The available sources have, to some extent, determined the form of this thesis, which was undertaken in the hope that a more detailed study of the relations between London and the Crown during the years 1 1400_1 1150 would place in perspective the crises with which it begins and ends. The most important source of material for this study has been the Journals of the Court of Aldermen and Common Council which survive from 1416 (the years 1429- 1436 are missing). Historians with the help of a nineteenth century index have quarried in these Journals, but they have never been read through systematically. Journals nos. 3 and 6, having been wrongly bound up, could not be used until, their pages bad been sorted into the correct order from the internal evidence of their contents. The scribes who compiled the Journals were both careless and cautious which increases the difficulty in interpreting their crabbed notes. From studying the Journals dominant themes emerged which were then followed up at the Public Record Office and elsewhere. The conclusions from this study fall into three main categories. The Journals provided a great deal of material from which it was possible to draw a much more detailed picture of the machinery and business of the government of medieval London. T1'e Aldermen and civic officials emerge as conservative, but conscientious, men who might press hardly upon minority interests, but had constantly before their eyes the needs of the City as a whole. Secondly it has been possible to tidy up the chronology of the crises themselves. At such times as Bolingbroke' s usurpation and Cade' a revolt the civic scribes were least active and most cautious. But it seems clear that the London support for both these men has been exaggerated and that the fundamental conservatism of the City governors was not easily rocked, whether by royal scions or Kentish peasants. But this study has proved most useful where the more mundane contact between the Crown and the citizens could be examined, In this way it has been possible to place the financial relations between the King and the City in perspective, and to realize that the King did not come as a beggar to the Londoners, since he had at his disposal all the chartered freedoms and privileges which were essential to the communal and economic life of the City. London, in spite of its great prestige and financial importance, still operated in the fifteenth century within a framework of royal privilege. While the memory of Richard II's action in 1392 was still green the Londoners were in no position to demand redress of grievances before supply. In understanding the delicate balance of the relationship between the Crown and the Londoners it is easier to understand the survival of the Lancastrian dynasty.

No description available.

Thesis (MSc)--University of Stellenbosch, 2002. / ENGLISH ABSTRACT: Variegate porphyria (VP, MIM 176200) is a low penetrance autosomal dominant disorder that stems from mutations in the protoporphyrinogen oxidase (PPOX) gene. VP is found in most populations, but has a high prevalence in the South African Afrikaner population with most patients inheriting the same PPOX mutation (R59W) from a common ancestor. The clinical manifestations of the disease include acute neurovisceral attacks and/or cutaneous photosensitivity. Great variation in the clinical presentation of VP is observed; even in members of the same family that share a common genetic background and that have been exposed to similar environmental factors. Candidate genes that may have an influence on phenotypic variation due to the regulatory function in the haem biosynthetic pathway include the two deltaaminolevulinic acid synthase (ALAS) genes and the porphobilinogen deaminase (PBGD) gene. Sequence homology searches between different species indicated that the ALAS-1, ALAS-2 and PBGD genes are highly conserved, indicating that these genes have an important function to fulfill in the haem biosynthetic pathway. The study population of 25 R59W individuals were divided in four categories according to their clinical presentation. The distribution of clinical symptoms observed in this study corresponds with results from previous studies. Conformation sensitive gel electrophoresis (CSGE), conventional single stranded conformation polymorphism analysis (SSCP) and two buffer SSCP analysis were implemented to screen for possible sequence variants. The exons of all three genes as well as the adjacent intronic sequences were investigated. A total of six sequence variation sites were identified of which five had previously been described single nucleotide polymorphisms (ALAS-1: 4713 T>C; PBGD: -64 C>T, 3581 A>G, 6479 G>T, 7064 C>A)] and a novel 8bp deletion (PBGD: 4582_ 4589del). No sequence variant was identified in the ALAS-2 gene. The CSGE method proved to have the highest sensitivity (83%), identifying five of six sequence variant sites. The conventional SSCP method identified only three (50%) sequence variant sites, while the two buffer system detected two (33%) of the sequence variants. The 4713 T>C SNP in exon 4 of the ALAS-1 gene and the -64 C>T SNP in the PBGD gene were selected for further investigation due to their location in the respective genes. These sequence variants were typed in 50 patients and 50 control subjects matched for ethnic background. The relationship between variation at these loci and clinical features was investigated. No statistical significant association was observed for either of the 4713 T>C SNP (P= 0.717) or the -64 C>T SNP (P= 0.931). Genetic modifying factors make a variable contribution to the total clinical picture and are difficult to identify in small populations. Due to the fact that we only had a limited number of VP samples, association cannot be ruled out. This study does, however, provide insight into investigational approaches that should be undertaken in future research concerning the ALAS and PBGD genes. Further knowledge concerning the haem biosynthetic pathway could ultimately lead to the understanding and assessment of the clinical expression observed in individuals with VP. / AFRIKAANSE OPSOMMING: Variegate porfirie (VP, MIM 176200) is 'n lae penetrasie outosomaal dominante siekte wat veroorsaak word deur mutasies in die protoporfirienogeen oksidase (PPOX) geen. VP word gevind in die meeste populasies, maar het 'n hoë voorkoms in die Suid- Afrikaanse populasie waar meeste pasiente dieselfde PPOX mutasie (R59W) van 'n gemeenskaplike voorouer oorgeërf het. VP word gekenmerk deur akute neuroviserale aanvalle en/of fotosensitiewe vel. Groot variasie word egter waargeneem in die kliniese uitdrukking van VP, selfs in lede van dieselfde familie wat 'n gemeenskaplike genetiese agtergrond deel en wat blootgestel is aan dieselfde omgewingsfaktore. Kandidaat gene wat as gevolg van hulle regulatoriese funksie in die heem biosintetiese padweg 'n effek op die ekspressie van VP mag hê, sluit in die twee deltaaminolevuliniese suur sintase (ALAS) en die porfobilinogeen deaminase (PBGD) gene. Homologie ondersoeke van die ALAS-1, ALAS-2 en PBGD gene in verskillende spesies dui daarop dat die gene hoogs gekonserveerd is en dus gevolglik 'n belangrike funksie in die heem biosintetiese padweg vertolk. Die studie populasie van 25 R59W individue is verdeel in vier kategorieë op grond van hulle kliniese simptome. Die verspreiding van die kliniese simptome wat waargeneem is tydens hierdie studie stem ooreen met die resultate van vorige studies. Konformasie sensitiewe gel elektroforese (CSGE), konvensionele enkelstring konformasie polimorfisme analise (SSCP) en twee buffer SSCP analise is gebruik vir die identifisering van genetiese variasie. Die eksons van al drie gene, sowel as die aangrensende intron volgordes, is ondersoek. 'n Totaal van ses areas van genetiese variasie is geïdentifiseer, waarvan vyf reeds beskryfde polimorfismes is (ALAS-1: 4713 T>C; PBGD: -64 C>T, 3581 A>G, 6479 G>T, 7064 C>A) en 'n nuwe 8bp delesie (PBGD: 4582_ 4589del). Geen genetiese volgorde variasie is gevind in die ALAS-2 geen nie. Die CSGE metode het die hoogste sensitiwiteit getoon (83%) en het vyf van die ses volgorde variasies geïdentifiseer. Die konvensionele SSCP metode het slegs drie volgorde variasies geïdentifiseer (50%), terwyl die twee buffer deteksie-sisteem twee variasies geïdentifiseer (33%) het. Die 4713 T>C polimorfisme in ekson 4 van die ALAS-1 geen en die -64 C>T polimorfisme in die PBGD geen, is geselekteer vir verdere ondersoek as gevolg van hulle posisie in die respektiewe gene. Die volgorde variasies is getipeer in 50 R59W pasiënte sowel as in 'n kontrole groep van 50 individue met dieselfde etniese agtergrond. Die verband tussen die variasie by die lokusse en die kliniese kenmerke is ondersoek. Geen statisties beduidende assosiasie is waargeneem vir hetsy die 4713 T>C SNP (P= 0.717) of die -64 C>T SNP (P= 0.931). Genetiese modifiserende faktore word moeilik geïdentifiseer in klein populasies omdat hulle afsonderlike bydra tot die geheelbeeld van die kliniese simptome so varieerbaar is. 'n Relatiewe klein groep van VP pasiënte was tydens die studie beskikbaar en dus kan assosiasie nie uitgesluit word nie. Die studie verskaf egter insig in verband met toekomstige benaderings wat volg kan word in verdere ondersoeke van die ALAS en PBGD gene. Verdere kennis in verband met die heem biosihtetiese padweg kan uiteiHdelik lei tot die verduideliking en assesering van die kliHiese uitdrukking in vI=' individue.

No description available.

published_or_final_version / Pathology / Doctoral / Doctor of Philosophy

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

published_or_final_version / Medicine / Master / Master of Philosophy

published_or_final_version / abstract / Biochemistry / Doctoral / Doctor of Philosophy

published_or_final_version / Psychiatry / Master / Master of Medical Sciences

An exploratory pilot study was conducted to identify specific experiences, perceptions and challenges of participants affected by Turner Syndrome in Hong Kong. It was important to discover how issues concerning fertility, menstruation, ovarian function and ovarian insufficiency and hormone replacement therapy, which are important to these women have impacted their psychosocial wellbeing, psychosocial experiences and their relationships. An ‘across the life span’ approach was used to explore significant issues at various stages or ‘moments’ of their lives, and which they perceive to be important to family and the Chinese culture. The findings of this study has implications for the role of genetic counselling in Turner Syndrome in Hong Kong, to facilitate individuals and their families to meet the challenge. When parents make prenatal decisions for the continuation of pregnancy of a fetus with Turner Syndrome, the quality of genetic counselling is considered to have direct effect on the decision making and continuance of pregnancy. Previous literature indicated that critical criteria for decision making during the prenatal period includes the potential future fertility of the fetus. These issues concerning fertility of patients with Turner Syndrome were explored in this study, in addition to a review of the existing literature. Methodology This was a study of qualitative research, using semi structured interviews. Triangulation techniques were employed in order to gain a rich insight into the care of patients with Turner Syndrome in Hong Kong. For this report, four participants were recruited, who were existing patients of the Department of Reproductive Medicine clinic in Queen Mary Hospital. Each consented to an in depth interview concerning their experiences and challenges of Turner Syndrome in Hong Kong. The narrative of the interview was analysed according to the themes which emerged. A review of medical notes of the participants from the Department of Reproductive Medicine clinic in Queen Mary Hospital, Hong Kong was also conducted. Results Of the participants included in this analysis, one individual with classical features of Turner Syndrome had a 45, X karyotype. The remaining three participants were cytogenetically diagnosed with a mosaicism for Turner Syndrome. It was anticipated that the knowledge gained would improve the provision of information and care by the genetic counsellor and medical practitioner, for patients or parents at initial diagnosis and across their lifespan. The study participants were able to provide rich body of data allowing insight into their lives, experiences and challenges. The pregnancy losses that they have endured, and the hope that all four individuals sustain became evident with each interaction. Significance This study has shown that patients require an in depth knowledge of their condition. They trust the medical professionals who care for them, and their care should be managed with continuity ‘across the life span’ by carers who are experts in Turner Syndrome. Their need for establishment of support groups, and a continuing support structure is essential to their well-being and their psychological health. This is a unique study in Hong Kong with these issues having not been explored previously. / published_or_final_version / Medicine / Master / Master of Medical Sciences