Metaphase chromosome aberrations were studied in cultured embryonic Syrian hamster cells after exposure to one of two potent mutagenic chemicals in combination with Adenovirus 12. The cultured cells were grown in Minimal Essential Medium supplemented with fetal calf serum. All cells were retained in Arginine Deficient Medium during treatments. Exposure to 4-nitroquinoline-1-oxide (4NQO) was followed at various intervals by Adenovirus 12 infection. Various concentrations of N-methyl-N¹-nitro-N-nitrosoguanidine (MNNG) were either followed or preceded at different time intervals by Adenovirus 12 infection. In all instances the rates of metaphase plates with chromosome abnormalities after combination treatments were approximately equal to the sums of the rates of abnormal plates induced by similar concentrations of each agent independently. A small proportion of the metaphase cells with chromosome abnormalities characteristic of both agents was observed, however, after combined treatments. The relationships between the rates and types of chromosome abnormalities induced by combination treatments and the rates of cell transformation as observed elsewhere but induced by similar treatments, are discussed. The rates of metaphase chromosome abnormalities induced by MNNG in virally transformed embryonic Syrian hamster cells were also investigated. It was found that these rates were simply equal to the sums of the rates of chromosome abnormalities induced by MNNG in the nontransformed control cultures plus the spontaneous rates of chromosome abnormalities in the transformed hamster cells. The significance of these findings are also discussed. / Science, Faculty of / Zoology, Department of / Graduate

The unique properties of nanomaterials, such as their small size and large surface area-to-volume ratios, have attracted tremendous interest in the scientific community over the last few decades. Thus, the synthesis and characterization of many different types of nanoparticles has been well defined and reported on in the literature. Current research efforts have redirected from the basic study of nanomaterial synthesis and their properties to more application-based studies where the development of functionally active materials is necessary. Today such nanoparticle-based systems exist for a range of biomedical applications including imaging, drug delivery and sensors. The inherent properties of the nanomaterial, although important, aren’t always ideal for specific applications. In order to optimize nanoparticles for biomedical applications it is often desirable to tune their surface properties. Researchers have shown that these surface properties (such as charge, hydrophobicity, or reactivity) play a direct role in the interactions between nanoparticles and biological systems can be altered by attaching molecules to the surface of nanoparticles. In this work, the effects of physicochemical properties of a wide variety of nanoparticles was investigated using in vitro and in vivo models. For example, copper oxide (CuO) nanoparticles were of interest due to their instability in biological media. These nanoparticles undergo dissolution when in an aqueous environment and tend to aggregate. Therefore, the cytotoxicity of two sizes of CuO NPs was evaluated in cultured cells to develop a better understanding of how these propertied effect toxicity outcomes in biological systems. From these studies, it was determined that CuO NPs are cytotoxic to lung cells in a size-dependent manner and that dissolved copper ions contribute to the cytotoxicity however it is not solely responsible for cell death. Moreover, silica nanoparticles are one of the most commonly used nanomaterials because they are easy to synthesize and their properties (such as size, porosity and surface chemistry) can be fine-tuned. Silica nanoparticles can be found in thousands of commercially available products such as toothpastes, cosmetics and detergents and are currently being developed for biomedical applications such as drug delivery and biomedical imaging. Our findings herein indicate that the surface chemistry of silica nanoparticles can have an effect on lung inflammation after exposure. Specifically, amine-modified silica NPs are considered to be less toxic compared to bare silica nanoparticles. Together, these studies provide insight into the role that material properties have on toxicity and allow for a better understanding of their impact on human and environmental health. The final aim of this thesis was to develop surface-modified nanoparticles for drug delivery applications. For this, biodegradable, polymeric NPs were used due to their inert nature and biocompatibility. Furthermore, polymeric NPs are excellent for loading drugs and using them as drug delivery vehicles. In this work, poly (lactic-co-glycolic acid) (PLGA) NPs were loaded with a therapeutic peptide. These NPs were then coated with chitosan (a mucoadhesive polymer) for the treatment of allergic asthma or coated with a small cationic mitochondrial targeting agent for the treatment of ischemia/reperfusion injury. Taken as a whole, this thesis sheds light on the impact of NPs on human health. First by providing useful toxological data for CuO and silica NPs as well as highlighting the potential of surface-modified polymeric NPs to be used in drug delivery-based applications.

archives@tulane.edu / 1 / Benjamin Vinson

No description available.

Biological systems, processes, and applications present modeling challenges in the form of system complexity, limited steady-state availability, and limited measurements. One primary issue is the lack of well-estimated parameters. This thesis presents two contributions in the area of modeling and parameter estimation for these kinds of biological processes. The primary contribution is the development of an adaptive parameter estimation process that includes parameter selection, evaluation, and estimation, applied along with modeling of cell growth in culture. The second contribution shows the importance of parameter estimation for evaluation of experiment and process design. / Thesis / Master of Applied Science (MASc)

No description available.

This study examined the effects of basic fibroblast growth factor (bFGF), insulin-like growth factor I (IGF-I) and transforming growth factor beta (TGF-β) on the proliferation and differentiation of bovine satellite cells (BSC) in vitro. Cells were treated with serum-free defined media containing varying concentrations of bFGF, IGF-I and TGF-β. On day 3 of treatment total cell nuclei and myotube nuclei were determined. bFGF stimulated BSC proliferation in a dose-dependent fashion with half-maximal stimulation observed at a concentration of 5 ng/ml (p < .05). Similar results were found for IGF-I and TGF-β in the presence of FGF, with half-maximal stimulation observed at 5 ng/ml and 1 ng/ml, respectively. With regard to differentiation, TGF-beta inhibited myotube formation at concentrations above 0.05 ng/ml. IGF-I stimulated myotube formation at concentrations as low as 10 ng/ml (p < .05). These results demonstrate that proliferation and differentiation of BSC in vitro are affected by growth factors, and consequently, similar effects may be found in vivo. This information may prove to be useful in future methods of manipulating muscle growth in vivo.

published_or_final_version / Obstetrics and Gynaecology / Doctoral / Doctor of Philosophy

Epidermal growth factor (EGF) markedly stimulates cell proliferation in a variety of mammalian systems. For this reason, EGF and factors related to EGF were examined for a possible role in the promotion and maintenance of the uncontrolled growth state that is a characteristic of malignant neoplasias. Phorbol ester tumor promoters, compounds that are capable of promoting tumors in the mouse skin carcinogenesis assay, act synergistically with EGF to stimulate DNA synthesis in cultured fibroblasts despite an inhibitory effect on the binding of EGF to its cellular receptor. Sparing of EGF degradation in combination with recovery of EGF binding was postulated to be responsible for the increased role of DNA synthesis in cells exposed to the phorbol esters. The hypothesis is presented that the hyperplasiogenic component of tumor promotion may be mediated, at least in part, by local alterations in growth factor levels. Recent evidence suggests the existance of a family of molecules related to EGF as defined by the ability to bind to the EGF receptor. These factors (transforming growth factors) appear to be responsible for the phenotypic alterations characteristic of transformed cells. Using a radioreceptor assay, two EGF-like factors were isolated from mouse submaxillary gland. These factors were not transforming growth factors and appeared to be modified EGF molecules. Two EGF-like factors, molecular weight 27,000 and 13,000, were identified in medium conditioned by Rous sarcoma virus (RSV)-transformed cells and were shown to possess the characteristics of a transforming growth factor. In addition, rat fetus extracts contained a 55,000 molecular weight EGF-like factor with the properties of a transforming growth factor. The EGF-effector system may therefore play an important role in embryonic development and in the maintenance of the neoplastic phenotype. The difference in the molecular weights of the RSV-factor and the fetus factor indicates that there are numerous members of the class of EGF-like molecules, and that RSV-transformation probably does not induce the re-expression of a fetal growth stimulatory factor. The results of these experiments suggest that EGF and EGF-like factors are biologically important growth-stimulating molecules that must be tightly regulated to maintain normal physiological conditions.

No description available.