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1
Björnberg, 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.
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Engelberts, Ingeborg. "Tumor necrosis factor during sepsis king of cytokines? /." Maastricht : Maastricht : Universitaire Pers Maastricht ; University Library, Maastricht University [Host], 1994. http://arno.unimaas.nl/show.cgi?fid=6955.
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Krugten, Michiel Volkert van. "Tumor necrosis factor gene polymorphisms and rheumatic diseases /." Leiden, 2003. http://catalogue.bnf.fr/ark:/12148/cb40223074h.
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4
Oukacha, Khadija. "Perturbation chimique du transport de Tumor Necrosis Factor." Electronic Thesis or Diss., Université Paris sciences et lettres, 2023. http://www.theses.fr/2023UPSLS067.
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Alors qu'il est essentiel pour lutter contre les agents pathogènes, TNF (Tumor Necrosis factor) secrété́ en excès devient nocif pour l'organisme comme dans le cas de maladies inflammatoires chroniques (polyarthrite rhumatoïde ou maladie de Crohn). Les thérapies actuelles sont basées sur des injections récurrentes d'anti-TNF contre lesquelles 30% des patients développent une résistance. Il existe donc un fort besoin de composés chimiques réduisant la sécrétion de TNF. Nous avons exploité la diversité́ des voies de sécrétion dépendantes de l’appareil de Golgi pour identifier des molécules inhibant spécifiquement la sécrétion de TNF. L’outil RUSH (Retention Using Selective Hooks) a permis la synchronisation et l’analyse du transport de TNF dans les cellules HeLa. En combinant le test RUSH à un criblage phénotypique différentiel de banques chimiques, 85 molécules inhibant le transport de TNF ont été sélectionnées. Les effets de certaines molécules ont été validés. Seules les molécules inhibantes au moins 40% de la sécrétion de TNF ont été retenues. La spécificité de ces molécules sur le transport d’autres protéines, à savoir EGFP-GPI et IL-6 a été évaluée. Les 14 molécules inhibantes plutôt spécifiquement la sécrétion de TNF ont été retenues pour poursuivre leur caractérisation en modèle physiologique.Les effets des molécules sur la sécrétion endogène de TNF et d’autres cytokines ont été mesurés dans des monocytes et des macrophages primaires humains issus du sang de donneurs après incubation avec du lipopolysaccharide (LPS) bactérien. Ces expériences en modèles physiologiques ont mis en évidence trois molécules capables d'inhiber significativement la sécrétion endogène de TNF sans affecter la sécrétion d'IL-8. Des expériences de dose-réponse et l’évaluation des effets des molécules sur l’expression de TNF ont été réalisées pour aider dans la compréhension du mode d’action de ces molécules.En conclusion, le criblage chimique, les expériences en modèle hétérologue puis en modèles physiologiques ont permis d'identifier 3 molécules inhibant la sécrétion de TNF. Ces résultats confirment que la diversité́ des voies sécrétoires est suffisamment grande pour cibler le transport d'une protéine impliquée dans une maladie et pourraient ouvrir la voie à des traitements alternatifs ou complémentaires contre les maladies inflammatoires<br>While it is essential to fight against pathogens, TNF (Tumor Necrosis factor) secreted in excess becomes harmful to the body as in the case of chronic inflammatory diseases (rheumatoid arthritis or Crohn's disease). Current therapies are based on recurrent injections of anti-TNF against which 30% of patients develop resistance. There is therefore a strong need for chemical compounds which reduce the secretion of TNF. We have exploited the diversity of secretory pathways dependent on the Golgi apparatus to identify molecules that specifically inhibit TNF secretion. The RUSH (Retention Using Selective Hooks) tool allowed the synchronization and analysis of TNF transport in HeLa cells. By combining the RUSH assay with a differential hight content screening of chemical libraries, 85 molecules inhibiting TNF transport were selected. The effects of certain molecules have been validated. Only molecules inhibiting at least 40% of TNF secretion were retained. The specificity of these molecules on the transport of other proteins, namely EGFP-GPI and IL-6 was evaluated. The 14 molecules rather specifically inhibiting the secretion of TNF were selected to continue their characterization in a physiological model.The effects of the molecules on the endogenous secretion of TNF and other cytokines were measured in human primary monocytes and macrophages obtained from blood donors after incubation with bacterial lipopolysaccharide (LPS). These experiments in physiological models have demonstrated three molecules capable of significantly inhibiting the endogenous secretion of TNF without affecting the secretion of IL-8. Dose-response experiments and the evaluation of the effects of molecules on the expression of TNF have been carried out to help in understanding the mode of action of these molecules.In conclusion, the chemical screening, the experiments in heterologous model then in physiological models made it possible to identify 3 molecules inhibiting the secretion of TNF. These results confirm that the diversity of secretory pathways is large enough to target the transport of a protein involved in a disease and could open the way to alternative or complementary treatments against inflammatory diseases
5
Watts, Alan D. "The biological role of transmembrane tumour necrosis factor [alpha]." Thesis, The University of Sydney, 1998. https://hdl.handle.net/2123/27668.
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Tumour necrosis factor (TNF) exists in two physiological forms. One is
a soluble polypeptide of 17 kDa, and the other a type II integral membrane
protein of 26 kDa designated transmembrane TNF. Soluble TNF is derived
from the transmembrane form by proteolytic processing. The soluble TNF
molecule exerts potent cytotoxic activity against certain types of cancer cells,
and plays a critical role in the functioning of the immune and inflammatory
system. The transmembrane TNF molecule shares many of the properties of
the soluble form in vitro, but its function in the immune system is not as clearly
defined as for the sTNF form. In this thesis the biological role of
transmembrane TNF was investigated.
The synthesis and expression of both soluble TNF and transmembrane
TNF forms was examined in macrophage cells stimulated with LPS. Basic
parameters for the production of transmembrane TNF were established to
enable further analysis of its function.
Using a hydroxamic acid-based inhibitor of TNF processing it was
possible to obtain macrophage cells that expressed transmembrane TNF, but
not soluble TNF; This enabled the investigation of transmembrane TNF free
from the complicating effects of soluble TNF. It was found that inhibition of
TNF processing in this way caused an accumulation of transmembrane TNF
on the macrophage cells surface 5.1-7.5-fold greater than in cells not treated
with the hydroxamic acid-based inhibitor. This corresponded to a 6.4-fold
increase in TNF-mediated cytotoxicity of macrophage cells towards cells
sensitive to transmembrane TNF.
By radiolabelling macrophages, and using a specialised
immunoprecipitation method, it was demonstrated that a soluble form of one of
the TNF receptors (sTNFFi) binds transmembrane TNF. The consequence of
this binding was neutralisation of transmembrane TNF-mediated cytotoxicity,
but not inhibition of proteolytic processing of transmembrane TNF to release
soluble TNF.
The possibility that transmembrane TNF is capable of transducing a
signal upon ligation with sTNFR was investigated. A broad range of cellular
parameters were measured to see whether sTNFFi treatment of macrophages
expressing transmembrane TNF induced a biochemical/physiochemical
change. It was found that sTNFR caused a large increase (~200%) in
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intracellular calcium levels after 15 min treatment. This is the first direct
evidence that transmembrane TNF is capable of acting like a receptor.
The composition of the predicted amino acid sequence of
transmembrane TNF was closely examined to determine the presence of
features important for both structure and intracellular signalling. A model is
presented in Chapter 6 which outlines in diagrammatic form likely structural
features of transmembrane TNF. The molecule is predicted to possess a
region of cytoplasmic alpha-helices corresponding to a highly conserved
domain of the sequence. The structure of transmembrane TNF is consistent
with that of a transmembrane receptor, capable of transducing signals initiated
by ligation with an extracellular ligand.
The comparison of predicted amino acid sequences of transmembrane
TNF from different mammalian species revealed the presence of a conserved
casein kinase | site. This site was also found to be present in most members
of the TNF ligand family. Using orthophosphate labelling, it was shown that
mouse transmembrane TNF is phosphorylated in macrophages. Ligation of
sTNFR with transmembrane TNF induced de-phosphorylation of mTNF. This
de-phosphorylation could be prevented by pre-incubation of the cells with
serine phosphatase inhibitors. A selective inhibitor of casein kinase |
dramatically reduced the phosphorylation of transmembrane TNF produced
by macrophages. In addition, a recombinant form of casein kinase l
phosphorylated transmembrane TNF in vitro on the site naturally
phosphorylated by the endogenous kinase in vivo.
The evidence presented in this study supports an entirely new role for
transmembrane TNF, one in which the molecule is capable of acting like a
transmembrane receptor, with the ligand being sTNFR. This phenomenon is
known as "reverse signalling", and has been shown by other researchers to
occur in the majority of members of the TNF ligand family. Implications of
mTNF "reverse signalling" are relevant to the treatment of human diseases in
which sTNFRs are currently being assessed in clinical trials.
6
Langton, Amy Jean. "The role of TRUSS in TNFα-TNFRI signalling : implications for inflammatory lung diseases". Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608019.
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Atkinson, Yvelle Hope. "Regulation of neutrophil functions by tumor necrosis factor-alpha /." Title page, contents and summary only, 1989. http://web4.library.adelaide.edu.au/theses/09PH/09pha878.pdf.
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Bond, Arden Lenore. "The production and characterization of a putative anti-idiotypic antibody to tumor necrosis factor-[alpha] /." This resource online, 1992. http://scholar.lib.vt.edu/theses/available/etd-05042010-020132/.
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Tan, Ern Yu. "Loss of protein folding gene expression in human tumors." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.670106.
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10
Han, Jiahuai. "Study of the regulation of cachectin/tumor necrosis factor expression." Doctoral thesis, Universite Libre de Bruxelles, 1990. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/213139.
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Hel, Zdenek. "Posttranscriptional regulation of tumor necrosis factor-Ã production in macrophages." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0010/NQ36980.pdf.
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Mustapha, Shareef. "Signaling pathways of tumor necrosis factor à in ventricular myocytes." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ41751.pdf.
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Hel, Zdenĕk. "Posttranscriptional regulation of tumor necrosis factor-a production in macrophages." Thesis, McGill University, 1997. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=34642.
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The production of tumor necrosis factor-alpha (TNF-alpha), a key cytokine regulator of an early immune response and a central mediator of the deleterious effects of systemic inflammatory response syndrome, is regulated at both the transcriptional and posttranscriptional level. The 3' -untranslated region (3'-UTR) of TNF-alpha mRNA contains sequences that confer its translational repression in quiescent cells and are responsible for the induction of TNF-alpha production following macrophage contact with bacterial lipopolysaccharide, live bacteria, or viruses.<br>We demonstrate that two distinct regions, located in a part of the 3 '-UTR of murine TNF-alpha mRNA previously shown to play a crucial role in the regulation of the stability and translatability, interact with macrophage nuclear and cytoplasmic proteins. The first protein binding region is located inside the AU-rich sequence 424 bp downstream of the end of the coding sequence, while the second protein binding region contains a single AUAUUUAU motif and is located 147 bp downstream of the first region. Six detectable protein species interact with the first protein binding region and seven proteins interact with the second binding region. Some of the RNA binding proteins mutually compete for the binding to both regions. TNF-alpha derived cRNA probes form complexes with proteins differentially distributed among the nuclear, cytosolic and particulate fractions of murine macrophages. Three of the TNF-alpha mRNA binding complexes cosediment in the polyribosomal fraction. The stimulation of macrophages with LPS, interferon-gamma, PMA or their combination significantly increases the stability and translational efficiency of TNF-alpha mRNA, yet does not alter the RNA binding activity nor the localization of TNF-alpha mRNA binding proteins, suggesting that regulation of gene expression by RNA-binding proteins may involve other mechanisms, such as posttranslational modification of these proteins or proteins interacting with them rather than global alteration of their amounts in particular cell compartements. The GA dinucleotide insertion inside the first protein binding region, found in NZW and several other strains of mice and associated with lowered ability of peritoneal macrophages to produce TNF-alpha, alters the formation of RNA-protein complexes, supporting their role in the posttranscriptional regulation of TNF-alpha production. Two candidate TNF-alpha mRNA binding proteins were cloned by direct screening of cDNA protein expression library using modified northwestern
14
Koelen, Jorien Anne. "Arming ColoAd1 with tumor necrosis factor α and lymphotoxin α". Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:bfc9d84f-2677-45db-8705-791219446348.
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Colon and rectum cancers (CRCs) are the third most prevalent cause of cancer-related mortality. Advanced metastatic CRC has a very poor prognosis; indicating the need for improved therapy. Tumour necrosis factor (TNF) can induce an immune response against tumours and cause cell death of the tumour-associated vasculature. However, dose-limiting toxicity occurs with systemic TNF treatment. In order to assess the effects of expressing TNF and lymphotoxin a (LTA) locally in the tumour microenvironment, a syngeneic CT26 CRC model expressing soluble (sm), full length (fm) or membranebound (mbm) murine TNF or LTA under a doxycyclin-dependent promoter. Moreover, an oncolytic adenovirus (ColoAd1) was modified to express fm or mbm TNF or LTA under its major late promoter (MLP). ColoAd1 is a novel chimeric species B adenovirus based on serotypes Ad11p and Ad3 and is currently in clinical phase 2 trials. In the CT26 model, expression of mbm TNF decreases tumour growth and increases survival compared to control mice not receiving doxycyclin. Expression of sm or fm TNF had no effect on tumour growth or survival. Increased immune infiltration, especially myeloid cells (CD45+ CD11b+) was seen in mice bearing tumours expressing sm, fm and mbm TNF. ColoAd1 can express functional TNF constructs without a substantial impact on virus replication or yield in vitro. Arming ColoAd1 with TNF did not increase efficacy or innate immune infiltration compared to parental ColoAd1, in vivo. Administration of ColoAd1, ColoAd1 fm TNF and ColoAd1 mbm TNF increases immune cell infiltration compared to PBS, especially dendritic (CD45+ CD11b+ F4/80- CD11c+), monocytic (CD45+ CD11b+ Ly6Chigh Ly6G- ) and granulocytic (CD45+ CD11b+ Ly6Clow Ly6G+) cell populations were enriched in virus treated tumours. Expression of TNF from ColoAd1 was well tolerated and systemic toxicity was not observed, in vivo. A statitistically significant derecrease in ColoAd1 mbm TNF genome copies and nonstatistically significant decrease in ColoAd1 fm TNF genome copies were found in tumours compared to ColoAd1. This may indicate increased viral clearance or decreased replication of these armed viruses. The decrease in virus progeny in tumours may have been a major hurdle for increasing the efficacy of ColoAd1 TNF. Synergy between adenoviruses and radiation has been observed for species C virus but little is known about the effects of species B virus on the DNA damage response. In vitro, induction of ?H2AX and phospho-ATM was seen upon ColoAd1 infection of DLD cells and compared to Ad5, less Rad50 and Mre11 degradation occurs in ColoAd1 or Ad11p infected cells. Like all other species of Ad studied, ligase IV is degraded during ColoAd1 infection. Combination of ColoAd1 with radiation therapy, in vivo, led to an increase in viral genome copies in the tumour lysate, 10 days post radiation. However, no synergistic effects of combining virus with radiation was observed. Additionally, contrary to other Ad5 viruses armed with TNF, no evidence for synergy between mTNF expressing ColoAd1 and radiation was found. In conclusion, ColoAd1 can deliver therapeutic proteins to the tumour microenvironment and could potentially be a very useful approach to treat refractive cancers. However, the limitations of relevant pre-clinical models will need to be overcome or new phase 0 mechanistic trial designs will be required to move the technology to reach full potential.
15
Steffen, Brian. "Efficacy of TNF inhibitor treatment in a model of heart failure and resulting cachexia." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/6001.
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Thesis (Ph. D.)--University of Missouri-Columbia, 2007.<br>"December 2007" The 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. Includes bibliographical references.
16
Debets, Jacobus Maria Hubert. "Studies on tumor necrosis factor endogenous mediators of sepsis and cachexia /." Maastricht : Maastricht : Datawyse ; University Library, Maastricht University [Host], 1989. http://arno.unimaas.nl/show.cgi?fid=5468.
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Karimi, Mahdad. "Functional analysis of the -308G/A polymorphism in the tumour necrosis factor promoter." University of Western Australia. School of Biomedical, Biomolecular and Chemical Sciences, 2007. http://theses.library.uwa.edu.au/adt-WU2007.0140.
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[Truncated abstract] Tumor Necrosis Factor (TNF) is a potent pro-inflammatory cytokine involved in a range of biological functions including the differentiation, proliferation and survival of many cell types. The TNF gene lies in the class III region of the major histocompatibility complex (MHC), approximately 250 Kbp centromeric of the HLA-B locus and 850 Kbp telomeric of HLA-DR. Due to the genomic location and biological relevance of TNF, it is thought that genetic heterogeneity at this locus may be associated with autoimmune and infectious diseases. A G-to-A single nucleotide polymorphism (SNP) at position -308 (relative to the transcriptional start site) in the TNF promoter has been well described. The less common -308A variant has been shown to be linked with the HLA-A1, B8, DR3 haplotype which in turn has been associated to a high TNF producing phenotype. Determining whether the -308 polymorphism contributes to elevated levels of expression has therefore been a priority for many research groups. Some investigators have shown differences in transcription between the -308G and -308A alleles while others could not. These contradicting results have led to conflicting views regarding the functional relevance of the -308 SNP. In this study, statistical analysis of 18 independent transient transfections of -308 biallelic TNF reporter constructs have provided evidence for a functional consequence of the polymorphism. ... In addition, chromatin accessibility of this region was maximal at greater levels of transcription suggesting a role for both chromatin structure and YY1 binding in -308G regulation. Surprisingly, chromatin structure did not seem to play a role in -308A regulation nor was there any significant binding of YY1, suggesting the -308 region does not affect transcriptional control of TNF. Taken as a whole, the G-to-A SNP relieves YY1 binding and demonstrates an allele-specific regulatory mechanism controlling expression. A growing list of promoter polymorphisms exists in the human genome having associations with certain diseases. Determining the functional consequence of these SNPs has proven difficult and utilized mainly in vitro approaches. In this thesis, a unique approach to investigating the functionality of promoter polymoprhisms has been developed, utilizing in vivo techniques which test their effects in a more natural system. It is hoped that the identification of the allele-specific YY1-mediated control of the -308 region of the TNF promoter may provide insight into overexpression as a consequence of the polymorphism and its role in the genetic susceptibility to MHC-associated autoimmune disease.
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Zwaveling, Jan Harm. "Systemic side effects of isolated limb perfusion with tumor necrosis factor alpha." [S.l. : [Groningen] : s.n.] ; [University Library Groningen] [Host], 1997. http://irs.ub.rug.nl/ppn/15723665X.
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Babu, Kesavan Suresh. "The role of tumor necrosis factor alpha (TNF-α) in asthma." Thesis, University of Southampton, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.439378.
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Di, Marco Sergio. "Posttranscrip[t]ional regulation of tumor necrosis factor production in macrophages." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=37648.
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Tumor necrosis factor alpha (TNFalpha) is a key proinflammatory cytokine which is produced primarily by macrophages. Although this cytokine is very beneficial to the host when released in small amounts or in localized fashion, abnormally high levels of TNFalpha can however be very detrimental. The biological effects of this cyokine is thus dependent on its timing, location and extent of release. In recent years major interest has been placed on the AU rich elements (ARE) present in the 3' untranslated region of the TNFalpha mRNA as it plays a pivitol role in the posttranscriptional control of TNFalpha protein production.<br>We have previously shown that a protein binding site within this main ARE (positioned between bases 1291 and 1320) has the ability to bind to three protein complexes (A,B,C). In this study we describe a second AU rich element which also has protein binding capabilities. This second protein binding site (located 158 bases downstream from the first ARE) is 31 nucleotides long and contains a single AUAUUUAU sequence. Fractionation experiments have enabled us to show that a protein complex (complex D) present in both nuclear and cytoplasmic cell compartments can interact with this second binding region. The binding of this second ARE to this complex is readily competed for by other AU rich elements present in the mRNA of certain protooncogenes and cytokines such as c-fos and IL-1beta. The importance of binding of macrophage proteins to the ARE in the posttranscriptional regulation of TNFalpha was evidenced by the fact that polymorphisms (GAU trinucleotide insertional mutation) in the main ARE (positioned between bases 1291 and 1320 of the 3 ' untranslated region) of TNFalpha mRNA results in the decreased binding of macrophage protein complexes to the element. The GAU insertional mutation in the main ARE hinders the binding of a protein named HuR to the region. This protein is a nucleo-cytoplamic shuttling protein previously shown to play a prominent role in the stability and translatability of mRNA containing ARE. In order in elucidate and further our understanding of signalling mechanisms which regulate the function of proteins binding to ARE we verified if priming of macrophages with IFNgamma is important in the posttranscriptional regulation of TNFalpha mRNA. We show that priming of macrophages with IFNgamma prior to LPS treatment posttranscriptionally upregulates TNFalpha production by increasing the stability of the message and the levels of mRNA present on translationally active polyribosomes. The involvement of IFNgamma in the posttranscriptional regulation of<br>Overall data presented in the thesis will further our understanding of how ARE in the 3'UTR of the TNFalpha mRNA posttranscriptionally regulates the expression of TNFalpha.
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Cantwell, Mark J. "The Tumor necrosis factor family : roles in disease pathology and therapy /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 1998. http://wwwlib.umi.com/cr/ucsd/fullcit?p9824693.
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Yang, Junbao. "Genetic engineering of a fusion protein possessing anti-tumor Fv and tumor necrosis factor alpha." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape8/PQDD_0030/NQ63940.pdf.
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Yadav, Ajay Kumar. "Relationship between human hemoglobin and tumor necrosis factor a : immunochemistry and bioactivity studies." Thesis, JAMIA HAMDARD (IIAMDARD UNIVERSITY), 2002. http://hdl.handle.net/123456789/1468.
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Hurst, Liam Andrew. "The role of tumour necrosis factor alpha in pulmonary arterial hypertension." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648471.
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Mallet, Dominique. "Interet du tumor necrosis factor alpha dans le suivi precoce des transplantations renales." Aix-Marseille 2, 1994. http://www.theses.fr/1994AIX20913.
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Sutherland, Andrew Peter Robert St Vincents Clinical School UNSW. "BAFF regulation of peripheral T cell responses." Awarded by:University of New South Wales. St Vincents Clinical School, 2005. http://handle.unsw.edu.au/1959.4/22788.
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The activation and effector function of CD4+ T cells are critical points of regulation during an antigen specific T cell response. Dysregulation of these processes can lead to the development of human diseases, encompassing both immunodeficiency and autoimmunity. Members of the TNF superfamily have recently emerged as important regulators of T cell responses, with their overexpression causing autoimmune inflammation in animal models. As overproduction of the novel TNF superfamily ligand BAFF is associated with several autoimmune conditions, we sought to examine the potential role of BAFF as a regulator of T cell activation and effector function. We initially demonstrated BAFF costimulation of T cell activation in vitro. Generation of specific monoclonal antibodies identified BAFF-R as the only BAFF receptor present on T cells, and showed that it was expressed in an activation-dependent and subset-specific manner. Impaired BAFF costimulation in BAFF-R deficient mice indicated that BAFF-R was crucial for mediating BAFF effects in T cells. Analysis of T cell responses in vivo revealed that BAFF transgenic mice have increased T cell priming and recall responses to protein antigens, and showed a corresponding increase in the DTH model of Th1 cell-dependent inflammation. In addition, Th2-dependent allergic airway responses are suppressed in BAFF transgenic mice. Crossing to a B cell deficient background revealed that the proinflammatory effects of BAFF on T cell priming and DTH rely on the presence of B cells, while the suppressive effects during allergic airway inflammation are B cell independent. These data demonstrated that BAFF regulated the outcome of T cell responses in vivo and identified BAFF dependent crosstalk between T and B cells. Stimulation of B cells with BAFF induced the upregulation of MHC class II and ICOS-L both in vitro and in vivo. Induction of these cell surface molecules was associated with an increased capacity to induce T cell proliferation, however this effect was independent of ICOS-L expression. Thus it was demonstrated that BAFF regulated T cell activation and effector function both directly, via stimulation of BAFF-R, and indirectly, by altering the function of B cells. These data suggest that BAFF dependent alterations in T cell function may be an additional causative factor in the association between elevated BAFF levels and the generation of autoimmunity.
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Ano, Monfils Nadhia. "Etude de la production et des caracteristiques biologiques du tnf alpha humain produit a partir d'une lignee cellulaire humaine." Lillle 2, 1993. http://www.theses.fr/1993LIL2P256.
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Li, Rui Xin. "Scutellarin inhibits TNF-induced proliferative expansion of Tregs by blocking TNF-TNFR2 interactions." Thesis, University of Macau, 2018. http://umaclib3.umac.mo/record=b3952140.
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Laureau, Serge. "Le tumor necrosis factor (tnf) en dermatologie : etude de la production de tnf par les monocytes circulants au cours du psoriasis : revue de la litterature." Aix-Marseille 2, 1990. http://www.theses.fr/1990AIX20817.
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劉耀南 and Yiu-nam Lau. "Interferons and tumour necrosis factor in chronic hepatitis B virus infection." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1990. http://hub.hku.hk/bib/B31981446.
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Lau, Yiu-nam. "Interferons and tumour necrosis factor in chronic hepatitis B virus infection." Hong Kong : University of Hong Kong, 1990. http://sunzi.lib.hku.hk/hkuto/record.jsp?B2158879X.
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Kam, Siu-kei Christy. "The role of TGF-[beta] signaling in the initiation of TNF-[beta] expression in human PBMC derived macrophages." Click to view the E-thesis via HKUTO, 2006. http://sunzi.lib.hku.hk/hkuto/record/B38746049.
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Kam, Siu-kei Christy, та 甘笑琪. "The role of TGF-{221} signaling in the initiation of TNF-α expression in human PBMC derived macrophages". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B38746049.
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Woo, Andrew Jonghan. "Characterization and identification of transcription factors that bind to the tumor necrosis factor -308 polymorphism." University of Western Australia. School of Biomedical and Chemical Sciences, 2003. http://theses.library.uwa.edu.au/adt-WU2004.0044.
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[Formulae and special characters can only be approximated. Please see the pdf version of this abstract for an accurate reproduction.] Tumor necrosis factor (TNF) is a pleiotropic cytokine that mediates a long list of immunological and pathophysiological processes. TNF is produced by a wide variety of cells including immune and non-immune cells, however in most cell types TNF is not expressed prior to stimulation. The function of TNF is mediated via its trimeric domain by binding to TNF receptors that are found on most types of cells, especially of the haematopoietic systems, hence transpiring its effects on a wide variety of cells and organ systems. The cytotoxic (apoptosis) and pro-inflammatory (differentiation, proliferation and activation) functions of TNF are protective but can also result in pathological or deleterious consequences. A biallelic G to A transition polymorphism in the promoter region of TNF at nucleotide position 308 from the transcription start site is suggested to be involved in differential transcriptional regulation of TNF expression. The high TNF producing 308A allele is associated with susceptibility to or worse outcome of many infectious diseases in addition to autoimmune and other pathophysiological conditions. A previous study in our laboratory observed a selective affinity towards the polymorphic 308A allele by an EMSA protein(s) complex, named E. Several other protein complexes were found along with complex E and one of them was identified as Sp1. The identification of complex E was unsuccessful but it was hypothesized to play a major role as transcriptional activator in 308A allele individuals hence transpiring its effect in various pathophysiological states. In this study, the EMSA complexes observed in the TNF promoter region between nucleotides 322 to 283, encompassing the 308 polymorphism, is characterized. EMSA using mutated oligonucleotides mapped the binding sites of complexes B, C, D and E. TRANSFAC database search in addition to previous work revealed the identity of complex C as Sp1 but the rest of complexes remained unknown. Moreover, in contrast to our previous study, the protein(s) in the complex E was found to preferentially bind 308G nucleotide hence posing as a transcriptional repressor, resulting in decreased production state of TNF in 308G allele individuals than 308A allele individuals. In order to characterize putative transcription factors binding to the promoter region, first the biochemical characteristics such as the effects of temperature, salts and cations on DNA binding ability of EMSA complexes were studied. EMSA complexes B, C, DI and E required cations, probably Zn+2, to bind DNA. By optimizing a technique that couples EMSA with SDS-PAGE, the molecular weight of C, DI and E was determined. A novel technique that couples EMSA with IEF determined the pI of complexes B, C, D, DI and E. Although a commonly used technique of identifying unknown DNA-binding protein of interest, Yeast One-Hybrid assay, did not identify complex E, the novel identification method involving chromatography, two-dimensional electrophoresis, EMSA, mass spectrometry and database interrogation successfully identified TNF EMSA complex E as transcription factor Ying Yang 1 (YY1). Supershift EMSA confirmed complex E as YY1. In addition, the supershift assay showed presence of Sp1 and Sp3 in complex C. Similarly, complex DI is identified as Sp3. The novel method in identifying DNA-binding proteins is particularly useful as this technique allows identification of protein seen in EMSA without the need of extensive identification process. YY1 binds to a 6 base pair sequence, 5? TTGAGG 3?, from nt 295 to 290 of TNF promoter. The loss of affinity in 308A allele is caused by transition of underlined G nucleotide to A. The determined and described molecular weight of YY1 in literature is 60 kDa while the theoretical weight is 45 kDa. Both the determined and theoretical pI of YY1 is 5.8. YY1 is a multifunctional transcription factor implicated in both positive and negative regulation of gene expression as well as in initiation of transcription. It is ubiquitously expressed in growing, differentiated, and growth-arrested cells. Although future experiment is yet to establish in vivo presence of YY1 in TNF promoter, our study so far provides convincing evidence that the putative transcription factor that has selective affinity towards 308G allele is indeed YY1.
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Youseff, Brian. "The Role of Tumor Necrosis Factor Receptor-Associated Factor 6 in Tick-Borne Flavivirus Infection." University of Toledo Health Science Campus / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=mco155691388498993.
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Emmanuel, Catherine. "Apoptotic And Morphometric Synergies Between Tumour Necrosis Factor-A And Transforming Growth Factor-B1 For Human Endothelial Cells." Thesis, The University of Sydney, 2006. http://hdl.handle.net/2123/4864.
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Pistilli, Emidio E. "The extrinsic apoptotic pathway in aged skeletal muscle roles of tumor necrosis factor-[alpha] and interleukin-15 /." Morgantown, W. Va. : [West Virginia University Libraries], 2006. https://eidr.wvu.edu/etd/documentdata.eTD?documentid=4912.
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Thesis (Ph. D.)--West Virginia University, 2006.<br>Title from document title page. Document formatted into pages; contains x, 189 p. : ill. (some col.). Includes abstract. Includes bibliographical references.
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Lampa, Jon. "Studies of pharmacological interventions and pathogenesis of rheumatoid arthritis /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-372-4/.
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Hakim, Akhlaq Waheed. "Tumor necrosis factor alpha and non-inflammatory sensitization of masseter muscle nociceptors." Thesis, University of British Columbia, 2011. http://hdl.handle.net/2429/34182.
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Behavioral evidence in rats indicates that injection of tumor necrosis factor alpha (TNFalpha into skeletal muscle results in a prolonged mechanical sensitization without gross inflammation. The present series of studies were conducted to test the idea that injection of TNFalpha causes mechanical sensitization of skeletal muscle through a peripheral mechanism that involves lowering of the mechanical threshold (MT) of muscle nociceptors without inflammation. In- vivo extracellular electrophysiological recording was used to assess the effect of TNFalpha (1 or 0.1microgram) and other drugs on the excitability and MT of masseter muscle nociceptors. Expression of TNFR1 (P55) and TNFR2 (P75) receptors by the masseter muscle and trigeminal ganglion neurons that innervate that muscle was determined by Western blot and immunohistochemical methodologies, respectively. The Evans blue dye technique and thermal camera recordings were used to assess inflammation in muscle tissues. Enzyme-linked immunoassays and glutamate biosensor probes were used to measure muscle concentrations of prostaglandin (PG) E2 and nerve growth factor, and glutamate, respectively. Intramuscular injection of 1mg TNFalpha did not excite nociceptors, but did significantly decrease MT compared to vehicle control. There was no evidence of gross inflammation 3 hours after injection of TNFalpha. Co-injection of TNFalpha with P55 or P75 receptor antibodies attenuated TNFalpha-induced mechanical sensitization. P55 and P75 receptors were expressed by 29% and 62% of masseter nociceptors, respectively. PGE2 and glutamate concentrations were significantly changed 3 hours after TNFalpha injection into the masseter muscle. Injection of diclofenac, a cycloxygenase inhibitor that attenuates prostaglandin synthesis, partially reversed the TNFalpha-induced decreases in the MT of masseter muscle nociceptors, while vehicle control, DL-2-amino-5-phophonovaleric acid, a competitive NMDA receptor antagonist, and a tyrosine kinase A receptor antibody, which blocks NGF-induced masseter muscle nociceptor sensitization, did not significantly alter nociceptor MT. These findings indicate that TNFalpha-induced mechanical sensitization of masseter nociceptors is mediated, in part, by increased PGE2 levels through activation of peripheral P55 and P75 receptors. Over all, these results suggest that injection of TNFalpha into skeletal muscle could be used as a model of myofascial trigger points to study the peripheral pain mechanisms of masticatory muscle pain.
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Vasconcelos, Daniel Fernando Pereira. "Analise do polimorfismo genetico do fator de necrose tumoral Beta (+252 A/G) em pacientes com periodontite cronica." [s.n.], 2005. http://repositorio.unicamp.br/jspui/handle/REPOSIP/290042.
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Orientadores: Silvana Pereira Barros, Sergio Roberto Peres Line<br>Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba<br>Made available in DSpace on 2018-08-04T03:46:37Z (GMT). No. of bitstreams: 1
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Previous issue date: 2005<br>Resumo: A doença periodontal (DP) é causada por interações entre fatores do hospedeiro, microrganismos específicos patogênicos e o sistema imunológico. TNF-b é um imunoregulador multifuncional que está relacionado com a patogênese de diversas desordens imunológicas, incluindo a DP. Nosso estudo analisou a associação entre DP e polimorfismo no gene TNF-b (+252 A/G). O DNA foi extraído de células da mucosa oral de 126 indivíduos brancos: 44 indivíduos controle e 82 indivíduos com DP. O polimorfismo foi analisado pela técnica de PCR, seguida pela RFLP. Os dados foram estatisticamente analisados pelo teste Exato Fisher (p<0,05) e Odds Ratio (OR). A freqüência do polimorfismo mostrou diferença estatisticamente significativa entre os grupos controle e com DP, revelando que indivíduos portadores do alelo G apresentavam 2,6 vezes mais chances de desenvolver a DP do que indivíduos saudáveis (G vs. A, p=0.0019, OR= 2.67, 95% CI 1.45 - 4.78), em relação aos genótipos a presença de pelo menos um alelo G predispõe 3,1 vezes à DP (G/G+ G/A vs. A/A, p=0,0059, OR= 3.1, 95% CI 1.45 - 6.65). Conclui-se que o TNF-b está envolvido na patogênese da periodontite crônica e pode ser utilizado como um marcador de risco para a DP na população estudada<br>Abstract: Background: Periodontitis is an inflammatory disease that leads to irreversible attachment loss, bone destruction and eventually bone loss, such cascade that culminates in tissue destruction initiates with pathogenic micro-organisms and depends on host response to disease expression. Tumor necrosis factor (TNF) a potent multifunctional immune modulator has been implicated in the pathogenesis of periodontal disease. Objective: In this study we investigated the hypothesis of association between chronic periodontitis (CP) and polymorphisms of the TNF-ß gene. Materials and Methods: One hundred twenty six individuals were evaluated by measuring clinical attachment loss and divided in 44 health individuals (control group-CG) and 82 subjects with CP. DNA samples were obtained from the individual's epithelial cells through scraping of the buccal mucosa. Polymorphism in the TNF-ß gene was analyzed by PCR, followed by NcoI restriction endonuclease digestion (RFLP). Results: The TNF-ß (+252A/G) polymorphism showed association with chronic periodontitis. Significant differences were found for the TNF-ß allele or carriage rate frequencies; odds ratio (OR)=2.67. Conclusions: These findings suggest that genotype composed of TNF- ß gene polymorphism may influence the susceptibility to chronic periodontitis<br>Mestrado<br>Histologia e Embriologia<br>Mestre em Biologia Buco-Dental
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Rogers, Gabrielle Marie. "Tumor necrosis factor- alpha production induced by peptidoglycan-polysaccharide in early pregnant ewes." Morgantown, W. Va. : [West Virginia University Libraries], 2006. https://eidr.wvu.edu/etd/documentdata.eTD?documentid=4712.
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Thesis (M.S.)--West Virginia University, 2006.<br>Title from document title page. Document formatted into pages; contains vi, 45 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 40-45).
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Zhang, Min. "The role of B cell activating factor in B cell development and autoimmunity." Click to view the E-thesis via HKUTO, 2006. http://sunzi.lib.hku.hk/hkuto/record/B37659807.
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Vaughan-Scott, Tarquin. "Serum concentrations of tumour necrosis factor in dogs naturally infected with Babesia Canis and its relation to severity of disease." Diss., University of Pretoria, 2002. http://hdl.handle.net/2263/29287.
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Please read the abstract in the section 00front of this document<br>Canine babesiosis, caused by the tick-borne protozoan Babesia canis rossi, is an
economically important and potentially fatal disease of dogs in South Africa. The host's
response to many infectious diseases is mediated (at least in part) by intercellular
messengers called cytokines. One of the most important cytokines released is tumour
necrosis factor (TNF).
A study was designed to measure serum concentrations of TNF in dogs naturally
infected with canine babesiosis and to relate TNF concentrations to clinical severity,
mortality, rectal temperature and parasitaemia.
There was a statistically significant difference in TNF concentrations between groups
of differing disease severity, with a general trend of increasing mean 10g(TNF) with
increasing severity of disease. A noteworthy finding was that dogs with hypoglycaemia
had very high TNF (mean 15.03 nglml compared to a mean of 2.32 nglml for other sick
dogs without hypoglycaemia). When TNF values were compared between survival and
non-survival groups, there was no significant difference. The rectal temperature of the
dogs in this study did not show any statistically significant association with TNF
concentrations. When parasitaemia and TNF were examined within groups of infected
dogs, there was no significant relationship. However, when the sample size was
increased by pooling all infected dogs and treating them as a single group, there was a
highly significant positive correlation (p = 0.003) between parasitaemia and serum TNF
concentrations.
The results ofthis study were encouraging and indicate that canine babesiosis may
share a similar pathophysiology with human malaria in terms ofTNF being associated
with disease severity. One ofthe most significant findings in this study was the
presence ofvery high TNF values in two ofthree dogs with hypoglycaemia.
Hypoglycaemia has not been previously recorded in dogs with babesiosis and is a
potentially important finding particularly in view ofthe hypoglycaemia associated with
malaria in humans. Malarial hypoglycaemia is correlated with a higher mortality in
humans, especially in pregnant women and children. If the findings ofthis study can be
Vl
confinned and expanded, they may lend further support to the use of canine babesiosis
as a model for some ofthe problems encountered in human malaria research.<br>Dissertation (MMed Vet (Med))--University of Pretoria, 2001.<br>Companion Animal Clinical Studies<br>unrestricted
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Pedro, Renato Nardi. "Uso da nanopartícula de ouro ligada a moléculas de fator alfa de necrose tumoral como adjuvante da termoablação por radiofrequência de tumores renais = modelo animal experimental." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310676.
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Orientadores: Marcelo Lopes de Lima, Nelson Rodrigues Netto Junior<br>Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas<br>Made available in DSpace on 2018-08-17T00:02:35Z (GMT). No. of bitstreams: 1
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Previous issue date: 2010<br>Resumo: O tratamento definitivo das massas renais malignas é primordialmente cirúrgico, sendo a nefrectomia radical eleita por muitos anos a cirurgia padrão para o tratamento do câncer renal localizado. Entretanto, com o envelhecimento populacional, maiores são as preocupações em se manter a capacidade funcional dos órgãos e sistemas do corpo humano. Portanto, a necessidade de se preservar tecido renal sadio durante o tratamento do câncer renal localizado, com auxílio de cirurgias parciais poupadoras de néfrons, se tornou imperativa. O tratamento de lesões renais sólidas pequenas passou a ter diferentes formas de abordagem, que variam desde técnicas de termoablação percutânea ou laparoscópica, nefrectomia parcial laparoscópica e aberta à até tradicional nefrectomia radical aberta. O uso de modalidades de tratamento cirúrgico com mínimo grau de agressão passou a ganhar atenção, devido à rápida recuperação do paciente, ao menor risco de complicações cirúrgicas e aos bons resultados oncológicos. Ablação por radiofreqüência (ARF) tem se mostrado um meio eficiente no tratamento de tumores renais pequenos e exofiticos. Atualmente, sua indicação é restrita a lesões de até 4 cm. O presente estudo foi montado para avaliar o uso conjunto da nanopartícula de ouro e fator alfa de necrose tumoral (TNF alfa) à ARF no tratamento de um modelo experimental de tumor renal. Materiais e Métodos: Trinta e sete coelhos brancos da raça New Zealand tiveram implantados em seus rins, através de uma laparotomia, um fragmento de 1 mm3 de tumor VX-2. Após 14 dias do implante, quando seus rins haviam desenvolvido uma lesão tumoral sólida menor que 1 cm, os animais foram divididos em 3 grupos de 10 e 1 grupo de 7 integrantes (sham) de acordo com o tratamento selecionado para o tumor renal focal: 1) Nanopartícula com TNF alfa; 2) Ablação por radiofreqüência; 3) Nanopartícula com TNF alfa seguido de Ablação por radiofreqüência; 4) Grupo sham. Todos os animais foram submetidos a mesma cronologia de tratamento, composta por 2 laparotomias e eutanásia. Os grupos tratados com as nanopartículas de ouro com fator alfa de necrose tumoral isolada ou complementarmente, as receberam 4 horas antes do procedimento cirúrgico na dose de 200 µm/Kg. A análise de resultados foi realizada com medidas macroscópicas e microscópicas do volume da área de ablação ou tumoral, segundo a fórmula do volume de uma elipsóide. Avaliação estatística foi realizada com Teste T Student, sendo considerado significante p<0.05. Resultados: O grupo que recebeu a nanopartícula com fator alfa de necrose tumoral e depois foi submetido à ARF apresentou maior zona de morte celular completa quando comparado ao grupo tratado somente com ablação por radiofreqüência (0.30 ± 0.07 vs 0.23 ± 0.03 mL, P=.03). A zona de transição foi menor no grupo que recebeu a nanopartícula com fator alfa de necrose tumoral e ablação por radiofreqüência quando comparada ao grupo tratado somente com ablação por radiofreqüência (0.08 ± 0.02 vs 0.13 ± 0.05 mL, P =.01). Conclusão: O presente estudo demonstrou que o uso da nanopartícula de ouro com TNF alfa sensibiliza o insulto térmico sofrido por tumores sólidos decorrentes da ablação por radiofreqüência<br>Abstract: Radical nephrectomy has long been considered as gold standard treatment for localized renal tumors. However due to an increase in life expectation, organ sparing surgeries have emerged with the purpose of preserving as much healthy tissue as possible. Therefore, nephron sparing surgeries have become another valid option for localized renal tumors. There are different modalities of nephron sparing procedures, including open partial nephrectomy, laparoscopic nephrectomy and termoablative procedures. The later is associated with less morbidity and fast patient recovery. Radiofrequency ablation (RFA) is a well-known termoablative procedure and it has been most effective when the tumors are small, exophytic, and away from vital structures. The present study was designed to analyze the adjuvant use of gold nanoparticle with tumor necrosis factor alpha prior to radiofrequency ablation in a translational model of localized renal tumor. Material and Methods: A total of 37 New Zealand White rabbits had VX-2 tumors implanted into their kidneys; they were allowed to grow for 14 days, when a tumor mass of less than 1 cm could be detected. The animals were then split into 3 treatment groups of 10 rabbits each and a sham group of 7 rabbits as follows: (1) Tumor necrosis factor alpha plus nanoparticle, (2) Radiofrequency ablation, (3) Tumor necrosis factor alpha nanoparticle (200 µm/Kg) followed 4 hours later by radiofrequency ablation. All groups were subjected to the same milestones of the experiment which was comprised of 2 laparotomies and sacrification. Gross and microscopic measurements of the ablation size as well as histological analysis using hematoxylin and eosin staining were performed to determine the effect of TNF alpha nanoparticle on the ablation. Statistical analysis was performed with Student's T test, considering p < 0.05 as significant. Results: The RFA plus TNF alpha nanoparticle group had a larger zone of complete cell death than the RFA-only group (0.30 ± 0.07 vs 0.23 ± 0.03 mL, P=.03). The zone of partially ablated tissue was smaller in the RFA plus TNF alpha nanoparticle group than in the RFA-only group (0.08 ± 0.02 vs 0.13 ± 0.05 mL, P =.01). Conclusions: We have demonstrated the efficacy of TNF alpha nanoparticle in enhancing RFA in a translational kidney tumor model. The potential usage of TNF alpha nanoparticle to improve RFA of renal cell carcinoma merits further study<br>Doutorado<br>Fisiopatologia Cirúrgica<br>Doutor em Ciências
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Catrina, Anca Irinel. "Studies of molecular mechanisms of action of TNF antagonists in rheumatoid arthritis /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-102-4/.
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Liddil, James Duncan 1960. "Mechanisms of the cytotoxic actions of tumor necrosis factor (TNF) in cultured cancer cells." Thesis, The University of Arizona, 1987. http://hdl.handle.net/10150/276602.
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Tumor necrosis factor's (TNF) cytotoxic mechanism of action was examined using cultured cancer cell lines. TNF demonstrated cytolytic and cytostatic effects on L929 fibrosarcoma and MCF-7 adenocarcinoma cells. TNF failed to show any specific effects on RNA, DNA or protein synthesis or ATP content in tumor cells in vitro. It did not cause DNA single strand breaks. Decreased cellular levels of reduced thiols did not predict sensitivity to the cytotoxic effects of TNF. Depletion of cellular glutathione failed to increase the sensitivity of TNF-sensitive or resistant cells. However, various non-specific and specific lysosomotropic agents lead to an inhibition of TNF's cytotoxic action. Differences in enzyme activity, primarily lysosomal, were noted between TNF-sensitive and resistant cells. These changes involved a general halving of lysosomal proteins and enzymes in the TNF-resistant cells. The antitumor activity of TNF does not involve specific inhibition of macromolecular synthesis but may involve alterations in lysosomes.
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Ayub, Qasim. "Prevention of endotoxic shock in mice using anti-tumor necrosis factor-alpha monoclonal antibody." Thesis, University of North Texas, 1991. https://digital.library.unt.edu/ark:/67531/metadc798464/.
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Howat, Sarah Lamont Telfer. "TSG6 : expression and influence on the stability of the extracellular matrix in joint tissues." Thesis, Imperial College London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326100.
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Neville, Matt J. "Characterisation of the genomic region around the TNF locus within the human major histocompatibility complex in the chromosome band 6p21.3." Thesis, University of Oxford, 2000. http://ora.ox.ac.uk/objects/uuid:1fcb0019-0b54-418a-a44c-b1b4a7d5a51e.
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It is becoming increasingly apparent that many of the genes in the class III region of the human Major Histocompatibility Complex encode proteins involved in the immune and inflammatory responses. Furthermore, genetic studies have indicated that genes within the class III region, particularly the telomeric segment containing the TNF gene, could contribute to susceptibility to diseases of immune-related aetiology. To further characterise this region and to identify candidate disease susceptibility genes, two overlapping cosmids, TN62 and TN82, covering an ~82kb segment of DNA around the TNF gene were selected for sequence analysis. The eight known genes in this region have been precisely positioned with the order: Gl/AIF-1, 1C7, LST1 (B144), LTB, TNF, LTA, IKBL, BAT1 (centromere to telomere) and their genomic structures have been defined. Comparison of the Gl genomic region with previously described cDNA and genomic sequences, together with the results of RT-PCR, indicates that three alternative transcripts, Gl, Allograft Inflammatory Factor-1 and Interferon-γ Responsive Transcript-1, are all derived from this gene. The completion of the sequence of 1C7 (D6S2570) has revealed that this gene encodes a putative novel member of the immunoglobulin superfamily. A number of alternatively spliced transcripts of 1C7 were identified by RT-PCR, all of which are expressed in immune-related cell lines. Alternative splicing within the immunoglobulin domain- encoding region was seen to result in possible set switching between an IgV domain and an IgC2 domain. In addition to this, a previously unidentified gene, homologous to a number of V- ATPase G-subunits, has been located 1kb telomeric of IKBL. Lastly, the pseudogene UCRH-L and an AIF-1 gene fragment have been identified in the intergenic region between AIF-1 and 1C7. In order to assess the contribution of loci in this region to disease susceptibility, the genes AIF-1, 1C7, ATP6G and the BAT1 promoter region were subjected to mutation analysis. A total of 28 polymorphisms have been identified, 8 in AIF-1, 10 in 1C7, 7 in ATP6G and 3 in the BAT1 promoter region. Work is at present underway to genotype a number of the identified polymorphisms in control DNAs and in DNA samples from patients with combined variable immunodeficiency (CVID). The information generated from this analysis will bring us closer to explaining the reported linkage of CVID with the telomeric end of the human MHC class III region.
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BOTTIER, DANIEL. "Interet clinique de l'immunodosage enzymatique de l'il-1 et du tnf dans les liquides biologiques." Nice, 1991. http://www.theses.fr/1991NICE6830.
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