Denna undersökning behandlar den småländska predikosjukan, vilken uppkom och spreds bland den småländska allmogen år 1841-1843. Av de uppskattningsvis flera hundra fall som behandlades av läkarkåren bestod den övervägande majoriteten av kvinnor. Undersökningen är medicinhistorisk och syftar till att undersöka hur den religiösa epidemin beskrevs, förstods och 2 tolkades som en sjukdom under 1840-talet. Således utgörs undersökningens källmaterial av läkarkårens utsagor, genom bl.a. provinsialläkarrapporter och skrifter. Undersökningen har utförts med ett socialkonstruktivistiskt perspektiv i enlighet med medicinhistorikern Roy Porters teorier, och består av en kontextnära och tematiskt orienterad närläsning. Inom den tidigare forskningen har predikosjukan främst undersökts som en av 1800-talets väckelserörelser, där allmogens agerande förstås som en upprorshandling mot en ”överhet” bestående av myndigheter, prästerskap och läkarkår såväl som det borgerliga skiktet. Benämningen av fenomenet som en sjukdom, förstås i tidigare forskning endast som ett bildligt uttryck och som en del av en medveten strategi för att slå ned väckelserörelsen. Undersökningen visar att läkarkåren förstod predikosjukan just som en sjukdom och behandlade den därefter. Sjukdomsdefinition och behandlingsmetoder gjordes i enlighet med rådande medicinvetenskapliga grundantaganden. Diskursen om den småländska predikosjukan aktualiserade en rad olika för tidsperioden rådande föreställningar om kropp, själ, sjuklighet, kön och religion. Inom den medicinska förståelsen av predikosjukan inbegrep dessa föreställningar ständigt i varandra, och innebar en komplicerad sjukdomsbild vilken i hög utsträckning var både kulturellt och tidsligt betingad. / This study centers around ‘the preaching disease’ (predikosjuka), an illness which arose and spread among the peasantry in the Swedish province Småland between 1841-1843. Out of the estimated hundreds of cases treated by the medical profession, the vast majority consisted of women. The disease was quickly described as epidemic, and had strong religious connotations. The purpose of the study is to examine how this religious epidemic was described, understood and interpreted as a disease in the 1840’s. Thus, the source material consists of the accounts of the medical professionals, mainly through provincial medical reports and medical publications. The study has been carried out with a social constructivist perspective in accordance with the theories of medical historian Roy Porter, and consists of a contextual and thematically oriented close reading. In previous research, ‘predikosjukan’ has mainly been examined as one of the 19th century Christian revival movements. Here, the activities of the peasantry are understood as a rebellious act against a vaguely defined ‘power’ consisting of authorities, clergy and doctors as well as the bourgeois class. Previous research has understood the phenomenon as only a sickness by the name, as a figurative expression and as part of a conscious strategy to suppress the revival movement. This study shows that the doctors who was confronted with ‘predikosjuka’ during the 1840’s understood the phenomenon as a disease, and chose to treat it accordingly. The doctors’ definitions and medical methods were made in accordance with prevailing and fundamental medical notions of the time. The discourse about ‘predikosjuka’ encapsulated a number of different notions about body, soul, morbidity, gender and religion, all deeply entrenched in the 1840’s. Within the medical understanding of the disease, these notions constantly intertwined, which made for a complicated clinical picture, which to a large extent was both culturally and temporally conditioned.

Huntington's disease (HD) is caused by an expanded plyglutamine repeat in the huntingtin protein. In this study, I focused on the effect of the mutant huntingtin protein (mhtt) on the subcellular localization of glutamic acid decarboxylase (GAD), the enzyme responsible for synthesizing gama-aminobutyric acid (GABA). Subcellular distribution of GAD65 is significantly altered in two neuronal cell lines that express either the N-terminus or full length mhtt. GAD65 is predominantly associated with the Golgi membrane in cells expressing normal huntingtin (Htt). However, it diffuses in the cytosol of cells expressing mhtt. Palmitoylation of GAD65 is required for GAD65 trafficking, and I demonstrated the palmitoylation of GAD65 is reduced in the HD model. Overexpression of huntingtin-interacting protein 14 (HIP14), the enzyme that palmitoylates GAD65, rescues GAD65 palmitoylation and vesicle-associated trafficking. This data suggests that impairment of GAD65 palmitoylation by mhtt may alter its localization and lead to altered inhibitory neurotransmission in HD. / by Daniel Rush. / Thesis (M.S.)--Florida Atlantic University, 2012. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2012. Mode of access: World Wide Web.

Polyglutamine-expanded fragments, derived from the human huntingtin protein, are aggregation-prone and toxic in yeast cells, bearing endogenous QN-rich proteins in the aggregated (prion) form. Attachment of the proline-rich region targets polyglutamine aggregates to the large perinuclear deposit (aggresome). Aggresome targeting ameliorates polyglutamine cytotoxicity in the presence of the prion form of Rnq1 protein, however, aggresome-forming construct remains toxic in the presence of the prion form of translation termination (release) factor Sup35 (eRF3). Disomy by chromosome II partly ameliorates polyglutamine toxicity in the strains containing Sup35 prion. The chromosome II gene, coding for another release factor, and interaction partner of Sup35, named Sup45 (eRF1), is responsible for amelioration of toxicity. Plasmid-mediated overproduction of Sup45, or expression of the Sup35 derivative that lacks the QN-rich domain and is unable to be incorporated into prion aggregates, also ameliorate polyglutamine toxicity. Protein analysis indicates that polyglutamines alter aggregation patterns of the Sup35 prion and promote aggregation of Sup45, while excess Sup45 counteracts these effects. In the absence of Sup35 prion, disomy by chromosome II is still able to decrease polyglutamine toxicity. However, SUP45 is no longer the gene responsible for such an effect. Taken together with the finding that the presence of both the Rnq1 prion and the Sup35 prion has an additive effect on polyQ toxicity, one gene or few genes on chromosome II are able to ameliorate polyQ toxicity through a SUP45-independent pathway. The identification of such a gene is currently ongoing. Monosomy by chromosome VIII in diploid heterozygous by AQT (Anti-polyQ Toxicity mutants that are disomic by chromosome II) counteracted the effect of AQT. Similarly, deletion of the arg4 gene in chromosome VIII in AQT haploid was able to eliminate the AQT effect. Moreover, analysis of genes involved in the arginine and polyamine synthesis indicated that loss of genes in later stages of arginine biosynthesis causes increase of polyglutamine toxicity. Deletion of genes arg1, arg4, arg8 (arginine pathway) and spe1 (polyamine pathway) all suppressed the Sup35 prion phenotype expression in the nonsense suppression system. Further analysis regarding the mechanisms behind those effects is needed. Our data uncover the mechanisms by which genetic and epigenetic factors may influence polyglutamine toxicity, and demonstrate that one and the same type of polyglutamine deposits could be cytoprotective or cytotoxic, depending on the prion composition of a eukaryotic cell.

Adolescence is a time when individuals begin to explore and examine psychological characteristics of the self in order to discover who they really are and how they fit in the social world in which they live. It is during this time of self-exploration that adolescents at risk for Huntington's Disease often learn of their risk status and witness the debilitating symptoms of the disease in their parents. Huntington Disease (HD) is an autosomal dominant neuropsychiatric disorder characterized by mid-life onset, involuntary movements, cognitive impairment, and depression. This dissertation investigated how adolescents experience living in a family with Huntington's Disease and therefore at risk for Huntington's Disease, and how this impacts their self-understanding and self-identity. The method of inquiry was based on a phenomenological approach. In-depth interviews were conducted with each of the adolescents. The data were analyzed using Van Manen's (1980) and Cochran and Claspell's (1987) format, resulting in an extraction of three themes. These themes are: (1) Naming the Legacy: Understanding and Misunderstanding; (2) Experiencing the Legacy: Huntington's Disease in Relation to Relationships; and (3) Integrating the Legacy: At the Crossroads of Self and Future Self. The analysis emphasizes that the at-risk adolescents' exploration of self-identity and future self was an individual process influenced by the cognitive, developmental, and socio-cultural contexts of the adolescents' lives. The process of learning about Huntington's Disease occurred through intuition and practical and experiential learning. The adolescents found support outside their family through friends and adult mentors. They engaged in complicated coping strategies and demonstrated a capacity for decision-making that displayed maturity beyond what would be expected for their age group. These findings led to specific recommendations for theory, research, and clinical practice in the area of the adolescent experience of HD. The research underscores the need for healthcare professionals to re-evaluate their view of adolescent autonomy and capacity for decision-making.

The reach-to-eat movement, in which a hand is advanced towards a food item, shapes to grasp the food item, and withdrawals to place the food item into the mouth for eating, is a behaviour that is performed daily. The movement is controlled by two sensory systems, vision to guide hand advance and grasping, and somatosensation to guide hand withdrawal and mouth placement. The purpose of the present thesis was to examine how the sensory control of reaching-to-eat develops in infancy and degenerates following neurodegenerative disorder. The tight coupling of vision to hand advance and somatosensation to hand withdrawal has a developmental profile from six months to one year of age. That is, six-month-old infants rely on vision to advance their hand, grasp the target, and withdrawal the target to the mouth. By twelve months of age, infants display the adult pattern of coupling vision to hand advance and grasping. The tight coupling of vision to hand advance degenerates with basal ganglia disease, such that subjects with Parkinson’s disease and Huntington’s disease show an overreliance on vision to guide hand advance for grasping and hand withdrawal for mouth placement. The results of the thesis demonstrate that efficient use of sensory control to guide motor behaviour is an important aspect of development that is disrupted by neurodegenerative disease. / xiv, 286 leaves : ill. ; 29 cm

Thesis (Ph. D.)--University of California, San Diego and San Diego State University, 1999. / Vita. Includes bibliographical references (leaves 105-113).

Thesis (M.Sc.)--University of Ottawa, 2008. / Includes bibliographies.

Thesis (M.Sc.)--University of Ottawa, 2008. / Includes bibliographies.

Thesis (Ph. D.)--University of Virginia, 2006. / Includes bibliographical references (leaves 181-233). Also available online through Digital Dissertations.

Introdução: A doença de Huntington (HD) é uma doença neurodegenerativa, autossômica dominante, causada pela expansão CAG que resulta em distúrbios do movimento, prejuízo cognitivo e alterações de personalidade. Muito pouco se sabe sobre a qualidade de vida de pacientes com HD e fatores associados e a influência dos mesmos nos sintomas depressivos dos cuidadores. Objetivo: Avaliar a qualidade de vida de indivíduos portadores da HD bem como suas implicações e, além disso, avaliar presença de sintomas depressivos no seu cuidador de convívio diário. Investigar os fatores que possam estar relacionados com o prejuízo da qualidade de vida do paciente tais como grau de comprometimento funcional, distúrbio motor, cognitivo e comportamental, sintomas de depressão, prejuízo no sono. Metodologia: Trata-se de um estudo quantitativo transversal. A população foi composta por pacientes com HD em acompanhamento no ambulatório de Distúrbios do Movimento e Neurogenética, que possuíam diagnóstico de HD confirmado por teste molecular. As entrevistas foram realizadas com auxilio de ferramentas estruturadas, as quais seguem: SF-36 e HQoLI, para qualidade de vida; UHDRS para avaliação funcional; MoCA para avaliação cognitiva; PSQI para avaliação do sono e BDI para avaliação de sintomas depressivos do paciente e cuidador. Resultados: Foram avaliados 28 pacientes com HD com idade média de 41 ± 9.5 e expansão CAG média de 45 ± 6. A duração da doença apresentou associação com os aspectos físicos da escala SF-36 (p<0.01). AUHDRS apresentou impacto em vários domínios da qualidade de vida, tais como domínios de saúde física e mental. A má qualidade do sono avaliada através da escala PSQI influenciou na QV do paciente nos dois grandes domínios de saúde física e saúde mental com (p<0.05) e (p<0.01) respectivamente. O nível cognitivo apresentado pelos pacientes avaliados pela escala MoCA apresentaram associação com domínio de funcionamento físico da escala SF-36 (p<0.01) Conclusão: As análises dos dados coletados permitem afirmar que se trata de uma doença que impacta de maneira significativa na QV das famílias. O apoio multidisciplinar a família afetada e o tratamento das comorbidades associadas se faz fundamental para amenizar os impactos da doença e melhorar a QV. / Background: The Huntington Disease (HD) is a neurodegenerative autosomal dominant disorder caused by the CAG expansion resulting in movement disorders, cognitive impairment and personality changes. Very little is known about the quality of life in HD patients associated factors and influence on depressive symptoms of caregivers. Objective: To evaluate the quality of life in individuals with HD, as well as its implications, and evaluate their daily caregiver for depressive symptoms. Factors that may be related to harm of patient's quality of life, such as functional impairment; motor, cognitive and behavioral disorder; symptoms of depression; and sleep loss were investigated. Methods: It is a quantitative cross-sectional study. The population was composed of patients with HD from Movement Disorders and Neurogenetics Clinic, who had positive molecular test. The interviews were carried out with support of the structured tools as follow: SF-36 and HQoLI for quality of life, UHDRS for functional evaluation, MoCA for cognitive evaluation, PSQI for sleep evaluation, and BDI for evaluation of depression of patient and caregiver. Results: Twenty-eight HD patients were evaluated with an average age of 41 ± 9.5 and an average CAG expansion of 45 ± 6. The duration of the disease was associated with the physical aspects of the SF-36 scale (p<0.01). UHDRS was associated with impairment in several domains of quality of life including mental and physical domains. It was identified that the bad sleep quality evaluated through the PSQI scale was associated with patient's QL (quality of life). The cognitive level evaluated by the MoCA scale presented association with the Physical functioning domain of SF-36 scale (p<0.01). Conclusion: The analysis of the collected data allows to affirm that HD impacts significantly on the families quality of life. The multidisciplinary support to the affected family is critical to mitigate the impacts of the disease and improve the QL.