Thesis (M.S.)--University of Michigan, 1998. / Includes bibliographical references.

Thesis (Ph. D.)--University of California, San Diego and San Diego State University, 2000. / Includes bibliographical references (leaves 118-135).

Thesis (Ph. D.)--University of Chicago, Committee on Immunology, December 1997. / Includes bibliographical references. Also available on the Internet.

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 91-101).

No description available.

No description available.

The overall goal of the work, described in this thesis was to investigate the molecular mechanisms that regulate normal pre-B cell proliferation and how these may be altered in transformed pre-B cells. Monoclonal antibodies and molecular biological techniques have allowed a number of stages of pre-B cell differentiation to be defined but little is known about mechanisms controlling their proliferation. Studies of pre-B cell production in animal models and in long-term cultures that support pre-B cell proliferation have suggested that stromal cells play a key role in this regard. As a first step to investigate the mechanisms involved, a number of pre-B cell supportive murine stromal cell lines were isolated and characterized. A number of pre-B cell lines were also isolated, cloned and characterized. From these, spontaneous and Abelson murine leukemia virus transformants were derived. These cell lines were then used in co-culture experiments to demonstrate that stromal cells constitutively secrete a pre-B stimulating factor. Characterization of the pre-B cell stimulating activity produced by one stromal cell line (M2-10B4) showed it to be a 10 Kd molecule sensitive to freezing and different from any cloned hemopoietic growth factor described to date. The possibility that extracellular matrix components might be involved in stromal cell-mediated control of pre-B cell growth was also investigated. It was found that pre-B cells attach specifically to fibronectin and that although fibronectin by itself cannot support pre-B cell proliferation, it contributes to stromal cell stimulation of pre-B cell growth. Both of these mechanisms were found to be affected in malignantly transformed pre-B cell populations irrespective of the mode of transformation. Transformed pre-B cells were found to have acquired the ability to secrete a novel 3 Kd autocrine factor that is also capable of stimulating normal pre-B cells. In addition transformed pre-B cells showed a greatly decreased ability to adhere to fibronectin and had become insensitive to the synergistic stimulating effect of fibronectin. It will be of interest to determine in the future whether these findings have a counterpart in human malignant pre-B cell populations. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

Recent studies suggest that the neural retinal response to light is compromised in diabetes. Electroretinogram studies suggest that the dim light retinal rod pathway is especially susceptible to diabetic damage. The purpose of this study was to determine whether diabetes alters rod pathway signaling.

No description available.

No description available.