáveis, SpO2 menor; FR maior; Ve/Kg menor; Te menor; maior P3Slop/Ve; VCO2 menor. Todas as variáveis capnográficas e espirométricas não mostraram diferenças significativas quando foram comparados os grupos de pacientes fibrocísticos e bronquectásicos. Conclusões: As conclusões foram de que ambos os grupos apresentaram defeitos semelhantes na espirometria (obstrução com concomitante redução da capacidade vital forçada), o padrão respiratório revelado durante a capnografia sugeriu a presença de uma restrição verdadeira (FR alta, Te e Ve baixos e PEF normal). As variáveis capnograficas nos grupos de pacientes mostraram aumentos do slope da fase 3 quando comparados aos controles, fato que provavelmente indica a presença de uma doença difusa de pequenas vias aéreas nas duas doenças, causadora de heterogeneidades de ventilação
Abstract: Objectives: The aim of this study was to use volumetric capnography to evaluate the breathing pattern and ventilation inhomogeneitis in patients with chronic sputum production and bronchiectasis and to correlate the phase 3 slope of the capnographic curve to spirometric measurements. Methods: Twenty-four patients with cystic fibrosis (CF) and 21 patients with non-cystic fibrosis idiopathic bronchiectasis (BC) were serially enrolled.The diagnosis of cystic fibrosis was based on the finding of at least two abnormal sweat chloride concentrations (iontophoresis sweat test). The diagnosis of bronchiectasis was made when the patient had a complaint of chronic sputum production and compatible findings at high resolution computed tomography (HRCT) scan of the thorax.. Spirometric tests and volumetric capnography were performed. One hundred and fourteen subjects of the control group for capnographic variables were non-smokers volunteers, who had no respiratory symptoms whatsoever and no past or present history of lung disease. Results: When compared to controls, patients in CF group had lower SpO2 (p<0.0001), higher respiratory rates (RR) (p<0.0001), smaller expiratory volumes normalized for weight (Ve/kg) (p<0.028), smaller expiratory times (Te) (p<0.0001) and greater phase 3 Slopes normalised for tidal volume (P3Slp/Ve) (p<0.0001). When compared to controls, patients in the BC group had lower SpO2 (p<0.0001), higher RR (p<0.004), smaller Ve/kg (p<0.04), smaller Te(p<0.007), greater P3Slp/Ve (p<0.0001), smaller VCO2 (p<0.0002). The pooled data from the two patient groups, when compared to controls showed that the patients had lower SpO2 (p<0.0001), higher RR (p<0.0001), smaller Ve/kg (p<0.05), smaller Te(p<0.0001), greater P3Slp/Ve (p<0.0001), smaller VCO2 (p<0.0003). All the capnographic and spirometric variables evaluated showed no significant differences between CF and BC patients. Conclusions: Spirometric data in this study reveals that the patients had obstructive defects with concomitant low vital capacities and both groups had very similar abnormalities. The capnographic variables in the patient group suggest a restrictive respiratory pattern (greater respiratory rates, smaller expiratory times and expiratory volumes, normal peak expiratory flows). Both groups of patients showed increased phase III slopes when compared to controls, fact that probably indicates the presence of diffuse disease of small airways in both conditions leading to inhomogeneitis of ventilation
Mestrado
Ciencias Basicas
Mestre em Clinica Medica