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Dissertations / Theses on the topic 'Health Sciences, Toxicology|Chemistry, Biochemistry'

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1

Wildfang, Eric Konrad. "Purification, sequencing and characterization of rabbit liver arsenite and methylarsonic acid methyltransferase." Diss., The University of Arizona, 2001. http://hdl.handle.net/10150/279851.

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Inorganic arsenic is an important environmental toxicant of both natural and anthropogenic sources. It is a human carcinogen for which appropriate animal models of most arsenic-induced cancers are lacking. Presently, 17 species of non-human primates were screened using an in vitro assay to determine their arsenic methylation ability as a predictive tool for better understanding the presence, and in some instances, deficiency of arsenic methyltransferase activity among animal species. Four of the 17 species investigated had arsenite methyltransferase activity, three of which were from the genus
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2

Radabaugh, Timothy. "Oxidation and reduction of inorganic arsenic in mammalian systems." Diss., The University of Arizona, 2003. http://hdl.handle.net/10150/280379.

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Arsenic is a toxic metalloid and is ubiquitous in our environment. In ancient cultures it was valued as a poison and today is becoming an increasing public health problem. Chronic arsenic exposure has a broad range of toxic effects including cancer. Currently millions of people are exposed to higher levels of arsenic in their food and drinking water than is considered safe by the World Health Organization. Although arsenic metabolism is not completely understood, it is known that inorganic arsenate is reduced to arsenite which can then be methylated and excreted in the urine. It is also known
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3

Stratton, Steven Paul 1968. "Photooxidation and beta-carotene: Effects in membrane models." Diss., The University of Arizona, 1996. http://hdl.handle.net/10150/282228.

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Intake and serum levels of β-carotene have inverse associations with cancer risk. Previous research indicates chemopreventive actions may be due to antioxidant properties. Photooxidation reactions are an important source of reactive oxygen species. Photosensitizers can damage tissue by catalyzing the formation of oxyradicals and singlet oxygen (¹O₂). β-Carotene efficiently quenches ¹O₂ catalytically via a physical reaction. However, concomitant chemical reactions during photosensitized oxidations consume β-carotene. This dissertation is a study of β-carotene antioxidant mechanisms in solution
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4

Malone-Stratton, Aaron A. "Elucidating the role of metallothionein isoforms in cellular zinc homeostasis." Thesis, California State University, Long Beach, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=1527330.

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<p> Metallothioneins (MT) are low molecular weight, cysteine-rich, metal-binding proteins that are thought to play key roles in detoxification and Zn homeostasis. Four metallothionein isoform families, termed MT 1-4, have been identified in mammalian species. The majority of studies on MT have focused on the biochemical properties of the widely expressed MT-1 and MT-2 and, in comparison, few studies have investigated the metal binding characteristics of the neuronal-specific MT-3. While the function of MT-3 in neurons is not fully understood, a better understanding of the biochemical propertie
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5

Chen, Tzu-chin 1965. "Partial purification and characterization of sodium channel phosphatases from rat brain: Similarity to phosphatase 2A." Thesis, The University of Arizona, 1991. http://hdl.handle.net/10150/278004.

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Four distinct serine/threonine protein phosphatases have been purified from and identified in various tissues. They are type 1 and type 2 phosphatases, which are further classified as phosphatase 2A, 2B, and 2C. In this study, endogenous brain phosphatases that dephosphorylate sodium channels were partially purified and characterized. Multiple peaks of sodium channel phosphatase were detected after DEAE-Sephadex chromatography and gel filtration. All peaks were sensitive to a low concentration of okadaic acid (10 nM), which strongly suggests that phosphatase 2A is the major brain phosphatase d
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6

Hatlelid, Kristina Mary 1967. "In vitro investigation of the toxic mechanism of action of arsine on the erythrocyte." Diss., The University of Arizona, 1996. http://hdl.handle.net/10150/282124.

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A novel test system using isolated erythrocytes (red blood cells, RBCs) and arsine (AsH₃ gas dissolved in aqueous solution was characterized which allows for the quantitation of RBC exposure to AsH₃ in vitro and for in vitro study of the toxicity of AsH₃. AsH₃ was found to be rapidly and strongly associated with RBCs. Toxicity, measured as hemolysis, was time- and dose-dependent and exhibited a lag phase of about 30 minutes in both dog and rat RBCs. Hemolysis of dog RBCs was completely blocked by carbon monoxide preincubation and was reduced by pure oxygen. Sodium nitrite induction of methemog
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7

Kramer-Stickland, Kimberly Ann 1970. "Fate of vitamin E in UVB-irradiated mouse skin and in vitro systems: Antioxidant and photochemistry." Diss., The University of Arizona, 1998. http://hdl.handle.net/10150/288782.

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Photochemical and antioxidant reactions of α-tocopherol (α-TH, vitamin E) were studied by monitoring the fate of α-TH in UVB irradiated liposomes, solution, and mouse skin. α-TH was rapidly depleted in UVB irradiated mouse skin and in vitro systems. Oxidative damage, assessed by monitoring lipid peroxidation, was suppressed in UVH-irradiated liposomes until α-TH was depleted to 20% of initial levels. In all three systems, products previously identified as marker products for peroxyl radical scavenging by α-TH were observed, including α-tocopherolquinone (α-TQ), α-tocopherolquinone 2,3-epoxide
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8

Born, Stephanie Lynn 1968. "Characterization of canine cytochromes P450 2B and 3A." Diss., The University of Arizona, 1996. http://hdl.handle.net/10150/290587.

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The objective of these studies was to functionally characterize canine cytochromes P450 from subfamilies 2B and 3A. Studies of the canine hepatic 2B form PBD-2 had previously revealed that this enzyme exhibits a species specific ability to metabolize 2,2',4,4',5,5'-hexachlorobiphenyl (245-HCB) and catalyze progesterone 21-hydroxylation. Expression of the putative PBD-2 cDNA, 2B11, in three different heterologous systems revealed that the recombinant enzymes' apparent substrate specificities varied based upon the expression system. 2B11 expressed in COS cells and yeast did not metabolize proges
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9

Healy, Sheila Marie. "Arsenic methylation in perspective." Diss., The University of Arizona, 2001. http://hdl.handle.net/10150/289727.

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The following arsenite methyltransferase activities (U/mg) were measured in untreated mice: liver, 1.42 ± 0.17 (mean ± SEM); kidney, 0.62 ± 0.18; lung, 0.33 ± 0.08; testis, 1.21 ± 0.01. Arsenite methyltransferase metabolites were not detectable using guinea pig liver, kidney, lung or testis cytosol as the source of enzyme. A twofold increase in liver arsenite methyltransferase activity was observed in mice exposed to 28.6 mg sodium arsenite/L drinking water after 24 hr compared to control. Trivalent arsenic species were separated from pentavalent arsenicals in liver homogenates of hamsters inj
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10

Suarez, Samuel Charles. "Molecular Determinants of Human DNA Polymerase eta Fidelity." Thesis, North Carolina State University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3584268.

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<p> DNA damage is a ubiquitous challenge to replication in cells, as damage causes replicative polymerase stalling. However, once DNA has been unwound at the replication fork, replication must proceed in the presence of damage to prevent more deleterious and almost assuredly mutagenic consequences. Alleviation of replicative polymerase stalling is accomplished by specialized DNA polymerases that can synthesize across from DNA lesions using the damage as a template, a process termed translesion synthesis (TLS). DNA polymerase &eta; pol &eta; is the best understood of these polymerases, and lack
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11

Cooper, Roland Arthur 1963. "Pyrrolizidine alkaloids: Chemical basis of toxicity." Diss., The University of Arizona, 1996. http://hdl.handle.net/10150/290581.

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In humans, livestock and experimental animals, pyrrolizidine alkaloids (PAs) are toxic as a consequence of their hepatic metabolism to reactive pyrrolic esters, or dehydroalkaloids (DHAs). Despite their similarity in structures, PAs often vary markedly in their lethality (LD₅₀s) and in the organs in which toxicity is expressed. We have examined whether there are differences in the physicochemical properties of certain DHAs which are associated with differences in patterns of metabolism and toxicity produced by the parent PA. Using a potentiometric method to measure hydrolysis, it was determine
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12

Hood, Darryl B. "Nitrogen Dioxide Reaction With Proteins: Evidence for Peptide Bond Cleavage at Lysine Residues." Digital Commons @ East Tennessee State University, 1991. https://dc.etsu.edu/etd/2734.

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Nitrogen dioxide (NO$\sb2$), an air pollutant produced by burning fossil fuels and a component of cigarette smoke, is thought to contribute to the pathogenesis of pulmonary diseases, such as emphysema. To gain information on the mechanism by which NO$\sb2$ damages the lung, in vitro exposures of $\alpha\sb1$-proteinase inhibitor ($\alpha\sb1$-PI), elastin, bovine serum albumin (BSA), human serum albumin (HSA) and synthetic poly-L-lysine were performed. A genetic deficiency of $\alpha\sb1$-PI predisposes humans to emphysema and NO$\sb2$ has been hypothesized to damage $\alpha\sb1$-PI, which wou
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13

MacFarlane, Amanda J. "Identification and characterization of the type 1 diabetes-related wheat storage globulin WP5212." Thesis, University of Ottawa (Canada), 2004. http://hdl.handle.net/10393/10823.

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Type 1 diabetes (T1D) affects approximately 200,000 Canadians and is increasing at a rate of about 3.0% per year. The development of autoimmune diabetes requires genetic susceptibility and is influenced by environmental agents. Diets in which wheat protein is the sole amino acid source are associated with high diabetes frequency in diabetes-prone BioBreeding (BBdp) rats and non-obese diabetic (NOD) mice, two models of spontaneous autoimmune diabetes. We hypothesized that an abnormal immune response to wheat, as indicated by circulating IgG antibodies, could be used to identify T1D-related whea
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14

Wright, Duncan Hamish. "Biochemistry, molecular biology and pharmacology of the prostanoid DP receptor." Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=36852.

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The term prostanoids collectively describes prostaglandins, prostacyclin and thromboxanes. These compounds are products of arachidonic acid metabolism by the cyclooxygenase pathway. Prostanoids mediate various physiological and pathophysiological effects through their interaction with membrane-bound receptors. In this research, a thorough characterization of the recombinant human (h) PGD2 receptor (DP) was performed, with respect to its radioligand binding and signal transduction properties using prostanoids and prostanoid analogues. The recombinant hDP receptor was then used along with other
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15

Stessman, Chad Christian 1972. "Synthesis of dolastatin 11 and analogs: Molecular modeling studies in this series." Diss., The University of Arizona, 1998. http://hdl.handle.net/10150/282652.

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The synthesis of dolastatin 11 was repeated on a much larger scale. Most of the yields and reaction conditions in the original synthesis were improved upon. Several problems that arose in the scale up were solved. The synthetic dolastatin 11 was obtained for the first time. The synthetic dolastatin 11 had good activity against a variety of cancer cell lines. The structure of the major by-product of the dolastatin 11 synthesis was determined. Several analogs of dolastatin 11 were synthesized. Testing results on the beta-alanine analog of dolastatin 11 showed it to have similar activity to the n
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16

Hu, Song 1969. "Thrombin exosite interactions studied by NMR spectroscopy." Thesis, McGill University, 1996. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=23897.

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Fibrinogen, thrombin receptor and heparin cofactor II are three major thrombin substrates recognized specifically through its exosite, a regulatory binding site. Based on the native protein sequences, four peptides were selected to study the specificity of exosite interactions on structural basis using transferred NOE methods. The binding sequences of all the peptides are identified and possible thrombin binding sites of thrombin receptor and heparin cofactor II peptides are speculated by comparing with known hirudin-thrombin complex structures. A new binding mode may exist in thrombin-fibrino
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17

Liu, Hsueh-Ning 1970. "Glutamatergic signaling in oligodendrocyte progenitors." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=82917.

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The excitatory neurotransmitter, glutamate, plays an important role in synaptic transmission, brain development and plasticity as well as excitotoxicity. The biological functions of glutamate in neurons are mediated by ion channel-gated or G-protein-coupled receptors that are also located on glial cells, including oligodendrocytes. However, the functions of glutamate receptors in oligodendrocytes and their progenitors remain unknown. The objective of work presented in this thesis was to characterize the effects of glutamate on oligodendrocyte progenitors and the intracellular signaling
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18

Querido, Emmanuelle. "Regulation of the p53 tumor suppressor by early products of adenovirus serotype 5." Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=36827.

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DNA tumor virus oncoproteins have evolved to regulate the p53 tumor suppressor. They must overcome p53-dependent cell cycle arrest and apoptosis, which would interfere with viral replication. Upon cellular stress, signalling to p53 takes the form of a large increase in the stability of the protein, by inhibition of the MDM2 protein which normally targets p53 for rapid degradation. Expression of the adenovirus type 5 early region 1 A (E1A) polypeptides can stimulate a quiescent cell to reenter the cell cycle and induces the accumulation of p53 protein and p53-dependent cell death under certain
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19

Pozzulo, Gina. "Analysis of proteolytic enzyme-derived fragments of murine alpha-fetoprotein." Thesis, McGill University, 1988. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=59596.

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The purpose of this study was (i) to generate proteolytic enzyme-derived fragments of murine alpha-fetoprotein (AFP); (ii) to characterize some of their physicochemical and immunological properties; and (iii) to isolate the fragments from proteolytic digests of mouse AFP. Significant differences in digestion patterns produced by the limited proteolysis of AFP were apparent. Proteolysis under denaturing conditions was most efficient and yielded smaller peptide fragments of narrower molecular weight range. Similar findings were observed for larger scale digests using milligram amounts of AFP. So
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20

Bi, Honggang. "Urinary metabolites of anabolic steroids : identification and synthesis." Thesis, McGill University, 1991. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=70304.

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The metabolism of several anabolic 17$ alpha$-methyl steroids, namely formebolone, mestanolone, methandienone, methyltestosterone, oxandrolone, oxymetholone and stanozolol, were investigated. The identification of metabolites was based on GC/MS analysis of different derivatives, and chemical synthesis of corresponding reference steroids. Common metabolic reactions have been studied and structure-metabolism relationships were discussed. New biotransformation routes, such as oxidative pathways of 2-formyl and 2-hydroxymethylene steroids, have been unveiled. The mechanism of 17-epimerization of t
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21

Keyston, Rebecca. "Homotypic and heterotypic adhesion mediated by biliary glycoprotein, BGP." Thesis, McGill University, 1996. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=23900.

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Glycophosphatidyl-inositol (GPI)-linked carcinoembryonic antigen (CEA) family members, including CEA itself, are absent in rodents and seem to have evolved recently. We have shown previously that CEA-CEA binding required for intercellular adhesion involves a double reciprocal interaction between the N-terminal (N domain) and internal A3B3 domains of anti-parallel molecules on apposed cell surfaces. To answer the question of whether this binding mechanism also evolved with CEA, the adhesive binding mechanism for transmembrane biliary glycoprotein (BGP), presumably more primordial, was investiga
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22

Xu, Hui 1958. "Characterization of the biochemical and functional properties of platelet proteins recognized by human hybridoma autoantibodies." Thesis, McGill University, 1994. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=28553.

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Anti-platelet autoantibodies may be responsible for hematological complications in patients with systemic lupus erythematosus (SLE), but the mechanisms by which these antibodies cause abnormal hemostasis remain unknown. In the present study, we demonstrate that an SLE-derived human hybridoma autoantibody, 9604, recognizes a surface antigen expressed on platelets activated by adenosine diphosphate (ADP), calcium ionophore A23187, or phorbol myristate acetate (PMA), showing saturation with approximately 2,000 antibody molecules bound and a K$ rm sb{d}$ of 41 nM. This antibody did not affect shap
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23

Halwani, Fawaz. "Isolation and partial characterization of a human pancreatic carcinoma-associated antigen defined by a novel monoclonal antibody, LD-B1." Thesis, McGill University, 1990. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=70160.

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The aim of this study is to define a cellular antigen associated with human pancreatic carcinoma by developing monoclonal antibodies against the post-microsomal fraction of fresh tumor tissue. One such antibody, LD-B1, was tested by immunohistochemistry and reacted strongly with 95% of cases of pancreatic ductal carcinomas. Amongst common types of non-pancreatic malignancies, 10% were immunostained by LD-B1 and, in these cases the reaction was focal or weak. On normal pancreas, staining was observed in ductal and ductular epithelium only. The antigen was purified to homogeneity by affinity chr
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24

Michaelidou, Aliki. "A human organ-specific neoantigen defined as a mycoplasma 40 KD protein (P40) /." Thesis, McGill University, 1991. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=70347.

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Human organ-specific-neoantigens (OSN) are tumor molecules found in crude cancer extracts to which patients with cancer of the same organ and histogenesis respond in the in vitro assay of leukocyte adherence inhibition (LAI). P40 is a molecule isolated from spent medium of lung and colon cancer cells, which exhibits OSN properties. Individual peptides of p40 exhibited organ-specificity. Distribution studies on a variety of cultured cell lines, fresh, and fetal tissues showed that p40 is present only on some cultured cells. Using the peptide sequences of p40 a collaborating laboratory isolated
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25

McCandless, John Richard 1954. "Alpha-6 beta-1 and alpha-6 beta-4 integrin expression and the vascularization of human prostate tumor xenografts." Thesis, The University of Arizona, 1997. http://hdl.handle.net/10150/278603.

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Growth and metastasis of tumors appear to be dependent on the ability of tumor cells to recruit blood vessels. Integrins are a class of cell adhesion molecules that may have a role in angiogenesis. In this study the effect of the expression of two integrins, α6β1 and α6β4, on microvessel density in human prostate tumor xenografts in SCID mice was evaluated. Five methods (one-person count, two-person count, digital analysis of immunostained tissues, and digital analysis of vascular corrosion casts) were used to measure microvessel density. Results indicate that alpha6 integrin expression correl
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26

Ibrahim, Mohab Mohamed. "Pain-modulating effects of peripheral (CB2) cannabinoid receptors." Diss., The University of Arizona, 2004. http://hdl.handle.net/10150/280554.

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Cannabinoid receptor agonists diminish responses to painful stimuli. Extensive evidence implicates the CB1, receptor in the production of antinociception, inflammatory hyperalgesia, and peripheral nerve injury-induced sensory hypersensitivity. In previous work included in my masters thesis, our laboratory has demonstrated the capacity of CB2 receptors located outside the central nervous system (CNS) to inhibit acute nociception and inflammatory hyperalgesia. In this thesis, I use AM1241, a CB2 receptor-selective agonist to test the hypothesis that CB2 receptor activation reverses the tactile a
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27

Lou, Qiang 1962. "Identification of peptide substrates and development of pseudosubstrate-based peptide inhibitors for p60(C-SRC) protein tyrosine kinase." Diss., The University of Arizona, 1996. http://hdl.handle.net/10150/282230.

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Protein tyrosine kinases (PTKs) mediate important signaling events associated with cellular growth, differentiation, and mitogenesis. The p60c-src protein is the first described cellular protein tyrosine kinase. Human p60c-src PTK has been implicated in the development of colon and breast cancer, and leukemia. However, the exact physiological role of p60c-src PTK or its physiological target proteins are not well known, and the mechanism by which the p60c-src PTK activity is regulated is not completely understood. Peptide substrates can be used to determine the substrate specificity and kinetic
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28

Khera, Smriti. "Drug lead discovery through plant bioprospecting in Latin America." Diss., The University of Arizona, 2005. http://hdl.handle.net/10150/282898.

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The bioassay guided fractionation of two Latin American plants, structure elucidation of pure isolates, and LC/MS studies of six plant extracts is presented here along with the structure determination of two compounds using X-ray diffraction. The bioassay guided fractionation of the antibacterial and antitubercular CH2Cl2-MeOH extracts of the Argentinean plant Caiophora coronata Hook. et Arn. (Loasaceae) and the Chilean plant Myrcianthes coquimbensis (Barn.) Landrum et Grifo (Myrtaceae) respectively led to the isolation and complete structure elucidation of nine compounds from the active fra
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29

Mancini, Duane. "Large Scale Synthesis of Amphiphiles for Biological Use and Analytical Profile of Polar Extracts from Mastic Gum." Thesis, The University of Toledo, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=1585716.

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<p> This thesis includes many different production and research projects that can help make many positive advances in the pharmaceutical and biomedical area. The first part of my thesis describes my practical experience at Anatrace Products, LLC. Included in this chapter is the large scale synthesis of amphiphiles for biological uses. The second part of the thesis describes my attempt to build an analytical profile of polar extracts from mastic gum for the potential treatment of chronic obstructive pulmonary disease.</p>
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30

Pathak, Preeti. "Retinoic acid related orphan nuclear receptor alpha (RORalpha) regulates diurnal rhythm and fasting induction of sterol 12alpha-hydroxylase (CYP8B1) in bile acid synthesis." Thesis, Kent State University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3618855.

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<p> Sterol 12a-hydroxylase (CYP8B1) is involved in cholic acid synthesis and plays a role in intestinal cholesterol absorption and pathogenesis of cholesterol gallstone disease and dyslipidemia. In this study, we investigated the underlying mechanism of a fasting-induced and cholesterol activated nuclear receptor and core clock gene RORa in regulation of circadian rhythm and fasting induction of CYP8B1 expression. In free fed mice, CYP8B1 expression was reduced to the lowest level at the onset of the dark cycle when RORa expression was the lowest. However, fasting stimulated, while re-feeding
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31

Lo, Andrew M. "Studies on antioxidant activity of flavonoids quercetin, keampferol, geneistein, and glutathione in proteins and 3T3-LA1 cells." Thesis, Tennessee State University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=1567571.

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<p> Oxidative stress can do extensive damage to all components of cells, and subsequently causing variety of diseases such as cancer. Studies had shown that oxidative stress can increase the level of Akt expressed within cells, while can potentially lead to development of cancer. Within most of the cells, there is a defense mechanism against oxidative stress that uses glutathione (GSH), a natural, ubiquitous tripeptide. Glutathione reductase, glutathione peroxidase, and superoxide dismutase are three enzyme that are the three major enzyme in the defense mechanism against oxidative stress. Rece
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32

Park, Joshua Inshik. "Matrix attachment therapy for cancer." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3311355.

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33

McVey, Mark. "Mechanisms of effects of phytoestrogens on reproduction, steroidogenesis and steroid action in male rats." Thesis, University of Ottawa (Canada), 2004. http://hdl.handle.net/10393/26715.

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The consequences of soy isoflavone consumption on steroidogenesis were examined in F1 male rats from a multi-generation reproduction study investigating the effects of diets varying in isoflavone content. F1 male rats were obtained from a multi-generation study where the parental generation was fed diets containing alcohol-washed soy protein supplemented with increasing amounts of Novasoy, a commercially available isoflavone supplement. A control group was maintained on a soy-free casein-based diet (AIN93G). Testicular and serum androgen levels were assayed with commercial kits and were approx
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34

Nguyen, Hoa P. "Structural studies of polyspecific anti-carbohydrate antibodies." Thesis, University of Ottawa (Canada), 2006. http://hdl.handle.net/10393/29307.

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The inheritance of germline immunoglobulin genes must ensure the recognition of prevalent pathogens and the ability to adapt to new pathogens. The current understanding of the generation of diversity of immunoglobulin binding sites involves the recombination of the B-lymphocyte germline genes during development. In general, the production of immunoglobulins proceeds with the help of T-lymphocytes through a process called "affinity maturation" involving mutations that increase antigen specificity. Carbohydrate epitopes, however, do not illicit such a response, and so are more dependent on the p
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35

Paterson, Jennifer Marie. "Investigation of the oncolytic activity of vesicular stomatitis virus in murine cancer models." Thesis, University of Ottawa (Canada), 2005. http://hdl.handle.net/10393/27005.

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Interferon (IFN) inducing strains of Vesicular stomatitis virus (VSV) replicate selectively in transformed cells and exert impressive oncolytic abilities in murine tumour models. Interestingly, in some tumour models, complete tumour cures can only be obtained by administering multiple intravenous doses of virus, indicating that there must be barriers that limit the ability of a single dose of virus to eliminate a tumour. The goal of the current research was to examine the intravenous delivery of IFN inducing VSV to subcutaneous tumours, as well as subsequent spread and tumour killing activity.
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36

Xiong, Chiyi. "Asymmetric synthesis of conformationally and topographically constrained amino acids as peptidomimetics: An approach to design and synthesis of opioid receptor selective ligands." Diss., The University of Arizona, 2003. http://hdl.handle.net/10150/280393.

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As part of continuing efforts to obtain backbone and side chain conformationally constrained, novel amino acids,¹⁻⁷ we have successfully developed the asymmetric synthesis of β-phenyl-substituted cysteine, tryptophan, and serene derivatives. In this approach, the key intermediate, enantiomerically pure 3-phenylaziridine-2-carboxylic ester, was prepared from an α, β-unsaturated ester by employing the Sharpless asymmetric dihydroxylation. The aziridine was treated with 4-methoxybenzylthiol, indole, and acetic acid to give β-phenyl-substituted cysteine, tryptophan, and serine, respectively, in a
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37

Bonner, Grady Gregg 1965. "Synthesis, pharmacology, and structural analysis of opioid peptides: Cyclic somatostatin analogs which include unusual amino acids with conformationally restricted side-chain groups." Diss., The University of Arizona, 1997. http://hdl.handle.net/10150/282318.

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This work relates the activities of Somatostatin-derived opioid peptides to their 3-dimensional structures. Due to the flexability of peptides, they adopt multiple conformations. This flexibility leads to ambiguity in the development of structure-activity profiles. Here flexibility is reduced by incorporation of amino acids with conformationally restricted side-chain groups. These groups are restricted to certain topographies by cyclization or biased through substitution at the beta carbon. The opioid activities of these peptides are determined by brain binding radioligand competition assay, i
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38

Christou, Marie-Grace. "Conditionally activated therapeutics for the treatment of hepatitis C." Thesis, University of Ottawa (Canada), 2004. http://hdl.handle.net/10393/26609.

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Hepatitis C virus (HCV) is the etiologic agent responsible for the majority of cases of non-A, non-B hepatitis. It is estimated that 2% of the world's population is infected with hepatitis C with roughly 75% of infections progressing into a chronic state. Current interferon therapy is largely ineffective against chronic Hepatitis C due to the induction of interferon-resistance by HCV. The underlying mechanisms for resistance to interferon therapy have been widely studied and documented and as is the case in interferon resistant malignancies, there is some evidence that HCV infected cells are m
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39

Lalovic, Aleksandra. "Genetic studies of suicidal behaviour : investigation of genes involved in the serotonergic system and cholesterol metabolism." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=79022.

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Substantial evidence has accumulated indicating that a genetic predisposition underlies suicidal behaviour, and that the mediating mechanism may involve decreased serotonergic activity and/or low serum cholesterol level. Most association studies have focused on genes involved in the serotonergic tophan hydroxylase (TPH) gene has been extensively examined and conflicting findings have been reported. The meta-analysis presented here was conducted to clarify the role of the TPH gene in suicidal behaviour. No overall association between the TPH gene and suicidal behaviour was found. A shift
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40

Murphy, Lise. "Regulation of human parainfluenza virus type 3 fusion protein expression." Thesis, University of Ottawa (Canada), 2004. http://hdl.handle.net/10393/26723.

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Human parainfluenza virus type 3 (HPIV3) is an enveloped, negative-strand, non-segmented RNA virus. HPIV3 is a human respiratory pathogen that primarily causes diseases such as croup, bronchiolitis and pneumonia in children. The virus has two glycoproteins that allow it to interact with host cells, the receptor binding protein hemagglutinin-neuraminidase (HN) and the fusion protein (F), which enables the virus to enter the cell by fusion of the viral envelope to the target cell plasma membrane. This research was initiated with the goal of determining mechanisms by which HPIV3 regulates the exp
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Lawson, Kathryn René. "Catabolism as a mechanism of polyamine detoxification." Diss., The University of Arizona, 1998. http://hdl.handle.net/10150/288919.

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Maintenance of optimal polyamine pool levels is critical for cell survival. Intracellular polyamine depletion is usually cytostatic, whereas unregulated polyamine accumulation can result in cytotoxicity. The purpose of this work was to examine the importance of polyamine depletion in cell survival, either through increased polyamine catabolism or decreased polyamine synthesis. The polyamine analogue CHENSpm, which induces apoptosis in several cell lines, was used to examine the role of polyamine catabolism in cell survival. The susceptibility of Chinese hamster ovary cells and HCT 116 human co
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42

Hahn, Mary Kathryn. "Exploring the Contribution of the Anti-Oxidant SOD1 to the Adaptation of Cancer Cells to Oxidative Stress Conditions." Thesis, Icahn School of Medicine at Mount Sinai, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=1547950.

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<p> Cancer cells are characterized by elevated ROS levels, which provide these cells with a distinct survival advantage, promoting proliferation, invasion, and resistance to apoptotic stimuli. In order to maintain ROS below a critical threshold that would otherwise result in death, cancer cells have appropriately adapted their anti-oxidative machinery. Here, I studied superoxide dismutase 1 (SOD1) as a potential contributor to cancer cell survival under conditions of high oxidative stress. I determined that SOD1 is up-regulated in a majority of cancer cells in which the activity of another dis
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43

Liu, Jane J. "Proteoglycans of the human intervertebral disc." Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=68204.

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The composition and heterogeneity of human intervertebral disc proteoglycans from different aged individuals were investigated. (1) The glycosaminoglycan content in the nucleus pulposus was greater than that in the annulus fibrosus at all ages. Glycosaminoglycan content increased from the infant to the young adult, and then decreased from the young to the mature adult. (2) Disc contained a higher content of hyaluronate than articular cartilage at all ages. (3) Proteolytically modified LP3 was predominant in the disc. (4) Very low link protein concentrations were observed in adult disc proteogl
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Sebastiani, Giovanna. "Genetic and functional dissection of resistance to gram-negative infection in wild-derived mice." Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=37833.

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Infectious diseases continue to be one of the leading causes of morbidity and mortality in the world. Infection of mice with Salmonella typhimurium causes a systemic disease reminiscent of human typhoid fever and constitutes one of the best-described models of infectious disease.<br>We show that wild-derived Mus musculus molossinus (MOLF/Ei) mice are extremely susceptible to infection with S. typhimurium, despite resistance alleles at known Salmonella-susceptibility loci. To identify the genes responsible for the innate susceptibility of MOLF/Ei mice, we performed a genome-wide scan using a pa
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Gradi, Alessandra. "Translational control in eukaryotes : discovery of a novel human eukaryotic translation initiation factor and its role in the shutoff of host cell protein synthesis following entero- and rhinovirus infections." Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=36809.

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The eukaryotic initiation factor (eIF) 4F complex is composed of three polypeptides: eIF4A, eIF4E and eIF4G. eIF4E is the cap-binding subunit; eIF4A is the component which exhibits RNA helicase activity and is thought to unwind the secondary structure present at the 5' leader sequences of mRNAs; eIF4G serves as a scaffold to bring together eIF4E, eIF4A, with eIF3, thus recruiting the mRNA to the 40S small ribosomal subunit. Here, I describe the identification and characterization of a novel homologue of eIF4G that we have termed eIF4GII. We renamed the previously discovered polypeptide, eIF4GI
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46

Kontolemos, Mario. "Chemokine receptors on airway epithelial cells and their potential role in regulating mucin production." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=78396.

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Chemokines, small molecular weight chemotactic cytokines, are produced mostly by airway epithelial cells and are known to play an instrumental role in the recruitment of inflammatory cells. Studies have documented a dramatic increase in the chemokine levels in the airways of asthmatics and many other studies have shown the induction of these chemokines by cytokines and growth factors in airway epithelial cells in vitro. Thus, given the high levels of chemokines in asthmatic airways and abundant evidence supporting strong interactions between cytokines and epithelial cells, we hypothesiz
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47

Srikumar, Ramakrishnan. "Topology of porin, the major outer membrane protein of Haemophilus influenzae type b." Thesis, McGill University, 1995. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=40261.

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Haemophilus influenzae type b (Hib) is a Gram-negative bacterium that causes meningitis in infants. A protein called porin of 341 amino acids, M$ rm sb{r}$ 37,782 daltons, is located in the outer membrane of Hib and allows for the diffusion into the periplasmic space of small solutes up to a molecular mass of 1400 daltons.<br>Based on parameters of hydrophilicity and amphiphilicity a model for Hib porin was generated. The model proposed an organization of sixteen anti-parallel $ beta$-strands that traverse the outer membrane, eight long loops that connect the $ beta$-strands on one side and sh
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Boismenu, Richard. "A molecular approach for elucidating biological functions of alpha-fetoprotein." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=41049.

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Alpha-fetoprotein (AFP) is a major plasma protein in the fetus and newborn. Extensive studies in both human and murine systems defined a selective down-regulatory role for AFP on certain types of immune reactions in vitro. Direct evidence was obtained in experimental models of autoimmune disease showing that mouse and human AFP can, in a predictable fashion, influence in vivo immune parameters. However, attempts to define the molecular basis of the immunoregulatory functions of AFP have until now been handicapped by the lack of an appropriate consistent source for pure AFP in quantities suitab
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Alizadeh-Khiavi, Kamel. "Amyloid enhancing factor activity is associated with ubiquitin." Thesis, McGill University, 1991. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=70161.

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Amyloidosis is a chronic degenerative disease that is characterized by the deposition of fibrous $ beta$-pleated amyloid proteins in various soft tissues and organs (Glenner 1980, Kisilevsky 1983 & 1987). Sporadic form of Alzheimer's disease is one of the most common forms of systemic amyloidosis, with the current prevalence of approximately 4 million cases in the United States and 6 to 8 million cases worldwide (Kisilevsky 1987, Coleman 1990).<br>Amyloidosis can be experimentally induced in animals. In the inflammation-associated mouse model of amyloidosis, the preamyloid phase, which usually
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Lepage, Pierre 1962. "Activation of the mouse mdr3 gene in multidrug resistant derivatives of the lymphoid tumor P388." Thesis, McGill University, 1995. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=28822.

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In independently derived drug resistant sublines of the mouse lymphoid tumor P388, multidrug resistance (MDR) is associated with the exclusive overexpression of the mdr3 gene, which occurs either from a single copy gene (P388/VGR-10) or after gene amplification (P388/ADM-2). The mechanism underlying mdr3 overexpression in these cells was investigated. Nucleotide sequence analysis revealed the presence of several putative cis-regulatory elements in the genomic region overlapping the transcription start site of mdr3. However, the 5$ sp prime$ end of mdr3 mRNAs was shown to be altered in the MDR
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