Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 5 uppsatser.

Dissertation (Ph.D.).--University of Texas Graduate School of Biomedical Sciences at San Antonio, 2007. / Vita. Includes bibliographical references.

Thesis (M.P.H.M.)--Mahidol University, 1999.

Thesis (M.S.)--University of Wisconsin-Madison, 1993. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 57-62).

Made available in DSpace on 2016-08-29T15:34:47Z (GMT). No. of bitstreams: 1 tese_4464_.pdf: 3204606 bytes, checksum: a23da35b5188c96d619b059f83d1577a (MD5) Previous issue date: 2010-12-15 / Os HPV são vírus epiteliotrópicos que infectam tecido cutâneo ou mucoso e estão relacionados com desenvolvimento de lesões que, no trato genital, variam de verrugas ao câncer cervical invasivo. As lesões são causadas por diferentes tipos de HPV, que são classificados em baixo e alto risco conforme sua associação com câncer cervical. Sabe-se que mulheres positivas para HIV são mais acometidas por infecções por HPV e estão mais propensas ao desenvolvimento de câncer cervical. O objetivo desse estudo foi avaliar a frequência de tipos de HPV em mulheres soropositivas e soronegativas para HIV. Para isso foram analisadas amostras de escovado cervical, mantidas congeladas, de mulheres conhecidamente positivas para HPV (n=87), atendidas no Centro de Referência DST/AIDS, em Vitória-ES, no período de março a dezembro de 2006. O DNA das amostras foi extraído utilizando kit comercial QIAamp® DNA Mini Kit ou através do método de isotiocinanato de guanidina e sílica. DNA do HPV foi amplificado por PCR utilizando os iniciadores degenerados MY09/MY11 e a genotipagem foi realizada por Restriction Fragment Length Polymorphism (RFLP) e por Reverse Line Blot (RLB). Do total de amostras, 97,7% foram genotipadas e 31 tipos distintos detectados: 6, 11, 13, 16, 18, 26, 31, 31b, 32, 33, 34, 35, 42, 44, 51, 52, 53, 55, 56, 58, 59, 61, 62, 64, 66, 68, 71, 81, 82, 83 e 84. O tipo mais prevalente foi o HPV16, tanto nas mulheres soropositivas quanto nas soronegativas para HIV, seguido pelos tipos 6, 53 e 11. O tipo 13, incomum em amostras cervicais, foi observado nesse estudo, porém a quantidade de amostras não foi suficiente para a realização de seqüenciamento para a confirmação deste tipo viral. Os tipos oncogênicos foram mais comuns nas amostras de mulheres soropositivas para HIV, porém com número semelhante e o número de infecções múltiplas foi maior entre as mulheres HIV positivas. Este estudo revelou uma grande diversidade de tipos de HPV na região. PALAVRAS CHAVES: Human papillomavirus (HPV), Human Immunodeficiency virus (HIV), Restriction Fragment Length Polymorphism (RFLP), Reverse Line Blot (RLB).

Made available in DSpace on 2014-06-11T19:27:55Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-26Bitstream added on 2014-06-13T19:56:56Z : No. of bitstreams: 1 leda_aro_me_botfm.pdf: 436850 bytes, checksum: e631607fe6c1cbb57e01981982378a57 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A história natural de infecção pelo HIV e a progressão para a aids podem variar entre diferentes indivíduos, possivelmente devido a fatores genéticos, entre eles os polimorfismos de nucleotídeo simples (SNPs). SNPs localizados em regiões promotoras de genes que codificam citocinas podem afetar a síntese e a regulação dessas moléculas, resultando em alterações nas respostas imunitárias. O presente estudo buscou avaliar as frequências e os possíveis efeitos de SNPs nas posições -589 e -1098 da região promotora do gene da IL-4 e SNPs nas posições -238 e -862 da região promotora do gene do TNF-α em pacientes portadores do HIV. Amostras de DNA de 157 pacientes foram obtidas através de células mononucleares de sangue periférico e a genotipagem dos SNPs foi realizada pela técnica de High Resolution Melting (HRM). Foi observado que pacientes portadores de TT em SNP/pIL-4 -589 apresentaram contagem de linfócitos T CD8 + menor em relação aos portadores de CC (p=0.0104). Além disso, portadores de TT em SNP/pIL-4 -1098 apresentaram contagem de linfócitos T CD8 + maior em comparação aos portadores de GT (p=0.0053). Em relação a SNP/pTNF-α -238, as proporções de pacientes portadores de GG e GA diferiu entre os pacientes sem HAART e pacientes com HAART e sem falha terapêutica (p=0.0205). Assim, os resultados obtidos no presente estudo fortalecem a hipótese de que SNPs em genes de citocinas podem alterar a história natural da infecção pelo HIV e o curso clínico da doença, principalmente devido a alterações no balanço da produção de citocinas pro- e antiinflamatórias. / The natural history of HIV infection and its progression towards aids may vary considerably among different individuals, possibly due to genetic factors, such as single nucleotide polymorphisms (SNPs). In cytokines genes promoters, SNPs may affect protein synthesis and regulation, resulting in more or less efficient immune responses against HIV. The present study evaluated the frequencies and possible effects of SNPs in the IL-4 gene promoter at positions -589 and -1098 and in the TNF-α gene promoter at positions -238 and -862 in HIV-infected patients from Brazil. DNA samples from 157 patients were obtained from peripheral blood mononuclear cells, and SNPs genotyping was performed by High Resolution Melting analysis (HRM). Patients carrying TT at SNP/pIL-4 -589 had lower circulating T CD8 + cells compared to CC carriers (p=0.0104). Moreover, carriers of TT at SNP/pIL-4 -1098 had more circulating T CD8 + cells compared to GT carriers (p=0.0053). Regarding SNP/pTNF-α -238, GG and GA proportions were significantly different between patients without HAART and patients on HAART without therapeutic failure (p=0.0205). In conclusion, these results provide compelling evidence that the presence of SNPs in cytokine-coding genes do modify the natural history of HIV infection, mainly due to changes in the balance between pro- and anti-inflammatory cytokines.

Magister Curationis - MCur / Background: In 2009, approximately 130 000 children in Southern Africa under the age of 15 were newly infected with HIV, with vertical transmission being the most common cause of HIV infection. HIV positive mothers are therefore faced with a unique dilemma about which infant feeding choice to make. Prior to 2006,formula feeding was the recommended feeding choice in an attempt to minimise vertical transmission of HIV. In 2006, the risks associated with formula feeding necessitated a change in the recommendations to allow for either exclusive formula feeding or exclusive breastfeeding. The clinical guidelines were reviewed in 2010, when research on the effectiveness of prevention of mother to child transmission efforts suggested a decrease in such transmissions, even when exclusive breastfeeding. Currently the recommendations focus on the contextual appropriateness of the infant feeding choice. The imminent withdrawal of free formula is a new development within the prevention efforts. Aims and Objectives: This study aimed to describe the infant feeding choices of HIV positive mothers on discharge from a level two hospital, in Cape Town. The study objectives included determining the infant feeding choice and the factors that influence HIV positive mothers’ infant feeding choice on discharge from the hospital. Research Methodology: A descriptive survey study design was used as it lends itself to the description of the new developments regarding prevention of mother to child transmission and the meaning it has for the infant feeding choices made by HIV positive mothers. A quantitative approach was used to establish the specified factors that currently affect HIV mothers’ infant feeding choices. A nonrandom consecutive sampling technique was used. The data collection method took the form of a questionnaire. Data analysis was performed through SPSS 20 to produce descriptive and inferential statistics to establish relationships between the independent and dependent variables. Results and Recommendations: The number of exclusive breastfeeding participants was higher (54%) than the exclusively formula feeding participants (46%), which is in keeping with the institution’s trends for the previous year (2011). Statistical significance was difficult to establish due to the small scale of the study, but clinical significance with the establishment of the factors influencing infant feeding choices was considered. These led to the following recommendations: reorientation of infant feeding counselling towards the criteria of acceptability, feasibility, affordability,sustainability and safety, in view of the withdrawal of free formula and promotion of exclusive breastfeeding as the single infant feeding strategy. Ethical Considerations: Ethical clearance was sought from the Ethics Committee of the University of the Western Cape, Research Committee of the level two hospital and informed consent was obtained from the participants.

Background : Host protein beta-2 microglobulin (β2m) is incorporated into the human immunodeficiency virus (HIV) -1 coat during budding. Antibodies directed to R7V, an epitope contained in β2m, increased with the duration of infection in long term non-progressor patients (LTNPs). Purified R7V antibodies neutralized HIV isolates and did not bind to human cells. These data suggested potential for R7V antibodies to be developed as therapeutic tools or prognostic markers and the R7V epitope as a vaccine candidate. However, the literature on R7V is still incomplete. For example, most published work on this epitope make no direct reference to HIV subtypes. The rationale for this study is the lack of information on whether all HIV-1 subtypes incorporate R7V and elicit immune responses to the same extent. In particular the response of HIV-1 subtype C infected individuals to R7V antigen is evaluated here. Methodology and results : A synthetic peptide of the R7V epitope of HIV-1 was synthesized and an “in-house” enzyme-linked immunosorbent assay (ELISA) developed. The peptide was able to detect antibodies generated during natural HIV-1 subtype C infection when used as antigen in the ELISA. This response was not as strong as that reported in the literature. A significantly lower ELISA response was observed for uninfected compared to infected sera (probability, p, value ≤ 0.000152), whereas no differences were noticed between antiretroviral (ARV) treated individuals compared to those who were treatment naïve or LTNPs compared to progressors. These data hold promise for the use of these antibodies as diagnostic rather than prognostic indicators. Polyclonal R7V antibodies produced in rabbits and recombinant R7V antibody fragments did not neutralize an HIV-1 subtype C isolate (Du151.2). However, the latter antibodies neutralized an HIV-1 subtype B strain (SF162), suggesting that the R7V epitope may be more exposed in this subtype. The recombinant R7V antibodies did not neutralize a vasicular stomatitis virus (VSV-G), indicating that no nonspecific neutralization occurred. Human immunodeficiency virus type 1 subtype C infected sera containing R7V antibodies (positive response in the R7V ELISA) neutralized Du151.2 while archive sera containing strong HIV-1 subtype C neutralizing antibodies did not recognize the R7V antigen ELISAs. The R7V peptide exogenously added to HIV-1 infected peripheral blood mononuclear cells (PBMCs) did not stimulate proliferation in vitro nor the production of interferon (IFN) gamma which if produced by CD8+ T-cells would have been indicative of a cellular immune response. The parent protein β2m could not initiate these responses either. Conclusion : Data collected here support a diagnostic rather than a prognostic application for R7V antibodies. R7V conjugated to keyhole limpet hemocyanin (KLH) induced non-neutralizing antibodies in rabbits, suggesting that other modifications (branching, lipid conjugation, etc.) may be needed before this epitope can be successfully utilized in vaccine studies. / Dissertation (MSc)--University of Pretoria, 2010. / Biochemistry / unrestricted