<p>Herpes simplex virus (HSV) is unusual in its ability to cause recurrent infection in a host with an ostensibly competent immune system. This thesis describes two mechanisms by which HSV evades the cellular immune response, which contribute to its ability to persist.</p> <p>Human cells infected with HSV inhibit lysis by natural killer (NK) and lymphokine-activated killer (LAK) cells. Contrary to the conclusions of previous workers, this effect is due to infection of the lytic effector cells, as shown by experiments with mutant HSV and by immunofluorescence staining of effector cells in contact with HSV-infected targets. The inhibition of lytic effector cells by HSV by cell-to-cell spread may play an important role late in the infectious cycle.</p> <p>Early in the infectious cycle, infectious virus is not present and the above mechanism cannot take effect. Instead, HSV imposes a block on the cellular pathway which presents antigen to CD8⁺ cytotoxic T lymphocytes. The result is that HSV-infected human fibroblasts show abnormalities of their class I major histocompatibility complex (MHC class I) similar to those seen in antigenpresenting mutant cell lines: the MHC class I is retained within the ER and is misfolded and unstable, implying that peptide is not associated with the heavy chain/β₂-microglobulin complex. Experiments with mutant and recombinant viruses established that this effect is due to an HSV irnmediate-early protein, ICP47, and showed that cells expressing ICP47 are not efficiently recognized and lysed by CD8+ CTL. Since ICP47 is not detectably membrane-associated, it presumably affects some cytoplasmic component of the antigen-processing pathway. One candidate for this cellular target is a small (8.5 - 9 kDa) protein, which, like ICP47, is located within the cytoplasm and nucleus of certain cell types. This protein was detected by its ability to bind to a protein consisting of ICP47 fused to the carboxy terminus of glutathione S-transferase (GST).</p> / Doctor of Philosophy (PhD)

It is important for doctors to be clinically competent and this clinical competence is influenced by their clinical reasoning ability. Most research in this area has focussed on clinical reasoning ability measured in a problem - solving context. For this study, clinical reasoning is described as the process of working through a clinical problem which is distinct from a clinical problem solving approach that focuses more on the outcome of a correct diagnosis. Although the research literature into clinical problem solving and clinical reasoning is extensive, little is known about how undergraduate medical students develop their clinical reasoning ability. Evidence to support the validity of existing measures of undergraduate medical student clinical reasoning is limited. In order better to train medical students to become competent doctors, further investigation into the development of clinical reasoning and its measurement is necessary. Therefore, this study explored the development of medical students' clinical reasoning ability as they progressed through the first two years of a student - directed undergraduate problem - based learning ( PBL ) program. The relationships between clinical reasoning, knowledge base, critical thinking ability and learning approach were also explored. Instruments to measure clinical reasoning and critical thinking ability were developed, validated and used to collect data. This study used both qualitative and quantitative approaches to investigate the development of students' clinical reasoning ability over the first two years of the undergraduate medical program, and the factors that may impact upon this process. 113 students participated in this two - year study and a subset sample ( N = 5 ) was investigated intensively as part of the longtitudinal qualitative research. The clinical reasoning instrument had good internal consistency ( Cronbach alpha coefficient 0.94 for N = 145 ), inter - rater reliability ( r = 0.84, p < 0.05 ), and intrarater reliability ( r = 0.81, p < 0.01 ) when used with undergraduate medical students. When the instrument designed to measure critical thinking ability was tested with two consecutive first year medical student cohorts ( N = 129, N = 104 ) and one first year science student cohort ( N = 92 ), the Cronbach Alpha coefficient was 0.23, 0.45 and 0.67 respectively. Students ' scores for clinical reasoning ability on the instrument designed as part of this research were consistent with the qualitative data reported in the case studies. The relationships between clinical reasoning, critical thinking ability, and approach to learning as measured through the instruments were unable to be defined. However, knowledge level and the ability to apply this knowledge did correlate with clinical reasoning ability. Five student - related factors extrapolated from the case study data that influenced the development of clinical reasoning were ( 1 ) reflecting upon the modeling of clinical reasoning, ( 2 ) practising clinical reasoning, ( 3 ) critical thinking about clinical reasoning, ( 4 ) acquiring knowledge for clinical reasoning and ( 5 ) the approach to learning for clinical reasoning. This study explored students' clinical reasoning development over only the first two years of medical school. Using the clinical reasoning instrument with students in later years of the medical program could validate this instrument further. The tool used to measure students' critical thinking ability had some psychometric weaknesses and more work is needed to develop and validate a critical thinking instrument for the medical program context. This study has identified factors contributing to clinical reasoning ability development, but further investigation is necessary to explore how and to what extent factors identified in this study and other qualities impact on the development of reasoning, and the implications this has for medical training. / Thesis (Ph.D.)-- Medicine Learning and Teaching Unit, 2006.

Thesis (Ed.D.) - Simon Fraser University, 2005. / Theses (Faculty of Education) / Simon Fraser University. Includes bibliographical references leaves 322-244. Also issued in digital format and available on the World Wide Web.

Thesis (M.P.A.)--University of Hong Kong, 2001. / Includes bibliographical references.

Thesis PlanB (M.S.)--University of Wisconsin--Stout, 2009. / Includes bibliographical references.

Thesis (Ph. D.)--University of Rhode Island, 2003. / Typescript. Includes bibliographical references (leaves 166-182).

Thesis (M.P.H.)--University of Hong Kong, 2008. / Includes bibliographical references (p. 38-41).

Thesis (Ph. D.)--University of California, San Diego, 2000. / Vita. Includes bibliographical references (leaves 661-707).

Thesis (Ph. D.)--Virginia Polytechnic Institute and State University, 1992. / Vita. Abstract. Includes bibliographical references (leaves 104-114). Also available via the Internet.

Thesis (Ph. D.)--Texas Woman's University, 1990. / Includes bibliographical references (leaves 91-96).