Thesis (M.Med.Sc.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 69-79). Also available in print.

Thesis (Ph.D.)--Aberdeen University, 2009. / Title from web page (viewed on July 8, 2009). Includes bibliographical references.

Inaug.--diss.--Leipzig. / At head of title: Aus dem veterinarinstitut der universität Leipzig. Vita. Literaturverzeichnis: p. [57]-58.

Thesis (M.P.H.) - University of Queensland, 2003. / Includes bibliography.

Thesis (Ph. D.)--Virginia Commonwealth University, 2006. / Prepared for: Dept. of Chemistry . Bibliography: leaves 102 - 109. Also available online.

Thesis (M.Sc.)--The University of Manitoba, 1999. / Includes bibliographical references.

Describe los factores (sociodemográficos y ambientales) asociados a recaídas por tuberculosis en el Hospital Nacional Sergio E. Bernales, en el periodo comprendido de octubre a diciembre del 2016. Concluye que los pacientes que presentan cualquiera de los siguientes factores: consumir drogas o alcohol, estar en un medio familiar conflictivo, tener una percepción errada de la enfermedad y no estar conforme con el tratamiento presentan riesgo de sufrir recaídas por TB. Se necesitan más estudios para confirmar estos hallazgos y considerarlos para el manejo de los pacientes incluidos en el Programa Nacional de Control de TB. / Tesis

Active tuberculosis is a frequent complication of Hodgkin's disease and it has been demonstrated recently that the circulating lymphocytes are abnormal in this disease (48). Furthermore, reactivation of tuberculosis following steroid therapy is a common complication (56) and it is now well established that steroids are toxic to lymphocytes (57). With this background evidence to suggest the importance of normal lymphocyte function in host resistance and the accidental finding of a poor lymphocyte response in a tuberculous patient, a study of the in vitro reaction of the lymphocytes in tuberculous patients was undertaken. In vitro cultures of peripheral white blood cells will undergo transformation and mitosis when in the presence of phytohemagglutinin (PHA), an extract of the red kidney bean Phaseolus vulgaris. The number of cells which transform or enter mitosis in the culture is representative of the individual's immune responsiveness. In the tuberculous patients studied, irrespective of the state of their disease, the mean mitotic index (the number of cells in mitosis per thousand cells) was found to be significantly lower than normal controls suggesting that their mean immunological capacity is below normal. During the course of the tuberculous study one of the individuals used as a normal control came down with the "flu" on the evening of the day her blood was taken. The PHA mitotic index was found to be severely depressed. To study the effect of such acute upper respiratory infections, presumably of viral origin, mitotic indices were determined on blood samples taken from laboratory volunteers who felt they were coming down with a cold. The indices were found to be depressed in all cases as compared to healthy normals. The reaction of delayed hypersensitivity and the relationship of this reaction to immunity and tuberculosis has been a matter of study for many years. It seems clear that the individuals in the population that later develop tuberculosis are drawn largely from those members who have a positive skin test while those with a negative skin test have been found unlikely to develop tuberculosis to the point of not being required to have X-rays in many instances. Tuberculin PPD (purified protein derivative) was one of the first antigens shown to be capable of transforming lymphocytes in vitro (60, 61) providing the individual had had prior sensitization. As all tuberculin negative student nurses entering training at the Vancouver General Hospital receive a bacillus Calmette Guerin vaccination (BCG), they were chosen for study in order to elucidate the relationship of in vivo and in vitro responses to the tubercle antigen, PPD. As the number of cells responding to PPD is much less than responding to PHA, the mitotic index is a very insensitive method to use in determination of in vitro responsiveness to antigen. Therefore, the response in vitro was determined by the incorporation of (3)H-thymidine into DNA of stimulated lymphocytes. It was found that in 12 to 18 months after vaccination with BCG nurses who had become skin test negative to PPD did not differ significantly in their in vitro response from nurses who had remained skin test positive. A correlation was found between the PHA and PPD in vitro responses which suggests that the response to the general stimulus, PHA, is an indicator of the reaction that can be mobilized to specific antigen. Varying the dose of BCG that was administered affected only in vivo responses. Finally, contrary to many reports, no quantitative correlation was found between in vivo and in vitro responses to PPD following BCG vaccination. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

Tuberculosis (TB) is the leading killer globally owing to an infectious disease. There is consequently an urgent need to develop novel TB drugs and shorter regimens to treat the causative agent, Mycobacterium tuberculosis, an imperative which demands the identification of new drug targets in essential mycobacterial pathways. To that end, the work presented in this dissertation aimed to functionally characterize ribF, an essential gene in the mycobacterial riboflavin (RF; vitamin B2) biosynthetic pathway. Given the role of RF as a core component of the essential flavin cofactors, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), it was hypothesized that silencing ribF would disrupt the biosynthesis of all flavoproteins, crippling numerous (essential) processes within the organism. Moreover, based on previous observations in Bacillus subtilis, it was predicted that the mycobacterial ribF homolog might play a role in regulating the rib operon (comprising a cluster of RF pathway genes) – either directly by binding to the FMN riboswitch, or indirectly through the production of FMN from RF, in turn enabling riboswitch-mediated repression of downstream genes. CRISPR interference (CRISPRi) technology was used to generate an anhydrotetracycline (ATc)-inducible ribF hypomorph of M. smegmatis, a widely exploited mycobacterial model. Consistent with other organisms, ribF was shown to be essential for in vitro growth of M. smegmatis: CRISPRi-mediated depletion of ribF was bacteriostatic, resulting in a 10-fold growth inhibition in liquid media and corresponding to no reduction (0 log-fold change) in colony forming units (CFU). Moreover, targeted metabolomic analyses revealed that ribF depletion was associated with accumulation of 6,7-Dimethylribityllumazine (DMRL), suggesting that the disruption of RibF function blocked conversion of RF to the essential cofactors, FMN and FAD, in turn inhibiting cell growth. Notably, the lethality of ribF depletion could not be complemented chemically by exogenous supplementation of growth media with RF, FMN or FAD. Downregulation of ribF also caused enhanced susceptibility to the known cell wall-targeting agent, vancomycin, but not to the putative RibF domain inhibitor, thonzonium bromide, suggesting an alternative mechanism of action or impaired bacillary permeation. In summary, these data support the inferred essentiality of ribF in mycobacteria, in turn supporting future work which aims to target this enzyme for new TB drug discovery.

Nuestro país se encuentra dentro de las regiones que se consideran endémicas para el Virus Linfotrópico Humano de células T tipo I (HTLV-I). En el Perú son escasas las investigaciones realizadas sobre la coinfección del virus asociado a pacientes con Tuberculosis (TB) y sobre todo a los pacientes con Tuberculosis Multidrogorresistente (TB MDR), por esto resulta importante realizar este tipo de trabajo de investigación. En el presente estudio se trabajó con pacientes clínicamente diagnosticados con TB y TB MDR de los Programas de Control de Tuberculosis (PCT) de 5 hospitales pertenecientes a la Red Asistencial del Almenara (RAA). Se analizaron 151 muestras de suero de las cuales 58 fueron de pacientes TB y 93 de TB MDR. A todos los pacientes entrevistados se les sensibilizó respecto a la importancia del descarte temprano del virus HTLV-I. Mediante las encuestas clínico-epidemiológicas se colectaron datos demográficos y factores de riesgo que condicionen la asociación virus-bacteria. El diagnóstico serológico para el virus HTLV-I se evaluó en dos etapas, la primera fue la prueba serológica, donde se detecta indirectamente la presencia de anticuerpos contra el virus HTLVI/II utilizando la técnica serológica de Ensayo de inmunoadsorción enzimática (ELISA) HTLV I/II (Bioelisa HTLV-I + II 5.0 Biokit); y en la segunda etapa, se empleó la prueba confirmatoria de Electroinmunotransferencia blot (Western blot) INNOLIA TM Innogenetics. Los resultados obtenidos se analizaron con el paquete estadístico SPSS versión 19 mediante el test del Chi cuadrado. En las muestras obtenidas correspondientes a pacientes TB MDR, se encontró una frecuencia de infección viral de 3,4% (2/58) ubicados en dos rangos de edad consecutivos; y en los TB de 3,2% (3/93), los cuales también se encontraban en rango consecutivos de edad, todos ellos procedentes de Lima con zonas de mayor incidencia para TB. La frecuencia global para la población estudiada fue de 3,3% (5/151). Los resultados estadísticos no indicaron un nivel de confianza aceptable para la asociación virus-bacteria. Este el primer reporte de coinfección de pacientes TB y TB MDR respecto al virus HTLV-I; por lo tanto, se requiere de estudios a futuro donde se realice el diagnóstico temprano del virus para una prevención y tratamiento adecuado. / --- Our country is within the considered endemic regions for human lymphotropic virus T cells (HTLV-I). In Peru there is little research on the associated coinfection patients with Tuberculosis (TB) and especially to patients with multidrug-resistant tuberculosis (MDR TB) is so important to this type of research. In the present study we worked with patients clinically diagnosed with TB and MDR TB who belonged to the Tuberculosis Control Program (TCP) of 5 hospitals of the Assistance Network of Almenara (RAA). We analyzed 151 serum samples of which 58 were TB patients and 93 patients were TB MDR. All patients interviewed were sensitized on the importance of early dismissal of HTLV-I virus. In clinical and epidemiological surveys were collected demographic and risk factors that condition the virus bacteria association. The serological diagnosis for the HTLV-I virus was evaluated in two stages, the first is where the serological test indirectly detects the presence of antibodies against the virus HTLVI / II. For this technique was used serological ELISA HTLV I / II (HTLV-I + Bioelisa II 5.0 Biokit), then used confirmatory Western Blot test Innolia Innogenetics TM. The results were analyzed with SPSS version 19 with the chi-square test. In samples obtained from patients with MDR TB was found a frequency of infection of 3,4% (2/58) located in two consecutive age ranges in addition to the origin of Lima and in patients with TB was found viral coinfection 3,2% (3/93) were also in consecutive age range of these patients were also from Lima. The overall frequency for a study population was 3,3% (5/151). The results indicated no statistical confidence level acceptable to the virus-parasite association. This the first report of coinfection of TB / MDR TB compared to HTLV-I virus, this study was conducted in areas of high TB incidence. Therefore it requires future studies where the diagnosis is made early for virus prevention and proper treatment. / Tesis