Thesis (Ph. D.)--University of Wisconsin--Madison, 1954. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 56-61).

Differentiation within the lymphoid system produces effector cells which are involved in a variety of immune functions. For T cells these include the provision of help, suppression, cytolytic activity and the regulation of cooperative cellular interactions. The primary function of B lineage cells is the production of specific antibody. Understanding the regulation of normal lymphocyte proliferation and differentiation may lead to a better appreciation of those factors which result in the development of malignancy. The non-Hodgkin's lymphomas are neoplasms of the immune system, the majority of which are B cell in origin. Despite advances in immunology and molecular biology, little is known about the mechanisms involved in B cell activation, proliferation and differentiation or about those events leading to their malignant transformation. The advent of monoclonal antibody technology a decade ago has revolutionized our ability to identify and characterize cell surface antigens. Because the activation and control of proliferation of B cells was already known to involve structures at the cell surface, it was logical to utilize monoclonal antibodies to identify additional cell surface molecules that might be important in the function of normal B lymphocytes and that might allow normal and various types of neoplastic B cells to be distinguished. To achieve this goal, we developed monoclonal antibodies that showed differential reactivity between large actively dividing lymphoma cells and small inactive (quiescent) lymphocytes. These were tested for their ability to inhibit various T and B lymphocyte functions (i.e. responses to anti-µ, lipopolysaccharide, phytohemagglutinin and the mixed lymphocyte response) as well as for their reactivity with cell suspensions from a variety of malignant and nonmalignant hematopoietic tissues. From these studies emerged the following: 1) Cell surface molecules other than Immunoglobulin are involved in regulating the activation of normal B cells. This was shown by the discovery that monoclonal antibodies to both lymphocyte function associated antigen (LFA-1) and certain HLA class II determinants were able to inhibit the activation of peripheral blood mononuclear cells by the B cell mitogens anti-p and LPS. This inhibition was shown to be mediated via effects of these antibodies on T cells and/or monocytes. 2) B lymphoma cells appear to express unique cell surface antigens (defined by monoclonal antibodies LM-26 and LM-155) not detectable on cells of other lineages, and absent from normal resting or activated B lymphocytes. Future investigations will attempt to define the mechanisms by which the indirect involvement of LFA-1 and HLA class II molecules in B cell activation in vitro suggests new regulatory interactions not previously identified. Further studies will be required to define the mechanisms underlying these interactions and their significance in vivo. Similarly, the structure and function of the antigens detected by LM-26 and LM-155 remains to be determined. Nevertheless, the expression of apparently unique molecules on B lymphoma cells holds new promise for the diagnosis, classification and treatment of this group of diseases. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

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Thesis (Ph. D.)--University of Wisconsin--Madison, 1955. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 54-57).

published_or_final_version / Pathology / Master / Master of Science

No description available.

No description available.

Thesis (M. Sc.)--University of Hong Kong, 1967. / Typewritten.

Background: Human neutrophil antigens (HNA) are involved in a variety of clinical conditions such as transfusion related acute lung injury (TRALI), alloimmune neutropenia (ANN), autoimmune neutropenia (AIN). There are a total of five HNA systems, namely HNA-1, HNA-2, HNA-3, HNA-4 and HNA-5. In this decade, the allelic and genotypic frequencies of HNA were gradually evaluated in Europe, America and East Asia. [1] Despite HNA system being less polymorphic than HLA antigens, genotypic and allelic frequencies differences can still be observed in different geographical locations even of close proximity. For instance, studies in Thailand and China displayed genotypic and allelic frequencies differences. [2] These data highlights the fact that HNA genotypic and allelic frequencies vary among different populations even within the same region, however, the degree of variation remains to be elucidated. However, there is no information on HNA genotypic and allelic frequencies of Hong Kong population. Commercial genotyping kit has been available in the market but given its high reagent cost, it is not very popular in clinical laboratory. For this reason, a comparative affordable and economical in-house PCR-SSP assay was developed in this study. Aim The aim of this study is to evaluate the HNA genotyping and allelic frequencies in Hong Kong Chinese population by the development of an economical in-house PCR-SSP assay. Methods A commercial HNA typing kit was tested with reference samples to ensure this project has a standard and clinical compliance method for HNA genotyping prior to adopting in-house genotyping method. After reference protocol was established, in-house primers were designed and tested in parallel with the commercial method for validation purpose. After in-house method has been validated, 113 local samples were tested to calculate the genotype and allele frequencies in Hong Kong Chinese population using the developed in-house assay. Results A total of 113 Hong Kong Chinese samples were typed for HNA genotyping and results shown that: HNA-1a was 0.664; HNA-1b was 0.336; whereas HNA-1c allele was not detected. HNA-3a was 0.735 and HNA-3b was 0.265. HNA-4a was 0.991 and HNA-4b was 0.009. HNA-5a was 0.845 and HNA-5b was 0.155. Overall, results echoed with an earlier study performed on Han Chinese. [3] The genotyping frequency distribution for HNA-1, 3, 4 and 5 were: HNA-1a/a was 0.451, HNA-1 b/b was 0.124 and HNA-1 a/b was 0.425; HNA-3 a/a was 0.549, HNA-3a/b was 0.372 and HNA-3b/b was 0.08; HNA-4a/a was 0.982, HNA-4a/b was 0.018; HNA-5a/a was 0.708, HNA-5a/b was 0.274 and HNA-5b/b was 0.018. Conclusion This is the first study attempted to define HNA genotype and allelic frequencies by the self-developed in-house PCR-SSP method in Hong Kong Chinese population. The obtained results were comparable to those of gene frequencies in previous Xia’s study in Guangzhou Chinese population but significant difference from earliest reported European frequencies, confirming geographical difference exist. [3-5] However, due to small sample size in this study, further examination in larger sample may allow more representative frequencies for the Hong Kong population. / published_or_final_version / Pathology / Master / Master of Medical Sciences

No description available.