Paracoccidioidomicosis, consideraciones de una micosis desatendida

El presente trabajo corresponde a una revisión bibliográfica sobre el estado del conocimiento de las especies de Paracoccidioides spp. y los cuadros clínicos asociados a este hongo. La revisión inicia con un marco histórico sobre el desarrollo del conocimiento de la paracoccidioidomicosis a nivel latinoamericano, incluyendo un apartado sobre Costa Rica. Se detallan temas relacionados a la etiología, ecología, aspectos veterinarios y la epidemiología de la micosis. Adicionalmente, se incluyen temas como la patogenicidad y los factores de virulencia de Paracoccidioides spp, así como la respuesta inmune que se desarrolla en el hospedero. Por último, y no menos importante, se describe lo encontrado en la literatura sobre los tópicos de diagnóstico diferencial, diagnóstico de laboratorio, el tratamiento contra la enfermedad, y las conclusiones del presente trabajo. Este trabajo pretende recopilar el conocimiento básico sobre esta micosis y los últimos avances científicos reportados en la literatura en el tema de la paracoccidiodomicosis y su agente etiológico.In this document, a literature review of the state of scientific knowledge about Paracoccidioides spp. species and their associated clinical manifestations was made. This review starts with a historical frame about knowledge development about paracoccidioidomycosis in Latin America, including Costa Rica. Etiology, ecology, veterinary aspects, and this mycosis epidemiology are reviewed. Additionally, pathogenicity and virulence factors of the causing agent, Paracoccidioides spp., are included, as well as the host immune response to the fungus. Finally, topics such as differential diagnosis, laboratory diagnosis and the disease treatment are discussed, and the concluding remarks of this literature review are detailed. This work tries to summarize basic knowledge about this mycosis and the latest scientific advances reported in literature about paracoccidioidomycisis and its etiological agent.UCR::Vicerrectoría de Investigación::Sistema de Estudios de Posgrado::Salud::Especialidad en Micología Médic

Comparative genomics and transcriptomics elucidate virulence mechanisms and host responses in infectious diseases

The main thematic area of the present thesis is the development and application of bioinformatics pipelines, namely whole-genome sequence (WGS) analysis and transcriptome profile analysis. These pipelines were applied to study the fungal pathogen Aspergillus fumigatus (Manuscripts I, III, and IV) and the early human immune mechanisms activated in response to different types of pathogens (bacteria, fungi, and co-infections) in sepsis patients (Manuscript II). The comparative genomic and transcriptomic analyses applied in my thesis have significantly improved our understanding of fungal pathogenicity as well as the pathogen-specific immune response mechanisms of the human host. Next to a number of novel insights, my work included in this thesis has generated a large number of new hypotheses based on big-data analysis, offering the scientific community the possibility to design exciting new research to confirm them in future experimental studies and bring us closer to actual precision medicine for infectious diseases

Molecular basis of C4 protein deficiency in Aboriginal Australians, and a molecular C4 allotyping technique

Since the initial discovery of the association between C4 protein deficiency and autoimmune disease, much effort has been devoted to the characterisation of C4 protein and its molecular composition (Dawkins et al., 1983). From the outset, researchers have found the C4 protein difficult to work with as it is unstable and degrades rapidly. However, with the advent of molecular techniques, studies of the C4 gene have accelerated, uncovering a very complicated and large duplicated gene region. This thesis reviews the literature on complement component C4, and reports on three interrelated research areas involving protein and DNA analysis of complement C4. Contributions to the molecular characterisation of the C4 complement gene region and population genetics are discussed in relation to current knowledge, and direction for further research is provided. This study set out to establish whether indigenous people of PNG and Aboriginal Australians have shared a common gene pool. By analysing the distribution of polymorphic C4 alleles these studies found the Aboriginal Australian and PNG populations to be distinctly different. Analysis of the distribution of C4 alleles in the two ethnic groups indicated that the two Aboriginal populations showed significant similarities but the three geographically distinct PNG populations were significantly different. Studies here suggested these ethnic populations are more reliably distinguished from each other by differences in the frequencies of the most frequently occurring C4 alleles, than by the incidence of rare alleles. The high frequency of C4 null alleles in northern located Darwin Aboriginal's reported by Ranford et al. (1987), is not an isolated incident as this study also found the highest frequencies of C4 null alleles in northern located Aboriginal Australian's compared to any ethnic group studied. This could be associated with the high occurrence of the autoimmune disease Systemic Lupus Erythematosus (SLE) in Aboriginal Australians, and strong susceptibility of Aboriginal Australians to this disease (Anstey et al., 1993). Accurate identification of C4 alleles including C4 null alleles is essential both for investigating gene-linked disease associations, as well as for advancing future population genetics studies. Studies here demonstrate that C4 protein allotyping does not accurately identify the C4 genotype of an individual. This was highlighted by the lack of Hardy-Weinberg equilibrium with respect to C4 allele frequencies of the East Cape York Aboriginal population as well as the identification of a number of alleles by molecular analysis which could not be identified by protein typing. The difficulties associated with determining C4 allotypes by C4 protein gel electrophoresis include instability of the C4 protein, high degree of technical expertise for interpretation of allotypes, and limitations of this technique in distinguishing overlapping alleles. It was established in these studies that the polymorphic C4d region of C4 genes may be used by molecular means to identify and type C4 alleles. With the advent of molecular biological techniques such as protein and DNA sequencing, and RFLP analysis of the C4 gene region, information required for development of a molecular-based typing protocol has become available. Some of the previously described C4A and C4B alleles have been found to have unique combinations of polymorphic amino acid residues distributed within a short stretch of DNA, otherwise known as the C4d region. This region of the gene is highly polymorphic encoding amino acid residues known to be involved in immune-complex binding, and also encodes antigenic determinants. Therefore the C4d region was considered an ideal candidate for the development of a molecularbased allotyping protocol. The molecular-based C4 typing technique developed here is based on PCR-RFLP analysis of the C4d region. Protein and DNA sequence information, C4 protein allotyping data, and computer analysis which estimates the predicted isoelectric value of a protein were used to develop this protocol. Application of the molecular C4 typing protocol enabled the identification of C4 alleles which co-migrate by C4 protein gel electrophoresis as well as a number of rare and novel C4 alleles. The molecular basis of C4 null alleles has been extensively studied in Caucasians, however, very little is known about the genetic basis of C4 null alleles in other ethnic populations. C4 null alleles from Aboriginal Australians were investigated here in order to identify the genetic basis of these alleles compared to those in Caucasians. Many Caucasian C4 null alleles result from large deletions. However, this study found that the C4B null allele in Aboriginal Australians results from either duplication of C4A genes on a single haplotype, or possession of a hybrid C4A/C4B type of novel allele, which was denoted as C4A *CAN1. These findings have considerable significance in relation to the high frequency of C4 null alleles found in Aboriginal Australian populations. Many of these "null alleles" may indeed be functional alleles which have been misinterpreted by C 4 protein typing. The molecular basis of C4A null alleles remains unresolved, however, this study indicates that the defect is likely to be due to post-transcriptional processing of the allele. This thesis describes a detailed investigation into the molecular basis of C4 alleles including rare and null alleles. This information together with the vast amount of molecular data available on C 4 enabled the development of a molecular-based C4 typing protocol. This protocol is considered to be a more reliable and accurate typing method than the traditional protein typing method, and can be easily adopted in any laboratory for routine allotyping

Skin Diseases and Sexually Transmitted Infections

ПОСОБИЯКОЖНЫЕ БОЛЕЗНИДЕРМАТОЛОГИЯВЕНЕРОЛОГИЯИНОСТРАННЫЕ СТУДЕНТЫВЕНЕРИЧЕСКИЕ БОЛЕЗНИПособие охватывает как общие, так и редкие вопросы дерматологии и венерологии. Содержатся главы о кожных и венерических заболеваниях, которые являются общими для Азии, Африки и Латинской Америки