Rozprawy doktorskie na temat „Cardiovascular system – Diseases – Genetic aspects”
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McCaskie, Pamela Ann. "Multiple-imputation approaches to haplotypic analysis of population-based data with applications to cardiovascular disease". University of Western Australia. School of Population Health, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0160.
Pełny tekst źródłaWilder, Steven P. "Computational analysis of susceptibility genes for diabetes and cardiovascular diseases in animal models". Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.670109.
Pełny tekst źródłaThomas, Saralene Iona. "Genetic markers in the differential diagnosis in a family setting of episodic loss of consciousness". Thesis, Stellenbosch : Stellenbosch University, 2000. http://hdl.handle.net/10019.1/51777.
Pełny tekst źródłaPretorius, Jakobus. "Investigation of the relationship between genetic and environmental risk factors associated with obesity and insulin resistance in South African patients with non-alcoholic fatty liver disease(NAFLD)". Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/71689.
Pełny tekst źródłaIncludes bibliography
ENGLISH ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in the world. The disease spectrum of NAFLD extends from steatosis (types 1,2) to non-alcoholic steatohepatitis (NASH) with inflammation (types 3,4). The aims of the study were 1) to analytically validate high-throughput real time polymerase chain reaction (RT-PCR) assays for three selected single nucleotide polymorphisms (SNPs), FTO rs9939609 (intron 1 T>A), TNF-α rs1800629 (-308 G>A) and PPARγ rs1801282 (Pro12Ala, 34 C>G), and 2) to perform genotype-phenotype association studies in relation to biochemical abnormalities, disease severity and age of onset. A total of 119 patients with fatty liver identified on ultrasound, including 88 histologically confirmed NAFLD patients, and 166 control individuals were genotyped for the three selected SNPs. RT-PCR validated against direct sequencing as the gold standard was used for detection of genetic variation. All three SNPs were in Hardy Weinberg equilibrium in the study population, except for a deviation in genotype distribution detected for PPARγ rs1801282 in the NAFLD patient subgroup (p<0.001). After adjustment for age and gender, the risk-associated FTO rs9939609 A-allele was detected at a significantly higher frequency in the Caucasian compared with Coloured patients (p=0.005). The opposite was detected for the risk-associated TNF-α rs1800629 A-allele, which occurred at a significantly higher frequency in the Coloured compared with Caucasian NAFLD patients (p=0.034). The onset of fatty liver disease symptoms was on average 5 years younger in the presence of each risk-associated TNF-α rs1800629 A-allele (p=0.028). When considered in the context of an inferred genotype risk score ranging from 0-6, disease onset occurred on average 3 years earlier (p=0.008) in the presence of each risk-associated FTO A-allele, TNF-α A-allele or PPARγ C-allele. After adjustment for age, gender and race, no differences in genotype distribution or allele frequencies were observed between histologically confirmed NAFLD (types 1,2) and NASH (types 3,4) patients, while the minor allele frequency for the TNF-α rs1800629 was significantly higher in the total NAFLD (types 1-4) (p=0.047) as well as NASH subgroup (NAFLD types 3,4) (p=0.030) compared with obese patients without a histologically confirmed NAFLD diagnosis. A significant correlation was furthermore observed between the number of TNF-α rs1800629 A-alleles and increasing CRP levels (p=0.029), with a favourable reduced effect in the presence of low- to moderate alcohol intake. The average waist circumference of physically active NAFLD patients was 12% lower than in physically inactive patients (p=0.004). In view of the results presented in this study, the inclusion of the selected SNPs, and in particular the pro-inflammatory TNF-α rs1800629 polymorphism, may be considered as part of a comprehensive cardiovascular risk evaluation of NAFLD patients. Ultimately, early detection of patients with fatty liver disease symptoms and effective intervention based on the underlying disease mechanism may prevent progression from NAFLD to NASH, shown to be an independent risk factor for cardiovascular diseases.
AFRIKAANSE OPSOMMING: Nie-alkoholiese lewervervetting (NALV) is die mees algemene kroniese lewersiekte in die wêreld. Die siektespektrum van NALV strek van steatose (vervette lewer tipes 1,2) tot steatohepatitis met inflammasie (NASH tipes 3,4). Die doel van die studie was 1) om analities die hoë omset polimerase kettingreaksie (RT-PKR) metode te valideer vir die geselekteerde enkel nukleotied polimorfismes (ENPs) FTO rs9939609 (intron 1 T>A), TNF-α rs1800629 (-308 G>A) en PPARγ rs1801282 (Pro12Ala, 34 C>G), en 2) om genotipe-fenotipe assosiasie studies uit te voer ten opsigte van relevante biochemiese abnormaliteite, graad van die siekte en aanvangsouderdom. ’n Totaal van 119 pasiënte met vervette lewers is geïdentifiseer met behulp van ultraklank, insluited 88 histologies-bevestigde NALV pasiënte, en 166 kontrole individue. Hierdie pasiënte is gegenotipeer vir die 3 geselekteerde ENP’s. RT-PKR gevalideer met direkte DNA volgorde bepaling as die goue standaard, is gebruik vir opsporing van genetiese variasie. Al die ENP’s was in Hardy Weinberg ekwilibrium in die studie populasie, behalwe vir ’n afwyking in genotipe verspreiding waargeneem vir PPARγ in die NALV subgroep (p<0.001). Nadat aanpassings gemaak is vir ouderdom en geslag, is die risiko-geassosieerde FTO rs9939609 A-alleel waargeneem teen ’n betekenisvol hoër frekwensie in die Kaukasiese pasiënte in vergelyking met Kleurling pasiënte (p=0.005). Die teenoorgestelde is waargeneem vir die risiko-geassosieerde TNF-α rs1800629 A-alleel wat voorgekom het teen ’n betekenisvol hoër frekwensie in die Kleurling NALV pasiënte, in vergelyking met Kaukasiese NALV pasiënte (p=0.034). Die aanvang van NALV was gemiddeld 5 jaar vroeër in die teenwoordigheid van elke risiko-geassosieerde TNF-α rs1800629 A-alleel (p=0.028). Met inagneming van ’n genotipe risiko telling tussen 0–6, het aanvang van siekte gemiddeld 3 jaar vroeër voorgekom (p=0.008) in die teenwoordigheid van elke toenemende risiko-geassosieerde FTO A-alleel, TNF-α A-alleel en PPARγ C-alleel. Nadat aanpassings gemaak is vir ouderdom, geslag en ras, is geen verskille waargeneem in genotipe verspreiding of alleel frekwensies tussen histologies bevestigde NALV (tipes 1,2) en NASH (tipes 3,4) pasiënte nie, terwyl die minor alleel telling vir die TNF-α rs1800629 betekenisvol hoër was in die totale NALV (tipes 1–4) (p=0.047) asook die NASH subgroep (NALV tipes 3,4) (p=0.03) in vergelyking met vetsugtige pasiënte sonder ’n histologies bevestigde diagnose. ‘n Statisties beteknisvolle korrelasie is verder waargeneem tussen die aantal TNF-α rs1800629 A-allele en toenemende CRP vlakke (p=0.029), met n gunstige verlaagde effek in die teenwoordigheid van lae alcohol gebruik. Die gemiddelde middellyf-omtrek van fisies aktiewe NALV pasiënte was 12% minder as fisies onaktiewe pasiente (p=0.004). Na aanleiding van die resultate van hierdie studie behoort insluiting van geselekteerde ENP’s, en in besonder die pro-inflammatoriese TNF-α rs1800629 polimorfisme, as deel van ’n omvattende kardiovaskulere risiko evaluasie oorweeg te word. Aan die einde van die dag mag vroeë identifikasie van NALV pasiente en effektieve intervensie gebasseer op die onderliggende siekte meganisme, vordering tot NASH verhoed wat getoon is om ’n onafhanklike risiko faktor vir kardiovaskulêre siekte te wees.
Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology
Chan, Hiu-ting, i 陳曉庭. "The effect of diet intake on vascular function and therapeutic effect of cardiovascular medicine in patients with cardiovascular disease". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hub.hku.hk/bib/B50434342.
Pełny tekst źródłapublished_or_final_version
Medicine
Doctoral
Doctor of Philosophy
Chow, Wai-sum, i 周瑋琛. "A systematic review on the role of chocolate in the prevention of cardiovascular diseases". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B47560198.
Pełny tekst źródłapublished_or_final_version
Community Medicine
Master
Master of Public Health
Ng, Kuen-to, i 伍權韜. "The gender difference and association between social position and cardiovascular risk factors in Hong Kong". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B45012775.
Pełny tekst źródłaChen, Hua, i 陳華. "Relationship between psychological status and vascular function in subjects with and without cardiovascular diseases". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41290409.
Pełny tekst źródłaCai, Wenjun, i 蔡文珺. "A review of the association between occasional and moderate alcohol consumption and cardiovascular disease". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206907.
Pełny tekst źródłapublished_or_final_version
Public Health
Master
Master of Public Health
Henning, Andrea L. "Monitoring Monocyte Oxldl Phagocytosis As a Cardiovascular Disease Risk Factor Following a High-fat Meal". Thesis, University of North Texas, 2014. https://digital.library.unt.edu/ark:/67531/metadc700101/.
Pełny tekst źródłaOrsatti, Cláudio Lera [UNESP]. "Avaliação do polimorfismo genético da lecitina ligante de manose (MBL2) e da expressão gênica dos receptores Toll-Like (TLR) como bio-marcadores do risco cardiovascular em mulheres na pós-menopausa". Universidade Estadual Paulista (UNESP), 2014. http://hdl.handle.net/11449/123279.
Pełny tekst źródłaFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
FAPESP: 2009/14884-9
Orsatti, Cláudio Lera. "Avaliação do polimorfismo genético da lecitina ligante de manose (MBL2) e da expressão gênica dos receptores Toll-Like (TLR) como bio-marcadores do risco cardiovascular em mulheres na pós-menopausa /". Botucatu, 2014. http://hdl.handle.net/11449/123279.
Pełny tekst źródłaCoorientador: Steven Witkins
Banca: Maria Terezinha Serrão Peraçoli
Banca: Cesar E. Fernandes
Banca: Aarão Mendes Pinto
Banca: Renata D. Jouiliano
Resumo: Não disponível
Abstract: Not available
Doutor
Hantke, Janina. "Positional cloning of the gene mutated in hereditary motor and sensory neuropathy-russe (HMSNR)". Western Australian Institute for Medical Research, 2005. http://theses.library.uwa.edu.au/adt-WU2005.0104.
Pełny tekst źródłaBrinkman, Patricia M. "A computer program on nutrition and cardiovascular disease for the junior and senior high level". CSUSB ScholarWorks, 1985. https://scholarworks.lib.csusb.edu/etd-project/304.
Pełny tekst źródłaNelson, Charles. "Autonomic Balance and Control of Stress for Participants Identified as High or Low Hostile and as Having a Positive or No Family History of Cardiovascular Disease". Thesis, University of North Texas, 2003. https://digital.library.unt.edu/ark:/67531/metadc4301/.
Pełny tekst źródłaLiu, Lixun. "Exploring ethnic inequalities in cardiovascular disease using Hospital Episode Statistics". Thesis, St Andrews, 2009. http://hdl.handle.net/10023/819.
Pełny tekst źródłaFong, Chung-yan Gardian, i 方頌恩. "A study of motor neuron disease in the community and in a large multigenerational kindred". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B37602263.
Pełny tekst źródłaHuff, Courtney L. "Investigating the binding of streptococcal monoclonal antibody 10F5 in the heart of the Lewis rat". CardinalScholar 1.0, 2009. http://liblink.bsu.edu/uhtbin/catkey/1538086.
Pełny tekst źródłaCheng, King-yip, i 鄭競業. "APPL1 as a novel signaling mediator of adiponectin and insulin: molecular mechanisms and physiologicalimplications". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B42182177.
Pełny tekst źródłaChen, Jing, i 陈静. "Economic evaluation of community pharmacy based smoking cessation on burden of chronic obstructive pulmonary disease (COPD) in Hong Kong". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B47157252.
Pełny tekst źródłapublished_or_final_version
Public Health
Doctoral
Doctor of Philosophy
Viljoen, Janet Erica. "Strength training and cardiovascular risk post-menses, with particular emphasis on the plasma lipoproteins: a controlled trial". Thesis, Rhodes University, 2014. http://hdl.handle.net/10962/d1013578.
Pełny tekst źródłaMaiden name: Kelly, Janet Erica
Figaji, Tamara Ann. "Impact of a lifestyle physical activity intervention on school going children's physical activity participation". Thesis, University of the Western Cape, 2009. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_6968_1297753030.
Pełny tekst źródłaAssociated with physical inactivity and obesity are numerous other health risks which have become a major health concern. A steady decrease in the levels of physical activity during childhood and adolescents have been noted in various parts of the world. The picture of low physical activity levels in developed countries is no different in developing countries. Children spend the majority of their day at school therefore a school setting is ideal to conduct physical activity intervention studies The primary aim of this study was to measure the effect of an intervention programme on the physical activity participation levels among school going children and adolescents. The study was carried out at an urban independent Catholic school. The sample, which was conveniently selected, which included 100 learners from grade 5 to 7 with parental consent. A quantitative approach using a quasi-experimental design was used in this study. Baseline data included levels of physical activity participation, Body Mass Index (BMI), hip-waist ratio, and socio-demographic variables. Physical activity was assessed with the Modifiable Activity Questionnaire for Adolescents. The Promoting Lifestyle activity for Youth (PLAY) programme was implemented at the school. This process-oriented programme shifts the focus from fitness toward regular participation in daily physical activity, and it is not intended to replace a comprehensive physical education programme.
Nelson, Mark 1957. "Aspects of pharmacological management of hypertension in general practice". Monash University, Dept. of Epidemiology and Preventive Medicine, 2002. http://arrow.monash.edu.au/hdl/1959.1/7923.
Pełny tekst źródłaBester, Dirk Jacobus. "The effect of red palm oil supplementation of an oxidative risk induced diet and a high saturated fat diet on ischaemia/perfusion injury in the isolated perfused rat heart". Thesis, Cape Peninsula University of Technology, 2006. http://hdl.handle.net/20.500.11838/1470.
Pełny tekst źródłaResearch has shown that the activation of the NO-cGMP pathway leads to myocardial protection from oxidative stress conditions, such as ischaemia and reperfusion. Few of these studies have however combined diet induced oxidative stress with ischaemia/reperfusion injury. Although little is known about the effects of supplements such as red palm oil (RPO) on the NO-cGMP pathway, research has shown that dietary RPO-supplementation improved reperfusion aortic output recovery through mechanisms that may include activation of the NO-cGMP- and inhibition of the cAMP pathway. RPO is an antioxidant-rich oil containing ~carotene and Vitamin E (tocopherols and tocotrienols). The aims of this study were to determine: 1) whether RPO-supplementation of an oxidative risk induced diet (ORD) and a high saturated fat diet (HFD) offers protection against ischaemia/reperfusion injury in the isolated perfused rat heart and 2) the possible mechanisms for this protection. Male Wistar rats were randomly divided into four groups for a period of 14 weeks according to the dietary supplementation they received. The control groups received either an oxidative risk induced diet (ORD) or a high saturated fat diet (HFD), while the experimental groups received an ORD supplemented with RPO (ORD+RPO) or a HFD supplemented with RPO (HFD+RPO).
Fitzgibbons, Timothy P. "Role of Perivascular and Visceral Adipose Tissues in Murine Models of Obesity and Atherosclerosis: A Dissertation". eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/619.
Pełny tekst źródłaGalhardi, Cristiano Machado [UNESP]. "Efeitos da elevada ingestão de sacarose e da restrição no tempo de ingestão alimentar sobre parâmetros morfométricos, bioquímicos séricos e cardíacos de ratos". Universidade Estadual Paulista (UNESP), 2007. http://hdl.handle.net/11449/102657.
Pełny tekst źródłaFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Estudos relacionados às conseqüências metabólicas da ingestão de dietas ricas em sacarose ou frutose ainda são limitados. Assim como os estudos que envolvem a restrição no número de refeições diárias. No presente trabalho foram utilizados 24 ratos machos wistar, de peso inicial médio de 222,69 l 16,49g, divididos aleatoriamente em quatro grupos AD, RT, ADS, RTS com seis ratos cada. O grupo AD foi considerado controle, recebendo dieta basal ad libitum. Os animais do grupo RT receberam a mesma quantidade de dieta ingerida pelo grupo AD, oferecida diariamente no período restrito de duas horas (9:00 às 11:00h). Os animais do grupo ADS receberam ração controle ad libitum e para beber, solução aquosa de sacarose 30% ad libitum. Ratos do grupo RTS foram tratados com a mesma quantidade de ração ingerida pelo grupo ADS, oferecida durante o tempo restrito de 2 horas diárias e solução aquosa de sacarose 30% ad libitum. Após 30 dias de tratamentos os animais foram sacrificados. O soro foi utilizado para determinação do perfil lipídico e marcadores do estresse oxidativo. Restrição no tempo de ingestão alimentar desenvolveu dislipidemia com elevação nos fatores de riscos para aterosclerose, elevação no estresse oxidativo, bem como, diminuição de marcadores de defesa antioxidantes. A elevação na atividade sérica da fosfatase alcalina sugere a existência de alteração hepática. O modelo de dieta rica em carboidratos apresentou característica fenotípica de síndrome metabólica, que foi confirmada pela dislipidemia, acompanhada de hipertrigliceridemia. A restrição no tempo de ingestão alimentar com dieta rica em carboidrato induziu dislipidemia, elevação na ALP sugerindo alteração hepática, bem como elevação nos marcadores de estresse oxidativo e diminuição nas defesas antioxidantes.
Not available.
Hene, Nceba Mzimkulu. "Physical fitness of elite women's rugby union players over a competition season". Thesis, University of the Western Cape, 2011. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_6193_1305016359.
Pełny tekst źródłaThe primary aim of this study was to investigate the changes in physical fitness characteristics of elite women&rsquo
s rugby union players over the duration of the season. Thirty two elite female rugby players who were identified as members of the South African Rugby Union High Performance Squad were assessed on three separate occasions (pre-season, mid-season and post-season) throughout the competition season. The players were sub-divided into two positional categories consisting of 17 forwards and 15 backs. On all testing occasions, players underwent anthropometric (stature, body mass and sum of 7 skinfolds) and physical performance measurements (sit-and-reach, vertical jump, 10m and 40m speed, 1 RM bench press
pull-ups
1 min push-ups and multi-stage shuttle run test). A two&ndash
factor analysis of variance evaluated differences in the physical fitness variables between and within playing positions over the competition season.
Galhardi, Cristiano Machado. "Efeitos da elevada ingestão de sacarose e da restrição no tempo de ingestão alimentar sobre parâmetros morfométricos, bioquímicos séricos e cardíacos de ratos /". Botucatu : [s.n.], 2007. http://hdl.handle.net/11449/102657.
Pełny tekst źródłaBanca: Marília Afonso Rabelo Buzalaf
Banca: Rodrigo Cardoso de Oliveira
Banca: Ana Angélica Henrique Fernandes
Banca: Regina Coeli de Miranda Burneiko
Resumo: Estudos relacionados às conseqüências metabólicas da ingestão de dietas ricas em sacarose ou frutose ainda são limitados. Assim como os estudos que envolvem a restrição no número de refeições diárias. No presente trabalho foram utilizados 24 ratos machos wistar, de peso inicial médio de 222,69 l 16,49g, divididos aleatoriamente em quatro grupos AD, RT, ADS, RTS com seis ratos cada. O grupo AD foi considerado controle, recebendo dieta basal ad libitum. Os animais do grupo RT receberam a mesma quantidade de dieta ingerida pelo grupo AD, oferecida diariamente no período restrito de duas horas (9:00 às 11:00h). Os animais do grupo ADS receberam ração controle ad libitum e para beber, solução aquosa de sacarose 30% ad libitum. Ratos do grupo RTS foram tratados com a mesma quantidade de ração ingerida pelo grupo ADS, oferecida durante o tempo restrito de 2 horas diárias e solução aquosa de sacarose 30% ad libitum. Após 30 dias de tratamentos os animais foram sacrificados. O soro foi utilizado para determinação do perfil lipídico e marcadores do estresse oxidativo. Restrição no tempo de ingestão alimentar desenvolveu dislipidemia com elevação nos fatores de riscos para aterosclerose, elevação no estresse oxidativo, bem como, diminuição de marcadores de defesa antioxidantes. A elevação na atividade sérica da fosfatase alcalina sugere a existência de alteração hepática. O modelo de dieta rica em carboidratos apresentou característica fenotípica de síndrome metabólica, que foi confirmada pela dislipidemia, acompanhada de hipertrigliceridemia. A restrição no tempo de ingestão alimentar com dieta rica em carboidrato induziu dislipidemia, elevação na ALP sugerindo alteração hepática, bem como elevação nos marcadores de estresse oxidativo e diminuição nas defesas antioxidantes.
Abstract: Not available.
Doutor
Jackson, Lindsay May. "Male and female cardiovascular risk in an urban, black working population". Thesis, Rhodes University, 2011. http://hdl.handle.net/10962/d1005205.
Pełny tekst źródłaCrymble, Tegan. "Cardiovascular disease risk in Black African females and the efficacy of a walking programme on blood pressure in a sub-sample". Thesis, Rhodes University, 2014. http://hdl.handle.net/10962/d1013234.
Pełny tekst źródłaWildschutt, Phillip Jacobus. "The effect of accumulative physical activity on the fitness and health status of rural school children". Thesis, University of the Western Cape, 2005. http://etd.uwc.ac.za/index.php?module=etd&.
Pełny tekst źródłaFisher, Leslie Reginald. "Evaluation of high-throughput methodology for multi-gene screening in patients with Non-Alcoholic Fatty Liver Disease (NAFLD)". Thesis, Stellenbosch : Stellenbosch University, 2011. http://hdl.handle.net/10019.1/17896.
Pełny tekst źródłaENGLISH ABSTRACT: Non-Alcoholic Fatty Liver Disease (NAFLD) is the most prevalent chronic liver disease in Western countries and is considered the hepatic manifestation of the Metabolic Syndrome (MetS). Its heterogeneous nature ranges from hepatic steatosis through steatohepatitis to advanced fibrosis and cirrhosis where the ingestion of significant amounts of alcohol has been excluded. The disease profile of NAFLD and its necro-inflammatory subset Nonalcoholic Steatohepatitis (NASH) were described in the parent study, which provided a clinically well-characterised patient cohort for the present investigation. South African patients with NASH had significantly higher mean serum cholesterol and triglyceride levels than those with fatty liver only. The objective of this study was to implement a high-throughput real-time polymerase chain reaction (PCR) method in our laboratory to enable the assessment of cardiovascular genetic risk factors in NAFLD patients. The specific aims were to determine the clinical utility and perform analytical validation of each mutation included in the multi-gene cardiovascular disease (CVD) screening assay. The Pathology Supported Genetic Testing (PSGT) concept developed at our department provides a practical approach to personalized medicine. The CVD multi-gene screen analyses key metabolic pathways relating to atherogenic dyslipidaemia, chronic inflammation, hypercoagulation and iron dysregulation implicated in insulin resistance, which is known to be a universal factor in the pathogenesis of NAFLD. Deleterious low-penetrance mutations in the APOE (APOE2 and E4 alleles), MTHFR (677C>T and 1298A>C), F2 (20210G>A), FV (1691G>A, Leiden) and HFE (C282Y and H63D) genes were included for analysis due to their important role as genetic contributors to these biological processes. A total of 178 patients diagnosed with NAFLD and 75 controls were studied using direct DNA sequencing and a RT-PCR system for mutation detection. In addition, two patients with high ferritin levels were included as case studies. A significant association was found between HFE mutations and elevated Alanine Transaminase (ALT) levels in the NAFLD population (p = 0.04). This discovery is interpreted as the identification of a subset of patients at greater risk of developing progressive liver damage who would benefit most from genetic testing to direct more aggressive therapy at an earlier stage. The necessity of an integrative, systems-based network approach was demonstrated to more accurately distinguish between Hereditary Haemochromatosis (HH) and Insulin Resistance-associated Hepatic Iron Overload (IR-HIO) syndrome in obese patients. The PSGT approach to personalized medicine facilitates diagnosis of CVD subtypes, prevention of cumulative risk and the formulation of gene-based intervention programs tailored to the needs of the patient. These findings support the clinical utility of the CVD multi-gene test to guide chronic disease risk management in patients with NAFLD. The HFE mutation detection component of this test is of particular relevance in directing an effective treatment strategy in patients with a medical history of CVD and/or high iron stores.
AFRIKAANSE OPSOMMING: Nie-Alkoholiese Vettige Lewer Siekte (NAFLD) is die mees algemene kroniese lewer siekte in Westerse lande en word bestempel as die hepatiese manifestasie van die Metaboliese Sindroom (MetS). Die heterogene natuur van NAFLD strek van hepatiese steatose deur steatohepatietis tot gevorderde fibrose en sirrose waar grootskaalse alkohol inname uitgesluit is. Die siekte-profiel van NAFLD en sy nekro-inflammatoriese subtipe Nie-Alkoholiese Steatohepatietis (NASH) is reeds beskryf in die ouer studie, wat ‗n klinies goed-gekarakteriseerde pasiënt groep vir die huidige ondersoek daar gestel het. Suid-Afrikaanse pasiënte met NASH het beduidend hoër gemiddelde serum cholesterol en trigliseried vlakke in vergelyking met slegs vettige lewer. Die doel van hierdie studie was om ‗n hoë deurvoer rieëltyd polimerase kettingreaksie (RT-PCR) metode in ons laboratorium te implimenteer om kardiovaskulêre genetiese risiko faktore in NAFLD pasiënte te ondersoek. Die spesifieke mikpunte was om die kliniese nut en analitiese geldigheid van elke mutasie wat ingesluit is in die multi-geen kardiovaskulêre siekte (KVS) siftings toets vas te stel. Die Patologie Ondersteunde Genetiese Toetsing (PSGT) konsep wat by ons departement ontwikkel is, verskaf ‗n praktiese benadering tot persoonlike medisyne. Die KVS multi-geen toets analiseer belangrike metaboliese weë verwant aan atherogene dyslipidemie, kroniese inflammasie, oormatige bloedstolling en yster disregulering wat betrokke is by insulien weerstand wat bekend is as ‗n universele factor in the patogenese van NAFLD. Nadelige lae-penetrasie mutasies in die APOE (APOE2 en E4 allele), MTHFR (677C>T en 1298A>C) F2 (20210G>A), FV (1691G>A, Leiden) en HFE (C282Y en H63D) gene was ingesluit vir analise as gevolg van hul belangrike rol as genetiese bydraers tot die bogenoemde biologiese prosesse. ‗n Totaal van 178 pasiënte gediagnoseer met NAFLD en 75 kontroles is bestudeer deur gebruik te maak van direkte DNA volgordebepaling en ‗n RT-PCR metode vir mutasie opsporing. Twee pasiënte met verhoogde ferritien vlakke is ook as gevalle studies ingesluit. ‗n Beduidende assosiasie is gevind tussen HFE mutasies en verhoogde Alanien Transaminase (ALT) vlakke in die NAFLD studiepopulasie (p = 0.04) wat aanduidend is van ‗n subgroup van pasiënte wat die meeste baat sal vind uit genetiese toetsing om meer aggressiewe behandeling te rig op' n vroeër stadium. Die noodsaaklikheid van 'n geïntegreerde, stelsels-gebaseerde netwerk benadering is gewys om meer akkuraat te onderskei tussen Oorerflike Hemochromatose (HH) en Insulien Weerstand-geassosieerde Hepatiese Yster Oorlading (IR-HIO) sindroom in vetsugtige pasiënte. Die PSGT benadering tot persoonlike medisyne formuleer geen-gebaseerde intervensie programme aangepas tot die behoeftes van die pasiënt ek maak diagnose van KVS-subtipes en voorkoming van kumulatiewe risiko moontlik. Hierdie bevindinge ondersteun die kliniese nut van die KVS multi-geen toets om riglyne vir die risikobestuur van kroniese siektes soos NAFLD daar te stel. Die HFE mutasie opsporings komponent van hierdie toets is van besondere belang om 'n effektiewe strategie vir die behandeling van pasiënte met 'n mediese geskiedenis van KVS en/of hoë yster vlakke daar te stel.
Johnson, Andrew Danner. "Search for functional alleles in the human genome with focus on cardiovascular disease candidate genes". Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1187018497.
Pełny tekst źródłaAdamopoulos, Dionysios. "Environmental determinants of arterial stiffness and wave reflection: pathophysiological mechanisms and clinical implications". Doctoral thesis, Universite Libre de Bruxelles, 2012. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209744.
Pełny tekst źródłaStudy 1: Effects of cold exposure on central and peripheral vascular tone. Our first study explored the effects of cold exposure on aortic stiffness and peripheral microvascular tone. We observed that cold exposure, in addition to its chronotropic effects, provoked an increase in aortic stiffness, as assessed by aortic pulse wave velocity, as well as significant vasoconstriction of peripheral arterioles in the microcirculation. Moreover, we explored the magnitude of this effect in a different population (Black subjects of African origin), which is traditionally characterized by exaggerated reactions to adrenergic stimuli. We noted that the vascular reactions, in terms of both aortic stiffness and microvascular vasoconstriction, were more profound in Black Africans than in age-matched Caucasian-Whites. These results argue for a direct effect of cold exposure on arterial stiffness and peripheral vascular tone, probably through activation of the orthosympathetic system.
Study 2: Exposure to ambient particulate matter and arterial stiffness. We explored the effects of acute exposure to outdoor particulate matter on aortic stiffness and aortic wave reflection. We studied the relationship between central hemodynamic parameters and ambient concentration of particulate matter in a population of patients who attended the Hypertension Clinics of Athens University. After statistical correction for a number of potential confounders, we did not observe an association between ambient concentrations of particulate matter and aortic stiffness. However, in men, particulate matter concentration was related to the amplitude of the reflected wave reaching the aorta from the periphery. These results suggest a direct acute interaction between particulate matter concentration and vascular tone, leading to an enhanced arterial wave reflection.
Study 3: The role of nicotine on the vascular effects of environmental tobacco smoke. Environmental tobacco smoke is considered as the most important source of particulate matter in the indoor environment. We recently demonstrated that exposure to tobacco smoke augmented wave reflection, an effect that was not seen after equivalent exposure to the smoke of non-tobacco, herbal cigarettes. We also noticed that the increased wave reflection was proportional to the plasma concentrations of nicotine. However, a direct causal effect between nicotine, arterial wave reflection and aortic stiffness has never been clearly demonstrated. We observed that increasing nicotine plasma concentration to levels comparable to those seen after extensive exposure to environmental tobacco smoke, provoked an increase in both aortic stiffness and arterial wave reflection after correction for heart rate and blood pressure changes. These results confirm the significant participation of nicotine in the vascular effects of passive smoking.
Conclusions. Globally, our results reveal the deleterious effects of cold, particulate matter exposure, and nicotinic stimulation on arterial stiffness, peripheral microcirculation and aortic wave reflection. The hemodynamic modifications associated with these effects may at least partially explain the causal relation between cold exposure, ambient air pollution and cardiovascular mortality.
Introduction-Objectifs. Le système cardiovasculaire est en relation directe et constante avec l’environnement. L’exposition au froid, la pollution atmosphérique et le tabagisme passif sont associés à des événements cardiovasculaires aigus graves et même fatals. La rigidification des artères et l’intensification de la réflexion de l’onde de pouls au niveau de l’aorte accompagnent le vieillissement et prédisent un risque cardiovasculaire accru. Nous avons testés l’hypothèse que les effets cardiovasculaires délétères des facteurs environnementaux comportent une altération des propriétés élastiques artérielles. Ceci pourrait être un des mécanismes physiopathologiques qui lie la mortalité cardiovasculaire aux variables environnementales.
Étude 1 :Exposition au froid ;effets centraux et périphériques. Notre première étude portait sur l’effet de l’exposition au froid sur la rigidité aortique et le tonus vasculaire des artérioles périphériques. Nous avons démontré que l’exposition au froid, hormis ses effets chronotropes, provoquait une augmentation de la rigidité artérielle – mesuré par la vitesse de l’onde de pouls au niveau de l’aorte - ainsi qu’une vasoconstriction importante au niveau des artérioles de la microcirculation. Nous avons ensuite déterminé l’amplitude de cet effet dans une autre population (sujets Africains-Noirs) qui se caractérise par des réactions plus prononcées aux différentes stimulations adrénergiques. Nous avons observé que les réactions vasculaires, tant au niveau de la rigidité aortique qu’au niveau de la microcirculation, étaient plus marquées chez les Africains-Noirs que chez les Caucasiens. Ces résultats révèlent un effet délétère de l’exposition au froid sur la rigidité aortique et le tonus vasculaire des artères périphériques, probablement via une activation du système orthosympathique.
Étude 2 :Exposition aux microparticules atmosphériques et rigidité artérielle. Nous avons ensuite investigué les effets de la pollution atmosphérique sur la rigidité artérielle et la réflexion de l’onde de pouls vers l’aorte. Nous avons étudié la relation entre les paramètres hémodynamiques centraux et la concentration atmosphérique de microparticules dans une population de patients qui ont consulté la Clinique Universitaire d’Hypertension Artérielle d’Athènes. Après correction statistique pour les facteurs confondants, nous n’avons pas observé de corrélation entre la rigidité artérielle et le taux de microparticules atmosphériques dans l’ensemble de la population investiguée. Par contre, si on restreint l’analyse aux résultats obtenus chez les sujets masculins, on s’aperçoit que la concentration atmosphérique de microparticules était associée de façon significative avec l’amplitude de l’onde réfléchie par la périphérie vers l’aorte et la pression pulsée aortique. Ces résultants suggèrent un effet direct des microparticules au niveau de la microcirculation. L’augmentation de l’amplitude de l’onde réfléchie consécutive à une vasoconstriction périphérique, modifie vraisemblablement les pressions au niveau de l’aorte chez le sujet masculin lors de pics de pollution.
Etude 3 :Le rôle de la nicotine dans les effets vasculaires du tabagisme passif. Le tabagisme passif est considéré comme la source la plus importante d’émission de microparticules au niveau domestique. Cependant, la composition chimique des particules semble jouer un rôle essentiel sur les ondes de réflexion. Nous avons démontré récemment que l’exposition passive à la fumée des cigarettes du tabac augmente l’intensité de la réflexion de l’onde de pouls. Ceci n’a pas été observé avec l’exposition à la fumée des cigarettes non tabagiques, en dépit d’une concentration ambiante tout à fait comparable de microparticules. Par ailleurs, nous avons observé que l’augmentation de l’incidence de l’onde de pouls au niveau de l’aorte était fortement associée à la concentration plasmatique de la nicotine. Un lien causal entre la nicotine, réflexion de l’onde de pouls et rigidité artérielle n’avait jamais clairement été établi. Nous avons testé cette hypothèse en administrant la nicotine pure chez des sujets sains. Nous avons observé que l’augmentation des taux plasmatiques de la nicotine à des valeurs comparables à celles qui surviennent après une exposition intensive au tabagisme passif, intensifiait la réflexion de l’onde de pouls et augmentait la rigidité artérielle. La correction statistique pour l’augmentation de la fréquence cardiaque et l’augmentation de la pression artérielle en réponse à la nicotine ne modifiait pas ces conclusions. Nos résultats démontrent ainsi les effets cardiovasculaires importants de faibles concentrations de nicotine, similaires à ceux qui sont atteints en cas d’exposition à un tabagisme passif.
Conclusions. Nos résultats révèlent les effets néfastes de l’exposition au froid et aux microparticules atmosphériques sur la rigidité artérielle, la microcirculation périphérique et la réflexion de l’onde de pouls. Nous avons pu également démontrer le rôle de la stimulation nicotinique dans les effets vasculaires aigus du tabagisme passif, comme en témoigne l’augmentation de la réflexion de l’onde de pouls au niveau aortique. Ces modifications hémodynamiques favorisent l’ischémie myocardique, et constituent un des mécanismes par lesquels l’exposition au froid et à la pollution atmosphérique favorisent la pathologie cardiovasculaire.
Doctorat en Sciences médicales
info:eu-repo/semantics/nonPublished
"Pharmacogenetics of rosuvastatin therapy and genetic determinants of some cardiovascular risk factors in Chinese patients". Thesis, 2010. http://library.cuhk.edu.hk/record=b6074864.
Pełny tekst źródłaSome novel genetic determinants of the LDL-C response to rosuvastatin treatment have been identified in this study. The responses in HDL-C and triglycerides were related more closely to the baseline levels of these lipids than to any of the polymorphisms examined. Genetic associations with baseline lipid parameters, hsCRP, uric acid and bilirubin were identified and generally correspond with some of the previous reports of studies in Chinese and other ethnic groups.
The key findings of the study are as follows: 1. The polymorphisms most highly associated with the low-density lipoprotein cholesterol (LDL-C) response were 421C>A in the ATP-binding cassette G2 (ABCG2) gene (P=9.2x10 -7), followed by 18281G>A (V257M) in the flavin-containing monooxygenase 3 (FMO3) gene (P=0.0002), 1421C>G in the lipoprotein lipase (LPL) gene (P=0.002), and rs4420638 in the apolipoprotein E/C-I/C-IV/C-II (APOE/C1/C4/C2) gene cluster (P=0.004). These genetic polymorphisms and having FH totally explained 13.6% of the variance in percentage change in LDL-C in response to rosuvastatin. The greater percentage reduction in LDL-C in patients with the ABCG2 421AA genotype compared to those with the ABCG2 421CC genotype was equivalent to at least doubling the dose of rosuvastatin. 2. Three SNPs (glucokinase regulator [ GCKR] rs1260326, apolipoprotein AS [APOA5] -1131T>C and the solute carrier organic anion transporter 1B1 [SLCO1B1] 521T>C) tended to be associated with percentage changes in high-density lipoprotein cholesterol (HDL-C) (P<0.05), but none of these reached the overall significance level. In multivariate stepwise regression analysis, baseline HDL-C (P=1.6x10 -6), having diabetes (P=0.0004) or RA (P=0.002) and the SLCO1B1 521T>C polymorphism (P=0.03) were determinants of HDL-C responses, contributing 9.9% of the variance in percentage change in HDL-C, but the genetic factors only contributed to 0.8% of the variance. 3. The triglyceride response to rosuvastatin was highly variable and was strongly related to baseline levels. The diacylglycerol acyltransferase-2 (DGAT2) rs10899113 C>T polymorphism tended to be associated with reduced triglyceride response in a gene-dose dependent manner. However, in multivariate stepwise regression analysis, baseline triglyceride level was the only factor that strongly related to the triglyceride response, explaining 14.4% of the variance. 4. This study has also analyzed relationships between on-treatment plasma hsCRP concentrations and cardiovascular risk factors and 14 single nucleotide polymorphisms in CRP and other candidate genes, which showed that central obesity, low HDL-C and CRP polymorphisms are major determinants of higher hsCRP levels in Chinese patients on treatment with rosuvastatin. 5. The association between genetic polymorphisms and lipid traits were analyzed in FH and non-FH patients separately due to their different lipid profiles. The analysis has shown that there were different genetic predictors of lipid levels in patients with and without FH and that more genetic factors appeared to affect the baseline lipid levels in patients with FH compared to non-FH patients, suggesting complex interactions between genetic and environmental factors and plasma cholesterol levels in patients with and without FH. 6. The SLC2A9 (solute carrier family 2, member 9) rs1014290 T>C was significantly associated with plasma uric acid levels in a gene-dose dependent manner (P=1.0x10-5) and the relationship was more pronounced in women or in patients without hypertension than in men or patients with hypertension. The ABCG2 421 C>A did not show a significant effect on uric acid levels. 7. The UGT1A1 (uridine diphosphate glucuronosyltransferases family, polypeptide A1) variants *28 (P=1.5x10 -9) and *6 (P=2.2x10-7) were independently associated with increased baseline bilirubin levels. Polymorphisms in SLCO1B1 did not appear to affect bilirubin levels in this study.
Hu, Miao.
Adviser: Brian Tomlinson.
Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: .
Thesis (Ph.D.)--Chinese University of Hong Kong, 2010.
Includes bibliographical references (leaves 230-264).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstract also in Chinese.
Downing, Brandon David. "Myeloid cells induce neurofibromatosis type 1 aneurysm formation through inflammation and oxidative stress". Thesis, 2014. http://hdl.handle.net/1805/5850.
Pełny tekst źródłaNeurofibromatosis Type 1 (NF1) is a genetic disorder resulting from mutations in the NF1 tumor suppressor gene. Neurofibromin is the protein product of NF1 and functions as a negative regulator of Ras activity in both hematopoietic and vascular wall cells, which are critical for maintaining blood vessel homeostasis. NF1 patients are predisposed to chronic inflammation and premature cardiovascular disease, including development of large arterial aneurysms, which may result in sudden death secondary to their rupture. However, the molecular pathogenesis of NF1 aneurysm formation is completely unknown. Utilizing a novel model of Nf1 murine aneurysm formation, we demonstrate that heterozygous inactivation of Nf1 (Nf1+/-) results in enhanced aneurysm formation with myeloid cell infiltration and increased reactive oxygen species in the vessel wall. Using cell lineage-restricted transgenic mice, we show that loss of a single Nf1 allele in myeloid cells is sufficient to recapitulate the Nf1+/- aneurysm phenotype in vivo. Additionally, oral administration of simvastatin, a statin with antioxidant and anti-inflammatory effects, significantly reduced aneurysm formation in Nf1+/- mice. Finally, the antioxidant apocynin was administered orally and also resulted in a significant reduction of Nf1+/- aneurysms. These data provide genetic and pharmacologic evidence that neurofibromin-deficient myeloid cells are the central cellular triggers for aneurysm formation in a novel model of NF1 vascular disease, implicated oxidative stress as the key biochemical mechanisms of NF1 aneurysm formation and provide a potential therapeutic target for NF1 vasculopathy.
Munthali, Richard Junganiko. "Longitudinal analysis of genetic risk factors for cardiovascular disease: the birth to twenty plus cohort". Thesis, 2017. http://hdl.handle.net/10539/23491.
Pełny tekst źródłaNon-communicable diseases (NCDs) pose an increasing burden on public health and economic growth worldwide. The highest increase in prevalence and death rates of NCDs has been seen in low and middle-income countries (LMICs). World Health Organization (WHO) estimates that by 2030, NCDs will account for five times as many deaths as communicable diseases in LMICs and that there will be more than 2.16 billion overweight and 1.12 billion obese individuals in the world. It is also estimated that by 2020 NCDs will contribute 80 percent of the global burden of disease and the largest increase in NCD deaths will occur in Africa. Recent reports indicate that six of the ten leading natural causes of death in South Africa are NCDs. There are few studies that have used longitudinal data to understand the effects of life-course childhood adiposity on future health risks and the early life factors responsible for variations in lifecourse childhood obesity. However, it is not known whether there is a genetic basis for the variability in BMI developmental patterns over time. Lack of comprehensive longitudinal and genetic association data for obesity have made it difficult to do such studies in an African setting. It is still not clear whether the same genetic variants associated with obesity in Europeans and other populations are also associated with these traits in African populations. Understanding the genetic contribution to obesity in the black South African population may help to come up with effective interventions to deal with this emerging epidemic in Africa. The aim of this thesis was to better understand the contribution of genetics and explain the longitudinal genetic basis of childhood and adolescence obesity in black South African children. To deal with this, I firstly studied identification of distinct trajectories of BMI and then relate the established BMI trajectories to the future health risks of elevated blood pressure. Secondly, I explored the early life factors behind BMI trajectory membership, this would help to identify factors that may accelerate an individual’s progression from a normal BMI trajectory pattern membership to the one characterized with elevated BMI. Then lastly, I looked at the additive genetic effect for BMI and determine whether genetic risk of obesity in early adulthood was mediated by early life rapid growth. Results showed variation in BMI developmental patterns between boys and girls; three and four distinct sex-specific BMI trajectories were identified in boys and girls respectively. Children belonging to early onset overweight or obese BMI trajectories, characterized by elevated BMI, had an increased risk of elevated blood pressure in late adolescence, compared to their peers in the normal trajectories. Rapid conditional relative weight gain in early life was associated with increased risk of belonging to a BMI trajectory characterized by consistent elevated BMI over time. Individuals in overweight or obese trajectories had a higher chance of being overweight or obese in early adulthood. I found that a genetic risk score, based on known adult BMI Caucasian risk variants, showed significant longitudinal effects of genetic loci with BMI in childhood and adolescent and significant age-GRS interactions were observed. A higher genetic risk score predicted membership of early onset obese or overweight BMI trajectories. The genetic risk of obesity at 18 years of age was mediated by pre-adolescence and adolescence rapid weight gain. The results from this thesis emphasize the importance of studying individual’s BMI developmental patterns when studying development and progression of obesity. These findings also show that the information obtained from GWAS done in other populations can be equally relevant to African populations and this could be used in early identification of individuals at increased risk of obesity and other NCDs risk factors. Combing genetic risk score, BMI trajectories membership and weight status can be used to help improve the screening process of individuals to be targeted in coming up with targeted educational and behavior intervention programmes for obesity. These programmes should target individuals at risk at early stage in order to reduce the adverse health risk outcomes later in life.
MT 2017
"Work-related stress and cardiovascular risk factors in Chinese". 2004. http://library.cuhk.edu.hk/record=b6073711.
Pełny tekst źródła"April 2004."
Thesis (Ph.D.)--Chinese University of Hong Kong, 2004.
Includes bibliographical references (p. 159-175)
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Mode of access: World Wide Web.
Abstracts in English and Chinese.
Wilkinson, Susan Susskind. "Predictors of exercise relapse in individuals with cardiovascular disease". 2003. http://wwwlib.umi.com/cr/utexas/fullcit?p3116233.
Pełny tekst źródłaCarbe, Christian J. "GENETIC CONTROL OF EYE AND CENTRAL NERVOUS SYSTEM DEVELOPMENT". Thesis, 2011. http://hdl.handle.net/1805/2605.
Pełny tekst źródłaAniridia, a congenital ocular disorder caused by haploinsufficiency of transcription factor PAX6, is characterized by complete or partial iris hypoplasia with associated foveal hypoplasia. Brain imaging performed in patients heterozygous for PAX6 mutations often reveal absence of the brain anterior or posterior commissure, absence of the pineal gland, and a present but reduced in size corpus callosum. Renal coloboma syndrome, another autosomal dominant inherited disease, is characterized by hypodysplastic kidneys and optic nerve defects, and is caused by haploinsufficiency of transcription factor PAX2. In the first part of this thesis we investigated the role of these Pax genes in neural development, by generating an allelic series of knock-in models at the Pax6 locus. We showed that Pax6(5a) and Pax2 could not replace Pax6 for its auto-regulation in lens induction or for neural differentiation in retina. In brain development, however, we demonstrated that cell proliferation in the cerebral cortex and dorsoventral patterning of the telencephalon and neural tube was partially rescued in either knock-in mutant. We believe our novel findings not only reveal Pax-protein functional specificity during neural development, but may also be utilized to understand the aberrant molecular mechanism that result in aniridia and/or renal coloboma syndrome. Aphakia (lack of lens) is a rare human congenital disorder with its genetic etiology largely unknown. In the second part of this thesis, we show that homozygous deletion of Nf1, the Ras GTPase gene underlying human neurofibromatosis type 1 syndrome, caused lens dysgenesis in mouse. While early lens specification proceeded normally in Nf1 mutants, lens induction was disrupted due to deficient cell proliferation. Further analysis showed that ERK signaling was initially elevated in invaginating lens placode, but by lens vesicle stage, Ras signaling antagonist Sprouty2 was up regulated, followed by rapid decrease in ERK phosphorylation. Only after intraperitoneal treatment of U0126, an inhibitor of ERK phosphorylation, was lens development restored in Nf1 mutants. Hyperactive RAS-MAPK signaling is known to cause neuro-cardiofacial-cutaneous (NCFC) syndromes in human. As a member of NCFC family genes, Nf1 represents the first example that attenuation of Ras-MAPK kinase signaling pathway is essential for normal lens development.
Chen, Jan-Yow, i 陳建佑. "Genetic and clinical predictors of sick sinus syndrome associated diseases: impact of renin-angiotensin system on cardiovascular disorders". Thesis, 2013. http://ndltd.ncl.edu.tw/handle/52750158978201094179.
Pełny tekst źródła國立中興大學
生命科學系所
101
Sick sinus syndrome (SSS) is a group of abnormal heart rhythm disorders that result from sinus node malfunction. The syndrome accounts for approximately 50% of pacemaker implantations for bradyarrhythmia. The pathologic findings of SSS have revealed fibrotic change over the sinus node and atrium. Evidences suggest genetic mutations in ion channels may lead to familial SSS. However, limited study is available regarding the mechanism of age-related non-familial SSS. Non-familial SSS is frequently associated with an atrial flutter and presents as tachycardia-bradycardia syndrome. The cavotricuspid isthmus (CTI) is a critical and slow conduction zone of the reentry circuit. Atrial fibrosis and the architecture of the atrial musculature have been suggested to be associated with the underlying mechanism of the slow conduction zone. Myocardial fibrosis is related to up-regulation of rennin-angiotensin system (RAS). These findings indicate the role of RAS in the underlying mechanism of atrial flutter. Radiofrequency catheter ablation therapy to block the CTI has been suggested as the method of choice for atrial flutter management. Anatomical variants of CTI have been related to the difficulty of ablation therapy. However, the detailed anatomical predictors of the CTI for the difficult procedure of radiofrequency catheter ablation have not been well described. We utilized transthoracic echocardiography to evaluate the anatomy of the CTI and found that a Eustachian valve variation of the CTI is an independent predictor for the difficult procedure of AFL ablation. The primary objective of the present study is utilizing gene study methods to investigate the possible candidate gene and underlying pathologic mechanism for non-familial SSS. We found that angiotensinogen promoter polymorphisms are associated with susceptibility to non-familial SSS through the modulation of angiotensinogen expression. In a gene association study, we found that the RAS system was associated with susceptibility to non-familial SSS. In addition, the RAS has also been reported to be associated with other cardiovascular disorders. Aortic dissection is a lethal cardiovascular disorder due to intimal tearing. The up-regulation in the RAS has been reported to be related to the underlying mechanism of aortic dissection. Besides, the clinical predictors for the outcome of aortic dissection are important. However, few reports have addressed this issue. We utilized computed tomography imaging to identify the anatomical predictors of the outcomes of aortic dissection. The false lumen size of an aortic dissection was found to be an independent predictor for the outcomes of aortic dissection. In conclusion, susceptibility to non-familial SSS is associated with RAS gene expression. This study identifies a biological predictor for susceptibility to non-familial SSS and clinical predictors for the outcomes of atrial flutter and aortic dissection, which are linked to non-familial SSS and RAS. The RAS is suggested to be closely linked to the pathophysiologic mechanisms of non-familial SSS and related cardiovascular diseases.
Adelekan, Adeboye Mutiu. "Establishment of screening procedures for genetic disorders and risk factors in the South African Caucasian population". Diss., 2003. http://hdl.handle.net/2263/26738.
Pełny tekst źródłaPatton, Beverly D. "The effect of the consumption of three types of dietary fish on cardiovascular risk predictors". Thesis, 1992. http://hdl.handle.net/1957/27085.
Pełny tekst źródłaGraduation date: 1993
"Effects of menopause and menopausal hormone therapy on vascular reactivity in Hong Kong Chinese women". Thesis, 2006. http://library.cuhk.edu.hk/record=b6074199.
Pełny tekst źródłaConclusion 2. The results of the research partly supported hypothesis 2a. The addition of unopposed oestrogen significantly improved endothelium-dependent but not endothelium-independent arterial relaxation. The results of the research supported hypothesis 2b. The addition of oestradiol combined with progestogen (norethisterone acetate) reversed the reduction in arterial relaxation caused by a surgical menopause. The results of the research partly supported hypothesis 2c. The addition of tibolone reversed the reduction endothelium-dependent but not endothelium-independent arterial relaxation. The results of the research partly supported hypothesis 2d. The addition of oestradiol combined with a progestogen (norethisterone acetate) reversed the reduction in endothelium-dependent but not endothelium-independent arterial relaxation.
Conclusion 3. The results of the research partly supported hypothesis 3a. Endothelium-dependent arterial relaxation but no endothelium-independent arterial relaxation was improved after the addition of menopausal hormone therapy using oestrogen combined with a progestogen in a continuous manner. The results of the research did not support hypothesis 3b. Neither endothelium-dependent arterial relaxation nor the endothelium-independent arterial relaxation was improved by cyclical menopausal HT.
Conclusion 4. The results of the research did not support hypothesis 4. The addition of menopausal hormone therapy using combined oestrogen with progestogen did not improve arterial relaxation in postmenopausal women with established coronary heart disease.
Hypothesis 2. This hypothesis examined three different types of commonly used menopausal HT. That unopposed oestrogen (2a), oestrogen combined with a progestogen (2b and 2d) or a synthetic steriod that has oestrogenic, progestogenic as well as androgenic activity (tibolone, 2c), reverse the reduction in arterial relaxation following menopause in Hong Kong Chinese women.
Hypothesis 3. That menopausal hormone therapy using oestrogen combined with progestogen given in either continuous (3a) or cyclical (3b) regimens improves arterial relaxation in postmenopausal Hong Kong Chinese women.
Hypothesis 4. That menopausal hormone therapy using combined oestrogen with progestogen improves arterial relaxation in postmenopausal Hong Kong Chinese women with established coronary heart disease.
Menopausal HT can in general at least partially reverse changes in arterial relaxation in postmenopausal women. Different types of menopausal HT exhibit different effects on arterial relaxation. In healthy vessels, menopause HT mainly reverses the endothelium-dependent vascular effect, but it remains unclear how menopausal HT affects the endothelium-independent vascular effect. However, with established coronary heart disease, menopausal HT cannot reverse the changes in vascular reactivity.
Summary. Menopause results in a reduction in arterial relaxation. However, GnRHa temporarily induced menopause in young women, the endothelium-independent vasodilatation was not impaired. This difference can be partly explained by the difference in age as vascular reactivity is age dependent. Secondly, GnRHa works with an initial phase of increase in oestrogen production resulting in a shorter duration of hypo-oestrogenism resulting in the lack of impairment on endothelium-independent vasodilatation.
This thesis tested the following hypotheses: Hypothesis 1. That vascular reactivity decreases after the menopause as shown in premenopausal Hong Kong Chinese women with either a surgical (1a) or a medically induced (1b) menopause.
This thesis will examine the effects of menopause and menopausal HT on arterial reactivity which is an indirect measurement of vascular function. Previous studies have shown that oestrogen is a potent coronary artery vasodilator, and this effect may be mediated via both endothelium-dependent and endothelium-independent mechanisms. One method of assessing vascular reactivity is to use ultrasound measurement of changes in brachial artery diameter in response to certain stimuli. Using this technique, changes in both endothelium-dependent and endothelium-independent vasodilatation can be measured. Increased rather than decreased arterial relaxation after stimulus can be viewed as a favourable response.
Yim, So-fan.
Adviser: C. J. Haines.
Source: Dissertation Abstracts International, Volume: 68-09, Section: B, page: 5873.
Thesis (M.D.)--Chinese University of Hong Kong, 2006.
Includes bibliographical references (p. 159-194).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
School code: 1307.
Palma, Anton. "Cardiovascular Disease Risk Behaviors in Human Immunodeficiency Virus-Positive Populations: Exploring a Stress-Coping Hypothesis". Thesis, 2020. https://doi.org/10.7916/d8-b7n0-n029.
Pełny tekst źródłaBoyle, Lia. "A Precision Medicine Approach to Understanding KIF1A Associated Neurological Disorder". Thesis, 2021. https://doi.org/10.7916/d8-0nef-s787.
Pełny tekst źródłaNaude, C. S. "'n Komponentanalise van aggressiwiteitsindekse by koronêre hartsiektes". Thesis, 2014. http://hdl.handle.net/10210/9993.
Pełny tekst źródłaThe health context of South Africa is on the one hand unique in comparison to the rest of the world. On the other hand does it also. show characteristics of both Third World and First World disease patterns. There is a substantial component of the South African health sector that is negatively affected. This can possibly be ascribed to previous health policies. South Africa has unique characteristics concerning the chronic degenerative aspects of the First World disease pattern. White South Africans have the same cardiovascular disease patterns as the rest of the world with the exception that the South African disease patterns has a much larger incidence and degree of seriousness that the rest of the world. Research in the area of the chronic degenerative nature of heart disease and vascular disease is of great importance. It becomes necessary to address degenerative disease and also lifestyle diseases not only medically but also in terms of an individual's lifestyle. The management of an individual's lifestyle will not only have preventive consequences in the South African context, but it can also be utilised in the treat~ent of cardiovascular disease. Research undertaken at the Clinic and Centre for Behavioral Medicine at the Rand Afrikaans University found that the management or treatment of the Type A behavior pattern for the prevention of recurrent cardiovascular diseases were particularly effective. It therefore seems that technology developed elsewhere proves to be effective for the South African context. According to Johnston (1992) two types of risk factors contribute to the development of cardiovascular disease. The first constitute of classical risk factors which include aspects of blood pressure and cholesterol. The second risk factor includes psychological aspects and in particular the Type A behavior pattern and its components. Johnson and Broman (1987) indicate that the components of anger and hostility of the Type A behavior pattern constitute the most important behavioral factor of Type A coronary-prone behavior and cardiovascular disease. Research also indicate that the component of hostility presents a significant predictor of cardiovascular disease (Helmers et al., 1993) . The role of aggression and its components in the Type A behavior pattern was investigated in this study. An attempt was made to establish whether there is a simultaneous reduction in aggression, its components and the Type A behavior pattern and whether certain components of aggression were more important that others. A group of 39 heart patients were investigated on the following indexes: psychological, cardiological and biochemical in order to establish heart disease risk factors in a biopsychosocial context. A modified Type A treatment progranme was administered to this group over a period of twelve weeks at a local heart rehabilitation centre. A second group of 19 patients served as a no-treatment waitinglist control group, but simultaneously underwent an aerobic exercise and cardiovascular counselling programne. The results of this study indicated that cynical hostility was probably the major risk factor of all the components of aggression in the Type A behavior pattern. The second most important component of aggression in the Type A behavior pattern is the expression of anger in general. The latter also corresponds with results found in research on this subj ect. Ov-ert or specific expression of anger .nd the control of anger also contribute to the psychosocial causation of Type A behavior pattern in cardiovascular disease. Comparisons of the experimental and control groups after the intervention showed statistically significant differences of anger expression in general, specific anger expression, inhibition of anger, control of anger, and hostility. It was concluded that significant differences for the diverse components of aggression have been found due to the experimental intervention programme.
Lee, Ye-Sun. "The effect of supplementation with n-9, n-6, and n-3 fatty acids on plasma lipid, lipoprotein, apolipoprotein B concentrations, LDL particle size, and oxidative susceptibility of two LDL subfractions in postmenopausal women". Thesis, 1999. http://hdl.handle.net/1957/26550.
Pełny tekst źródłaGraduation date: 2000
"Type A behaviour, values and coronary heart disease". Thesis, 2015. http://hdl.handle.net/10210/14318.
Pełny tekst źródłaHa, Mai Dung Biotechnology & Biomolecular Sciences Faculty of Science UNSW. "The role of specific genetic host factors, specific dietary factors and Helicobacter pylori infection on the risk of gastric cancer". 2007. http://handle.unsw.edu.au/1959.4/40873.
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