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REGULATION OF PHENOTYPIC EXPRESSION AND PROLIFERATION OF S91 MELANOMA CELLS BY POTENT HORMONE ANALOGUES.ABDEL MALEK, ZALFA AMMAR. January 1984 (has links)
Cloudman S91 melanoma cells respond to a variety of endocrine factors, including melanotropins and steroid hormones. The murine S91 melanoma cell line, CCL 53.1, responded to α-melanocyte-stimulating hormone (α-MSH) in a dose- and a time-dependent manner, by increased tyrosinase activity. The minimal effective dose of α-MSH required to stimulate tyrosinase activity was 10⁻⁹M. By prolonging the exposure period of the cells to the hormone from 24 to 48, to 72 hours, the magnitude of tyrosinase stimulation was increased, but the minimal effective dose was not changed. α-MSH action involved elevation of intracellular cyclic AMP levels, and did not require the influx of extracellular calcium. Three melanotropin analogues, [Nle⁴, D-Phe⁷]-α-MSH, Ac-[Nle⁴, D-Phe⁷]-α-MSH₄₋₁₁-NH₂, and Ac-[Nle⁴, D-Phe⁷]- α-MSH₄₋₁₀-NH₂, have been shown to be more active than (alpha)-MSH in dispersing melanosomes within amphibian and reptilian integumental melanophores. These analogues also demonstrate prolonged activities and resistance to enzymatic degradation. The unique properties of these melanotropin analogues led to investigate their effects on the phenotypic expression and on the proliferation of S91 melanoma cells. The relative potency and the possible prolonged actions of the three [Nle⁴, D-Phe⁷] -substituted analogues were investigated and compared to those of α-MSH. The melanotropin analogues proved to be 100-1000 fold more active than α-MSH in stimulating tyrosinase activity. These analogues elicited significant tyrosinase activation following brief contact times with the cells, and maintained their stimulatory effects for days after removal from the culture flasks, and after the α-MSH effect had totally dissipated. Contrary to previous reports that melanotropins inhibit the proliferation of melanoma cells, α-MSH and [Nle⁴, D-Phe⁷] -α-MSH stimulated, rather than inhibited, the proliferation of CCL cells under culture conditions that allowed optimal phenotypic expression. Also, the effects of the steroids, β-estradiol, progesterone, and dexamethasone, on CCL cells were studied. Dexamethasone had the most remarkable effects, which involved stimulation of tyrosinase activity and inhibition of proliferation in monolayer culture and in soft agar. Furthermore, this study defined some of the factors that influence the endocrine responsiveness of melanoma cells. The results of this study have important implications for the regulation of phenotypic expression and of proliferation in S91 melanoma cells, and for the properties of the melanoma melanotropin receptor.
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EFFECTS OF EPIDERMAL GROWTH FACTOR AND DIET ON CULTURED PANCREATIC ACINAR CELLS.Demarest, Alison Sue. January 1984 (has links)
No description available.
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The Functional Characterization of Two Regulators of G-protein Signaling Proteins Abundantly Expressed in Vascular Smooth Muscle CellsGu, Steven 03 March 2010 (has links)
Precise regulation of heterotrimeric G-protein signaling is important for maintaining proper cardiovascular system function. Indeed, G-protein signaling is frequently upregulated during cardiovascular disease suggesting that identifying mechanisms for inhibiting G-protein signaling may be an effective therapeutic strategy for the treatment and prevention of disease. The work presented in this thesis is directed at two RGS proteins, RGS2 and RGS5, the two highest expressing RGS proteins in VSMCs. Despite the large number of studies published on them, there is still much to be learned about the specific G-protein pathways that each RGS protein controls. Using genetic and molecular models, we set out to identify novel regulatory pathways controlling RGS2 and RGS5 function. We hypothesize that characterizing the determinants and regulation of RGS protein function will provide a better understanding of the signaling that occurs within VSMCs under both physiologic and pathophysiologic conditions.
Our work presented in the first three studies of this thesis, describes novel regulatory pathways that are involved in regulating RGS2 protein function. We describe the production of RGS2 protein isoforms that are the result of alternative translational start site usage. Interestingly, the expression pattern of these proteins is controlled by the signaling status of the cell. In the second two studies, we identify a functional consequence of RGS2-interaction with the plasma membrane. We show that this is dependent on the interaction between the amphipathic α-helix and anionic phospholipids present in the plasma membrane. We further show that disruptions in this interaction, as occurs in the human population, can lead to reduced RGS2 function and thus potentially hypertension.
Finally, our last study focuses on the function and regulation of RGS5, the single highest expressing RGS protein in VSMCs. We show that the regulation of RGS5 is dependent, similar to other VSMC-specific genes, on the activity of SRF and myocardin. However, interestingly, RGS5 expression is further controlled by the extent of DNA methylation that occurs in its proximal promoter. We show that this is an important regulator of RGS5 expression both in development as well as during disease, specifically in-stent restenosis.
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Immunotoxic and immunodisruptive effects of selected dense non-aqueous phase liquids in immunocompromised cells31 March 2009 (has links)
M.Sc. / Dense non-aqueous phase liquids (DNAPLs) are groups of chemicals often found beneath the water surface when chemical contamination of water occurs and they are called groundwater contaminants. Their improper storage and extensive use in industries as well as their slow degradation provide a long term source for of low level contamination of ground- and river water. Evidence from both human and animal studies suggests that volatile organic and organochlorinated compounds (specific types of DNAPLs), may increase host susceptibility to microbial infection, induce alterations in the maturation of effector immune cells and compromise immune surveillance mechanisms. These effects of DNAPLs hold special relevance for people living with HIV/AIDS. In light of this, the present study investigated the in vitro immunological effects of the two most common DNAPLs contaminants, Trichloroethylene (TCE) and Aroclor-1254 (ARO) in peripheral blood mononuclear cells (PBMCs) of immunocompromised and healthy donors. TCE and ARO were successfully dissolved in cell culture medium and added to freshly isolated PBMCs in a 1:1 ratio. Following incubation, cell functionality and cytotoxicity (or immunotoxicity) were assessed using MTT and LDH. Viability was confirmed and/or cell death analyzed by flow cytometry. Culture supernatants were used to assess NO and cytokine production as well as for quantification of viral replication. TCE and ARO induced a significant (p<0.05) decrease in cell viability/functionality in a dose-dependent manner. Flow cytometric analysis of cell death pathways indicated that TCE and ARO induced apoptosis. These chemicals also induced the secretion of both NO and proinflammatory cytokines suggesting that they may induce apoptosis via an inflammatory pathway, which may explain the mitochondrial dysfunction as determined by the MTT assay. ARO effects were more prominent than those of TCE, and both were more detrimental to HIV positive PBMCs compared to uninfected cells. The viral p24 levels increased in a dose-dependent fashion suggesting an effect for TCE and ARO on viral replication. This research concludes that DNAPL-contamination is detrimental to especially immuno-compromised systems.
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Calcium imaging of the entire muscle system of Hydra reveals extensive cellular multifunctionalitySzymanski, John Robert January 2018 (has links)
Hydra vulgaris is a Cnidarian species with a life cycle containing only a polyp stage, and with a simple body plan in which ectodermal and endodermal epitheliomuscular cells play many roles. These two epithelia generate motion of the polyp by exerting contractile force on myonemes. The function of this musculature was studied on a system scale using whole-animal calcium imaging to measure functional activity in all epitheliomuscular cells simultaneously. This approach maps the diversity of functional activation patterns underlying the behavior of Hydra, and reveals that individual epitheliomuscular cells participate in multiple patterns using at least two different types of calcium signaling that propagate by different mechanisms and at vastly different rates. These studies establish the functional basis for the epithelial muscle systems of Cnidaria, revealing new operational principles and deep evolutionary ties to mechanisms of contractile activity that exist elsewhere in Metazoa.
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Transcriptional repression of the microsomal triglyceride transfer protein gene in L35 hepatoma cells /Kang, Sohye. January 2004 (has links)
Thesis (Ph. D.)--University of California, San Diego and San Diego State University, 2004. / Vita. Includes bibliographical references (leaves 181-227).
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The Functional Characterization of Two Regulators of G-protein Signaling Proteins Abundantly Expressed in Vascular Smooth Muscle CellsGu, Steven 03 March 2010 (has links)
Precise regulation of heterotrimeric G-protein signaling is important for maintaining proper cardiovascular system function. Indeed, G-protein signaling is frequently upregulated during cardiovascular disease suggesting that identifying mechanisms for inhibiting G-protein signaling may be an effective therapeutic strategy for the treatment and prevention of disease. The work presented in this thesis is directed at two RGS proteins, RGS2 and RGS5, the two highest expressing RGS proteins in VSMCs. Despite the large number of studies published on them, there is still much to be learned about the specific G-protein pathways that each RGS protein controls. Using genetic and molecular models, we set out to identify novel regulatory pathways controlling RGS2 and RGS5 function. We hypothesize that characterizing the determinants and regulation of RGS protein function will provide a better understanding of the signaling that occurs within VSMCs under both physiologic and pathophysiologic conditions.
Our work presented in the first three studies of this thesis, describes novel regulatory pathways that are involved in regulating RGS2 protein function. We describe the production of RGS2 protein isoforms that are the result of alternative translational start site usage. Interestingly, the expression pattern of these proteins is controlled by the signaling status of the cell. In the second two studies, we identify a functional consequence of RGS2-interaction with the plasma membrane. We show that this is dependent on the interaction between the amphipathic α-helix and anionic phospholipids present in the plasma membrane. We further show that disruptions in this interaction, as occurs in the human population, can lead to reduced RGS2 function and thus potentially hypertension.
Finally, our last study focuses on the function and regulation of RGS5, the single highest expressing RGS protein in VSMCs. We show that the regulation of RGS5 is dependent, similar to other VSMC-specific genes, on the activity of SRF and myocardin. However, interestingly, RGS5 expression is further controlled by the extent of DNA methylation that occurs in its proximal promoter. We show that this is an important regulator of RGS5 expression both in development as well as during disease, specifically in-stent restenosis.
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The role of the Activator Protein-2 transcription factor family in human skin and its appendagesPopa, C. Unknown Date (has links)
No description available.
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The lysosomal nature of hormonally induced enzymes in wheat aleurone cellsGibson, Robert Alan January 1974 (has links)
xx, 277 leaves : ill. ; 26 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.1974) from the Dept. of Plant Physiology, University of Adelaide
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The lysosomal nature of hormonally induced enzymes in wheat aleurone cells.Gibson, Robert Alan. January 1974 (has links) (PDF)
Thesis (Ph.D. 1974) from the Dept. of Plant Physiology, University of Adelaide.
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