by Lam Tin Lun. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 131-151). / Abstracts in English and Chinese. / Acknowledgment --- p.I / Table of content --- p.II / List of Tables --- p.IX / List of Figures --- p.XI / Abbreviation --- p.XIII / Abstract --- p.XIV / 論文摘要 --- p.XVI / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Acquired immunodeficiency syndrome (AIDS) --- p.1 / Chapter 1.1.1 --- History of AIDS --- p.1 / Chapter 1.1.2 --- Definition of AIDS --- p.2 / Chapter 1.1.3 --- HIV/AIDS Around the World --- p.4 / Chapter 1.1.4 --- HIV/AIDS in Hong Kong --- p.4 / Chapter 1.1.4.1 --- Hong Kong AIDS Update --- p.4 / Chapter 1.1.4.2 --- AIDS Transmission --- p.6 / Chapter 1.1.4.3 --- Main AIDS Complications Occur in Hong Kong --- p.6 / Chapter 1.2 --- Human Immunodeficiency Virus (HIV) --- p.7 / Chapter 1.2.1 --- Classification of HIV --- p.7 / Chapter 1.2.2 --- The Structure of HIV Virion --- p.9 / Chapter 1.2.3 --- The HIV Genome --- p.11 / Chapter 1.2.4 --- The Life Cycle of HIV --- p.12 / Chapter 1.2.4.1 --- Invasion of the Cells --- p.12 / Chapter 1.2.4.2 --- Integration into cell genome --- p.13 / Chapter 1.2.4.3 --- Protease and assembly to the virus --- p.13 / Chapter 1.2.5 --- Three Essential Enzymes for HTV-1 Replication --- p.16 / Chapter 1.2.5.1 --- HIV-1 Reverse Transcriptase (HIV-1 RT) --- p.16 / Chapter 1.2.5.2 --- HIV-1 Integrase (HIV-1 IN) --- p.17 / Chapter 1.2.5.3 --- HIV-1 Protease (HIV-1 PR) --- p.18 / Chapter 1.2.6 --- The Different Stages of HIV Infection --- p.19 / Chapter 1.3 --- AIDS therapy --- p.23 / Chapter 1.3.1 --- Drugs Approved by US Food and Drug Administration (FDA) --- p.23 / Chapter 1.3.2 --- Vaccine --- p.26 / Chapter 1.3.3 --- Chemokine Receptor Inhibitor --- p.27 / Chapter 1.3.4 --- Antisense Oligonucleotides Therpay --- p.28 / Chapter 1.3.5 --- Traditional Chinese Medicine (TCM) --- p.29 / Chapter 1.4 --- Objective of My Project --- p.32 / Chapter CHAPTER 2 --- SCREENING OF TRADITIONAL CHINESE MEDICINAL PLANTS FOR HIV-1 PROTEASE INHIBITION --- p.33 / Chapter 2.1 --- Introduction --- p.33 / Chapter 2.2 --- Materials and Methods --- p.35 / Chapter 2.2.1 --- Materials --- p.35 / Chapter 2.2.2 --- Extraction Methods --- p.36 / Chapter 2.2.2.1 --- Aqueous Extraction --- p.36 / Chapter 2.2.2.2 --- Methanol Extraction --- p.37 / Chapter 2.2.3 --- Preparation of Recombinant HIV-1 Protease --- p.37 / Chapter 2.2.3.1 --- Selection of Appropriate Clone --- p.37 / Chapter 2.2.3.2 --- Large-scale Expression of Recombinant HIV-1 Protease --- p.38 / Chapter 2.2.2.3 --- Purification of Recombinant HIV-1 Protease by DEAE Sepharose CL-6B Chromatography --- p.38 / Chapter 2.2.3.4 --- Purification of Recombinant HIV-1 Protease by Mono-S Cation Chromatography --- p.39 / Chapter 2.2.3.5 --- Refolding of Purified Recombinant HIV-1 Protease --- p.40 / Chapter 2.2.3.6 --- Protein Concentration Determination --- p.41 / Chapter 2.2.3.7 --- Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE) --- p.41 / Chapter 2.2.4 --- Characterization of HTV-1 Protease --- p.42 / Chapter 2.2.4.1 --- HIV-1 PR Fluorogenic Assays --- p.42 / Chapter 2.2.4.2 --- HIV-1 PR Assay by Reverse Phase HPLC Separation of Cleavage Products of the Synthetic Peptide Substrate --- p.43 / Chapter 2.3 --- Results --- p.44 / Chapter 2.3.1 --- Functional Analysis of Recombinant HIV-1 PR Activity --- p.44 / Chapter 2.3.2 --- Screening of Crude Extracts for Inhibition of HIV-1 PR Activity --- p.48 / Chapter 2.4 --- Discussion --- p.53 / Chapter CHAPTER 3 --- ISOLATION AND CHARACTERIZATION OF ACTIVE CONSTITUENTS FROM METHANOL EXTRACTS OF WOODWARDIA UNIGEMMATA AGAINST HIV-1 PROTEASE --- p.56 / Chapter 3.1 --- Introduction --- p.56 / Chapter 3.2 --- Materials and Methods --- p.57 / Chapter 3.2.1 --- Materials --- p.57 / Chapter 3.2.2 --- Methods --- p.58 / Chapter 3.2.2.1 --- Methanol Extraction --- p.58 / Chapter 3.2.2.2 --- Removal of Tannins --- p.60 / Chapter 3.2.2.3 --- Glucosidase Digestion --- p.60 / Chapter 3.2.2.4 --- Analytical Thin Layer Chromatographic (TLC) --- p.61 / Chapter 3.2.2.5 --- A cid Hydrolysis --- p.62 / Chapter 3.2.2.6 --- Electrospray Mass Spectrometry --- p.62 / Chapter 3.2.2.7 --- Dose-response Curve --- p.63 / Chapter 3.2.2.8 --- Kinetic Studies --- p.63 / Chapter 3.2.2.9 --- Activity of the HPLC-purified principle (s) on Other Aspartyl Proteases --- p.63 / Chapter 3.3 --- Results --- p.66 / Chapter 3.3.1 --- Purification of Methanol Extracts of Woocdwardia unigemmata --- p.66 / Chapter 3.2.2 --- Removal of Tannins --- p.70 / Chapter 3.2.3 --- Glucosidase Digestion --- p.73 / Chapter 3.2.4 --- Acid Hydrolysis --- p.73 / Chapter 3.2.5 --- Analytical Thin Layer Chromatography --- p.74 / Chapter 3.2.6 --- Electrospray Mass Spectrometry --- p.80 / Chapter 3.2.7 --- Dose-response Inhibition of HIV-1 Protease --- p.80 / Chapter 3.2.8 --- Kinetic Studies --- p.85 / Chapter 3.2.9 --- Effects of HPLC-purified Active Principle on Other Aspartyl Proteases --- p.87 / Chapter 3.3 --- Discussion --- p.89 / Chapter CHATPER 4 --- IDENTIFICATION OF SELECTIVE RNA APTAMERS AGAINST HIV-1 PROTEASE BY SYSTEMATIC EVOLUTION OF LIGANDS BY EXPONENTIAL ENRICHMENT (SELEX) --- p.95 / Chapter 4.1 --- Introduction --- p.95 / Chapter 4.2 --- Materials and Methods --- p.101 / Chapter 4.2.1 --- Materials --- p.101 / Chapter 4.2.2 --- Methods --- p.102 / Chapter 4.2.2.1 --- PCR Amplification for the Generation of a Double-Stranded DNA Library --- p.103 / Chapter 4.2.2.2 --- Preparation of RNA Pools --- p.104 / Chapter 4.2.2.3 --- In vitro Selection of RNA Ligands --- p.104 / Chapter 4.2.2.4 --- Reverse Transcription Reaction of Selected RNA --- p.108 / Chapter 4.2.2.5 --- Cloning of the Amplified cDNA pools --- p.108 / Chapter 4.2.2.6 --- Subcloning of the digested DNA product into pBluescript® IIKS (-) --- p.108 / Chapter 4.2.2.8 --- RNA Labeling with Digoxigenin (DIG) --- p.109 / Chapter 4.2.2.9 --- Binding Affinity of RNA Ligands for HIV-1 PR --- p.109 / Chapter 4.2.2.10 --- Competition Binding Reactions --- p.111 / Chapter 4.2.2.11 --- HIV-1 PR Inhibitory Activities of the Selected RNA Ligands --- p.112 / Chapter 4.3 --- Results --- p.113 / Chapter 4.3.1 --- In Vitro Selection of RNA Ligands --- p.113 / Chapter 4.3.2 --- Sequences of RNA Ligands --- p.114 / Chapter 4.3.3 --- Binding Affinity of RNA Ligands --- p.114 / Chapter 4.3.4 --- Inhibitory Activity of RNA Ligands --- p.119 / Chapter 4.4 --- Discussion --- p.122 / Chapter CHAPTER 5 --- GENERAL DISCUSSION --- p.128 / REFERENCES --- p.132

Ventricular dysfunction and dilated cardiomyopathy (DCM) develop among untreated HIV-infected people at much higher rates than among HIV-negative individuals, resulting in significant contributions to morbidity and mortality. Mechanisms underlying development of HIV-associated cardiomyopathy (HIVCM) are as yet poorly understood. The well-characterized simian immunodeficiency virus (SIV) model of HIV infection provides a unique context for HIVCM pathogenesis studies in that SIV-infected rhesus monkeys develop myocardial lesions and contractile dysfunction similar to those described in HIV-infected people, suggesting a shared disease mechanism. Lymphocytic myocarditis is a commonly reported finding in AIDS patients at autopsy and constitutes one of several conditions known to predispose to development of DCM, irrespective of HIV-infection status. As lymphocytic myocarditis also occurs with high frequency among SIV-infected rhesus monkeys, a retrospective analysis of rhesus monkey cardiac tissue collected at necropsy was performed to examine viral and cellular correlates of lymphocytic inflammation within myocardial tissue. One subpopulation of macrophages, which has been reported by other groups to be associated with an anti-inflammatory phenotype, was found to correlate inversely with lymphocytic infiltration and positively with numbers of virus infected cells, suggesting effects of an anti-inflammatory cytokine production profile. In contrast, the detrimental effects of inflammatory cytokines on myocardial structure and function are well-recognized and HIV infection in general is characterized by chronic immune activation and inflammatory cytokine dysregulation. To further investigate a role for myocardial cytokine production in development of HIVCM, a prospective study was conducted in which SIV-infected rhesus monkeys and uninfected controls were treated with recurrent administration of inactivated Mycobacterium aviumcomplex bacteria (MAC). SIV-infected, MAC-treated animals rapidly developed significant ventricular systolic dysfunction and chamber dilatation not seen in control groups, suggesting an exaggerated myocardial sensitivity to exogenous antigenic stimulation. Concurrent treatment with the TNFα antagonist etanercept completely abrogated development of these changes, strongly implicating a causative role for TNFα in evolution of the contractile dysfunction and chamber remodeling. Findings reported from the current studies suggest that characteristics of local myocardial macrophage populations and the myocardial tissue cytokine milieu may play more important roles than lymphocytic infiltration, cardiomyocyte damage, or viral proteins in the pathogenesis of HIVCM.

Thesis (MPH.) -- University of Limpopo, 2022 / Background: Acquired Immunodeficiency Syndrome still remains the leading cause of death globally. Understanding students’ views about the risk of Human Immunodeficiency Virus infection by exploring and describing their perceptions may help to design effective Human Immunodeficiency Virus prevention interventions. The tertiary institution environment offers a great opportunity for Human Immunodeficiency Virus high risk behaviours, including alcohol and drug abuse, unsafe sex, multiple sexual relationships, intergenerational and transactional sex. Despite the decline in the overall incidence of Human Immunodeficiency Virus infection, still a significant proportion of the youth population are at risk of Human Immunodeficiency Virus infection. Objectives: The study was to explore and describe perception of risk of Human Immunodeficiency Virus among students at the Institute of Development Management, Gaborone, Botswana Campus. Methodology: A qualitative, exploratory, descriptive study using semi-structured interviews with purposively selected second year Public Health students was conducted. Interviews were conducted using an interview guide. It was audio recorded until data saturation was reached, where eight students participated in the study. Voice recordings were transcribed verbatim and analysed thematically. Results: The findings reveals that some participants perceive themselves to be at risk of contracting Human Immunodeficiency Virus, while others perceive themselves as being not at risk of Human Immunodeficiency Virus infection. Several risk factors associated with Human Immunodeficiency Virus infection, for example, alcohol and drug abuse, multiple concurrent sexual relationships, intergenerational and transactional sex are revealed as challenges. They also expressed their fears in relation to Human Immunodefiency Virus testing, pregnancy and disclosure of Human Immunodeficiency Virus positive status due to the stigma and discrimination. Conclusion: High risk behaviours leading to Human Immunodeficiency Virus and Acquired Immunodeficiency Syndrome prevalence are still common among young people, hence the need for government and all stakeholders to specifically address them by coming up with specific behavioural intervention programmes.

Thesis (MScMedSc)--University of Stellenbosch, 2011. / ENGLISH SUMMARY: Background: Primary immunodeficiency disorders (PID) disrupt the proper functioning of the immune system. The prototypic PID is X-linked Agammaglobulinemia (XLA). This disorder is caused by mutations in the Bruton tyrosine kinase (Btk) gene and results in an arrest in B cell development which leads to a profound reduction of all classes of serum immunoglobulins (i.e antibodies). Patients with a lack of antibodies experience recurring bacterial infections during early childhood that can be fatal if not treated. Intravenous gammaglobulin replacement therapy (IVIg) is the standard treatment for XLA. It provides passive immunity thereby reducing the number and severity of infections as well as limiting many of the infectious complications. Early detection and treatment of XLA allows affected individuals to live a relatively normal life. Objective: The purpose of this study was to determine the molecular basis of XLA in South Africa using a direct sequence-based method to detect abnormalities in the Btk gene to aid clinical diagnosis of the disease. Methods : Male patients with a clinical diagnosis of XLA were included in this study. Genetic analysis was used to explore the exonic region of the Btk gene of 5 unrelated male patients and compared to 10 healthy controls. Family members were followed up to determine carrier status, where possible. Results: Mutational analysis revealed Btk abnormalities in 4 of the 5 patients leading to a definitive diagnosis of XLA. Two of the three mutations found in this study have been previously described while one mutation appears to be novel. The novel mutation is a one base pair deletion in exon 16 which leads to the truncation of the Btk protein. Despite the clinical findings suggestive of XLA, no mutation was identified in the exonic region of the Btk gene of the remaining patient, indicating that this patient might have a different form of PID. Maternal follow-up confirmed the maternal inheritance pattern as all mothers screened were carriers of the Btk mutation present in the affected individual. Discussion : Using a direct sequence-based method abnormalities were identified in the Btk gene of three patients. Molecular diagnosis coupled to clinical history of the patient provides a definitive XLA diagnosis. This study supports the use of molecular techniques in the diagnosis of PID and underlines the synergy that could be possible in a clinical setting. / AFRIKAANSE OPSOMMING: Agtergrond: Primêre immuungebrek siektes (PIGS) word gekenmerk aan ‘n gebrek aan teenliggame in die immuunsisteem wat lei tot herhaalde infeksies in jong kinders wat fataal kan wees indien dit nie vroegtydig behandel word nie. Die prototype van die bekende PIGS is X-gekoppelde Agammaglobulinemia (XGA). Die siekte word veroorsaak deur mutasies in die Bruton Tirosien kinase (Btk) geen en lei tot ʼn stilstand in B sel ontwikkeling en gevolglik ʼn vermindering van alle klasse van serum immuunoglobulins (teenliggaam). Intraveneuse gammaglobulien vervangingsterapie(IVIg) is die standaard behandeling vir XGA. Dit voorsien passiewe immunitiet en gevolglik verminder dit die getal en erns van infeksies en beperk baie van die aansteeklike komplikasies. Vroeë diagnose en behandeling van XGA laat toe dat geaffekteerde individue ʼn relatiewe normale lewe ly. Doel: Die doel van hierdie studie is om die molekulêre basis van XGA in Suid Afrika te ondersoek, deur gebruik te maak van direkte volgorde bepaling van die Btk geen in die hoop om die kliniese diagnose van die siekte aan te help. Metode : Manlike pasiente met ‘n kliniese diagnose wan XGA was by die studie ingesluit. Genetiese analise was gebruik om die “exonic” omgewing van die Btk geen te ondersoek van 5 onverwante manlike pasiente en vergelyk teenoor 10 gesonde kontrole. Waar moontlik was familie lede ogevolg om draers te bepaal. Resultaat: Mutasies in die Btk geen is geidentifiseer in 3 van die 4 pasiente, klinies gediagnoseer meet XGA. Die mutasies sluit 2 reeds beskryfde variante in en een nuwe mutasie, ‘n een basis paar delesie in ekson 16 van die Btk geen, Ten spyte van die kliniese profiel suggestief van XGA in die 5de pasient, was geen mutasies geidentifiseer in die “exconic” omgewing van die Btk geen nie, dit kan moontlik toegeskryf word aan die teenwoordigheid van ‘n ander vorm van PIGS in hierdie pasient. Opvolg analise op die DNA van die moeders van die pasiente het die moederlike oorerwings patroon van die siekte bevestig aangesien al die moeders draers van die geidentifiseerde mutasie in die Btk geen van die gaffekteerde individu was. Gevolgtrekking: Genetiese analise van die Btk geen blyk ʼn sensitiewe en spesefieke metode te wees om individue met XGA te diagnoseer. Hierdie studie ondersteun die gebruik van molekulêre metodes in die diagnose van PIGS en beklemtoon die moontlike sinergie wat kan bestaan tussen hierdie tipe benadering in die kliniese omgewing. / National Research Foundation / National Health Laboratory Services : Pathology Research Development Grant of NHLS Research Trust Grants

A implementação da integralidade é um grande desafio à consolidação do Sistema Único de Saúde e a vulnerabilidade na Atenção Básica às DST/HIV/aids foi o objeto deste estudo, cujos objetivos foram: caracterizar as Unidades Básicas de Saúde (UBS) segundo as Coordenadorias Regionais de Saúde, as Supervisões Técnicas de Saúde, os modelos de organização da atenção à saúde, as Organizações Sociais de Saúde em contratos de gestão na cogestão da saúde com a Secretaria Municipal de Saúde de São Paulo e a formação profissional do gerente; identificar o grau de Vulnerabilidade Programática das UBS e discuti-lo segundo os componentes: acessibilidade, porta de entrada, vínculo, enfoque familiar, profissionais da saúde e coordenação/integração. A perspectiva conceitual utilizada foi da vulnerabilidade, em sua dimensão programática. Realizou-se estudo descritivo transversal com abordagem quantitativa, tendo sido utilizado um questionário com 51 questões, aplicado online, na plataforma FormSUS, com gerentes das 442 UBS do Município de São Paulo. Foram obtidas respostas de 328 gerentes das UBS; 40,9% eram exclusivas \"tradicionais\"; 55,8% das OSS eram do tipo \"Associação\" e mais da metade dos gerentes das UBS eram Enfermeiros. Há graus diferenciados de vulnerabilidade programático, mas de um modo geral nas UBS é baixo. Há vulnerabilidade na efetivação da integralidade: falta de materiais para atividades educativas; baixa oferta de testes de detecção de sífilis à gestante e teste anti- HIV no pré-natal; demora no retorno do resultado do exame anti-HIV; baixa indicação do tratamento com Penicilina Benzatina ao parceiro da gestante com diagnóstico de sífilis; não realização da abordagem consentida para solicitação de teste para HIV à gestante ou para a população geral; falta de capacitação para realização da abordagem sindrômica das DST e aconselhamento na oferta do teste do HIV; falta de contrarreferência às UBS, DST/aids. Conclui-se que a integralidade traduzida em práticas de saúde na atenção às DST/HIV/aids possibilitou visualizar as vulnerabilidades programáticas nas UBS e apontou desafios para sua efetivação. / Implementation of comprehensive attention is a huge challenge in the consolidation of the Brazilian Unified Health System. The vulnerability to STD/HIV/Aids in Primary Care was focused on this study, aiming to provide tools to improve healthcare. The objectives of the study were: 1) to characterize Primary Care Units (PCU) according to selected variables such as: administrative hierarchy position (Regional Health Coordination, Healthcare Technical Supervision), administrative issues (models healthcare attention of organization, Healthcare Social Organization (HSO) in management or co-management with the Township Healthcare Office in São Paulo), and manager formal professional qualification; 2) to identify the level of Programmatic Vulnerability; and 3) to assess the Programmatic Vulnerability according to the following components: accessibility, point of entry, links, family approach, health professional and integration / coordination. The conceptual approach was the vulnerability in its programmatic dimension. This was a transversal descriptive and quantitative study based on an online survey with 51 questions applied in the FormSUS platform and involving managers from 442 PCU of the city of São Paulo. Responses were received from 328 PCU managers; among them more than half were Nurses. PCU were exclusively \"conventional in 40.9% and 55.8% of the HSO were classified as \"association\". There were different levels of programmatic vulnerability; in general however, the vulnerability was low. There was vulnerability in making comprehensive attention effective: lacking of material for educational activities; insufficiency of availability of tests to detect syphilis in pregnant women and anti-HIV test in the pre-natal period; excessive delay in results of anti-HIV tests causing them to be not time-opportune; low practice of indication of syphilis treatment with Benzathine Penicillin for the pregnant partner; lacking of informed consent to request HIV testing to pregnant women as well general population; lacking of training for the syndromic approach to STDs; lacking of counseling when offering HIV testing; lacking of counter-reference to PCU, STD/Aids. It was concluded that the translation of the comprehensiveness concept into health practices regarding STD/HIV/aids enabled us to assess programmatic vulnerabilities in the PCU, and pointed out challenges to achieve a true comprehensive healthcare attention.

INTRODUÇÃO: A deficiência de IgA (DIgA) é a imunodeficiência primária mais comum e caracteriza-se pela presença de concentrações de IgA sérica abaixo de 7 mg/dL e níveis normais de IgM e IgG. A maioria dos indivíduos acometidos não apresenta doença aparente embora alguns possam apresentar infecções recorrentes ou crônicas de mucosas, atopia e/ou doenças autoimunes (DAIs). Presumivelmente, a doença resulta de um defeito na troca de isótipo para IgA ou de falha na maturação de linfócitos produtores de IgA. A imunodeficiência comum variável (ICV) constitui uma deficiência primária de anticorpos caracterizada por níveis séricos baixos de IgG, IgA e/ou IgM, ao lado de valores normais ou diminuídos de linfócitos B e/ou T, levando a infecções crônicas ou recorrentes principalmente dos tratos respiratório e gastrintestinal. Embora a fisiopatologia da ICV ainda não esteja esclarecida, em muitos pacientes ela pode ser decorrente de algum defeito intrínseco de linfócitos B. De modo especial, as células B de memória (CD27+) têm sido correlacionadas com alguns aspectos clínicos da doença. Números elevados de células B de memória com persistência de IgM (CD27+IgM+) parecem estar correlacionados com a presença de infecções, enquanto valores diminuídos de células B de memória clássicas ou class-switched (CD27+IgG-IgM-) parecem estar associados a baixos níveis de IgG e presença de autoimunidade. A progressão de DIgA para ICV tem sido descrita em alguns pacientes embora não constitua regra geral. Uma hipótese é a de que uma base genética comum e a associação com DAIs possam constituir fatores de risco para a progressão de DIgA para ICV. Há relato anterior de que a persistência de células B imaturas IgM+ IgD+ em alguns pacientes com DIgA estava associada à progressão para ICV. Adicionalmente, há evidências de que a diminuição de células B de memória em uma proporção de pacientes com ICV esteja associada à presença de autoimunidade. OBJETIVOS: comparar em pacientes com DIgA e ICV várias subpopulações de células B e analisar a relação entre estas populações celulares e a presença de DAIs em ambos grupos. MÉTODO: Este estudo incluiu 56 pacientes adultos de ambos sexos com DIgA e ICV, distribuídos em grupos de acordo com a associação com DAI: grupo DIgA sem DAI (14 pacientes), grupo DIgA com DAI (14 pacientes), grupo ICV sem DAI (14 pacientes) e grupo ICV com DAI (14 pacientes). As seguintes subpopulações de células B foram determinadas por citometria de fluxo de quatro-cores: células B naive (CD19+IgM+), células B de memória clássicas ou class-switched (CD27+IgM-IgD-) e células B de memória imaturas (CD27+IgM+ or CD27+IgD+). Na análise estatística foi aplicado o teste de ANOVA; valores significativos foram determinados pela correção de Bonferoni. RESULTADOS: os grupos analisados foram homogêneos quanto à idade e distribuição de gêneros. Os valores de linfócitos totais e de células B naive foram similares nos quatro grupos estudados. Os pacientes com deficiência de IgA e ICV com DAIs associadas apresentaram valores igualmente aumentados de células B de memória imaturas CD27+IgM+ e CD27+IgD+ quando comparados a pacientes sem doenças autoimunes. CONCLUSÕES: estes resultados sugerem que a persistência de células B de memória imaturas possa estar relacionada à presença de autoimunidade em pacientes com DIgA e ICV. Especula-se se a persistência destas células em pacientes com DIgA e DAI associada possa constituir fator preditivo da progressão de DIgA para ICV. / INTRODUCTION: IgA deficiency (IgAD) is the most common primary immunodeficiency disorder and is characterized by serum IgA concentration below 7 mg/dL and normal serum IgM and IgG levels. Most of the affected individuals have no apparent disease, whereas selected patients suffer from recurrent or chronic mucosal infections, atopy and/or autoimmune diseases (AIDs). This defect is presumed to result from impaired class-switching to IgA or from maturational failure of IgA-producing lymphocytes. Common variable immunodeficiency (CVID) is a primary antibody deficiency disease characterized by low serum levels of IgG, IgA and/or IgM, and normal or decreased B and/or T cell numbers, leading to chronic or recurrent infections, noted mostly in the respiratory and gastrointestinal tract. While the pathophysiology of CVID remains elusive, in many patients it may be due to an intrinsic B cell defect. Memory B cells (CD27+) in particular, have been noted to correlate with certain clinical aspects of the disease. High numbers of IgM+ memory B cells (CD27+IgM+) appear to correlate with the presence of infections, whereas decreased numbers of classic (class-switched) memory B cells (CD27+IgG-IgM- ) correlate with lower serum IgG levels and increased rates of autoimmune features. Progression from IgAD to common variable immunodeficiency (CVID) has been reported in some patients, but is not a general rule. It is postulated that a common genetic base and association with AIDs could be risk factors for progression from IgAD to CVID. OBJECTIVES: The aim of this study was to compare B cell subpopulations of patients with IgAD and with CVID, and to assess the relationship between these populations and the presence of autoimmune diseases in both group of patients: . METHOD: The study included 56 adult patients of both genders with IgAD or CVID. Patients were grouped, according to the association with autoimmune disease,as follows: group IgAD with AID (14 patients), group IgAD without AID (14 patients), group CVID with AID (14 patients) and group CVID without AID (14 patients). We determined by immunophenotyping of lymphocytes by four-colour cytometry the following subpopulations of B cells: naïve B cells (CD19+IgM+), class-switched memory B cells (CD27+IgM-IgD-) and immature B memory cells (CD27+IgM+ or CD27+IgD+). Statistical analysis was performed by the ANOVA test; significant P-values were determined by means of Bonferonis correction. RESULTS: there is no statistically significant difference between the average ages and the gender of patients between the groups. the distribution of the sample values seem to indicating that, there is no statistically significant difference in the CD19 levels between the groups. patients with AID represent greater values of CD27 IgM+ and CD27+ IgD+ than patients without AID, independent of the group studied. CONCLUSIONS: These results suggest that the persistence of immature memory B cells in patients with IgAD and CVID can be related to autoimmune diseases. We speculate if the persistence of immature B cells can constitute risk factor to progression of IgAD for CVID.

Thesis (Ph.D.)--Memorial University of Newfoundland, 2002. / Restricted until October 2003. Bibliography: leaves 148-161.

No description available.

Development of a suitable animal model of AIDS is much needed in AIDS research to study infection and pathogenesis as well as to evaluate methods of prevention and treatment of HIV infection. Small animals such as rodents are attractive candidates for AIDS research due to the availability of various inbred and genetically engineered strains, extensive knowledge or their immune system, especially in mice, and the relative ease of breeding and maintaining animal colonies. Transgenic small animal models carrying entire HIV genome or selected genes have been instrumental to understand functions of HIV genes in vivo and their role in HIV pathogenesis. The type of cells in which HIV genes are expressed seems to be an import prerequisite for the study of HIV gene functions in transgenic mice. Mice constitutively expressing the entire HIV-1 genome or HIV-1 nef gene in CD4 + T cells and in the cells of macrophage/dendritic lineage develop an AIDS-like disease very similar to AIDS disease in humans. Similarly, expression of Nef in adult mice, using inducible system, results in the AIDS-like disease. This disease is characterized by thymic atrophy, impaired thymocyte maturation, loss of CD4+ T cells, increased activation and turnover of T cells, which can occur in the absence of lymphypenia, and non-lymphoid organ disease involving the lungs and kidneys. Susceptibility of adult mice to the pathological effects of Nef suggests that the AIDS-like disease in the constitutively expressing Nef Tg mice is not due to developmental defects caused by early expression of Nef. This model highlights the important role of Nef in HIV-1 pathogenesis. The high similarity in the disease in these Tg mice with human AIDS strongly suggest that these mice are a relevant model to study AIDS. This study further evidence that mouse cells can support functions of Nef and these Tg mice represent a unique model to study Nef functions in vivo in the context of the primary immune system. Moreover, the inducible Nef Tg model has given us the ability to control the level and time of expression of Nef which was impossible to do in the previously reported constitutive Nef Tg mouse models. These mice will be useful to study immune reconstitution since Nef expression can be turned off after withdrawal from dox.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.