Dissertations / Theses on the topic 'NO receptor'
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Ott, Thomas Ruthard. "Receptor activation in GNRH receptors." Doctoral thesis, University of Cape Town, 2000. http://hdl.handle.net/11427/2700.
Full textZHANG, SHENGWEN. "THE OPIOID RECEPTOR-LIKE RECEPTOR ORL1: SIGNALING AND INTERACTION WITH OPIOID RECEPTORS." University of Cincinnati / OhioLINK, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1029419843.
Full textZhang, Shengwen. "The opioid receptor-like receptor ORL1 signaling and interaction with opioid receptors /." Cincinnati, Ohio : University of Cincinnati, 2002. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=ucin1029419843.
Full textOliveira-Giacomelli, Ágatha. "Papel dos receptores purinérgicos em modelo animal de doença de Parkinson." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-26112018-074709/.
Full textParkinson\'s disease is a highly disabling and prevalent disease. Little is known about its etiology and the current treatments consist in the reduction of the symptoms, since there is no known method to reverse the dopaminergic neurons deficit observed in patients. Purinergic receptors are found throughout the central nervous system, not only in the adult individual but also at different stages of embryonic development, and are involved in proliferation and differentiation. This work investigated the role of purinergic receptors in the animal model of Parkinson\'s disease induced by 6-OH dopamine (6-OHDA) injection and consequent death of dopaminergic neurons of the nigrostriatal pathway. Patterns of purinergic receptors gene expression after the lesion and subsequent modulation were analyzed. We observed altered gene expression of P2X7 and P2Y6 receptors within 5 weeks of injury. The use of the P2X7 receptor antagonist Brilliant Blue G (BBG) induced the regeneration of the nigrostriatal pathway and treatment with P2Y6 receptor antagonist MRS2578 prevented the death of the neurons. Since these effects were accompanied by the inactivation of microglial cells, it is assumed that the control of neuroinflammatory milieu caused by the 6-OHDA injection is the main cause of the antiparkinsonian effect observed by the treatment with BBG and MRS2578. In addition, transplantation with neural precursor cells was not able to reverse the hemiparkinsonian behavior of injured animals. Although concomitant use with BBG improved cell engraftment, it appears that this effect is due to BBG per se, since treatment with only this P2X7receptor antagonist was more effective. In general, modulation of purinergic receptor activity showed to be a promising tool in the research of cure and understanding of the molecular bases of Parkinson\'s Disease.
Sokolovski, Alexandra. "Sigma-1 Receptors Modulate NMDA Receptor Function." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/23652.
Full textChakraborty, Raja. "Structure function studies on prostanoid receptors: Thromboxane A2 receptor (TP) and Prostacyclin receptor (IP)." Elsevier Ltd, 2011. http://hdl.handle.net/1993/23744.
Full textJiang, Ning. "Kinetic analysis of Fcγ receptor and T cell receptor interacting with respective ligands." Diss., Georgia Institute of Technology, 2005. http://hdl.handle.net/1853/26716.
Full textWeaver, Richard Emyr. "Ligand-receptor interactions at the parathyroid hormone receptors." Thesis, University of Leeds, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.531595.
Full textBjörnström, Linda. "Molecular mechanisms of alternative estrogen receptor signaling /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-509-3/.
Full textChu, Kwun Pok. "Computational studies of nuclear receptors : estrogen receptors, glucocorticoid receptors, and farnesoid X receptor." HKBU Institutional Repository, 2009. http://repository.hkbu.edu.hk/etd_ra/1058.
Full textPaula, Karina de. "Estudos estruturais de novos ligantes sintéticos do receptor PPARY." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/76/76132/tde-29012018-102600/.
Full textNuclear receptors comprise a superfamily of structurally-related regulated intracellular proteins capable of recognizing specific DNA sequences and regulating the transcription of target genes responding to metabolic signals, hormones and other regulatory molecules integrating many signaling pathways. Peroxisome proliferator-activating receptors (PPARs) are nuclear receptors that govern the transcription of several genes involved primarily in fatty acid and energy metabolism. Activation of PPARY has a broad aspect of biological functions, regulating metabolism, reducing inflammation, influencing immune cell balance, inhibiting apoptosis and oxidative stress, and improving endothelial function. These effects appear to be beneficial not only in diabetes and atherosclerosis, but also in several other conditions. PPARY agonists are used as insulin sensitizers for the treatment of diabetes II, being a molecular target of the thiazolidinediones drugs. A number of severe side effects associated with the use of drugs of this class and the importance of PPARY in glucose metabolism and insulin sensitization, the present work is justified as an effort to advance the understanding of the interaction between synthetic ligands with the PPARY receptor and proposing safer and more effective molecules for the maintenance of euglycemic levels. The expression, purification, followed by crystallographic studies in five ligands selected from docking steps previously performed by our Molecular Biotechnology group of the Physics Institute of São Carlos. The crystallization assays of PPARY complexed to synthetic ligands resulted in two crystallographic structures that exhibited a conformation in which the ligands did not interact directly in helix 12 as described for total PPARY agonists, adopting characteristics of partial agonists. These ligands showed hydrophobic interactions that stabilize the β-ribbons. This set of structural information presented in this work for the PPARY was of great value for the understanding of the interactions that this receptor is able to make in the presence of a ligand, besides that they could be useful in the development of new selective modulators of the PPARY similar to that are already on the market, but with reduced side effects.
Meira, Guilherme Louzada Silva. "Analíse da expressão do receptor olfativo M93 em sistemas heterólogos." Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-31082016-115408/.
Full textThe mammalian olfactory system can discrim inate thousands of odorants present in the environrnent. Approximately 1000 different olfactory receptors (ORs) are expressed in the olfactory epithelium (OE) of the nose. The ORs detect odorants and transmit the resulting signals to the olfactory bulb (OB) of the brain. ORs belong to the G-protein-coupled receptor (GPCR) super family and have seven putative transmembrane domains. For unknown reasons, the ORs are retained in the endoplasmatic reticulum when expressed in heterologous mammalian cell lines. Probably accessory proteins are required for the sorting of the ORs to the cell surface. In the present work, we used the OR M93 to study the mechanisms of OR expression. Our goals were to (1) construct an expression vector for OR M93 in fusion with GFP in yeast and (2) to identify proteins expressed in the mouse OE that interact with ORs. The analysis by fluorescence microscopy suggested that OR M93 in fusion with GFP was retained in the endoplasmic reticulum (ER) of yeast. We used the yeast two-hybrid system to screen a mouse OE cDNA library with a bait corresponding to the N-terminal region ofthe üR M93. Four potential candidates were identified: HLA-B associated transcript 3 (BAT-3/Scythe), transmembrane 4 superfamily (CD82 member), transmembrane 4 superfamily (TSPN-3 member) and syndecan (SDC2). In situ hybridization analysis suggests that OAP-l protein represents the best candidate for interaction with OR M93. We suggest the OAP-l protein could be an accessory protein required for the sorting of the ORs to the cell surface in heterologous cell lines.
MacPhee, Ian J. "Receptor transmodulation in the p75 neurotrophin receptor/trkA receptor system." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0034/NQ64611.pdf.
Full textPettersson, Katarina. "Signal transduction via estrogen receptors (ERs) and estrogen receptor-related receptors (ERRs) /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4184-X/.
Full textDucheix, Simon. "Rôle du Liver X Receptor dans la régulation transcriptionnelle de la lipogenèse." Thesis, Toulouse, INPT, 2013. http://www.theses.fr/2013INPT0034/document.
Full textIn mammals, lipogenesis or de novo fatty acid synthesis plays an essential part in energy homeostasis. It is particularly active in the liver. The Liver X Receptor (LXR) is a class II nuclear receptor that regulates the expression of important genes involved in this pathway. In the liver, LXR directly controls the expression of lipogenic genes and also the expression of transcription factors such as SREBP-1c and ChREBP required for the hepatic response to insulin and glucose respectively. Natural ligands for LXR are oxysterols, which are oxygenated derivatives of cholesterol. Therefore, LXR is primarily considered and known as a cholesterol sensor. In this work, we were interested in the role of LXR in the transcriptional control of hepatic lipogenesis in vivo in response to distinct stimuli: pharmacological agonists, gut inflammation and changes in diet composition. Through a pharmacological study, we highlighted the cross-talk between LXR signaling and the regulation of the Peroxisome Proliferator Activated Receptor (PPAR ). We have also evidenced that experimentally induced colitis induces a potent inhibition of hepatic lipogenesis. Finally, we have shown that LXR is involved in the regulation of lipogenesis in response to essential fatty acid deficiency and to high fructose
Tran, Thuyet Van. "Modulation of Folate Receptor-alpha by Glucocorticoid Receptor and Progesterone Receptor." University of Toledo Health Science Campus / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=mco1104777244.
Full textTran, Thuyet Van. "Modulation of folate receptor-[alpha] by glucocorticoid receptor and progesterone receptor." Connect to full-text via OhioLINK ETD Center, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=mco1104777244.
Full text"In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Medical Sciences." Major advisor: Manohar Ratnam. Includes abstract. Document formatted into pages: iii, 293 p. Title from title page of PDF document. Includes bibliographical references (p. 175-281).
Vestergaard, Henrik Tang. "Diversity in competitive ligand-receptor interactions : electrophysiological studies of ligand-receptor interactions at native and recombinant GABAA receptors /." Cph. : Department of Pharmacology, The Danish University of Pharmaceutical Sciences, 2003. http://www.dfh.dk/phd/defences/henriktangvestergaard.htm.
Full textGandía, Sánchez Jorge. "Oligomerización del receptor A2A de adenosina: interpretando el receptorsoma." Doctoral thesis, Universitat de Barcelona, 2013. http://hdl.handle.net/10803/134352.
Full textG protein-coupled receptors (GPCR) consitute the biggest family of membrane receptors. Since they detect a large and diverse number of signals, they have a growing pharmacological interest. Furthermore, the interactions between different types of GPCR form oligomeric complexes that show different biochemical properties than the protomers they are made of. Different aspects of these interactions have been studied in this Doctoral Thesis, focusing the experiments around the adenosine A2A receptor, being adenosine an important modulator of the Central Nervous System. Firstly, by means of the combination of the bioluminescent ressonant energy transfer (BRET) and bimolecular fluorescent combination (BiFC) techniques we have detected in vivo that A2AR is able to form oligomers made up of more than two protomers, leading to homomeric complexes (Gandía et al., 2008) as well as others of heteromeric nature. In this latter case, we have studied the oligomer of A2AR with the dopamine D2 and glutamate metabotropic 5 receptors (Cabello et al., 2009). Following these experiments, we have applied a modified version of the yeast two-hybrid technique set up for membrane proteins (MYTH) in order to detect A2AR-interacting proteins. Thanks to this approach, we have found new potential interactors, and among them an orphan GPCR has stood out: GPR37. By means of physical and functional techniques in cell culture and animal models we have validated the A2AR/GPR37 interaction and we have demonstrated that the presence of GPR37 modifies the functionality of A2AR. Finally, in order to better understand the rather less studied structural characteristics of GPR37, we have studied its C-terminal tail. Thus, we have observed the presence of a cysteine-rich region that regulates the trafficking of the receptor to the plasma membrane. Furthermore, this cystein-rich domain modulates the GPR37-dependent endoplasmic reticulum stress, as well as the induction of apoptotic pathways (capase-3 activity) (Gandía et al., 2013).
Tchetchelnitski, V. "Regulation of neurotrophin receptors by receptor-type protein tyrosine phosphatases." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1310477/.
Full textLee, ChangWoo. "CIS- AND TRANS-ACTIVATION OF HORMONE RECEPTORS: THE LH RECEPTOR." Lexington, Ky. : [University of Kentucky Libraries], 2003. http://lib.uky.edu/ETD/ukybiol2003d00082/changwoo.pdf.
Full textTitle from document title page. Document formatted into pages; contains xix, 74p. : ill. Includes abstract. Includes bibliographical references (p. 62-72).
VERGASSOLA, MATTEO. "Presynaptic release regulating metabotropic receptors: dimerization and receptor cross talk." Doctoral thesis, Università degli studi di Genova, 2020. http://hdl.handle.net/11567/993002.
Full textNascimento, Alessandro Silva. "Interações dos receptores nucleares com seus ligantes: Estudos estruturais do receptor de hormônio tireoidiano, do receptor de mineralocorticóide e do receptor ativado por proliferadores peroxissomais." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/76/76132/tde-13032009-124546/.
Full textNuclear receptors are a superfamily of hormone-regulated transcriptional factors. This superfamily includes, for example, the receptor for thyroid hormone, estrogen, androgen, gluco and mineralocorticoid. In this work, we used structural biology and bioinformatic tools to study the interactions between some members of the nuclear receptor superfamily and its respective ligands. We showed by the analysis of the crystal structures of both thyroid hormone receptor isoforms bound to the thyromimetic Triac that the enthalpic components visible in the structures do not explain the ligand selectivity. Molecular dynamics simulation data confirmed later that the hormone selectivity has an important entropic component. Using the molecular dynamics simulation, we studied, in a second stage, the interaction between the human mineralocorticoid receptor bound to aldosterone, cortisol, spironolactone and cortisone and also simulated the effects of the mutations S810L, known to convert the antagonist properties of spironolactone and cortisone in an agonist activity. The analysis of the simulations showed a similar profile in hydrogen bonds established between the wild type receptor bound to cortisol and aldosterone. Cortisone looses an important hydrogen bond with Asn770 because of the insertion of a carbonyl group in the 11 position and shows a decreased binding potential energy. Spironolactone loses the same interaction but has an increased number of van der Waals contacts because of the insertion of a tioacetyl group in the 7 position. The mutant S810L simulated in complex with cortisol, cortisone and spironolactone showed that the mutation do not interfere with the hydrogen bond profile established between the receptor and the ligands but changes the mobility of a region in the receptor previously proposed as a ligand dissociation route. Ligand unbinding simulations through steered molecular dynamics (SMD) confirm that aldosterone and cortisol unbind differentially and the mutation S810L alters the unbinding profile. We then propose that the mutation changes the kinetics of ligand association/dissociation without changing the profile of the interactions established in the equilibrium. In the last stage, we used the experimentally determined structural model of the peroxissome proliferator-activated receptor gamma to search for novel ligands using the molecular docking technique. For this work, we used a database containing about 1 million compounds. Among those, four compounds were selected after the docking computation and experimentally tested. One of these compounds was found to be active in the receptor, showing about 60-70% of the agonistic activity of rosiglitzone, a known PPARg total agonist.
Joseph, Christine G. "Design, synthesis, and characterization of peptides and peptidomimetics for mouse melanocortin receptors." [Gainesville, Fla.] : University of Florida, 2004. http://purl.fcla.edu/fcla/etd/UFE0008368.
Full textTypescript. Title from title page of source document. Document formatted into pages; contains 202 pages. Includes Vita. Includes bibliographical references.
Pires, Luis Antonio. "Efeitos da quimioterapia neoadjuvante sobre os receptores de lipoproteínas no tecido tumoral em pacientes com carcinoma da mama localmente avançado." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/5/5139/tde-02092010-173950/.
Full textProliferative tumor cells present a high expression of LDL receptors due to accelerated mitosis rates which takes to increased need of lipids internalization for building new membranes. Upregulation of LDL receptors may be used as a gate to deliver anticancer drugs to tumor tissues using lipoproteins or artificial nanoemulsions as vehicle. This study investigated the effects of conventional chemotherapy on the expression of LDL and LRP-1 receptors in 16 patients with breast cancer in stage II or III who were not candidates to conservative surgery and with indication of neo-adjuvant chemotherapy. Expression of LDL and LRP-1 receptor was evaluated by immunohistochemistry in normal and neoplastic breast tissue before and after chemotherapy. For absence of tumor in the surgical fragments, 4 patients who presented complete response to chemotherapy were excluded from this analysis. In relation of LDLR, the expression in neoplastic tissue was higher than in normal tissue in 8 of 11 patients. After chemotherapy, LDL receptor expression diminished in 6, increased in 4 and unchanged in 2 patients. Expression of LRP-1 in tumor tissue was higher in 4 of 12 patients when compared to normal tissue. After chemotherapy, the expression of LRP-1 diminished in 6, increased in 4 and showed no difference in 2 patients. These data show that the chemotherapy effects on the tumor expression of LDL receptors were very heterogeneous. The diminution of the receptor expression is not the post-chemotherapy pattern, allowing the use of drug carrier systems that target cancer cells via the LDL receptor pathway. These results may contribute for the design of future clinical assays
Cordeiro, Raquel Cristina Tancsik. "Striae distensae : estudo clinico e da expressão de receptores de estrogeno, androgeno e glicocorticoide por Western blot." [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308409.
Full textTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: A estria atrófica cutânea ou striae distensae (SD) é uma afecção muito comum, sendo causa freqüente de procura por consultas dermatológicas. Ainda que não representem qualquer risco à saúde física, produzem impacto emocional e induzem busca por tratamentos trabalhosos, caros e dolorosos e, com freqüência, inadequados. Além disso, o surgimento de striae distensae pode refletir alteração do tecido conjuntivo e indicar condições patológicas locais e sistêmicas. Alguns autores descrevem as estrias cutâneas como uma condição de estiramento ou distensão da pele, com perda ou ruptura das fibras elásticas na região acometida. Entretanto, vários autores observam que as estrias não surgem com frequência sobre a pele acima de tumores abdominais, ascites, hemorragias extensas ou grandes hérnias. Atualmente admite-se que sua etiopatogenia é multifatorial, englobando aspectos mecânicos, bioquímicos e genéticos. No entanto, considerando-se a multiplicidade de fatores envolvidos, a literatura é divergente e inconclusiva. Portanto, através do estudo de fatores clínicos associados às SD e dos receptores hormonais (estrógeno, andrógeno e glicocorticóide), pretendeu-se entender melhor a participação dos hormônios na fisiopatogênese das estrias. Para o estudo clínico foram selecionados pacientes com queixa de estrias cutâneas e a comparação foi feita com grupo controle de número semelhante, atendido aleatoriamente por outras queixas no Ambulatório Geral de Dermatologia do HC, FCM/UNICAMP. O estudo da expressão dos receptores hormonais foi realizado por Western blot em oito amostras de pele de estrias recentes, com menos de um ano de evolução, comparando com a avaliação de pele sem lesão de região palpebral de oito pacientes que se submenteram a blefaroplastia. Observou-se que fatores como adolescência, gestação e obesidade estão significativamente relacionados ao surgimento das SD. Constatou-se ainda que a idade materna jovem e o ganho ponderal durante a gestação são importantes fatores associados ao desenvolvimento das lesões. Além disso, a localização das lesões correlaciona-se ao fator causador das estrias. Em relação ao estudo dos receptores hormonais, observou-se que na SD recentes há duas vezes mais expressão de receptores de estrógeno e 1,7 vezes mais expressão receptores de andrógeno e glicocorticóide. Alguns autores interpretam SD como cicatrizes. Após influência hormonal, haveria uma reação inflamatória inicial que determinaria a destruição de fibras elásticas e colágenas. O processo seria seguido de regeneração das fibras, um fenômeno de remodelação dinâmica,ou seja, um balanço entre síntese de colágeno e sua quebra, o qual reestrutura o tecido para acomodar as forças que agem sobre ele, resultando na formação das SD. O balanço entre a expressão de receptores de estrógeno, andrógeno e glicocorticóide poderia induzir as modificações específicas da matriz extracelular, o que levaria a esse fenômeno de remodelação. Em concordância com outros estudos, observamos que as estrias surgem em situação de grande modificação sistêmica, como adolescência e gestação. Através das observações morfológicas e moleculares, nota-se que as SD estão correlacionadas com intensas alterações do tecido conectivo. Os resultados mostram-se relevantes e representam mais um passo na compreensão do mecanismo fisiopatológico da estrias cutâneas e abrem espaço para novas linhas de pesquisa, relacionadas às SD e a outras alterações do tecido conectivo.
Abstract: Stretch marks or striae distensae (SD) are a very common condition which often results in persons searching dermatological treatment. While not presenting any risk to one's physical health, the emotional impact often induces those so affected to demand medical treatments, which are often laborious, expensive and painful, and frequently ineffective. Beyond this, the appearance of SD may indicate other alterations in conjunctive tissues, including both local and systemic pathologies. Some authors described cutaneous strias as a condition of stretching or distension of the skin which results in the loss or rupture of elastic fibers in the affected areas. However, many authors have also observed that SD do not occur frequently associated with abdominal tumors, ascites, extensive hemorrhages or large hernias. Current medical opinion is that its etiopathogenesis is multifactored, englobing mechanical, biochemical and genetic aspects. Nevertheless, in view of the multiplicity of the factors involved, the literature is divergent and inconclusive. This study was proposed to look for better understanding of the role played by hormones in the physiopathology of SD studying clinical factors associated with SD and hormone receptors (estrogen, androgen and glycocorticoid). Patients complaining of SD were selected for inclusion in this clinical study, and comparisons were made with a control group of a similar number of persons who had been treated for other medical conditions at the General Ambulatory Dermatology Care Facility at HC, FCM/UNICAMP. The expression of hormone receptors was undertaken of the Western Blot testing of recent skin striations, in comparison with lesion-free skin taken from the eyelids of patients who had undergone blepharoplasty. The study revealed that factors such as adolescence, pregnancy and obesity are significantly related to the appearance of SD. It was further established that age (the younger the gravid, the greater the possibility of SD) and significant weight gain during pregnancy are important factors associated with the development of SD lesions. In addition, there was a positive correlation with the location of the lesions. In relation to the study of hormone receptors, it was observed that recently-formed SD have two times more expression of estrogen receptors, and 1,7 times more expression of androgen and glycocorticoid receptors. Some authors classify SD as scars. Under hormonal influence, there is an initial inflammatory reaction which results in the destruction of elastic fibers and collagens. This is followed by the regeneration of the destroyed fibers, a phenomenon of dynamic remodeling, a balance between the synthesis and destruction of collagens, which restructures the tissue in order to accommodate the forces acting upon it, resulting in the formation of SD. The balance between the expression of estrogen, androgen and glycocorticoid may elicit the specific modifications of the extracellular matrix which leads to the phenomenon of remodalation. In agreement with other studies, we observed that the strias arise under conditions of significant system modification, such as adolescence and pregnancy. The observation of morphological and molecular changes showed that there is a correlation between SD and with intense alterations in connective tissue. The results of this study are relevant and represent an important step in the understanding of physiopathological mechanisms in stretch marks, opening new horizons for new directions in research of SD and other alterations in connective tissues as well.
Doutorado
Clinica Medica
Doutor em Clínica Médica
Plouffe, Bianca. "Comprehensive Model of G Protein-coupled Receptor Regulation by Protein Kinase C: Insight from Dopamine D1 and D5 Receptor Studies." Thesis, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/20577.
Full textShi, Haifeng. "Structural studies on GABAA̳ receptor and glycine receptor /." View Abstract or Full-Text, 2002. http://library.ust.hk/cgi/db/thesis.pl?BICH%202002%20SHI.
Full textOn t.p. "A̳" is subsript. Includes bibliographical references (leaves 160-177). Also available in electronic version. Access restricted to campus users.
Mayuzumi, Daisuke. "Role of receptor ubiquitination in erythropoietin receptor signaling." Diss., University of Iowa, 2010. https://ir.uiowa.edu/etd/854.
Full textSallander, Eva Jessica. "The mechanism of G protein coupled receptor activation: the serotonin receptors." Doctoral thesis, Universitat Pompeu Fabra, 2011. http://hdl.handle.net/10803/77901.
Full textOne of the main questions in G protein coupled receptors (GPCRs) molecular pharmacology is to understand the structural arrangements of the seven transmembrane (TM) helices that occur to stabilize either the ground state (Rg) or different active states (R*) of the receptors. In order to understand the mechanism that shift the equilibrium of the ensemble to an active R* state models of the inactive and the active state of three serotonin receptors (5-HT4, 5-HT6, and 5-HT7) were built based on the latest information from X-ray crystallography. The resulting models were mainly used to understand the interaction between a ligand and its receptor and the mechanism of action. With the help of pharmacological and chemical data these models and complexes were improved and evaluated. These findings may prove valuable for structural based drug discovery efforts and facilitate the design of more effective and selective pharmaceuticals.
Castro, Diogo Sampaio e. "Functional studies on the orphan receptor Nurr1 and related retinoid receptors /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4608-6/.
Full textMalouitre, Sylvanie DeÌsireÌe Marie. "Glucocorticoid receptor function, interactions with oestrogen receptors and a steroid inhibitor." Thesis, Queen Mary, University of London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.413737.
Full textPringle, Ashley Ker. "Modulation of cerebellar GABAâ†A receptors by benzodiazephine receptor inverse agonists." Thesis, University of Southampton, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295917.
Full textBjörnberg, Flemming. "Processing of TNF-receptors to soluble receptor forms in myeloid cells." Lund : Dept. of Hematology, Lund University, 1998. http://catalog.hathitrust.org/api/volumes/oclc/39176479.html.
Full textSpyridon, Michael. "Study of the role of the nuclear receptors peroxisome proliferator-activated receptor y (PPATy) and liver X receptor (LXR) in platelets." Thesis, University of Reading, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.541958.
Full textKiss, Debra Lois. "Regulation of the Chemokine Receptors CXCR4, CXCR7 , and the Androgen Receptor in Prostate Cancer." Thesis, Griffith University, 2013. http://hdl.handle.net/10072/367690.
Full textThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
Eskitis Institute for Cell and Molecular Therapies
Science, Environment, Engineering and Technology
Full Text
Szymanski, de Toledo Maria Carolina 1982. "Expressão dos receptores de estrógeno, progesterona, andrógeno e HER2 no câncer epitelial de ovário : Expression of estrogen, progesterone, androgen and HER2 receptors in the epithelial ovarian cancer." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310530.
Full textDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Introdução: o câncer de ovário é comumente diagnosticado em estágios avançados, sendo atualmente a neoplasia ginecológica de maior letalidade. As pesquisas têm direcionado esforços na tentativa de descobrir novos fatores prognósticos e métodos terapêuticos. Muitos trabalhos estudam a expressão dos receptores de esteróides (dentre eles, estrógeno (RE), progesterona (RP) e andrógeno (RA)) e HER2 (receptor estimulador de crescimento epitelial - subtipo 2) como fatores prognósticos e associados à resposta terapêutica, apresentando; entretanto, resultados conflitantes. Até onde conhecemos, não há estudos desta natureza no Brasil. Objetivo: Correlacionar à expressão dos RE, RP, RA e HER2 aos fatores clínico patológicos, ao intervalo livre de doença e à sobrevida nos cânceres epiteliais de ovário. Material e métodos: Este é um estudo observacional de coorte retrospectiva. Foram incluídas 152 mulheres com tumores epiteliais malignos, selecionados através dos prontuários no período de 1993 a 2008, no Centro de Atenção Integral à Saúde da Mulher (CAISM) da Universidade Estadual de Campinas - UNICAMP, São Paulo, Brasil. A avaliação da expressão dos RE [subtipos alfa (RE?) e beta (RE?)], RP, RA e HER2 foram realizadas por imunoistoquímica através da construção de microarranjos de tecidos (TMA). Inicialmente, foi realizada análise uni variada da expressão dos receptores acima quanto à idade, estado menopausal, índice de massa corpórea (IMC), tipo histológico, grau histológico, estadiamento inicial de acordo com a classificação proposta pela FIGO e presença de doença residual pós-tratamento cirúrgico. Em seguida, as pacientes foram divididas em dois grupos: ausência da expressão de RE?, RP e HER2 (triplo negativo) e positividade para pelo menos um desses receptores (não triplo negativo); e, avaliadas em relação aos critérios clínicos e epidemiológicos acima. Foram, então, realizadas análises multivariadas dos padrões de expressão de RE ? e ?, RP, RA, HER2 e triplo negativo em relação a estes mesmos critérios. Por fim, análise de sobrevida multivariada foi realizada utilizando-se todos os padrões de expressão e os fatores clínicos epidemiológicos estudados. Resultados: Nas análises multivariadas, mostraram-se significativas as seguintes associações: do receptor de estrógeno alfa (ER?) com tumores de grau histológico menos diferenciado (p=0.01); do receptor de progesterona (RP) à obesidade (p= 0.01); do receptor de andrógeno (RA) com tumores do subtipo seroso (p= 0.01); do receptor de HER2 com tumores dos graus histológicos II-III (p=0.02); do subgrupo triplo negativo com tumores de grau histológico menos diferenciado (II-III) (p<0.01). Não houve associação do RE? com nenhum dos fatores estudados. Quanto à análise multivariada de sobrevida livre de doença e sobrevida global; dentre os padrões de expressão de receptores, apenas o RE? esteve associado com melhor sobrevida livre de doença (RR=0.39; 95%CI 0.17 -0.90). Conclusões: A expressão do RE? esteve mais significativamente associada a fatores clínicos de pior prognóstico. O RP esteve associado à obesidade. O RA esteve significativamente mais presente nos tumores serosos. A expressão do HER2 e a presença de tumores triplo negativo foram maiores em tumores menos diferenciados. Paradoxalmente; o RE? foi o único receptor a apresentar associação com maior sobrevida livre de doença apesar de sua relação significativa com fatores reconhecidos de pior evolução clínica. Não houve diferença estatística significativa na análise multivariada de sobrevida total e sobrevida livre de doença quanto ao grupo de tumores triplo negativo
Abstract: Introduction: Ovarian cancer is commonly diagnosed in advanced stages and currently is the most lethal gynecological malignancy. Surveys have focused efforts in an attempt to discover new prognostic and therapeutic methods. A plenty of studies investigates the expression of steroid receptors (among them, estrogen (ER), progesterone (PR) and androgen AR)) and HER2 (epidermal growth receptor stimulator - subtype 2) as prognostic factors and associated to therapeutic response, presenting, however, conflicting results. As far as we know, there are no studies of this nature in Brazil. Objective: The aim of this study was to correlate the expression of ER (subtypes ? (ER ?) and ? (ER ?), PR, AR and HER2 to clinical pathological factors, the disease-free survival and overall survival of epithelial ovarian cancers. Methods: This is a retrospective observational cohort study. The study included 152 women with malignant epithelial tumors, selected through the records from 1993 to 2008, in the Centro de Atenção Integral à Saúde da Mulher (CAISM) at the State University of Campinas - UNICAMP, São Paulo, Brazil. The expression of ER (? and ?), PR, AR and HER2 was evaluated by immuno histochemistry through tissue microarray (TMA) technique. Initially, univariate analyses were performed, evaluating the expression of each receptor mentioned above to age, menopausal status, body mass index (BMI), histological type, histological grade, initial staging as preconized by FIGO staging of ovarian tumors and presence of residual disease after surgical treatment. Then, the patients were divided into two groups: absence of the expression of ER?, PR and HER2 (triple negative) and positive for at least one of these receptors (not triple negative), and evaluated in relation to the clinical and epidemiological criteria mentioned above. Multivariate analyzes were performed with ER ?, ER?, PR, AR, HER2 and triple negative towards these same criteria. At last, multivariate survival analyses were conducted using all the patterns of receptors' expression, epidemiological and clinical factors studied. Results: In multivariate analyzes, there were the following significant associations: of the estrogen receptor alpha (ER?) with less differentiated histological grade tumors (p = 0.01); of the progesterone receptor (PR) to obesity (p = 0.01); of the androgen receptor (AR) with the serous tumors (p = 0.01); of the HER2 receptor with tumors of histological grades II-III ( p = 0.02); of the triple negative subgroup with less differentiated histological grade tumors (II-III) (p <0.01). There was no association of the ER? with any of the factors studied. In the multivariate analysis of disease-free survival and overall survival; considering the patterns of receptors' expression, only the ER? expression was associated with better disease-free survival (RR= 0.39, 95% CI 0.17 to 0.90). Conclusions: The expression of ER? was more significantly associated with clinical factors of poor prognosis. The PR was associated with obesity. The AR was significantly more prevalent in serous tumors. The HER2 expression and the presence of triple negative epithelial ovarian cancer tumors were higher in less differentiated tumors. Paradoxically, the ER? was the only receptor which showed association with better disease-free survival despite its significant relationship with recognized factors of worse clinical outcome. There was no statistically significant difference in multivariate analysis of overall survival and disease-free survival regarding to the triple negative group
Mestrado
Oncologia Ginecológica e Mamária
Mestra em Ciências da Saúde
Lüttgen, Maria. "Serotonergic receptor subtypes in learning and memory : focus on 5-HT1A, 5-HT1B and 5-HT2A receptors /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-628-6148-4/.
Full textWang, Jixin. "Bioinformatic analysis of chicken chemokines, chemokine receptors, and Toll-like receptor 21." Texas A&M University, 2006. http://hdl.handle.net/1969.1/4212.
Full textOre, Mikhail. "Neurokinin-1 receptor: neurokinin-1 receptor, purification and refolding." Doctoral thesis, Universitat Autònoma de Barcelona, 2012. http://hdl.handle.net/10803/96874.
Full textNeurokinin-1 receptor (NK1R) is a GPCR found in the central and peripheral nervous system of vertebrates, responsible for such physiological processes as pain transmission, exocrine and endocrine secretion, vasodilatation, modulation of cell proliferation and many others. NK1R antagonists could be potential analgesics and anti-depressants and may also be used for treatment of bipolar disorder, alcoholism, cancer, immune system diseases and selected infections. Spectroscopic studies and high resolution structural techniques, as NMR and crystallography, require milligram amounts of active purified receptor. One of the strategies to produce recombinant GPCRs for structural studies is an E.coli expression system. However, many GPCRs due to their toxic effect for bacterial host cell are expressed in form of inclusion bodies and require refolding. The refolding of GPCRs is a complicated task that requires screening and adjustment of buffer conditions. The first part of this work was centered on the refolding of hNK1R-366 and hNK1R-311 truncated forms expressed in E.coli inclusion bodies. To obtain properly folded receptor, we established an original on-column refolding protocol. Different spectroscopic techniques were applied to study the refolded receptor. The results obtained from CD measurements showed that hNK1R-366 refolded in DDM presents similar α-helical content as rhodopsin extracted from bovine retinas and solubilized in non-denaturing DDM micelles. In the intrinsic tryptophan fluorescence studies, at low concentrations of GuHCl we observed a blue-shift in the emission spectrum peak, typical for tryptophan in hydrophobic environment. Furthermore, the emission spectra of hNK1R-366 expressed in COS-1 cells and solubilized in DDM micelles show very similar emission maximum around 335 nm to that of the receptor refolded from the inclusion bodies, which may be indicative of proper protein refolding. The refolded in physiological buffer hNK1R-366 was prone to aggregate in about 24 hours, however, the presence of 0.05% DDM was found to stabilize the receptor. Saturation radioligand-binding assays for the refolded hNK1R-366 showed that the amount of the active receptor is about 1% of the total protein the sample. However, the binding of SP to the refolded hNK1R-366 in nanomolar range is significant and can be considered as a promising result, since until now the intents to produce any detectable amounts of functional NK1 receptor in E. coli were unsuccessful. On the other hand, we were unable to get any saturation binding curve for hNK1R-311 truncated form of the receptor, which could be explained by incorrect folding caused by the lack of 96 residues of the C-terminus of the receptor. The second part of the present study is centered on hNK1R C-terminus expression, purification and characterization to elucidate its structural properties. The C-terminus domain seems to be essential for the coupling to corresponding G protein and β-arrestin, and is essential for receptor desensitization, internalization and recycling. However, the role of this domain was underestimated by researchers for a long time and as a result very little information is known about its structure. UV and fluorescence spectroscopic studies revealed abnormal tyrosine red-shifted absorbance band at 292 nm and intrinsic tyrosine emission at 345 nm which could be attributed to ionized form of tyrosine and possibly arises from the proximity of one or more tyrosines to carboxyl groups of glutamic o aspartic residues. Based on secondary and tertiary structure prediction as well as on the results of spectroscopic studies we propose a 3D-model for hNK1R C-terminus. Th following assignment of the secondary structure was made: 25% α-helix, 27% unordered structure, 48% β-sheets and β-turns. The obtained ressults give evidence that hNK1R C-terminus is not an unordered region but has clearly defined secondary and tertiary structures which certainly are tightly related to its multiple functions.
McAinsh, Kristina. "Investigations of GABAA receptor phosphorylation and receptor-protein interactions." Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/1445690/.
Full textTorvinen, Maria. "Adenosine receptor/dopamine receptor interactions : molecular and biochemical aspects /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-298-1/.
Full textSpragg, Elizabeth. "The role of receptor phosphorylation in M3 receptor signalling." Thesis, University of Leicester, 2006. http://hdl.handle.net/2381/29955.
Full textArnatt, Christopher Kent. "DEVELOPMENT OF ANTAGONISTS TARGETING CHEMOKINE RECEPTOR CCR5 AND THE CHEMOKINE RECEPTOR CCR5 – MU OPIOID RECEPTOR HETERODIMER." VCU Scholars Compass, 2013. http://scholarscompass.vcu.edu/etd/517.
Full textSmith, Robert A. "The Role of the Steroid Nuclear Receptor Genes in Breast Cancer." Thesis, Griffith University, 2006. http://hdl.handle.net/10072/365401.
Full textThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
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Ferreira, Larissa Gorayb [UNIFESP]. "Avaliação dos polimorfismos do receptor de vitamina D (VDR) e do receptor sensor de cálcio (CaSR) em pacientes portadores de litíase renal." Universidade Federal de São Paulo (UNIFESP), 2009. http://repositorio.unifesp.br/handle/11600/9114.
Full textCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação Oswaldo Ramos
Alguns estudos identificaram uma associação entre nefrolitíase e os polimorfismos do Receptor de Vitamina D (VDR) ou do Receptor Sensor de Cálcio (CaSR). O objetivo deste estudo foi avaliar uma possível associação destes polimorfismos com a excreção de cálcio urinário (CaU) em pacientes litiásicos. O polimorfismo do VDR, detectado através da digestão com a enzima de restrição BsmI, e três polimorfismos do CaSR (G/T no codon 986, G/A no codon 990 e C/G no codon 1011), detectados através de sequenciamento direto, foram avaliados em pacientes litiásicos, sendo 100 hipercalciúricos (HCa) e 101 normocalciúricos (NCa). A frequência alélica do polimorfismo do VDR na amostra total foi: 16% BB, 49% Bb e 35% bb. A prevalência do genótipo bb foi significantemente maior nos pacientes HCa quando comparados ao grupo NCa (43 versus 27%). Em relação aos polimorfismos do CaSR, as três variantes alélicas (986S, 990G e 1011E) foram detectadas respectivamente em 5, 4 e 3% da amostra total e cinco haplótipos para os polimorfismos do CaSR foram identificados: 94% ARQ (selvagem), 3% SRQ, 1,5% AGQ, 1,0% ARE e 0,5% AGE. Nenhuma diferença estatística foi observada entre os pacientes NCa e HCa em relação à distribuição destes haplótipos do CaSR. Estes achados sugerem uma associação entre a excreção urinária de cálcio com o polimorfismo BsmI do VDR mas não com os três polimorfismos do CaSR em pacientes litiásicos.
TEDE
BV UNIFESP: Teses e dissertações
Tong, Huaxia. "Modulation of NMDA receptor activity by dopamine receptors in the rat striatum." Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/1445880/.
Full textShaffer, Hally A. "Engineering the pregnane X receptor and estrogen receptor alpha to bind novel small molecules using negative chemical complementation." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/39620.
Full textNahas, Roger I. "Synthesis and structure-activity relationship of a series of sigma receptor ligands." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/4840.
Full textThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on February 26, 2008) Vita. Includes bibliographical references.
Wacker, Douglas W. "Steroid regulation of seasonal territorial aggression in the male song sparrow, Melospiza melodia morphna /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/10625.
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