Dissertations / Theses on the topic 'Castlemaine'

This study, set within the contextual background of Victorian politics, ‘seeks to identify the economic, political and social implications of tariff protection for the Castlemaine region from 1870-1901. The introduction of the Victorian tariff in 1865 precipitated a reversal of earlier attitudes towards protection by politicians and their constituents. Reasons are sought for changes in the perceptions of the Castlemaine electorate and its political representatives towards the tariff between 1870 and Federation. An examination has been made of the role of the tariff in the creation of employment in the region’s primary and secondary industries together with its influence on politicians, primary and secondary industry leaders and workers. Also explored is the relative impact of the tariff on the economic performance of Castlemaine industries, whether producing for export or domestic markets.

Background: Castleman disease (CD) is a lymphoproliferative disorder with four subtypes, some of which are aetiologically linked to Human Herpes virus 8 (HHV-8) which is known to cause diseases preferentially occurring in HIV-infected individuals. There has been a notable increase in the number of patients with HIV/HHV-8 associated CD diagnosed in the Groote Schuur hospital complex. Aims: The aim of the study was to determine the role of DC-SIGN, DC-SIGNR, p24 and HHV-8 (LANA-1) in Castleman disease. Our objectives were to identify the presence of DC-SIGN and DC-SIGNR in HHV-8 infected cells, determine whether HHV-8 and p24 (HIV) co-infection occurs in the same cells and to determine whether HHV-8 infects B and/or T cells. This study not only represents the largest and first immunophenotypic investigative evaluation of CD but also signifies the first double staining immunohistochemical analysis of CD diagnosed at Groote Schuur hospital. Methods: This was both a retrospective descriptive as well as an analytic cross-sectional immunohistochemistry study. Fifty cases of CD diagnosed at the Division of Anatomical Pathology, National Health Laboratory Service, Groote Schuur hospital over a ten and half year period were included in the study. Double immunohistochemistry was used to characterise HHV-8 infected cells using LANA-1 antibody, in conjunction with DC-SIGN, DC-SIGNR, p24, CD20 and CD3. Immunophenotypic analysis was then performed to assess 1) the number of infected HHV-8 cells and 2) number and distribution of cells co-expressing HHV-8 and DC-SIGN, DC-SIGNR, p24, CD20 and CD3. The immunophenotypic profiles were then compared to the CD morphologic subtypes. Results: The study cohort included 26 male and 24 female patients (M: F = 1.08:1), mean age 37.7 years. There were 16 hyaline vascular CD (HV-CD), 16 plasmablastic CD (Pb-CD). Nine plasma cell CD and 9 mixed-CD subtypes. There was a statistically significant association between HIV (n=45) and HHV-8 (n=40) positivity (p < 0.0002). CD4 counts and HAART enrolment were not predictive of CD development (p = 0.6120). Concurrent Kaposi sarcoma was seen in 16% (n=8) of the cohort. When comparing Pb-CD and HV-CD, there were statistically significant differences in density of LANA-1 infected cells (p<0.0002), LANA-1/DC-SIGN co-expressing cells (p <0.0072) and LANA-1/p24 co-expressing cells (p<0.0001). Conclusions: The findings of this study suggest that DC-SIGN may have a role in HHV-8 entry into cells. Furthermore, there is evidence that HIV and HHV-8 co-infection may function synergistically in CD. It is possible that DC-SIGN and DC-SIGNR facilitate dual viral entry into cells and influence viral replication and persistent infection.

Le Virus Humain Herpès 8 (HHV-8) est un Herpèsvirus lymphotrope proche du virus d’Epstein Barr (EBV). Au cours de la lymphoprolifération B qu’est la Maladie de Castleman Multicentrique (MCM) HHV-8 est spécifiquement associé à une profifération de plasmablastes monotypiques IgM/. Ces cellules expriment des facteurs de transcription qui suggèrent que ces cellules sont au stade plasmablastique ou pré-plasmocytaire de la différenciation B.Les cellules invariantes Natural Killer (iNKT) sont des cellules innées qui jouent un rôle dans l’immunité antivirale, en particulier dans le contrôle des Herpèsvirus. Une diminution de ces cellules est associée à l’infection VIH ou l’âge, deux situations associées aux pathologies tumorales associées à HHV-8. Dans la première partie du travail nous avons analysés les iNKT chez des patients MCM et montrés des anomalies de fréquence et de prolifération de ces cellules. Les anomalies des cellules sont associées à des anomalies de répartition des sous populations B mémoires dans le sang circulants et la rate de ces patients. Des expériences de co-cultures montrent que les cellules iNKT pourraient être nécessaires au maintien de ces populations BDans la seconde partie de ce travail, nous avons démontré que la MCM HHV-8 est associée pendant les poussées de a maladie à une circulation dans le sang périphérique de cellules présentant les caractéristiques typiques des plasmablastes décrits jusqu’à présent uniquement dans les tissus lymphoïdes. Nous avons ensuite analysé le profil d’expression génique des cellules B infectées par HHV-8 par rapport à celui de sous populations B normales. Nos résultats montrent clairement que les cellules infectées par HHV-8 présentent un profil d’expression génique très différent de celui des sous populations B normales. Leur profil est par ailleurs caractéristique de plasmablastes. De plus, ces cellules sont en prolifération, modulent négativement l’expression de beaucoup de gènes associés à l’immunité et l’adhésion cellulaire. Enfin, nous confirmons que les cellules B infectées par HHV-8 de la MCM sont bien polyclonales même dans le sang circulant et sans mutations somatiques.Au total, ces résultats nous permettent de proposer un modèle de la physiopathologie de la MCM associée à l’infection HHV-8
Human Herpesvirus-8 is a B-lymphotropic \γ-herpesvirus closely related to the Epstein-Barr virus (EBV). He is specifically associated with monotypic (IgM/λ) plasmablasts in Multicentric Castleman disease (HHV-8 MCD), which is a B lymphoproliferative disorder. These cells express transcription factors suggesting they are at the plasmablast or pre-pasma cell stage of differentiation. Invariant natural killer T (iNKT) cells are innate-like T cells that play a role in antiviral immunity, specifically in controlling viral replication in EBV-infected B cells. Decline of iNKT cells is associated with age or HIV infection, both situations associated with HHV-8-related diseases. We demonstrated that iNKT cell abnormalities are associated with HHV-8 MCD. These iNKT cell alterations were found to be associated with an imbalance in the frequency of circulating and splenic B cell subsets, and results of Coculturing experiments indicate that iNKT cells may be required for maintaining this cell population. In the second part of our work thesis, we demonstrate that HHV-8 MCD is associated with a unique population of circulating plasmablasts detected during the flare of the disease, with the typical phenotype of the MCD HHV-8-infected plasmablasts in MCD lesions. Then, we used gene expression profile analysis (about 48 000 genes) to further define the phenotype of this MCD HHV-8-infected cells and to investigate the lymphoma relationship to normal B cell subpopulations. The results showed that MCD HHV-8-infected cells displayed a common gene expression profile that is clearly distinct from all the normal B cell subpopulations. The gene expression profile of MCD HHV-8-infected cells was defined as plasmablastic. Moreover, the transcriptomic pattern of MCD HHV-8-infected cells demonstrates that these cells are proliferating and escaping the immune system. Finally, we determined the clonality and the cellular origin of the monotypic circulating plasmablasts by studying the rearranged immunoglobulin heavy genes in LANA+ HHV-8-infected B cells from patients with HHV-8 MCD. Our results show that these cells are polyclonal without somatic mutation. Altogether our results allowed us to elaborate a model of MCD physiopathology

This thesis explores the socio-economic and political history of the rural community on the Marquis of Anglesey’s Dorset and Somerset estate through the correspondence, rental accounts and estate vouchers of the Castleman family. Existing historiography which relates to both the role of the land agent and the rural community remains sparse. The research for this study has taken a new and unique approach which challenges many of the existing theories. Through close textual analysis it has examined six broadly defined themes which relate to all aspects of the rural society. Firstly an in depth and detailed survey of how the rural community was organised, worked and changed over time was undertaken. Secondly it investigates the tripartite relationship between landowner, agent and tenant rather than the more traditional affiliation of landowner, tenant and labourer. Using this new configuration the archive explains how this association worked in practice with regard to estate improvement, repairs and functional schemes to relieve tenant distress. Thirdly this thesis surveyed the political landscape of Milborne Port and in particular it sought to define the role of the election agent in pre-reformed England. Fourthly it analyses the labouring poor, with particular attention to the issue of low wages, under- and un-employment and the role of the landed estate in the economy of makeshifts. The plight of the poor culminated in the Swing riots of 1830 and this archive provides new and important information in the on-going debate of this phenomenon. Fifthly the estate vouchers which contain the minutiae of estate life have never been examined and yet in the absence of recognisable accounts these contain essential quantitative information. Finally this thesis assesses the ways and means that large estates sought to exert social control, through the creation of a deference community, education and the accruing of rental arrears. Significantly this study illustrates the pivotal role played by the land agent in maintaining the equilibrium within the rural community.

La myasthénie auto-immune (MG) est caractérisée par une faiblesse musculaire liée à des auto-anticorps ciblant le récepteur de l’acétylcholine (RACh). Cette maladie multifactorielle est hétérogène, sa forme la plus fréquente associant une hyperplasie folliculaire du thymus (TFH). Le complexe majeur d’histocompatibilité (CMH) occupe une place prédominante dans la composante génétique de cette forme, avec l’association de l’haplotype 8. 1 (HLA-A1-B8-DR3). A l’aide de microsatellites (STR), le laboratoire avait entrepris de décrire en détail les effets de cet haplotype. Celui-ci n’explique cependant que partiellement l’impact du CMH sur le risque de développer la maladie. Le but de mon travail était donc d’identifier au sein du CMH de nouveaux allèles influençant la MG avec TFH ou le titre des auto-anticorps. Une première approche focalisée sur la région distale de classe I combinant STR et SNPs a mis en évidence deux haplotypes protecteurs au niveau des locus HLA-F et ZNRD1-AS1 ainsi qu’un haplotype prédisposant comprenant le gène RNF39. Une étude par re-séquençage du gène candidat de classe III, NCR3, a ensuite révélé une accumulation de variants rares chez les patients dont trois mutations codantes. Enfin, une cartographie fine de SNPs portant sur l’ensemble du CMH a montré l’association à la MG avec TFH d’allèles non 8. 1 autour du locus TAPBP, dans la région de classe II étendue, et celle d’allèles à la frontière des régions de classe II et III avec le titre des auto-anticorps anti-RACh. Ainsi, bien que les variants fonctionnels restent à identifier, l’ensemble de ces travaux fournit une meilleure compréhension du rôle complexe du CMH dans la MG avec TFH
Autoimmune myasthenia gravis (MG) is characterized by muscular weakness due to autoantibodies targeting the acetylcholine receptor (AChR). This complex disorder is heterogeneous, its more common form associating a thymic follicular hyperplasia (TFH). The major histocompatibility complex (MHC) plays a predominant part in the genetic component of this form, with the association of the 8. 1 haplotype (HLA-A1-B8-DR3). Using microsatellites (STR), the laboratory had undertaken a detailed description of the effects of this haplotype. However, this haplotype explains only partly the impact of MHC on the risk of developing the disease. The goal of my work was to identify new MHC alleles influencing MG with TFH or the autoantibody titer. A first approach focusing on the distal class I region combining STR and SNPs has delineated two protective haplotypes around the HLA-F and ZNRD1-AS1 loci as well as a predisposing haplotype including the RNF39 gene. A re-sequencing study of the class III candidate gene, NCR3, has then revealed an accumulation in the patients group of rare variants, including three coding mutations. Finally, a SNP-based fine mapping of the entire MHC has shown an association between MG with TFH and non 8. 1 alleles around the TAPBP locus, in the extended class II region, and also an influence of non 8. 1 alleles at the border of class II and III regions on the anti-AChR autoantibody titers. Hence, although functional variants remain to be identify, overall our work provides a better understanding of the complex role of the MHC in MG with TFH

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2017
O Síndrome de POEMS é uma entidade clínica rara, de índole paraneoplásica, cujo acrónimo representa as suas principais manifestações – polineuropatia (P), organonomegália (O), endocrinopatia (E), gamapatia monoclonal (M), alterações da pele (S). A sua fisiopatologia é intrincada e carece ainda de investigação, assumindo-se no entanto que o Fator de Crescimento Endotelial Vascular (VEGF), em conjunto com os seus co-indutores, seja responsável pelas manifestações cardinais. Por se tratar de uma patologia rara e com uma vasta panóplia de sinais/sintomas que podem mimificar outras patologias mais frequentes, o seu diagnóstico é frequentemente tardio e exige um elevado nível de suspeição clínica. Estima-se que cerca de 11-30% dos doentes com Síndrome de POEMS exibam concomitantemente Doença de Castleman (DC). Dado que existe partilha de vias fisiopatológicas, principalmente ao nível da produção de IL-6 e VEGF, foi proposto um sinergismo entre ambas as patologias. O presente Case Report descreve um quadro clássico de Síndrome de POEMS, associado a DC, sendo ilustrativo da complexidade diagnóstica e raridade destas duas patologias.
POEMS syndrome is a rare parenoplasic syndrome, whose acronym stands for the main manifestations - polyneuropathy (P), organomegaly (O), endocrinopathy (E), monoclonal gammopathy (M) and skin abnormalities (S). Its pathophysiology is intricate and still requires investigation. However, it is assumed that the Vascular Endothelial Growth Factor (VEGF), together with its co-inducers, is responsible for the cardinal manifestations. Due to its rarity and multiplicity of symptoms that mimic other more frequent pathologies, POEMS is frequently a late diagnosis, requiring high levels of clinical suspicion. It is estimated that about 11-30% of patients with POEMS syndrome, exhibit concomitant Castleman Disease (CD). Since POEMS syndrome and CD share pathophysiological features, mainly regarding VEGF and IL-6 production, a synergism is proposed between these diseases. This case report describes a classic POEMS syndrome, associated with Castleman's disease, emphasizing the rarity and diagnostic complexity of these pathologies.

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2018
A doença de Castleman é uma doença linfoproliferativa benigna rara que abrange todos os grupos etários. A forma multicêntrica apresenta uma heterogeneidade de manifestações clínicas e tem um mau prognóstico. O presente trabalho faz uma revisão da literatura da doença de Castleman multicêntrica idiopática, havendo uma focalização na vertente diagnóstica. Verifico que a confirmação histológica por biópsia ganglionar é um dos parâmetros obrigatórios e que a PET-TC é o método imagiológico mais sensível. A semiologia e as alterações laboratoriais são variáveis e coincidentes com um estado inflamatório sistémico. A ausência de hipergamaglobulinémia associada a trombocitopenia constituem sinais de alerta para a pesquisa da síndrome TAFRO (do inglês Thrombocytopenia, Anasarca, Fever, Reticulin fibrosis, Organomegaly), variante mais grave da doença. Os principais diagnósticos diferenciais da doença de Castleman multicêntrica são as neoplasias, tais como: linfomas, mieloma múltiplo, síndrome POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes), as doenças auto-imunes do tecido conjuntivo e as infeções, sobretudo o herpes vírus humano 8. De modo a facilitar a abordagem diagnóstica, proponho uma tabela onde se encontram descriminados os parâmetros a avaliar na biópsia ganglionar que devem ser completados com outros exames. Concluo que para o futuro é necessário: a existência de informação agregada facilmente disponível para a comunidade médica, assim como, o estabelecimento de critérios universais de gravidade e de protocolos de seguimento.
Castleman’s disease is a rare benign lymphoproliferative disease that can occur in individuals of all ages. The multicentric subtype has very heterogeneous clinical manifestations and is associated with a poor prognosis. This thesis aims to survey the literature in the field of idiopathic multicentric Castleman’s disease, focusing mainly on the diagnosis. It has been ascertained that the histological confirmation (which falls back on biopsies) is compulsory and that the PET-CT scan is the most sensitive imaging method. The semiology and laboratorial alterations are variable and coincident with a systemic inflammatory state. The absence of hypergammaglobulinemia associated with thrombocytopenia are red flags that determine the investigation of TAFRO (Thrombocytopenia, Anasarca, Fever, Reticulin fibrosis, Organomegaly), most severe subtype of the disease. The main differential diagnosis are neoplasms, such as: lymphoma, multiple myeloma, POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes), connective tissue autoimmune disease and infections, mostly HHV8. In order to facilitate the diagnostic approach, a table has been proposed, in which all findings that should be evaluated in a lymph node biopsy are listed. These findings will then require additional exams. In conclusion, in the future we will need compiled information that is readily available for the medical community, as well as established universal criteria of disease severity and follow-up guidelines.