The concentration of insulin-like growth factor I (IGF-I) in tissue taken from human non-small cell lung carcinoma (NSCLC) is 1.4- to 7-fold higher than the concentration of IGF-I in the surrounding normal lung tissue and therefore IGF-I may be involved in the growth of NSCLC. In this study it was determined that NSCLC cell lines (A549, A427, SK-LU-1) expressed the type I IGF-I receptor protein and IGF-I stimulated the proliferation of low density plated (2000 cells/cm² growth area) carcinoma cells by 1.6- to 3- fold above control after a four day inCUbation period under serum-free conditions (A549, A427) or in the presence of 0.25% serum (SK-LU-1). In addition, when added to detergent-solubilized type I IGF receptors from A549 cells, IGF-I stimulated [1] a dose-dependent increase in the autophosphorylation of the type I IGF receptor, and [2] a dose-dependent increase (1.5- to 4-fold) in the phosphorylation of a tyrosine kinase-specific substrate. These results suggest that the growth promoting activity of IGF-I for the lung carcinoma cells was mediated through the activation of the type I IGF receptor. / Ph. D.

Absence of functional phenylalanine hydroxylase results in phenylketonuria (PKU). Viable treatments remain few, expensive and secondary conditions such as osteopenia occur in most PKU patients. Objective 1: Given the recently described roles of gut microbes to aid host digestion, an orally administered genetically engineered probiotic as the delivery vehicle for enzyme replacement therapy was created. The engineered probiotic, pHENOMMenal, produced phenylalanine ammonia lyase with significant production of trans-cinnamate (phenylalanine cleavage product) in vitro and resulted in a reduction of 515 μM in blood phenylalanine when fed to PKU animals for 14 days (from 2307µM ± 264µM to 1792µM ± 261µM, n = 6, P < 0.05). The control probiotic produced no change in blood phenylalanine. Thus, pHENOMMenal treatment in PKU mice demonstrated engineered microbes could compensate for a metabolic deficiency of the host. Objective 2: Evaluate the PAHenu2 mouse model of PKU for a genetic discrepancy causing ocular enlargement and delayed development observed only after the PAHenu2 mutation was crossed to the C57BL/6J mouse. When compared to healthy littermates, ELISA indicated a consistent but insignificant decrease in plasma IGF-1 and an increase in ocular IGF-1 in PKU animals. SNP screening demonstrated a differential inheritance of IGF-1 alleles in healthy and PKU animals based on PAH allele inheritance. Ocular and developmental phenotypes in the PAHenu2 colony match those described in previous IGF-1 studies. Understanding the IGF-1 inheritance discrepancy will enable better osteopenia research using PAHenu2 mice and allow breeding of a healthier mouse colony for continued research. Collectively the results from this work describe a new therapeutic approach for treatment of PKU as well as a better understanding of the PAHenu2 mouse model to study this disease.

Tse Chui-ling. / "July 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 172-185). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

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Includes bibliography (leaves 191-219). Examines the levels of insulin-like growth factor and the presence of IGF binding proteins in human wound fluid. Tests the potency of IGF-1 and 2 analogues in in vitro models of fibroblast activity and their effect on healing in normal and diabetic rodent wounds. Shows that IGF-1, IGF-2 and their binding proteins are present in fluid from a partial thickness cutaneous wound; that the binding proteins negatively modulate the activity of insulin-like growth factors in vitro, but that the IGFs do not necessarily show enhanced activity in vivo at the wound site if binding protein affinity is decreased. Discusses possible roles of these binding proteins in wound repair.

Includes bibliography (leaves 191-219). / Copy 2 lacks some pages. / x, 219 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Examines the levels of insulin-like growth factor and the presence of IGF binding proteins in human wound fluid. Tests the potency of IGF-1 and 2 analogues in in vitro models of fibroblast activity and their effect on healing in normal and diabetic rodent wounds. Shows that IGF-1, IGF-2 and their binding proteins are present in fluid from a partial thickness cutaneous wound; that the binding proteins negatively modulate the activity of insulin-like growth factors in vitro, but that the IGFs do not necessarily show enhanced activity in vivo at the wound site if binding protein affinity is decreased. Discusses possible roles of these binding proteins in wound repair. / Thesis (M.D.)--Dept. of Surgery, University of Adelaide, 2001?

Addenda held in pocket pasted onto back end paper. / Bibliography: leaves 137-165. / xvi, 165 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / This thesis involves the retrospective investigation of the insulin-like growth factors and their binding proteins in the serum of children with chronic renal failure (CRF) and transplantation, before and after treatment with recombinant human growth hormone (rhGH). IGF-IGFBP complexes in pooled serum from prepubertal and pubertal children of both sexes with CRF and renal transplantation, before and after treatment with rhGH, are analysed by fast protein liquid chromatography under neutral conditions. / Thesis (M.D.)--University of Adelaide, Dept. of Paediatrics, 1997?

Graduation date: 1997

Thesis (Ph. D.)--Auburn University, 2008. / Abstract. Vita. Includes bibliographical references (p. 62-77).

Insulin-like growth factor-I (IGF-I) and its principle binding protein (IGFBP-3) are believed to play a role in mediating the anabolic effects of exercise. The purpose of this study was to assess the effect of 4 months of training on IGF-I and IGFBP-3, and to determine if changes in IGF-I or IGFBP-3 were related to changes in training status. Twelve varsity swimmers (5 males, 7 females) were tested pre-season, and again after 8 and 16 weeks of training. Measures included: VO2 max, nutritional status, athletic performance, subjective symptoms of overtraining, and serum levels of IGF-I and IGFBP-3. There was no significant change across time in VO2 max, athletic performance, IGF-I or IGFBP-3. Resting IGFBP-3 was positively correlated to symptoms of overtraining at week 0 (p=0.017), however, this relationship did not persist at week 8 or 16. These findings can not confirm that resting levels of IGF-I and IGFBP-3 are sensitive markers of training status. / ix, 105 leaves : ill. ; 29 cm.