Thesis (MSc)--University of Stellenbosch, 2004. / ENGLISH ABSTRACT: Progressive familial heart block type II (PFHBII) is an inherited cardiac conduction disorder of unknown aetiology, which has been described in a South African family. The disorder was mapped to a 2.9 centimorgan (cM) locus on chromosome 1q32.2-32.3. Clinically, PFHBII manifests cardiac conduction aberrations, that progress to a disease of the heart muscle, dilated cardiomyopathy (DCM). DCM is also reported as an end phase in hypertrophic cardiomyopathy (HCM), another heart muscle disorder. These cardiomyopathies are genetically heterogeneous with some of the genes reported as causes of both disorders. Therefore, genes identified as causes of HCM and DCM were considered plausible candidates for PFHBII mutation analysis. Additionally, this study provided an opportunity to assess potential modifiers of HCM. HCM exhibits marked phenotypic variability, observed within and between families harbouring the same causative mutation. Genes within the PFHBII locus were selected for PCR-SSCP analysis based on homology to genes previously reported as causing conduction system disorders associated with arrhythmias, DCM and/or HCM. Results were confirmed by direct sequencing and association between the detected variants and HCM parameters was assessed using a quantitative transmission disequilibrium test (QTDT). Eleven plausible candidate genes were selected within the PFHBII locus and two of the genes, PFKFB2 and ATF3, that encode for 6-phosphofructo-2,6-bisphosphatase (PFK-2/FBPase-2) and activating transcription factor 3 (ATF3), respectively, were analysed for PFHBII-causing and HCM main locus and/or HCM modifying mutations. Mutation analysis of PFKFB2 and ATF3 in the PFHBII family revealed no PFHBII causal mutation. PFKFB2 and ATF3 were later localised outside the PFHBII locus, and, therefore, were excluded as PFHBII plausible candidates. Further analysis of the two genes for HCM main locus and/or HCM modifying mutations in the HCM panel identified several sequence variants. QTDT analysis of these variants showed no significant association. Completion of the Human Genome Project (HGP) and annotation of new genes within the PFHBII locus allowed the identification of more PFHBII plausible candidate genes. Identification of causal mutations in plausible PFHBII candidate genes will allow molecular diagnosis of PFHBII pathophysiology. Furthermore, identification of both HCM-modifying and HCM-causing genes will give insight into the phenotypic variability noted among South African HCM-affected individuals and into the molecular cause of the disease among individuals with HCM-like clinical features. / AFRIKAANSE OPSOMMING: Progressiewe familiële hartblok tipe II (PFHBII) is ʼn oorgeërfde hart geleidingsiekte van onbekende etiologie wat in ʼn Suid-Afrikaanse familie beskryf is. Die siekte is ʼn 2.9 sentimorgan (cM) lokus op chromosoom 1q32.2-32.3 gekarteer. Klinies presenteer PFHBII met geleidingsfwykings wat uitloop op gedilateerde kardiomiopatie (DCM). DCM word ook gerapporteer as ʼn endfase in hipertrofiese kardiomiopatie (HCM), ʼn ander hartspiersiekte. Die kardiomiopatieë is geneties heterogeen, met ʼn aantal gene wat as oorsaak van altwee siektetoestande gerapporteer word. Daarom is alle gene wat geïdentifiseer is as oorsake van DCM en HCM, as moontlike kandidaatgene vir PFHBII mutasieanaliese beskou. Bykomend het hierdie studie die geleentheid gebied om potensiële modifiseerders van HCM te assesseer. HCM toon beduidende fenotipiese variasie binne en tussen families wat dieselfde siekteveroorsakende mutasie het. Gene binne die PFHBII-lokus is geselekteer vir PCR-SSCP-analiese gebaseer op homologie met gene wat voorheen gerapporteer is om betrokke te wees by geleidingsiesisteemsiektes, geassosieerde arritmieë, DCM en/of HCM. Resultate is bevestig deur volgordebepaling. Assosiasie tusssen ontdekte variante en die siekteparameter is bepaal met ʼn kwantitatiewe transmissie disekwilibrium toets (QTDT). Elf moontlike kandidaatgene in die PFHBII-lokus is geselekteer en twee van die gene, PFKFB2 en ATF3, wat kodeer vir 6-fosfofrukto-2,6-bifosfatase (PFK-2/FBPase-2) en aktiveringstranskripsiefaktor 3 (ATF3) respektiewelik, is vir PFHBII-oorsakende en HCMhooflokus en/of HCM-modifiseerende mutasies ondersoek. Mutasie-analiese van PFKFB2 en ATF3 in die PFHBII-familie het nie ʼn siekteveroorsakende mutasie onthul/uitgelig nie. PFKFB2 en ATF3 is later buite die PFHBII-lokus geplaas en dus ook as moontlike PFHBII-kandidate uitgesluit. Verdere ondersoek van díe twee gene vir HCM-hooflokus en/of HCM-modifiserende mutasies in die HCM-paneel het ʼn aantal volgorde variante geïdentifiseer. QTDT-analiese van die variante het geen beduidende assosiasies aangetoon nie. Voltooiing van die Menslike Genoom Projek (HGP) en annotasie van nuwe gene in die PFHBIIlokus het tot die identifikasie van verdere moontlike PFHBII-kandidaatgene gelei. Identifikase van siekte-veroorsaakende mutasies in die moontlike PFHBII-kandidaatgene sal die molekulêre diagnose van PFHBII toelaat en insig in die patofisiologie van die siekte gee. Verder, identifikasie van beide HCM-veroorsakende of HCM-modifiserende gene kan insig gee in die fenotipiese varieerbaarheid wat onder Suid-Afrikaanse HCM-geaffekteerde individue waargeneem word en ook in die molekulêre oorsake van die siekte in individue met HCMsoortige kliniese kenmerke.

The direct effect of spouse presence during graded exercise testing on anxiety and performance has not been previously delineated. Therefore, the purposes of this study were to (a) ascertain if spouse presence during graded exercise testing affects state anxiety or physiological performance variables, and (b) determine differences in psychological status between cardiac patients and healthy adults.

This study evaluated a mandatory fitness assessment and counseling program designed to reduce coronary risk factors related to diet and exercise. The study was conducted at a southwestern graduate level theological institution. There were 19 mandatory and 22 voluntary participants. Each subject initially had either high blood pressure, high percentage body fat, or high total cholesterol. Significant changes were made within both groups regarding body fat percentage and diastolic blood pressure. Total cholesterol levels decreased for the voluntary group only. The mandatory group significantly improved their exercise level, yet still showed a significantly less positive attitude towards exercise. Overall, the fitness assessment and counseling was somewhat beneficial for both the mandatory and voluntary groups.

For cardiotonic actions, DF caused a transient increase in contractility and a transient decrease in contraction rate in an isolated rat heart perfusion system. The positive inotropic effect and the negative chronotropic effect were generated by the dose-dependent inhibitions of Na+/K +-ATPase and Ca2+-ATPase respectively in rat heart homogenate. In both assays, Danshen exhibited more potent inhibitions than DF, while Fenge showed negligible inhibitory actions. / In vivo study on Spontaneously Hypertensive Rats (SHR) showed that DF could not restore the established high blood pressure to the normal level. Earlier DF treatment attenuated, but could not prevent, hypertension development. In aorta, DF improved endothelium-dependent vasodilation by potentiating acetylcholine-induced relaxation and basal nitric oxide (NO) production, and inhibiting endothelial Ca2+ATPases. Relaxation of vascular smooth muscle cells (VSMC) towards NO donors was also enhanced. For anti-oxidation, upon DF treatment, mRNA levels of superoxide dismutase (SOD), extracellular superoxide dismutase (ecSOD), catalase and glutathione peroxidase (GPx) were elevated in heart and aorta. However, studies on SOD and catalase demonstrated insignificant changes in the protein expression levels in both organs. For vasodilation, mRNA level of endothelial nitric oxide synthase (eNOS) in the aorta was upregulated, but no change on eNOS and phosphorylated eNOS (peNOS) proteins were detected. A parallel study showed that DF did not cause hypotension or improve antioxidant defense in normotensive Wistar Kyoto rats (WKY). These findings suggest the use of the Danshen and Fenge 7:3 (w/w) formulation on the comprehensive cardiovascular protection. / Previously established Danshen and Fenge 7:3 (w/w) formulation (DF) was shown to exhibit antioxidative activity by preventing oxidant-induced red blood cell hemolysis and H9c2 rat myoblast cell death in a dose-dependent manner, in which Danshen was demonstrated to be a more potent antioxidant than DF. Fenge showed no antioxidative property. The effect of in vivo ischemia-reperfusion was mimicked by the hypoxia-reoxygenation model of primary culture of neonatal rat heart cardiomyocytes. Danshen could protect cardiomyocytes against hypoxiareoxygenation damage. / Reactive oxygen species attack on cardiovascular system can lead to atherosclerosis and finally cardiac ischemia. Reperfusion, allowing the restoration of blood flow in treating atherosclerosis, in turn generates free radicals which irreversibly damage cardiomyocytes and endothelial cells. Endothelial cell damage eventually leads to hypertension. Radix Salviae Miltiorrhizae (Danshen) and Radix Puerariae Thomsonii (Fenge) have long been used together to treat various heart diseases in China. This project was focused on the antioxidative, cardiotonic and vasodilative effects of the aqueous extracts of Danshen and Fenge. / Lam Hung Ming. / "September 2006." / Adviser: Miu Yee Mary Waye. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1381. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 218-230). / 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. / Abstracts in English and Chinese. / School code: 1307.

No description available.

Thesis (MScMedSc (Biomedical Sciences. Molecular Biology and Human Genetics. Medical Biochemistry))--University of Stellenbosch, 2007. / Connexins (Cx) are major proteins of gap junctions, dynamic pores mediating the relay of ions and metabolites between cells. Cxs 40, 43 and 45 are the predominant cardiac isoforms and their distinct distribution raises questions about their functional differences. Their cytoplasmic (C)-terminal domains are involved in protein-protein interactions. Furthermore, mutations in the myotonic dystrophy protein kinase (DMPK)-causative gene are associated with disruptions in cardiac conduction similar to that described for Cx knock-out mice. DMPK is a Cx43 ligand, raising the possibility that defects in Cx40 ligands may be involved in the development of cardiac conduction disturbances. We hypothesised that delineation of the protein ligands of the C-termini of Cx40 and of Cx45 (parallel study conducted by N Nxumalo) would help elucidate their functional roles. Yeast-two-hybrid methodology was used to identify putative Cx40 ligands. Primers were designed to amplify the C-terminus-encoding domain of the human Cx40 gene (Cx40), the DNA product was cloned into the pGBKT7 vector which was used to screen a cardiac cDNA library in Saccharomyces cerevisiae. Successive selection stages reduced the number of putative Cx40 ligand-containing colonies (preys) from 324 to 33. The DNA sequences of the 33 ligands were subjected to BLAST-searches and internet database literature searches to assign identity and function and to exclude false positive ligands based on subcellular location and function. Eleven plausible ligands were identified: cysteine-rich protein 2 (CRP2), beta-actin (ACTB), creatine kinase, muscle type (CKM), myosin, heavy polypeptide 7 (MYH7), mucolipin1 (MCOLN1), voltage-dependent anion channel 2 (VDAC2), aldehyde dehydrogenase 2 (ALDH2), DEAH box polypeptide 30 (DHX30), NADH dehydrogenase, 6, (NDUFA6), prosaposin (PSAP) and filamin A (FLNA). Cxs 40 and 45 showed differences in the classes of proteins with which they interacted; the majority of putative Cx40 interactors were cytoplasmic proteins, while Cx45 interactors were mitochondrial proteins. These results suggest that Cxs 40 and 45 are not only functionally different, but may also have different cellular distributions. Further analyses of these protein interactions will shed light on the independent roles of Cxs 40 and 45.

Thesis (MScPhysio (Physiotherapy))--University of Stellenbosch, 2007. / Study Aim: To describe the profile and selected outcomes of CABG patients admitted in the Cape metropolitan area. Design: A prospective descriptive study design with a multicentre observational approach was followed. Method: All patients undergoing isolated CABG surgery, whether elective or emergency, during a three-month period (15 August–15 November 2005) were included in the study. Demographic data, pre-operative medical status, intra-operative, as well as post-operative information were collected using a self-designed structured initial assessment form (SIA). Means and standard deviations were calculated where applicable. Relationships between different variables were analyzed by means of: ANOVA, correlations, linear and logistic regressions. Where it appeared that the ANOVA assumptions were violated, non-parametric bootstrap techniques were employed. Results: Two hundred and forty five patients were admitted to the seven hospitals which provide CABG surgery in the Cape metropolitan area in the allotted period. The profile of patients admitted to private and state institutions were similar. The mean age of the sample was 60 (±10). The mean LOS of the total cohort was 12 (±5.5) days, with patients in the state hospitals staying longer 13.4 days (± 7.1). Patients who were older than 60 were twice as likely to have a LOS >12days (odds ratio = 2.49; 95% confidence interval = 1.33 to 4.65). The development of a pleural effusion or pneumothorax was associated with an increased LOS (p<0.01). At least one PPC was reported in 65% of the population. A mortality rate of only 3% was reported. Conclusion: Patients in this cohort were younger than in developed countries. An age greater than 60 years was a predictor of an LOS >12days in the current cohort. Patients were most likely to develop a PPC on day three after CABG surgery. Physiotherapeutic intervention, if any, would be well aimed at those patients older than 60 years of age. Screening of patients in the first three post-operative days for the development of PPCs is also advised.

Myxomatous mitral valve disease (MMVD) is the single most common acquired cardiac disease of dogs, and is a disease of significant veterinary importance. It also bears close similarities to mitral valve prolapse in humans and therefore is a disease of emerging comparative interest. Realising the importance of collagen fibres in mitral heart valves and considering the paramount significance of myxomatous mitral valve disease, a better understanding of the pathogenesis of MMVD is essential. Thus, this study was designed to investigate the changes in collagen molecules, including fibril structure, fibril orientation, d-spacing, collagen density, collagen content, thermal stability, and the status of mature and immature crosslinks. A combination of biophysical and biochemical tools such as x-ray diffraction, neutron diffraction, HPLC were utilised in order to fulfil the objectives. Biochemical assay of hydroxyproline revealed a 10% depletion of collagen in mildly affacted (grade I and II) leaflets, while a 20% depletion of fibrillar collagen was revealed by mapping the collagen fibrils onto the anatomy of cardiac leaflets using x-ray data. Differential scanning calorimetry showed that there were no significant differences in the onset temperature of denaturation of collagen between the healthy and affected leaflets. However, in affected areas of leaflets, the enthalpy of denaturation significantly dropped by 20%. In the affected regions, neutron diffraction results showed an increase in the immature reducible cross-links though the low number of the samples can be considered a limiting factor in this regard. However, the HPLC results showed a 25% decrease in the number of mature cross-links. Additionally, the recently introduced imaging technologies to biology and medicine such as differential enhancing imaging (DEI) and coherent anti-Stokes Raman scattering spectroscopy (CARS) were, to the author’s best knowledge, applied for the first time to this disease. In doing so, this thesis furthers our understanding of the pathogenesis of MMVD, especially in relation to the collagen. The thesis provides new findings about MMVD and demonstrates the potential of biophysical tools for studying similar conditions.

Background: Coronary heart disease can have a long lasting impact on affected individuals in terms of both physical and psychological adjustment and quality of life. It is, therefore, important to investigate determinants of outcome in these patients. The thesis has four main aims; (i) to investigate predictors of outcome (adherence, quality of life, functional impairment, psychological distress and benefit finding) post-myocardial infarction (MI); (ii) to determine the prevalence and stability of Type D personality in the UK; (iii) to determine if personality predicts outcome after controlling for mood, demographic and clinical factors, and (iv) to investigate potential mechanisms which may explain the link between personality and poor prognosis in cardiac patients. Method: Five studies were conducted. In Studies 1-3, participants completed measures of Type D personality, health-related behaviour, social support and neuroticism. In Study 4, participants completed an experimental stressor with cardiovascular monitoring. Study 5 was a prospective study in which 131 MI patients completed measures of personality, illness cognitions and outcome at two time points, 3-5 days post-MI, then again 3 months later. Results: The prevalence of Type D personality in the UK is 39% in the healthy population, and 34% in the cardiac population. In addition, Type D is predictive of adherence, quality of life, and functional impairment in post-MI patients after controlling for mood, demographics, and clinical factors. Five possible mechanisms (health-related behaviour, adherence, social support, cardiovascular reactivity, and illness perceptions) by which Type D may lead to adverse outcome in cardiac patients were identified. Mood predicted quality of life and functional impairment post-MI, illness perceptions predicted quality of life post-MI, and future thinking predicted quality of life, functional impairment and depression post-MI. Discussion: These findings have important therapeutic and theoretical implications for understanding the role of personality and illness cognitions in the short-term recovery of post-MI patients.

Two major troponin I (TnI) genes, fetal TnI (ssTnI) and adult TnI (cTnI), are expressed in the mammalian heart under the control of a developmentally regulated program. In this study, the up-stream domain (~1,800 bp) of mouse fetal TnI gene has been cloned and characterized. There is a high homology of this region among mouse, rat and human. Transfection assays indicated that conserved GA-rich sequences, CREB and a CCAAT box within the first 300 bp upstream of the transcription start site were critical for the gene expression. Electrophoretic mobility shift assays (EMSAs) and chromatin immunoprecipitation (ChIP) assays revealed binding proteins to CREB site in nuclear extracts from myocardial cells. Thyroid hormone (T3) caused a significant inhibitory effect on ssTnI expression in myocardial cells. Cardiac troponin I (cTnI) mutations have been linked to the development of restrictive cardiomyopathy (RCM) in human patients. We modeled one mutation in human cTnI Cv terminus, arginine1 92 histidine (R192H) by cardiac specific expression of the mutated protein (cTnI193His in mouse sequence) in transgenic mice. The main functional alteration detected in cTnI193His mice by ultrasound cardiac imaging examinations was impaired cardiac relaxation manifested by a decreased left ventricular end diastolic dimension (LVEDD) and an increased end diastolic dimension in both atria. Echocardiography revealed a series of changes on the transgenic mice including a reversed E-to-A ratio, increased deceleration time, and prolonged isovolumetric relaxation time. At the age of 12 months, cardiac output in cTnI193His mice was significantly declined, and some transgenic mice showed congestive heart failure. The negative impact of cTnI193His on ventricular contraction and relaxation was further demonstrated in isolated mouse working heart preparations. / Dobutamine stimulation increased heart rate in cTnI193His mice but did not improve CO.The cTnI193His mice had a phenotype similar to that in human RCM patients carrying the cTnI mutation. The results demonstrate a critical role of the COOH-terminal domain of cTnI in the diastolic function of cardiac muscle. This mouse model provides us with a tool to further investigate the pathophysiology and the development of RCM. / by Jianfeng Du. / Thesis (Ph.D.)--Florida Atlantic University, 2008. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2008. Mode of access: World Wide Web.