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京都大学 / 新制・課程博士 / 博士(生命科学) / 甲第25515号 / 生博第531号 / 新制||生||70(附属図書館) / 京都大学大学院生命科学研究科統合生命科学専攻 / (主査)教授 荒木 崇, 教授 野田 岳志, 教授 谷口 雄一 / 学位規則第4条第1項該当 / Doctor of Philosophy in Life Sciences / Kyoto University / DFAM

The HIV and AIDS pandemic is arguably the greatest threat facing the world today. The pandemic has a far-reaching impact on society, including the workplace. The effect in the workplace is observed in various areas including a reduction in certain skills levels, mortality and declining job performance of employees living with HIV or AIDS. In addition, the fear of discrimination and stigmatisation prevents infected employees from disclosing their HIV status, thus driving the pandemic underground. Despite the potential negative impact that is looming, many employers still do not have any workplace support programmes in place to manage HIV and AIDS in their organisations. However, some employers have implemented workplace support programmes. This research thus explored the influence of workplace support programmes on the job performance of employees that were living with HIV or AIDS. The findings suggest that job performance is positively influenced where workplace support programmes have been implemented. / Industrial and Organisational Psychology / M.Comm. (Industrial and Organisational Psychology)

The study sought to explore and describe the breastfeeding practices of Human Immunodeficiency Virus (HIV) positive postnatal clients’ non-commitment to exclusive breastfeeding in George Mukhari Hospital, South Africa. A non-experimental quantitative design was used. Inferences drawn from the study were that HIV positive clients that opted for exclusive breastfeeding did not commit for fear of transmission of HIV to the baby and exclusive breastfeeding was stopped before the recommended 6 months. Most of the respondents’ partners did not come for counselling. There was lack of emotional support by staff after testing. Health education and emotional support of HIV positive clients has to be intensified. / Health Studies / M. A. (Health Studies)

Thesis (PhD)--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: Background: Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) is an accessory protein that interacts with a number of host cellular and other viral proteins. Vpr exerts several functions such as induction of apoptosis, induction of cell cycle G2 arrest, modulation of gene expression, and suppression of immune activation. The functionality of subtype C Vpr, especially South African strains, has not been studied. The aim of this study was to describe the diversity of South African HIV-1 subtype C vpr genes and to investigate selected functions of these Vpr proteins. Methodology: The HIV-1 vpr region of 58 strains was amplified, sequenced, and subtyped using phylogenetic analysis. Fragments containing natural mutations were cloned in mammalian expression vectors. A consensus subtype C vpr gene was constructed and site-directed mutagenesis was used to induce mutations in postions in which no natural mutations have been described. The functionality of all constructs was compared with the wild-type subtype B Vpr, by transfecting human 293T cell line to investigate subcellular localization, induction of apoptosis and cell cycle G2 arrest. The modulation of genes expressed in the induction of apoptosis using TaqMan Low density arrays (TLDA) was also investigated. Results: Phylogenetic analysis characterized 54 strains as HIV-1 subtype C and 4 strains as HIV-1 subtype B. The overall amino acid sequence of Vpr was conserved including motifs FPRPWL and TYGDTW, but the C-terminal was more variable. The following mutations were constructed using site-directed mutagenesis: P14I, W18C, Y47N, Q65H and Q88S. Subtype B and all natural mutants of subtype C Vpr localized to the nucleus but the W18C mutation disturbed the nuclear localization of Vpr. The cell cycle G2 arrest activity of all the mutants, as well as consensus-C, was lower than that of subtype B Vpr. All the natural mutants of subtype C Vpr induced cell cycle G2 arrest in 54.0-66.3% of the cells, while subtype B Vpr induced cell cycle G2 arrest in 71.5% of the cells. Subtype B and the natural mutant Vpr proteins induced apoptosis in a similar manner, ranging from 95.3-98.6% of transfected cells. However, an artificially designed Vpr protein containing the consensus sequences of subtype C Vpr indicated a reduced ability to induce apoptosis. While consensus-C Vpr induced apoptosis in only 82.0% of the transfected cells, the artificial mutants of Vpr induced apoptosis in 88.4 to 96.2% of the cells. The induction of apoptosis associated gene expression was similar for all constructs, indicated that apoptosis was efficiently induced through the intrinsic pathway by the mutants. Conclusion: This study indicated that both HIV-1 subtype B and C Vpr display a similar ability for nuclear localization and apoptosis induction. The induction of cell cycle G2 arrest by HIV-1 subtype B Vpr may be more robust than many subtype C Vpr proteins. The natural mutations studied in the isolates did not disturb the functions of subtype C Vpr and in some cases even potentiated the protein to induce apoptosis. Naturally occurring mutations in HIV-1 Vpr cannot be regarded as defective, since enhanced functionality would be more indicative of an adaptive role. The increased potency of the mutated Vpr proteins suggests that Vpr may increase the pathogenicity of HIV-1 by adapting apoptotic enhancing mutations. / AFRIKAANSE OPSOMMING: Agtergrond: Die virus protein R (Vpr) van Menslike Immuungebrek Virus tipe 1 (MIV-1) is ‘n bykomstige protein wat met ‘n aantal sellulêre proteine van die gasheer en ander virus proteine in wisselwerking tree. Vpr het 'n invloed op verskeie funksies onder andere die induksie van apoptose, die induksie van selsiklus G2 staking, modulering van geen uitdrukking en onderdrukking van immuun aktivering. Die funksionaliteit van subtipe C Vpr, en veral die van Suid-Afrikaanse stamme, is nie beskryf nie. Die doelwit van die studie was om die diversiteit van Suid Afrikaanse MIV-1 subtipe C vpr gene te beskryf en ook om selektiewe funksies van die Vpr proteine te ondersoek Metodiek: Die MIV-1 vpr streek van 58 stamme is vermeerder, die DNA volgordes is bepaal en die stamme is gesubtipeer deur filogenetiese analise. Fragmente met natuurlike mutasies is in ekspressie vektore gekloon. ‘n Konsensus subtipe C Vpr geen is ontwerp en mutasies in posisies waar geen natuurlike mutasies beskryf is nie, is ontwerp deur mutagenese. Die funksionaliteit van die konstrukte is met die wilde tipe subtype B vergelyk deur 293T sellyn te transfekteer en te ondersoek vir subsellulêre lokalisering, induksie van apoptose, en G2 selsiklus stilstand. Die modulering van geen uitdrukking in die induksie van apoptose is deur TLDA ondersoek. Resultate: Filogenetiese analise het 54 stamme as HIV-1 subtipe C geklassifiseer en 4 stamme as subtype B. Die Vpr aminosuur volgordes was konstant insluitend die FPRPWL en TYGDTW motiewe, maar die C-terminaal was meer variëerbaar. Deur mutagenese is die volgende mutasies ontwerp: P14I, W18C, Y47N, Q65H and Q88S. Subtipe B en al die natuurlike mutante van subtipe C het in die selkern gelokaliseer, maar die W18C mutasie het die lokalisasie versteur. Die G2 selsiklus stilstand van alle mutante en konsensus C was laer as die van subtype B. Al die natuurlike subtipe C mutante het G2 selsiklus tot stilstand gebring in 54.0-66.3% van die selle, terwyl subtype B selsiklus tot stilstand gebring het in 71.5% van die selle. Subtipe B en die natuurlike Vpr mutante het apoptose op ‘n soortgelyke wyse geinduseer, wat wissel tussen 95.3-98.6% van getransfekteerde selle. Die protein met die kunsmatig ontwerpte konsensus C volgorde het egter ‘n verlaagde vermoë gehad om apoptose te induseer. Die konsensus subtipe C het apoptose in 82.0% van getransfekteerde selle geinduseer en die kunsmatige mutante in 88.4 – 96.2% van die selle. Die induksie van die apoptose verwante geen ekspressie deur die mutante was soortgelyk as die van konsensus C en subtipe B Vpr wat ’n aangeduiding is dat apoptose effektief veroorsaak is deur die intrinsieke roete. Gevolgtrekking: Hierdie studie het aangetoon dat kern lokalisering en apoptose op ‘n soortgelyke wyse by beide MIV-1 subtipe B en C Vpr plaasvind. Die induksie van selsiklus G2 stilstand deur MIV-1 subtipe B Vpr is egter meer robuust as baie van die subtipe C Vpr proteïene. Natuurlike mutasies in MIV-1 Vpr kan nie as gebrekkig beskou word nie, aangesien beter funksionaliteit 'n aanduiding is vandie aanpasbare rol. Die verhoogde krag van die gemuteerde Vpr proteïen dui daarop dat Vpr die patogenisiteit van MIV-1 kan verbeter deur die aanpassing van mutasies.

<p>The devastation caused by the Human Immunodeficiency Virus/ Acquired Immune Deficiency Syndrome (HIV/AIDS) is having a major impact on both the social and economic environment in South Africa. HIV/AIDS hits at the core of the businesses structure - the bottom line. In the absence of a cure for the disease or an effective vaccine, the challenge for all the stakeholders is how to successfully contain and limit the impact of the disease. Intervention programmes such as awareness, knowledge sharing and sero-prevailance testing have the potential to limit HIV/AIDS infections and reduce high-risk behaviours. Whilst education and awareness programmes have been relatively successful in highlighting the dangers of HIV infection, perception, attitudes and behaviours of employees towards HIV/AIDS have dampened voluntary HIV screening initiatives. Many South African organisations have commendable HIV/AIDS education and awareness programmes, however, a concerning fact is that employees are reluctant to avail themselves to voluntary HIV/AIDS testing. Stigmatising attitudes toward persons living with HIV/AIDS may reduce people&rsquo / s willingness to have themselves tested for the Human Immunodeficiency Virus (HIV). This may increase the risk of transmission. It may also lead to increased absenteeism in the workplace, and workdays lost resulting from excessive sick.<br /> <br /> The aim of the study was to establish what the perceptions and attitudes are of employees at different levels of the organisation with regard to HIV/AIDS testing. A further aim was to identify possible reasons for the poor employee response to voluntary HIV/AIDS testing. It was thus important for this research to gauge employee knowledge, attitude and behaviour toward HIV/AIDS in order for organisations to develop strategies for effective HIV/AIDS counselling and testing programmes.<br /> <br /> The data for this study was collected by means of a self report questionnaire. The questionnaire was administered to a sample of employees across all levels of the organisation using the convenient sample approach to identify the respondents. Two hundred and forty six (246) out of a total of 600 questionnaires distributed were returned, making the response rate a credible 41%.<br /> The Statistical Package for Social Science (SPSS) was used to analyse the data obtained from the questionnaire. Both inferential and descriptive statistical approaches were used to analyse the data. The Analyses Of Variance (ANOVA) was used to determine whether differences exist in the perceptions and attitudes of employees at different levels and groupings in the organisation. Additionally post hoc tests (i.e. the Scheffe test) were applied to all comparisons of means after the analysis of variance.<br /> <br /> The findings of this research are important for the role of HIV/AIDS testing and awareness/preventions strategies implemented in South Africa. It provides more insight as to why employees resist HIV/AIDS testing. It can furthermore assist organisations in developing strategies for implementing effective HIV/AIDS awareness and/or prevention programmes. More specifically, the findings identified ways in which organisations can redesign their intervention programmes so as to encourage a greater number of employees to submit to voluntary HIV/AIDS testing.</p>

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

The study sought to explore and describe the breastfeeding practices of Human Immunodeficiency Virus (HIV) positive postnatal clients’ non-commitment to exclusive breastfeeding in George Mukhari Hospital, South Africa. A non-experimental quantitative design was used. Inferences drawn from the study were that HIV positive clients that opted for exclusive breastfeeding did not commit for fear of transmission of HIV to the baby and exclusive breastfeeding was stopped before the recommended 6 months. Most of the respondents’ partners did not come for counselling. There was lack of emotional support by staff after testing. Health education and emotional support of HIV positive clients has to be intensified. / Health Studies / M. A. (Health Studies)

BACKGROUND: The needle exchange programme (NEP) started in Sweden in 1986 in Lund and shortly after in Malmo. The first NEP in Stockholm opened in spring 2013. The NEP is a service aimed at intravenous drug users (IDU) from 18 years old, with a goal of preventing the blood borne diseases, such as HIV, Hepatitis B (HBV), and Hepatitis C (HCV). With the on going HIV and Hepatitis epidemics, numerous countries around the world have adopted control strategies, such as the NEP to halt the spread of HIV, HBV, and HCV. The objective of this study was to examine if the needle exchange programme has decreased the incidence of HIV, HBV, and HCV in Sweden over a six-year period.  METHODS: Data for incidence and prevalence was extracted from the yearly reports of the Stockholm’s needle exchange programme from 2013 to 2018 and the yearly reports of the public health agency in Sweden from 2013 to 2018. The data was collected for Stockholm, and compared to Västra Götaland, and the whole of Sweden. RESULTS: The incidence of HIV was zero in 2013 and 2015 in the NEP. The incidence of HBV decreased to zero in 2013 in the NEP. There is an increased incidence of HCV in the NEP. CONCLUSION: The NEP has a protective effect through its combination of needle exchange, opiate substitute therapy, counselling, and vaccinations in reducing and stabilising incidences of the infections, in some instances to zero, as well as providing surveillance and treating infections.

O Epstein-Barr Vírus (EBV) é um vírus da família Herpes (HHV-4), presente em grande parte da população mundial. É o agente etiológico da mononucleose infecciosa e da leucoplasia pilosa. A leucoplasia pilosa é uma doença epitelial benigna associada ao EBV, caracterizada pela reprodução replicativa do EBV nas células do epitélio oral, e é uma das mais freqüentes lesões oportunistas em pacientes HIV positivos, sendo menos freqüente apenas que a candidíase, com uma prevalência média entre 10 % e 30%. Por ser uma lesão oportunista bucal fortemente relacionada com a infecção pelo HIV e com a imunossupressão, seu diagnóstico é importante, pois pode sugerir o diagnóstico da infecção em pacientes de sorologia desconhecida para o HIV, e auxiliar no estadiamento da doença. Sua detecção e correto diagnóstico são de particular importância por essa condição estar relacionada à capacidade imune do paciente. Além disso, em pacientes já diagnosticados, ela é indicadora da progressão da doença e da eficácia da terapia antirretroviral. O objetivo desse estudo foi avaliar a presença e a quantidade do EBV na saliva e no sangue de pacientes infectados pelo HIV atendidos no CAPE-FOUSP, verificar a presença clínica de leucoplasia pilosa, estabelecendo a possibilidade da existência de vínculo entre a carga viral do EBV, a manifestação clínica da lesão e a carga viral do HIV. Também se buscou estabelecer relação entre o tipo de terapia antirretroviral em uso e a presença de leucoplasia pilosa, bem como estabelecer relação entre a carga viral do EBV na saliva e no sangue. Foram analisadas 20 lesões de leucoplasia pilosa, num total de 94 pacientes avaliados. Foi encontrada uma correlação positiva entre a Carga Viral do EBV no sangue e na saliva (p=0,001). Quanto maior a carga viral no sangue, maior a carga viral na saliva. Foi encontrada associação entre a Carga Viral do EBV na saliva e a presença de Leucoplasia Pilosa (p=0,045). Indivíduos com Leucoplasia Pilosa apresentam maior Carga Viral de EBV na saliva do que indivíduos sem essa lesão. Foi encontrada uma correlação positiva entre a Carga Viral do HIV e a Carga Viral do EBV na saliva (p=0,006) porém não no sangue. Quanto maior a carga viral de HIV, maior a carga viral do EBV na saliva. Foi encontrada correlação positiva entre a Carga Viral do EBV no sangue e as contagens de CD4 mais baixa registrada e a mais atual (p=0,028 e p=0,030 respectivamente). Quanto maior Carga Viral do EBV no sangue, maior a contagem de CD4. Não foi encontrada associação entre o tipo de medicação antirretroviral em uso e presença de lesão de leucoplasia pilosa. / The Epstein-Barr Virus (EBV) is a herpes virus family (HHV-4), is present in great part of the world population. It is the causative agent of infectious mononucleosis and oral hairy leukoplakia. Oral hairy leukoplakia is a benign epithelial disease associated with EBV, which is characterized by the replicative reproduction of EBV in oral epithelial cells, and is one of the most frequent opportunistic lesions in HIV positive patients, only less frequent than candidiasis, with an average prevalence between 10% and 30%. Being an opportunistic oral lesion strongly associated with HIV infection and immunosuppression, its diagnosis is important, because it may suggests the diagnosis of infection in patients of unknown HIV serology, and assist in the staging of the disease. Its detection and correct diagnosis are particularly important because this condition is related to the patient\'s immune capacity. Moreover, in patients already diagnosed, it is indicative of disease progression and effectiveness of antiretroviral therapy. The aim of this study was to evaluate the presence and quantity of EBV in saliva and blood of HIV-infected patients treated at the CAPE-FOUSP, verifying the presence of clinical OHL, establishing the possibility of the existence of a link between viral load and EBV, clinical manifestation of the lesion, and HIV viral load. It was also aimed to establish the relationship between the type of antiretroviral therapy in use and the presence of oral hairy leukoplakia, as well as establish the relationship between viral load of EBV in saliva and blood. We analyzed 20 lesions of oral hairy leukoplakia, a total of 94 patients. Found a positive correlation between viral load of EBV in blood and saliva (p = 0.001). The higher the viral load in blood, the higher the viral load in saliva. Association was found between viral load of EBV in saliva and the presence of oral hairy leukoplakia (p = 0.045).Individuals with oral hairy leukoplakia have a higher viral load of EBV in saliva than those without such injury. Found a positive correlation between viral load and HIV viral load of EBV in saliva (p = 0.006) but not in blood. The higher the viral load of HIV, the higher the viral load of EBV in saliva. A positive correlation was found between viral load of EBV in blood and CD4 counts the lowest recorded and most current (p = 0.028 and p = 0.030 respectively). The higher viral load of EBV in blood, increased CD4 count. No association was found between the type of antiretroviral medications in use and presence of oral hairy leukoplakia lesions.