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1

Balu, Sucharitha. "Cloning and characterisation of chicken interleukin-12 and the interleukin-12 receptor." Thesis, University of Bristol, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.419213.

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2

Werner, Christoph. "Von Interleukin-12 zur p40-Zytokinfamilie Interleukin-12-unabhängige Wirkungen von p40-Zytokinen in der Infekt- und Tumorabwehr /." [S.l.] : [s.n.], 2003. http://dol.uni-leipzig.de/pub/2003-34.

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3

Werner, Christoph. "Von Interleukin-12 zur p40-Zytokinfamilie: Interleukin-12-unabhängige Wirkungen von p40-Zytokinen in der Infekt- und Tumorabwehr." Doctoral thesis, Universitätsbibliothek Leipzig, 2004. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-37550.

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Interleukin-12 (IL-12) ist ein zentrales Zytokin in der Entwicklung einer protektiven, zellulären Typ 1-Immunantwort. Es ist aus einer p40- und einer p35-Untereinheit aufgebaut. Es stimuliert NK- und T-Zellen zur Ausschüttung großer Mengen IFN-gamma und setzt so eine Typ 1-Immunantwort in Gang. Die p40-Untereinheit des IL-12 kommt auch in anderen biologisch wirksamen Verbindungen wie beispielsweise als Monomer, Homodimer oder als IL-23 (in Verbindung mit einer p19-Untereinheit) vor. Während das Homodimer in der vorliegenden Arbeit als reiner Antagonist zu IL-12 zu wirken scheint, wurden für IL
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4

Walter, Claudia. "Bestimmung der Zytokine Interleukin-1ra, Interleukin-6, Interleukin-10 und Interleukin-12 im Vaginalsekret bei Frauen mit Bakterieller Vaginose." Diss., lmu, 2004. http://nbn-resolving.de/urn:nbn:de:bvb:19-28461.

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5

Chakir, Habiba. "Role of interleukin-12 and interleukin-18 in murine immune cell regulation." Thesis, University of Ottawa (Canada), 2003. http://hdl.handle.net/10393/28980.

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Interleukin 12 plays a central role in NK cell activation and CD4 +T cell differentiation. IL-12 acts via a receptor composed of IL-12Rbeta1 and IL-12Rbeta2 subunits. IL-12Rbeta1 plays a primary role in ligand binding whereas IL-12Rbeta2 is responsible for signaling. IL-18 shares some functional activities of IL-12. However, there is a considerable amount of contradictory data in the literature regarding the requirements for IL-12 and IL-18 responsiveness. This work examined the expression of IL-12Rbeta2 on murine NK and T cells and the requirements for acquisition of IL-12/IL-18 responsivenes
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6

Swinburne, Sarah Jane. "A study of the molecular and biological characteristics of ovine interleukin-12." Title page, contents and summary only, 2000. http://web4.library.adelaide.edu.au/theses/09PH/09phs9777.pdf.

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Bibliography: leaves 172-214. Interleukin-12 (IL-12) is a heterodimeric cytokine composed of two disulphide-linked subunits, p35 and p40, which form biologically active p70. IL-12 is able to induce IFN-y production from T and NK cells, and promote the proliferation of mitogen-activated T cells. It is thought that IL-12 may be an important cytokine in the initiation and progression of allograft destruction. This thesis describes the characterisation of ovine IL-12.
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7

Rempel, Julia D. "Interleukin-12 and interleukin-10 regulation of antibody responses upon protein antigen immunization." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ41623.pdf.

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8

Athie, Morales Veronica. "Interleukin 12 signalling pathways in human T lymphocytes." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249566.

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9

Schardt, Victor. "Vergleichende Untersuchungen zur Hefepilzbesiedelung von Mundhöhle und Vagina und Bestimmung von Interleukin-4, Interleukin-10 und Interleukin-12." Diss., lmu, 2013. http://nbn-resolving.de/urn:nbn:de:bvb:19-155152.

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10

Naseer, Tanveer 1971. "In vivo expression of interleukin-12 and interleukin-13 in the pathogenesis of asthma." Thesis, McGill University, 1996. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=23925.

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IL-12 and IL-13 are recently discovered cytokines which belong to Th1 and Th2 subtypes, respectively. To further support the hypothesis that Th2-type cytokines are involved in asthma, mRNA levels for IL-12 and IL-13 were measured in bronchial biopsies from asthmatics and normal controls as well as in moderately severe asthmatics before and after corticosteroid therapy using the technique of in situ hybridization. The number of IL-13 mRNA positive cells in asthmatics was significantly higher than that found in normal controls. However, there was a significant decrease in the number of IL-12 mRN
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11

Dreisbach, Julia. "Klonierung, Expression und funktionelle Analyse von Hühner-Interleukin-12." Diss., lmu, 2005. http://nbn-resolving.de/urn:nbn:de:bvb:19-33383.

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12

Azbil, Tatiana. "Nachweis von Candida-Spezies und Bestimmung der Zytokine Interleukin-1 beta, Interleukin-1ra, Interleukin-4, Interleukin-6, Interleukin-8, Interleukin-10 und Interleukin-12 im Vaginalsekret und im Serum bei Schwangeren in Relation zum Gestationsalter." Diss., lmu, 2006. http://nbn-resolving.de/urn:nbn:de:bvb:19-57576.

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13

Tso, Hoi-wan, and 曹凱韻. "Interleukin 12P40 genetic polymorphisms and tuberculosis in Chinese." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B29246933.

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14

Wagner, Frank. "Die Bedeutung von Interleukin-12p75 und Interleukin-12p40 für die Abwehr einer Infektion mit Cryptococcus neoformans im murinen Modell." Doctoral thesis, Universitätsbibliothek Leipzig, 2004. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-37485.

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Um die Rolle von Interleukin-12p75 (IL-12p75) und Interleukin-12p40 (IL-12p40) in der Abwehr einer Kryptokokken-Infektion im Mausmodell zu untersuchen, wurden Mäuse auf 129Sv/Ev Stammhintergrund intraperitoneal und intranasal mit Cryptococcus neoformans (C. neoformans) infiziert. Dabei wurden die Unterschiede im Infektionsverlauf und in der Immunreaktion von Wildtyp-, IL-12p35-/- und IL-12p35/p40-/--Mäusen analysiert. Unterschiede zwischen den Wildtyp- und den IL-12p35-/--Mäusen lassen auf die Bedeutung von IL-12p75 schließen, wogegen Unterschiede zwischen IL-12p35-/-- und IL-12p35/p40-/--Mäus
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15

Suri, Deepak. "Non-cytolytic control of hepatitis virus replication and the role of interleukin-12(IL-12)." Thesis, University College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.411248.

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16

D'Avila, Tiago Landim. "Administração de plasmídeos codificantes de IL-12 e IL-1 em cães e expressão de IL- 12 em células de inseto por baculovírus recombinante." reponame:Repositório Institucional da FIOCRUZ, 2011. https://www.arca.fiocruz.br/handle/icict/4317.

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Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2012-09-04T16:57:00Z No. of bitstreams: 1 Tiago Landim d'Avila Administração de plasmídeos....pdf: 1447180 bytes, checksum: b65ad3c9ece2b6f29cc032b2fa22c49a (MD5)<br>Made available in DSpace on 2012-09-04T16:57:00Z (GMT). No. of bitstreams: 1 Tiago Landim d'Avila Administração de plasmídeos....pdf: 1447180 bytes, checksum: b65ad3c9ece2b6f29cc032b2fa22c49a (MD5) Previous issue date: 2011<br>Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil<br>A interleucina-12 (IL-12) é uma glicoproteína h
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17

Rietschoten, Johanna Goverta Ingeborg van. "Transcriptional regulation of the human interleukin-12 receptor ß2 gene." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2002. http://dare.uva.nl/document/66510.

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18

Fu, Hangfei. "Interleukin 35 inhibits ischemia-induced angiogenesis essentially through the key receptor subunit Interleukin 12 receptor beta 2." Diss., Temple University Libraries, 2019. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/546609.

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Biomedical Sciences<br>Ph.D.<br>Peripheral arterial disease (PAD) is a worldwide disease caused by atherosclerosis. It is a circulatory condition where narrowed blood vessels reduce blood flow to the peripheral such as legs. Although current gold standard treatment for advanced PAD patients is still based on surgical revascularization, there is no effective therapy for many patients that are not suitable for surgery. In addition, better recovery from surgical revascularization largely relies on angiogenesis in the adjacent ischemic tissue. Thus, novel pro-angiogenic therapies to improve post-i
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19

Gedge, Vicki L. "Natural killer cell responses to exercise : changes in cellular activation and/or distribution /." [St. Lucia, Qld.], 2002. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16841.pdf.

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20

Renton, Louise Margaret. "Studies of some antiparasitic agents." Thesis, University of St Andrews, 1997. http://hdl.handle.net/10023/13992.

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Each year, between 300 and 500 million people develop malaria. Close to 3 million people die as a result. Due to resistance there are now few drugs left which are effective against malaria; one is a Chinese herbal remedy called qinghaosu (artemisinin). A section of this thesis represents an attempt to understand further the mode of action of this antimalarial agent. Several mechanisms involving iron have been proposed and the main categories reviewed (chapter 3). Techniques including ESR spectrometry, fluorescence and absorbance measurements were used to further probe the mode of action of qin
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21

Harker, Rosamond. "The role of interleukin-12 (IL-12) in respiratory syncytial virus disease in BALB/c mice." Thesis, University of Newcastle Upon Tyne, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.394681.

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22

Frellstedt, Linda. "Induction and characterization of endotoxin tolerance in equine peripheral blood mononuclear cells in vitro." Thesis, Virginia Tech, 2010. http://hdl.handle.net/10919/44307.

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Endotoxemia is responsible for severe illness in horses. Individuals can become unresponsive to the endotoxin molecule after an initial exposure; this phenomenon has been called developing a state of â endotoxin toleranceâ (ET). ET has been induced in horses in vivo; however, cytokine expression associated with ET has not been investigated. The purpose of this study was to develop and validate a method for inducing ET in equine peripheral blood mononuclear cells (PBMCs) in vitro, and to describe the cytokine profile which is associated with the ET. <p> Blood was collected from 6 healthy hor
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23

Bacon, Christopher M. "Lymphocyte regulation and JAK-STAT signal tranduction by interleukin-12 : comparison with interleukin-2 and other related cytokines." Thesis, University of Sheffield, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301669.

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24

Becker, Christoph. "Die Regulation des Interleukin-12-p40-Promotors in Monozyten und Makrophagen." [S.l.] : [s.n.], 2000. http://ArchiMeD.uni-mainz.de/pub/2001/0100/diss.pdf.

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25

Schardt, Victor [Verfasser], and Ernst Rainer [Akademischer Betreuer] Weissenbacher. "Vergleichende Untersuchungen zur Hefepilzbesiedelung von Mundhöhle und Vagina und Bestimmung von Interleukin-4, Interleukin-10 und Interleukin-12 / Victor Schardt. Betreuer: Ernst Rainer Weissenbacher." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2013. http://d-nb.info/1032862645/34.

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26

劉鐵夫 and Tiefu Liu. "The role of interleukin-12 in the pathogenesis of human systemic lupuserythematosus." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1998. http://hub.hku.hk/bib/B31237459.

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27

Howes, A. F. "The regulation of interleukin-10 and interleukin-12 in macrophages : investigating the differential regulation of IL-10 and IL-12 in C57BL/6 and BALB/c mice." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1409974/.

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Pattern recognition receptors (PRR) detect microbial products and induce cytokines which shape the immunological response. Interleukin-12 (IL-12) is a proinflammatory cytokine important for the differentiation of T helper 1 (Th1) cells which produce IFN-γ to activate macrophages and eradicate intracellular pathogens. In contrast, interleukin-10 (IL-10) is an immunosuppressive cytokine that minimises immune-driven host pathology, but can also lead to defective pathogen clearance. The regulation of IL-10 and IL-12 is therefore of interest due to their central roles in the orchestration of an eff
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28

Costa, Sidnei Ferro. "Estimulação combinada de IL-12 e IL-15 promove a resposta imune celular em cães com leishmaniose via IFN-y /." Araçatuba, 2019. http://hdl.handle.net/11449/182241.

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Orientador: Valéria Marçal Felix de Lima<br>Resumo: A Leishmaniose Visceral (LV) é causada nas Américas, pelo protozoário intracelular obrigatório Leishmania infantum e os cães domésticos são os principais reservatórios urbanos do parasita e em áreas endêmicas, o aumento da LV em humanos tem sido associado ao aumento da infecção canina. Os atuais medicamentos disponíveis para a Leishmaniose Canina (CanL) não são completamente eficientes e meses após o tratamento a maioria dos cães apresentam recidiva, indicando a necessidade de buscar formas alternativas de tratamento. Na CanL, cães desenvolve
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29

Entleutner, Markus Jörg Michael. "Die Rolle von Interleukin-12 und Interleukin-18 bei bakterieller Peritonitis in dem Mausmodell "Colon-Ascendens-Stent-Peritonitis" (CASP)." [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=964490595.

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30

Rao, Vittal Sree Rama. "Significance of interleukin-10 and interleukin-12 levels in breast cancer patients and their possible role in tumour immunology." Thesis, University of Hull, 2006. http://hydra.hull.ac.uk/resources/hull:16056.

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Patients with cancer are thought to have significant impairment of the immune system. One of the manifestations is believed to be skewing of the cytokine profile in favour of the immunosuppressive Th2 cytokine family as opposed to the immunofacilitatory Th1 cytokine family. In this MD thesis, a prospective study was undertaken to determine whether this occurred in breast cancer patients. IL-IO (representing the Th2 cytokine family) and IL-12 (representing the Th1 cytokine family) levels in the serum, IL-12 production capability of peripheral blood mononuclear cells (PBMC) along with the levels
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31

Bauer, Julia [Verfasser], та Tobias [Akademischer Betreuer] Weissenbacher. "Die Bestimmung der Zytokine Interleukin-23, Interleukin-17a, Interleukin-12, Interleukin-10, Interleukin-6, Tumor-Nekrose-Faktor-α und MIP-1β im Vaginalsekret und deren Bedeutung im Rahmen der Frühgeburtlichkeit / Julia Bauer ; Betreuer: Tobias Weissenbacher". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2016. http://d-nb.info/1128074052/34.

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32

Klenk, Erin Ingersoll. "Endoplasmic Reticulum Stress and the Unfolded Protein Response Result in Synergistic Upregulation of Interleukin-23 and Interleukin-12 by LPS." University of Cincinnati / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1250092843.

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33

Bechara, Rami. "Étude de la coopération entre les cellules dendritiques et les lymphocytes T dans les allergies aux produits chimiques et aux médicaments." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS474/document.

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Les allergies aux produits chimiques et aux médicaments constituent un problème majeur de santé publique. L’objectif de ce travail est de mieux comprendre l’interaction entre les cellules dendritiques (DC) et les lymphocytes T (LT) dans les allergies induites par les haptènes métalliques (nickel et cobalt) et les médicaments [benzylpénicilline (BP)]. En présence des signaux de danger, les DC acquièrent un phénotype dit « mature » et présentent l’antigène apprêté aux LT spécifiques de cet antigène. Les LT représentent les cellules effectrices responsables d’une manière directe ou non des symptô
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34

Kelleher, William Peter. "The influence of interleukin-12 and Rauscher leukaemia virus on dendritic cell function." Thesis, Imperial College London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.402485.

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35

Liu, Tiefu. "The role of interleukin-12 in the pathogenesis of human systemic lupus erythematosus /." Hong Kong : University of Hong Kong, 1998. http://sunzi.lib.hku.hk/hkuto/record.jsp?B20381505.

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36

Li, Lijin. "Immunopathology of Coccidioidal Granulomata and the Regulation of Interleukin-12 Signal Transduction in Human Coccidioidomycosis." Diss., The University of Arizona, 2005. http://hdl.handle.net/10150/193826.

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Coccidioidomycosis is a growing problem in the United States. There is still an incomplete understanding of the immunological response associated with human coccidioido-mycosis, although previous studies have indicated that cell-mediated immunity (CMI) is critical in the control of this disease. We have examined necrotizing pulmonary coccidioidal granulomata using immunohistochemical staining for lymphocyte subsets and for the cytokines interleukin-10 (IL-10) and gamma interferon (IFN-?). Discrete perigranulomatous lymphocytic clusters were identified containing roughly equal numbers of T (
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37

Alkayyal, Almohanad. "Exploiting the Antitumor Immune Response Using IL-12 Armed Oncolytic MG1 Virus In An Infected Cell Vaccine." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/35599.

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Despite improvements in chemotherapy and radical surgical debulking, peritoneal carcinomatosis (PC) remains among the most common causes of death for abdominal cancers. Immunotherapies have demonstrated efficacy in selected solid malignancies but their potential in PC is poorly explored. Here I report that intraperitoneal injection of an infected cell vaccine (ICV), consisting of autologous tumor cells infected ex-vivo with an oncolytic Maraba MG1 virus expressing interleukin-12 (IL-12), promotes the migration of activated natural killer (NK) cells to the peritoneal cavity in response to the s
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38

Schnabel, Christiane Liliane [Verfasser]. "Acute immune response of healthy horses to linear DNA encoding Interleukin 12 and Interleukin 18 complexed with SAINT-18 / Christiane Liliane Schnabel." Hannover : Bibliothek der Tierärztlichen Hochschule Hannover, 2015. http://d-nb.info/1073931110/34.

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39

O'Hara, Richard James. "Interleukin-12 a pivotal cytokine in cell mediated immunity : the role in colorectal cancer." Thesis, University of Hull, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.395426.

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40

Holanda, Flávia Mendes da Cunha. "Estudo da associação entre paracoccidioidomicose e os polimorfismos dos genes IL12B (posição 3' UTR+1188 A/C), IL12RB1 ( posição 11014 A/G no éxon 7) e IFNG ( posição + 874 T/A)." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/5/5134/tde-02052016-141504/.

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Introdução. A paracoccidioidomicose (PCM) é uma micose sistêmica crônica, endêmica na América Latina, principalmente Brasil, sendo a oitava causa de morte entre as doenças infecciosas crônicas recorrentes. A PCM infecção é caracterizada por uma resposta Th1, a forma aguda por um perfil misto da resposta Th2/Th9, enquanto na forma crônica caracteriza-se pelo perfil Th17/Th22. A ocorrência e gravidade da PCM humana podem também estar associadas a fatores genéticos como os polimorfismos dos genes de citocinas. Objetivos. 1. Descrever a frequência dos polimorfismos de (SNPs) IFNG +874 T/A, IL12B 3
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41

Müller, Stephanie Irene [Verfasser], Matthias J. [Akademischer Betreuer] Feige, Martin [Gutachter] Zacharias, Johannes [Gutachter] Buchner, and Matthias J. [Gutachter] Feige. "Folding and quality control of the interleukin 12 family cytokines interleukin 27 and interleukin 35 / Stephanie Irene Müller ; Gutachter: Martin Zacharias, Johannes Buchner, Matthias J. Feige ; Betreuer: Matthias J. Feige." München : Universitätsbibliothek der TU München, 2019. http://d-nb.info/1200547667/34.

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42

Brenner, Stephan. "Auswirkungen plazentarer Plasmodium falciparum-Infektionen primigravider Mütter auf die Ausbildungeiner Immunantwort bei Neugeborenen." [S.l. : s.n.], 2006.

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43

Nomura, Takamasa. "Essential role of interleukin-12(IL-12)and IL-18 for gamma interferon production induced by listeriolysin O in mouse spleen cells." Kyoto University, 2002. http://hdl.handle.net/2433/149709.

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44

Dodd, Christopher H. "Toll-like receptor stimulation can lead to differential production of IL-23 and IL-12." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2008. https://www.mhsl.uab.edu/dt/2009r/dodd.pdf.

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45

Meier, Susanne [Verfasser], Matthias J. [Akademischer Betreuer] Feige, Johannes [Gutachter] Buchner, and Matthias J. [Gutachter] Feige. "Folding and quality control of the cytokines interleukin 12 and interleukin 23 / Susanne Meier ; Gutachter: Johannes Buchner, Matthias J. Feige ; Betreuer: Matthias J. Feige." München : Universitätsbibliothek der TU München, 2019. http://d-nb.info/1212178084/34.

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46

Gri, Giorgia. "The role of interferon gamma and other cytokines in the antitumour activity of interleukin 12." Thesis, Open University, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.251409.

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47

Furumoto, Katsuyoshi. "Spleen-derived dendritic cells engineered to enhance interleukin-12 production elicit therapeutic antitumor immune responses." Kyoto University, 2001. http://hdl.handle.net/2433/150175.

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48

Sam, Hakeem. "Mechanism(s) of interleukin-12-induced protection against early murine blood-stage P. chabaudi AS malaria." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape8/PQDD_0025/NQ50255.pdf.

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49

Sam, Hakeem. "Mechanism(s) of interleukin-12-induced protection against early murine blood-stage P. Chabaudi AS malaria." Thesis, McGill University, 1998. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=35939.

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Previous studies suggest that IL-12, the potent Th1-inducing cytokine, IFN-gamma, TNF-alpha and nitric oxide (NO) contribute to resistance against blood-stage malaria. Early Th1 responses correlate with resistance, whereas predominantly Th2 responses are associated with susceptibility. In the present studies, the requirements for endogenous IL-12 and its role in host defense against blood-stage P. chabaudi AS malaria were investigated. Our results reveal, for the first time, significant differences in the kinetics of endogenous IL-12 p70 synthesis and splenic IL-12R beta1 and beta2 mRNA expres
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50

Louw, Renate. "A study of the molecular mechanism of progestin-induced regulation of IL-12 and IL-10 and implications for HIV pathogenesis." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/79822.

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Thesis (PhD)--Stellenbosch University, 2013.<br>ENGLISH ABSTRACT: Medroxyprogesterone acetate (MPA) and norethisterone (NET) and its derivatives (norethisterone enanthate (NET-EN); norethisterone acetate (NET-A)), designed to mimic the actions of the endogenous hormone progesterone (Prog), are extensively used by women as contraceptives and in hormone replacement therapy (HRT). A number of reports have indicated that these synthetic progestins affect immune function in the female genital tract thereby increasing the risk of acquiring sexual transmitted infections. Despite these findings,
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