Rozprawy doktorskie: „Platelet activating factor”

1

Scarlett, Julie Anne. "Platelet activating factor in the horse". Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.387750.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

2

Murphy, Christine Therese. "Mechanisms of stimulus-response coupling in platelet-activating factor stimulated platelets". Thesis, University of Bath, 1992. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.304999.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

3

DENTAN, CHRISTINE. "Platelet-activating factor (paf), acetylhydrolase et atherosclerose". Paris 6, 1996. http://www.theses.fr/1996PA066772.

Pełny tekst źródła

Streszczenie:

L'atherosclerose est une pathologie des vaisseaux, multifactorielle, qui a un caractere immuno-inflammatoire chronique. Or, de plus en plus de donnees argumentent le role pro-atherogene et pro-thrombogene d'un puissant mediateur glycerophospholipidique, le platelet-activating factor (paf), qui est degrade specifiquement par l'acetylhydrolase. Cette hypothese est etayee par nos travaux qui ont mis en evidence la formation du paf dans un modele de cellules spumeuses, riches en esters de cholesterol, stimulees par phagocytose. Ces cellules, qui representent la principale composante cellulaire du noyau lipidique des plaques d'atherome, pourraient donc constituer in vivo une source importante de paf. Nous avons montre egalement que l'acetylhydrolase regule la quantite du paf present dans ces cellules activees. Par la suite, nous avons focalise nos etudes sur cette enzyme. Nous avons d'abord caracterise un nouvel inhibiteur de l'acetylhydrolase : le 4-2-aminoethyl benzenesulfonyl fluoride (pefabloc) qui se fixe sur le groupement serine du site actif enzymatique. Nous avons ensuite mis en evidence, chez des sujets normolipidemiques, une heterogeneite de la distribution de l'activite acetylhydrolase au sein des lipoproteines plasmatiques. En effet, parmi les lipoproteines de faible et haute densite (ldl et hdl), les particules les plus denses et les plus petites (ldl-5 et vhdl-1) possedent une grande proportion de l'activite acetylhydrolase plasmatique au sein desquelles celle-ci presente des proprietes catalytiques distinctes. De plus, les ldl denses seraient notamment le vecteur principal de l'acetylhydrolase secretee par les monocytes humains adherents. Ainsi, puisque l'entree des lipoproteines plasmatiques dans l'espace sous-endothelial serait inversement proportionnelle a la taille des particules, les ldl denses et les vhdl-1 pourraient jouer un role-cle anti-inflammatoire au sein de l'intima arterielle. Cependant, par la suite, nos travaux ont montre que l'acetylhydrolase associee aux ldl est totalement inactivee lorsque les particules sont oxydees. De meme, l'activite anti-coagulante de l'inhibiteur du facteur tissulaire (tfpi) est inhibee dans les ldl oxydees. Nous avons donc demontre une nouvelle propriete atherogene des ldl oxydees qui, in vivo au sein des lesions atherosclerotiques, ne seraient notamment plus capables d'inhiber les effets atherogenes du paf ainsi que ceux des phosphatidylcholines oxydees, egalement substrats et presentes dans les ldl oxydees. Ces travaux apportent des donnees nouvelles sur le metabolisme du paf ; ce dernier interviendrait certainement dans la constitution et l'evolution des lesions atherosclerotiques ainsi que dans les evenements menant a la rupture de la plaque et a la thrombose. L'acetylhydrolase jouerait un role-cle dans la regulation des effets inflammatoires du paf et les etudes a venir devront preciser les fonctions de cette enzyme in vivo au sein de l'intima arterielle.

Style APA, Harvard, Vancouver, ISO itp.

4

Bonin, Fanny. "Cytoprotective effects of intracellular platelet activating factor acetylhydrolases". Thesis, University of Ottawa (Canada), 2003. http://hdl.handle.net/10393/26529.

Pełny tekst źródła

Streszczenie:

Platelet activating factor (PAF) is a biologically active phospholipid implicated in the developmental brain disorder Miller-Dieker Syndrome (MDS) and purported to be a primary mediator of cell death in HIV-dementia, ischemia, and epilepsy. As part of my honour's thesis, I demonstrated that PAF can elicit cell death independently of its G-protein coupled receptor (PAFR) in PC12 cells. In my M.Sc. research, I have sought to identify how PAF-mediated cell death is regulated in PC12 cells. PAF is inactivated in brain by two intracellular PAF-acetylhydrolases (PAF-AHs): PAF-AH I and PAF-AH II. PAF-AH I is a trimeric complex composed of two catalytic subunits (alpha1 and alpha2) and one regulatory subunit (beta). Mutations in the Lis1 gene, coding for the beta subunit of PAF-AH I, are the genetic determinant of MDS. However, it is not clear whether these mutations impact on PAF-AH I enzymatic activity in MDS. Furthermore, it is not known whether cytosolic PAF-AH activity regulates the kinetics of neuronal loss following pathophysiological challenge. To begin to address these questions, I sought to identify an in vitro model system suitable for study of PAF-AH activity.* (Abstract shortened by UMI.) *This dissertation is a compound document (contains both a paper copy and a CD as part of the dissertation). The CD requires the following system requirements: QuickTime.

Style APA, Harvard, Vancouver, ISO itp.

5

Gomez, Jorge. "Characterization and regulation of platelet activating factor receptors". Diss., The University of Arizona, 1990. http://hdl.handle.net/10150/185248.

Pełny tekst źródła

Streszczenie:

Platelet activating factor (PAF) is a potent mediator in a variety of inflammatory events. Determining whether PAF participates in the bronchial hyperresponsiveness characteristic of asthma is the long term obj ecti ve for which the studies described here represent an initial step. PAF is a potent agonist that causes contraction of guinea pig peripheral lung strips. To determine if specific receptor sites for PAF could be demonstrated in guinea pig lung membranes (GPLM), direct radioligand binding studies were performed with [³H]C₁₆-PAF (l-0-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine) and the PAF antagonists [³H]WEB 2086 and [³H]RP52770. Binding parameters were compared to those from rabbit platelet membranes (RPM). These studies demonstrated specific binding sites for [³H] C₁₆-PAF of high affinity in GPLM with a Kd of 3 nM,• and in RPM with a K(d) of 1 nM. [³H]C₁₆-PAF identified receptor densities in GPLM of 200 fmol/mg protein and in RPM of 1922 fmol/mg protein. In both tissue preparations binding of inhibited to the same maximum degree by C₁₆-PAF, C₁₈-PAF, WEB 2086, and RP52770, all with pseudo-Hill coefficients of unity. The PAF antagonist [³H]WEB 2086 identified a receptor density similar to that of [³H]C₁₆-PAF. The binding of [³H]WEB 2086 was inhibited to the same degree by C₁₆-PAF, C₁₈-PAF, WEB 2086 and RP52770, indicating WEB 2086 and PAF interact at the same receptor sites in both GPLM and RPM. Although inhibition curves for antagonists yielded pseudo-Hill coefficients of unity, inhibition by agonists yielded shallow inhibition curves suggesting two types or states for the PAF receptor. The PAF antagonist [³H]RP52770 was found to be an unsuitable ligand because it labeled a much larger density of binding sites (1200 fmol/mg protein in GPLM, and 10105 fmol/mg protein in RPM) and was inhibited to little or no extent by C₁₆-PAF, C₁₈-PAF, WEB 2086 or lyso-C₁₆-PAF . studies of signal transduction suggest that the binding affinity of the agonists C₁₆-PAF and C₁₈-PAF (but not for the antagonist WEB 2086) is regulated by GTPgamroa- S and Na⁺, providing indirect evidence that the PAF receptor in both tissue preparations is coupled to a guanine nucleotide regulatory protein. However, agonist binding retained shallow inhibition curves indicating heterogeneity of sites with respect to this regulation. Binding affinity for the agonists was not affected by cholera toxin or pertussis toxin. These results indicate PAF receptors in lung tissue could not be distinguished from those in RPM, however, both tissues appear to show heterogeneity of binding indicating the existence of receptor subtypes or states.

Style APA, Harvard, Vancouver, ISO itp.

6

Vanags, Daina M. "Adrenergic and serotonergic potentiation of platelet aggregation /". Title page, summary and contents only, 1993. http://web4.library.adelaide.edu.au/theses/09PH/09phv217.pdf.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

7

Kabbani, Nazir. "Chemical-genetic profiling of platelet-activating factor in yeast". Thesis, University of Ottawa (Canada), 2009. http://hdl.handle.net/10393/28189.

Pełny tekst źródła

Streszczenie:

The basic biological processes between the yeast Saccharomyces cerevisiae and mammals are highly conserved. Yeast posses many genes that are implicated in human diseases and have been successfully used as a model for the study of neurodegeneration. Platelet-Activating Factor (C16:0 PAF) causes neuronal cell death independent of its receptor and has been implicated in Alzheimer's disease. I hypothesized that yeast could be used as a model system for deciphering PAF receptor-independent signalling and have utilized genome-wide chemical genomic screening in yeast to further characterize the molecular mechanism of PAF toxicity. Two complementary screens implicate PAF in many cellular processes, some of which parallel results obtained in mammalian studies. I have found that PAF challenge is cytotoxic, delays cell cycle progression, and affects actin stability leading to spindle misorientation and bi-nucleate mother cells.

Style APA, Harvard, Vancouver, ISO itp.

8

Rowe, Anna-Louise. "The role of platelet-activating factor in necrotising enterocolitis". Thesis, University of Birmingham, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.434713.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

9

Göggel, Rolf. "The mechanisms of platelet activating factor induced alterations in lung functions /". Konstanz : Hartung-Gorre, 2002. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=009757517&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

10

Bosnic, Anthony Martin. "Human antibody responses to a chlamydia-secreted protease factor : a thesis /". San Antonio : UTHSC, 2005. http://learningobjects.library.uthscsa.edu/cdm4/item%5Fviewer.php?CISOROOT=/theses&CISOPTR=14&REC=5.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

11

Huang, Yihui. "Platelet-activating factor and lysophosphatidylcholine in oxidized low density lipoprotein-mediated immune activation /". Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3450-9/.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

12

Foster, Adrian Paul. "Platelet activating factor : a putative mediator of equine cutaneous inflammation". Thesis, Royal Veterinary College (University of London), 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.519548.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

13

Court, Elaine N. "Platelet-activating factor : its actions and release in the lung". Thesis, University of Sunderland, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.327832.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

14

Griffiths, Rachael. "The Regulation of Platelet Activating Factor Acetylhydrolase by Oxidized Phospholipids". VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1913.

Pełny tekst źródła

Streszczenie:

Platelet-activating factor acetylhydrolase (PAFAH) is elevated in atherosclerosis and may play a role in pathogenesis of this disease. Molecular mechanisms regulating the expression of this lipoprotein-associated PLA2 are indistinct. Mildy oxidized low density lipoprotein (oxLDL) and monocytes (the primary source of PAFAH) are co-localized in early atheromas. Monocytes are activated by oxidized phospholipids (oxPL) in the oxLDL particle. We hypothesized that oxPL-activated monocytes are the source of increased levels of PAFAH in atherosclerosis. We found that PAFAH expression is significantly induced by OxPAPC and in particular long-chain fractions of oxPAPC in monocytes and cytokine-differentiated DC, but not cytokine-differentiated MO. Furthermore, spontaneously differentiated MO and DC from monocytes of non-periodontitis and aggressive periodontitis subjects, oxPAPC induced PAFAH in DC alone. 1-palmitoyl-2-epoxyisoprostane-sn-glycero-3-phosphocholine (PEIPC) is a particularly bioactive component of long-chain oxPAPC fractions that binds the prostaglandin receptor subtypes DP1 and EP2. We revealed using selective agonists and antagonists of these receptors that DP1 and EP2 are required for the induction of PAFAH expression. OxPAPC stimulates IL-6 release from monocytes and this cytokine is required for oxPAPC-induced PAFAH expression. We next tested the hypothesis that oxPAPC did not induce PAFAH in MO because a key component of the signaling machinery was lacking. Flow cytometric and immunoblot analyses demonstrated that MO express very low levels of IL-6 receptor in comparison to DC and monocytes. Based on these observations, we propose that long-chain oxPL induce PAFAH expression by binding DP1 and/or EP2 and stimulating IL-6 production. These data strongly support the hypothesis that oxLDL-activated DC are the source of high PAFAH levels in atherosclerosis. Platelet activating factor (PAF) is the inflammatory phospholipids for which PAFAH is named. PAF has been shown by other investigators to induce the expression of PAFAH. In our physiologically relevant monocytes, PAF suppresses PAFAH transcription and expression. 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphatidylcholine (POVPC) is a short-chain oxPL that signals through the PAF receptor. Our preliminary data suggest that like PAF, POVPC suppresses PAFAH expression in monocytes. Further investigation into the effects of the short-chain oxPL are warranted. Our data support the hypothesies that oxPL-activated DC are the source of high PAFAH levels in atherosclerosis.

Style APA, Harvard, Vancouver, ISO itp.

15

Chase, Peter Burritt 1955. "The molecular pharmacology of a human platelet-activating factor receptor". Diss., The University of Arizona, 1996. http://hdl.handle.net/10150/290574.

Pełny tekst źródła

Streszczenie:

Platelet-activating factor (PAF) is a broadly bioactive family of phospholipids which contribute to the pathogenesis of numerous diseases as well as to many normal physiologic processes. The pleiotropic nature of PAFs actions may be due to the activation of several intracellular signaling pathways or the presence of PAF receptor subtypes. Therefore, to begin to understand the complex mechanisms by which PAF molecules induce cellular responses, a molecular approach was initiated to provide tools to investigate many of the issues surrounding PAF receptors. Using a strategy based upon homology cross hybridization, a coding sequence homologous to that of the guinea pig PAF receptor cDNA was identified in a 20 kb insert obtained from human genomic DNA. A portion of the insert was sequenced and appears to be the human homolog of the cloned guinea pig receptor. Although the sequence identity shows that the gene for the human PAF receptor does not contain introns in the coding region, the 5'-untranslated sequence deviates from previously reported cDNA sequences suggesting that at least one intron is present in the untranslated region and represents evidence for alternative mRNA splicing. The 20 kb human genomic fragment also allowed for regional mapping of the PAF receptor gene by fluorescence in situ hybridization and found to localize to chromosome 1 (1p35-> p34.3). Specific localization of the PAF receptor gene to the distal portion of chromosome 1 may assist in understanding the genetic predisposition of certain patients to inflammatory diseases. To examine the second messenger coupling of the cloned PAF receptor and adenylyl cyclase, a cAMP-responsive reporter gene has been used in transiently transfected human choriocarcinoma cells. Preliminary data suggests that PAF receptor signal transduction does result in inhibition of basal and agonist-stimulated adenylyl cyclase activity. PAF receptor specific antibodies could assist in tissue localization of the cloned PAF receptor as well as provide evidence for PAF receptor subtypes. Antibodies were produced against fusion protein consisting of glutathione-S-transferase and a peptide from the purported 2nd extracellular region of the cloned PAF receptor which recognized the native protein in transfected COS-7 cells.

Style APA, Harvard, Vancouver, ISO itp.

16

管漢偉 i Hon-wai Michael Koon. "Potentiating effects of platelet activating factor on endothelin-1 induced rat arota vasoconstriction". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1998. http://hub.hku.hk/bib/B31221014.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

17

Koon, Hon-wai Michael. "Potentiating effects of platelet activating factor on endothelin-1 induced rat arota vasoconstriction /". Hong Kong : University of Hong Kong, 1998. http://sunzi.lib.hku.hk/hkuto/record.jsp?B20565689.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

18

Usman, Rukhsana. "Platelet activity and arachidonic acid metabolism: modulation by factors in plasma and cerebrospinal fluidand by diet". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1994. http://hub.hku.hk/bib/B31233934.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

19

Muller, Michael John. "Modulation of the response to cutaneous injury /". [St. Lucia, Qld.], 2000. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16146.pdf.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

20

Usman, Rukhsana. "Platelet activity and arachidonic acid metabolism : modulation by factors in plasma and cerebrospinal fluid and by diet /". [Hong Kong] : University of Hong Kong, 1994. http://sunzi.lib.hku.hk/hkuto/record.jsp?B13787263.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

21

Bennett, Steffany Ann Larwill. "The role of platelet activating factor in tumour progression and neurodegeneration". Thesis, University of Ottawa (Canada), 1995. http://hdl.handle.net/10393/10728.

Pełny tekst źródła

Streszczenie:

Tumourigenesis is the result of increased cell number. Progressive neurodegenerative disorders are characterized by decreased cell number. These illnesses emphasize the life-threatening consequences of disrupting the delicate balance between cell growth, cell differentiation, and cell death. Exposure to chronic inflammation is a recognized risk factor for a variety of human cancers and progressive neurodegenerative diseases. This thesis represents an attempt to determine whether one endogenous proinflammatory agent, platelet activating factor (PAF), may participate in tumourigenesis and/or neurodegeneration. Data are presented to indicate that PAF is capable of inducing sustained alterations in both the rate of cell growth and the rate of cell death in non-inflammatory cells. This ability can be characterized as follows: (1) Brief stimulation (<1 hr) of rodent and human fibroblasts and epithelial cells cultured in vitro induced PAF receptor activation, PKC activity, phosphorylation of proteins on tyrosine residues, oxyradical production, and de novo gene expression of the proto-oncogene c-fos and the active cell death (ACD)-related gene clusterin. (2) Transient stimulation (1-6 hr) elicited long-term growth enhancement (60-80 days) characterized by increased focus formation, saturation density, autonomous cell growth, and AI growth in the absence of further ligand exposure. Cell proliferation was, apparently, mediated by increases in intracellular PAF concentrations triggering the synthesis and release of mitogenic factors. Growth enhancement was accompanied by induction of clusterin and urokinase plasminogen activator gene expression. (3) Prolonged exposure (72 hr) to PAF induced ACD when cells were cultured in the absence of excess growth factors. ACD was determined by changes in nuclear and cytoplasmic morphology and by DNA analysis. (4) The kinetics of these responses to PAF could be altered by introduction of an activated ras oncogene into cells. Transient exposure to PAF under suboptimal growth conditions was sufficient to elicit a defined period of cell loss in ras-transformed fibroblasts followed by growth enhancement in surviving cells. (5) Increased PAFR expression was associated with chronic neurodegenerative lesions and cell death in vivo using a kainic acid model of myoclonic epilepsy. In summary, PAF, was shown to be capable of disrupting the delicate balance between cell growth and cell death. In this manner, PAF may contribute to tumour progression and progressive neurodegenerative disorders.

Style APA, Harvard, Vancouver, ISO itp.

22

Teoh, Diane Marie. "Platelet-Activating Factor, PAF, and its effects on human neutrophil CD43". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0018/MQ49657.pdf.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

23

Furno-de, Winter Agnès. "Synthese d'agonistes et d'antagonistes du paf (platelet activating factor) : etude pharmacotoxicologique". Paris 7, 1988. http://www.theses.fr/1988PA077055.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

24

Furno-de, Winter Agnès. "Synthèse d'agonistes et d'antagonistes du PAF, Platelet Activating Factor étude pharmacotoxicologique /". Grenoble 2 : ANRT, 1988. http://catalogue.bnf.fr/ark:/12148/cb37613711w.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

25

Noël, Cynthia Jenny. "Modulation orthostérique et allostérique du PAFR par des molécules synthétiques". Mémoire, Université de Sherbrooke, 2008. http://savoirs.usherbrooke.ca/handle/11143/3974.

Pełny tekst źródła

Streszczenie:

Le PAF (facteur d'activation des plaquettes) est un médiateur lipidique de l'inflammation très puissant impliqué dans plusieurs conditions pathophysiologiques.Le PAF agit principalement via un seul récepteur, le PAFR qui appartient à la famille des récepteurs couplés aux protéines G, les GPCRs. Le"two state model" assume que les GPCRs existent dans un état d'équilibre entre un état inactif (R) et un état actif (R*). L'isomérisation de R vers R* peut arriver de façon spontanée, c'est à dire indépendamment de la liaison d'un agoniste. Dans ces travaux de recherche, nous avons tenté de déterminer la propriété antagoniste et agoniste inverse des molécules orthostériques (WEB2086, PCA4248, FR49175, bromure d'octylonium, CV3988 et le Trans BTP dioxolane) à activer la voie des MAPK ainsi que le cycle biochimique des inositols phosphates dans la lignée cellulaire HEK 293 transfectée de façon stable avec le récepteur du PAF. De plus, l'activité potentiellement allostérique sur le PAFR de modulateurs synthétiques tels le THG-315, le THG-316 et MAREK a également été investiguée dans la même lignée cellulaire. Finalement, des surnageants d'hybridome 9H1/1C1, 9F5/1H4, 9F5/1H4, 9F5/1F8, 9F5/2B3 et 9F5/2E4 contenant des anticorps monoclonaux, dirigés tous contre un peptide qui équivaut à la région C-terminale de la troisième boucle extracellulaire du PAFR: GFQDSKfHQA ont également été utilisés, afin : (1) de déterminer le meilleur clone en terme d'affinité et de spécificité et (2) effectuer des tests pour savoir s'ils possèdent des propriétés agonistes ou antagonistes sur le PAFR. En conclusion, les résultats obtenus nous indiquent que : (1) l'efficacité des molécules orthostériques à antagoniser les réponses induites par le PAF dépend de leur nature et de leur concentration, (2) les modulateurs potentiellement allostériques utilisés ne modulent aucune des voies majoritairement connues pour être activées par le PAFR, et (3) qu'il n'y a aucun marquage spécifique du PAFR avec les surnageants d'hybridomes utilisés.

Style APA, Harvard, Vancouver, ISO itp.

26

Qureshi, Shahryar Jamshed. "Nanomaterial Charge-Dependent Platelet Activating Factor Receptor Agonism in Human Epidermal Cells". Wright State University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=wright1535391805311408.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

27

Marrache, Anne Marilise. "Platelet activating factor receptors : nuclear localization and signaling in microvascular endothelial cells". Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=82928.

Pełny tekst źródła

Streszczenie:

It has been postulated that intracellular binding sites for platelet activating factor (PAF) contribute to pro-inflammatory responses to PAF. Isolated nuclei from porcine cerebral microvascular endothelial cells (PCEC) produced PAF-molecular species in response to H2O2 . Using fluorescent-activated cell sorter analysis, we demonstrated the expression of PAF receptors (PAFR) on cell and nuclear surfaces of PCEC. Confocal microscopy studies performed on PCEC, Chinese hamster ovary cells stably overexpressing PAFR and on isolated nuclei from PCEC also showed a robust nuclear distribution of PAFR. Presence of PAFR at the cell nucleus was further revealed in brain endothelial cells by radioligand binding experiments, immunoblotting, and in situ in brain by immunoelectron microscopy. Stimulation of nuclei with PAF evoked a decrease in cAMP production and a pertussis toxin (PTX)-sensitive rise in nuclear calcium, unlike observations in plasma membrane, which exhibited a PTX-insensitive elevation in inositol phosphates. Moreover, on isolated nuclei C-PAF evoked the expression of pro-inflammatory genes inducible nitric oxide synthase and cyclooxygenase-2 (COX-2), and was associated with augmented ERK1/2 phosphorylation and NF-kappaB binding to DNA consensus sequence; COX-2 expression was prevented by MEK/ERK1/2 and NF-kappaB inhibitors. This study describes for the first time the nucleus as a putative organelle capable of generating PAF and expresses its receptor, which upon stimulation induces the expression of pro-inflammatory gene COX-2.

Style APA, Harvard, Vancouver, ISO itp.

28

Appleyard, Caroline Barbara. "The synthesis and catabolism of Platelet Activating Factor in human colon mucosa". Thesis, University of Southampton, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359303.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

29

Rivier, François. "Le Platelet-Activating Factor (PAF) : effets physiopathologiques : implication dans la néphrotoxicité médicamenteuse". Paris 5, 1996. http://www.theses.fr/1996PA05P100.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

30

Dupuis, Fabienne. "Contribution à l'étude du role du platelet-activating factor dans l'hematopoi͏̈ese humaine". Limoges, 1997. http://www.theses.fr/1997LIMO104D.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

31

Cluzel, Jacques. "Étude métabolique et autoradiographique du Platelet-Activating Factor (PAF) dans la rétine". Clermont-Ferrand 1, 1994. http://www.theses.fr/1994CLF1PP01.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

32

Cluzel, Marc. "Etude de l'excrétion de Platelet Activating Factor (PAF) par les neutrophiles humains". Montpellier 2, 1990. http://www.theses.fr/1990MON20275.

Pełny tekst źródła

Streszczenie:

Le platelet activating factor (paf), un ether-phospholipide doue de nombreux effets biologiques est produit en grande quantite par les neutrophiles humains. Dans les conditions standard de stimulation (suspension cellulaire). La majorite du paf produit reste associee aux cellules, ce qui a fait douter du role du paf comme mediateur extracellulaire. Avec pour hypothese que le paf est excrete mais est ensuite recapture par les cellules, nous avons montre que l'excretion observee du paf est variable et peut atteindre 50% de la quantite totale de paf produite dans des conditions de stimulation ou la recapture est diminuee (perfusion ou dillution cellulaire). A l'aide d'une technique de double marquage isotopique et d'un modele mathematique nous avons pu estimer la quantite de paf theoriquement excretee dans une suspension de neutrophiles. Celle-ci est 5 fois superieure a la quantite observee. Par ailleurs nos resultats suggerent qu'une certaine quantite de paf est excretee plusieurs fois et recircule entre cellules et milieu. En conclusion, les neutrophiles humains excretent une large part du paf qu'ils produisent et nous avons defini un modele pour etudier separement excretion et capture

Style APA, Harvard, Vancouver, ISO itp.

33

Mukkamala, Muralikrishna. "Regulation of Platelet-Activating Factor Acetylhydrolase by Oxidized Phospholipids and Proinflammatory Cytokines". VCU Scholars Compass, 2008. http://scholarscompass.vcu.edu/etd/653.

Pełny tekst źródła

Streszczenie:

Platelet-Activating Factor Acetylhydrolase (PAFAH) is a monocyte-derived phospholipase A2 that catalyzes the hydrolysis of platelet-activating factor (PAF) and has been implicated in atherosclerosis. Although PAF and other proinflammatory stimuli are postulated to induce the enzyme, mechanisms controlling PAFAH expression are largely unknown at present. We have shown that PAFAH induction in monocytes is increased in response to oxidized phospholipids. The PAFAH 5' flanking region has at least 10 putative Stat elements, and IL-6 has been shown to be downstream from the prostaglandin receptor, EP2, which has been shown to bind oxidized phospholipids, prompting the hypothesis that Stat proteins might regulate its expression. To test this hypothesis, we treated human monocytes with IL-6, a monocyte-derived cytokine that activates Stat3, IL-8, a monocyte-derived cytokine induced by Stat3, and oxidized 1-palmitoyl-2-arachidonoyl-sn-3-phosphocholine (oxPAPC), a major component of the oxidized LDL particle. Two monocyte-derived cell types, macrophages (MO) and dendritic cells (DC) were prepared from primary human monocytes. The cells were treated with various doses of IL-6, IL-8, or oxPAPC for various time frames in the absence of serum. Culture supernatants from the cytokine-treated cells were harvested and screened for PAFAH protein and activity and cell monolayers were assessed for PAFAH mRNA by quantitative real time PCR (qPCR). Cells treated with oxPAPC were further analyzed for secreted IL-6 using ELISA and activation of Stat3 using Western Blot. Both IL-6 and IL-8 induced PAFAH expression in a dose-dependent manner. Although both MO and DC responded to the cytokines, preliminary experiments suggested that induction of PAFAH is more robust in DC than MO. Cytokine-treated cells exhibited increased PAFAH activity in their culture supernatants that correlated with increased PAFAH protein levels. Treatment with oxPAPC induced IL-6 secretion and subsequent Stat3 activation in DC. Together, these data support the hypothesis that PAFAH expression is regulated by oxidized phospholipids and proinflammatory cytokines in developing atheromas.

Style APA, Harvard, Vancouver, ISO itp.

34

Lukashova, Viktoria. "Involvement of the Jak/STAT pathway in platelet-activating factor receptor signaling". Thèse, Sherbrooke : Université de Sherbrooke, 2003. http://savoirs.usherbrooke.ca/handle/11143/4173.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

35

Bücher, Karen. "Nachweis des Platelet-activating factor (PAF) in der bovinen Plazenta anhand der Expression des PAF-Rezeptors und der zugehörigen PAF-Azetylhydrolasen". Wettenberg : VVB Laufersweiler, 2005. http://deposit.d-nb.de/cgi-bin/dokserv?idn=978037847.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

36

Marr, Kathryn Anne. "Mediators of neutrophil activation and bronchoconstriction in equine chronic obstructive pulmonary disease". Thesis, Royal Veterinary College (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362393.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

37

Connor, David Ewan Clinical School St Vincent's Hospital Faculty of Medicine UNSW. "A study of the characterisation, procoagulant activity and Annexin V binding properties of platelet-derived microparticles". Awarded by:University of New South Wales, 2007. http://handle.unsw.edu.au/1959.4/37303.

Pełny tekst źródła

Streszczenie:

Platelet-derived microparticles, released as a result of platelet activation, promote coagulation through the surface exposure of phosphatidylserine, acting as the catalytic site for the conversion of prothrombin to thrombin by the activated coagulation factors X and V. Although elevated numbers of circulating platelet-derived microparticles can be detected in a number of clinical disorders, the methods for the detection of these microparticles are far from standardised. In addition, recent reports have also speculated that not all microparticles may expose phosphatidylserine, demonstrating that the binding of Annexin V, a phosphatidylserine-specific binding protein, is not detectable on a population of microparticles. The initial stage of this thesis was to establish a flow cytometric method for the detection and enumeration of microparticles based on their capacity to bind Annexin V and to utilise this assay to investigate a number of the issues that have limited assay standardisation. The assay could be performed on either stimulated or unstimulated plasma or whole blood samples. Interestingly, plasma microparticle counts were significantly higher than whole blood microparticle counts. The effects of centrifugation alone could not be attributed as the sole source of this discrepancy. The antigenic characteristics of platelet-derived microparticles were also investigated, with platelet-derived microparticles demonstrated to express the platelet glycoproteins CD31, CD41a, CD42a and CD61. Platelet-derived microparticles also expressed CD42b, and this expression was significantly decreased when compared to their progenitor platelets. The expression of the platelet activation markers CD62p, CD63, CD40L and PAC-1 was dependent upon the sample milieu, suggesting that the centrifugation conditions required to generate platelet-poor plasma may lead to artefactual increases in the expression of platelet activation markers. An investigation of the role of the GpIIb/IIIa complex on the formation of platelet-derived microparticles was also performed. A monoclonal antibody to the GpIIb/IIIa complex (Abciximab) significantly inhibited in vitro collagen-stimulated platelet-derived microparticle formation. Interestingly, platelets obtained from two subjects with impaired GpIIb/IIIa activation, demonstrated normal microparticle formation following collagen stimulation, suggesting that the presence of GpIIb/IIIa complex, but not its activation, is required for collagen-induced microparticle formation. A novel mechanism for microparticle formation was also investigated, with platelet-derived microparticles demonstrated to form in response to the sclerosing agents sodium-tetradecyl sulphate and polidocanol. Interestingly, the removal of plasma proteins by the washing of platelets left platelets more susceptible to sclerosant-induced microparticle formation, suggesting that plasma proteins may protect platelets from microparticle formation. The procoagulant activity of platelet-derived microparticles was also investigated using a novel coagulation assay (XACT) specific for the procoagulant phospholipid. An evaluation of this assay demonstrated a significant correlation between Annexin V binding microparticle counts and procoagulant activity in both whole blood and plasma samples. There was more procoagulant activity in whole blood samples than in plasma samples, suggesting that the procoagulant phospholipid activity was also associated with erythrocytes or leukocytes. To further investigate this phenomenon, a whole blood flow cytometric assay was developed to assess Annexin V binding to erythrocytes, leukocytes, platelets and microparticles. This assay demonstrated that a large proportion of Annexin V binding (51.0%) was associated with erythrocytes. Interestingly, a proportion of the Annexin V binding erythrocytes (24.5%) and leukocytes (78.8%) were also associated with platelet CD61 antigen, suggesting that they also bound a platelet or platelet-derived microparticle. The effect of sample anticoagulant on microparticle procoagulant activity was investigated. Microparticle counts were most stable in EDTA anticoagulated samples, but were stable in sodium citrate for up to 15 minutes following sample collection. The procoagulant activity of microparticles was significantly inhibited by EDTA in collagen-stimulated platelet-rich plasma samples, when compared to sodium citrate anticoagulated samples. Although the initial method used to investigate microparticles was based upon their ability to bind Annexin V, it was consistently observed that a large proportion of events in the size region of a microparticle were Annexin V negative. An investigation was therefore commenced into the procoagulant activity of microparticles based on their capacity to bind Annexin V. The presence of Annexin V negative microparticles was confirmed by flow cytometry and the proportion of microparticles that bound Annexin V was dependent upon type of agonist used to stimulate microparticle formation. Varying the assay constituents (calcium concentration / Annexin V concentration / buffer type) did not alter the proportion of Annexin V binding microparticles. When compared to Annexin V positive microparticles, Annexin V negative microparticles expressed significantly higher levels of CD42b on their surface, but possessed significantly decreased expressions of CD62p, and CD63. A significant correlation between the percentage of Annexin V binding and XACT procoagulant activity was found (p=0.03). Furthermore, Annexin V binding inhibited greater than 98% of procoagulant phospholipid activity, suggesting that Annexin V binding was a true reflection of procoagulant activity. Microparticles could be sorted using either a flow cytometric or magnetic sorting strategy. By electron microscopy, Annexin V negative events isolated following magnetic sorting were vesicular structures and not small platelets or the remnants of activated platelets. In summary, this thesis has demonstrated the ability of the flow cytometer and XACT assays to detect microparticles and their procoagulant activity. It has also shown that the use of Annexin V to detect microparticles may warrant further investigation.

Style APA, Harvard, Vancouver, ISO itp.

38

Lehmberg, Jens Matthias. "Die Mediatorfunktion von Bradykinin und Platelet-Activating Factor bei der globalen zerebralen Ischämie". Diss., lmu, 2002. http://nbn-resolving.de/urn:nbn:de:bvb:19-7775.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

39

Khoury, Joseph. "Endotoxin, platelet-activating factor, and sepsis-related cytokines: Effects on lung pericyte growth". Thesis, McGill University, 1997. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=95583.

Pełny tekst źródła

Streszczenie:

Gram-negative sepsis is an important cause of the acute respiratory distress syndrome (ARDS). Pulmonary hypertension (PH), which often develops in ARDS, results in part from the remodelling of the pulmonary microvasculature. Vascular pericytes (PC), dedifferentiated smooth muscle-like cells, are thought to playa role in the remodelling and neomuscularization of pulmonary microvessels. Endotoxin, lipopolysaccharide (LPS) from the outer membrane of gram-negative bacteria, activates macrophages, endothelial cells, and other cells to release potent cytokine and phospholipid mediators such as plateletactivating factor (PAF). The effects of these mediators on inflammation, vascular permeabilization, and progression of injury have been previously described. However, the role of these mediators in stimulating PC growth during the remodelling process is unknown. We show that compared with control growth, PAF (lO-gM, semisynthetic) stimulates the 7-day mean grovvth of proliferating PC by 31% in medium with serum, and 29% without serum. Furthermore, PAF stimulates the growth of quiescent PC by 12% with serum and 23% without serum. These proliferative effects are blocked by the addition of the PAF-receptor antagonist CV-3988 (lO-7M). The addition of the individual cytokines does not affect PC proliferation in vitro. A mixture of these cytokines, simulating in vivo conditions, does not alter PC proliferation in the iii presence of serum, but reduces it in its absence. LPS from E.coli increases proliferation by 72%, compared with control. The proliferative effect of endotoxin requires the presence of serum. Thus, LPS and PAF, but not inflammatory cytokines. are direct mitogens of lung pericytes in vitro. This is the first demonstration that these molecules have direct effects on cells found in substantial areas of the vessel wall, possibly contributing to the neomuscularization and vascular remodelling of the pulmonary wasculature in acute lung injury.
La septicémie à bactéries gram-négatives est une cause importante du syndrome de détresse respiratoire de l’adulte (SDRA). L’hypertension pulmonaire, qui se développe souvent durant le SDRA, se manifeste en partie par des modifications des micro-vaisseaux pulmonaires. Les péricytes (PC), qui sont des cellules précurseures des muscles lisses, sont impliqués dans la reconfiguration et la néovascularisation des micro-vaisseaux pulmonaires. L’endotoxine, qui est une lipopolysaccharide (LPS) provenant de la membrane extérieure des bactéries gram-négatives, peut activer les cellules macrophagiques, endothéliales, et d’autres cellules de façon à libérer des médiateurs puissants, comprenant aussi les cytokines et le facteur activateur des plaquettes (FAP). Les effets de ces médiateurs sur l’inflammation, la perméabilité vasculaire, et la progression du dommage furent déjà décrits. Mais le rôle de ces médiateurs en stimulant la prolifération des PC durant le processus de la modification vasculaire est inconnu. Nous démontrons que, par rapport au contrôle, FAP (10-9M, semi-synthétique) stimule la croissance moyenne au septième jour des PC “proliférants” de 31% et 29% respectivement avec et sans sérum. En plus, PAF stimule la croissance des PC “dormants” par 12% et 23% respectivement avec et sans sérum. Ces effets prolifératifs sont bloqués en ajoutant l’antagoniste du récepteur de PAF CV-3988 (10-7M). L’addition subséquente et séquentielle des cytokines n’affecte pas la croissance des PC in vitro. Ajoutées simultanement pour reproduire les conditions in vivo, l’addition des cytokines n’affecte pas la croissance des PC en présence de sérum, mais la réduit en son absence. LPS provenant de E.coli augmente de 72% la prolifération par rapport au contrôle. Les effets prolifératifs de l’endotoxine exigent la présence de sérum. LPS et FAP, mais pas les cytokines, peuvent jouer un rôle direct sur les PC$

Style APA, Harvard, Vancouver, ISO itp.

40

Khan, Nighat Murad. "An investigation of platelet-activating factor metabolism during normal and pre-eclamptic pregnancies". Thesis, University of Bath, 1993. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.332312.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

41

Taylor, Matthew W. "Targeting Neurodegeneration in Alzheimer’s Disease Using Natural Products Derived from Maya Traditional Medicine". Thesis, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/30688.

Pełny tekst źródła

Streszczenie:

Alzheimer’s disease (AD) is a complex neurodegenerative disorder with limited treatment options. Previous research has shown that metabolism of the platelet activating factor (PAF) family of lipid second messengers is impaired in AD. While PAFs are known to exacerbate glutamate excitotoxicity, signal tau hyperphosphorylation, and mediate amyloid β neurotoxicity, it is not yet clear whether cognitive decline can be ascribed to activation of the G-protein-coupled PAF receptor (PAFR). Here, I assessed whether loss of PAFR would alter Morris water maze performance in the TgCRND8 (Tg) mouse model of AD. I show that learning is impaired in Tg PAFR+/+ but not in Tg PAFR-/- mice. Together, these findings suggested that blocking PAFR-mediated glutamate overload or inhibiting PAF-synthesizing enzymes are two relevant therapeutic strategies. As traditional medicine is a major form of health care in regions like Mesoamerica, I conducted an ethnobotanical survey of medicinal plants used by Q’eqchi’ Maya healers of southern Belize to treat symptoms relevant to AD. I collected a total of 22 plants, 19 of which were identified to the species level. None of the plant extracts used for symptoms of AD were neurotoxic when tested on cerebellar granule neurons (CGNs). I found that extracts of Margraviaceae gentlei and Gonzalagunia panamensis protected CGNs from glutamate-induced excitotoxicity, in vitro, and Peperomia hirta inhibited sPLA2 activity. These results demonstrate a pharmacological basis for Q’eqchi’ Maya traditional medicine used to treat symptoms relevant to AD, and highlight several plants with potential for future development into natural products for the treatment of AD.

Style APA, Harvard, Vancouver, ISO itp.

42

Dunn, Anita Marie 1956. "The role of neutrophils in systemic anaphylaxis in the rabbit". Thesis, The University of Arizona, 1989. http://hdl.handle.net/10150/276960.

Pełny tekst źródła

Streszczenie:

The objective of this study was to determine whether neutrophils play a significant role in anaphylaxis or in the response to the anaphylactic mediator platelet activating factor (PAF) in the rabbit. Vinblastine and anti-neutrophil antibodies were compared as neutrophil depleting agents, and 0.35 mg/kg vinblastine was selected as optimal for efficiency and specificity of depletion. Anaphylaxis was induced in sensitized rabbits by intravenous antigen challenge. Neutrophil depletion to 399 ± 101 cells/mm³ blood (14 ± 3%) did not significantly inhibit the physiologic and hematologic events associated with anaphylaxis except tachycardia. However, vinblastine pretreatment significantly reduced tachycardia and the right ventricular pressure increase and abolished the increase in pulmonary resistance caused by intravenous PAF. We conclude that although neutrophils do not play a significant role in IgE-anaphylaxis, they are important in the PAF-induced increases in right ventricular pressure and pulmonary resistance. PAF may not be a major mediator of these two physiologic alterations in IgE-anaphylaxis.

Style APA, Harvard, Vancouver, ISO itp.

43

Min, Jung-Hyun. "Enzyme mechanism, substrate specificity, and lipoprotein association of human plasma platelet-activating factor acetylhydrolase /". Thesis, Connect to this title online; UW restricted, 2000. http://hdl.handle.net/1773/9254.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

44

Iqbal, Shehzad Mustafa. "The role of cytokines in regulating platelet-activating factor (PAF) synthesis in endothelial cells". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ64961.pdf.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

45

Lohmeyer, Matthias. "The mechanism of action of antitumour lipid agents related to platelet-activating factor (PAF)". Thesis, University of Cambridge, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.319528.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

46

Hing-lun, Lee. "Hemodynamic effects of endothelin-1 and platelet-activating factor after nitric oxide synthase inhibition in the rat". Hong Kong : University of Hong Kong, 1999. http://sunzi.lib.hku.hk/hkuto/record.jsp?B21903967.

Pełny tekst źródła

Style APA, Harvard, Vancouver, ISO itp.

47

Syrett, Andrew J. "Bioactive Glycerophospholipids and Their Role in Modulating Neuronal Vulnerability Following Cerebral Ischemia". Thesis, Université d'Ottawa / University of Ottawa, 2011. http://hdl.handle.net/10393/20536.

Pełny tekst źródła

Streszczenie:

Stroke is a devastating and debilitating condition resulting from a blockage or hemorrhage in the vasculature of the brain. Despite extensive research, the etiology and pathophysiology of the disease at the level of the cell membrane are poorly understood, and effective treatment has been elusive. Though much research has shown marked increases in lipid metabolism following stroke, the impact of these changes have often been overlooked given the technical challenges associated with identifying regionally specific changes in degenerating tissue. The advent of lipidomics – a systems biology approach to the large-scale profiling of individual lipid species in tissues – has renewed interest in understanding the role of membrane lipids and their metabolites in the cell and in ischemic injury. In this thesis, I have used an unbiased LC-ESI-MS-based lipidomic approach to profile the small molecular weight glycerophosphocholine second messenger lipidome in anterior and posterior regions of cortex and striatum in the forebrain of wild-type and platelet activating factor receptor (PAFR) null-mutant mice before and after middle cerebral artery occlusion (MCAO). From these profiles, I have outlined the potential use of lipid second messenger distribution as topographic landmarks to identify functional subdomains within neural tissue. Further, I have demonstrated that ischemia does not simply disrupt lipid second messenger metabolism globally but produces regionally specific changes in discrete species and that these changes are altered by the loss of lipid regulatory effectors (i.e., PAFR null mutation). Based on the lipid species identified in this profile of healthy and ischemic tissue, I proposed that tight regulation of PC(O-22:6/2:0) homeostasis by PAFR-expressing microglia is ii required for proper dopaminergic signaling in prefrontal cortex. Finally, I have outlined a model whereby increased PAF synthesis following ischemia contributes the inflammatory response by promoting blood-brain barrier permeability, microglial activation and immune cell infiltration in a PAFR-dependent manner.

Style APA, Harvard, Vancouver, ISO itp.

48

De, Leon Ellen Jane Biotechnology &amp Biomolecular Sciences Faculty of Science UNSW. "Engineering antibodies against complex platelet antigens using phage display technology". Awarded by:University of New South Wales, 2007. http://handle.unsw.edu.au/1959.4/37009.

Pełny tekst źródła

Streszczenie:

Platelets are small anucleate cell fragments found in blood whose physiological role is important in maintaining haemostasis. In vivo, platelet surface glycoproteins mediate the mechanistic roles of platelets, and polymorphic changes to these glycoproteins have been observed to have significant effects on the platelet cellular function and such changes may include over-expression, under-expression and antigenicity of the protein. Human platelet antigens (HPA) are a result of polymorphic differences in platelet surface glycoproteins which have been found to be variably expressed in the population. Foetal maternal alloimmune thrombocytopaenia (FMAIT) is a condition that is observed in the unborn foetus and neonates due to HPA incompatibility between the mother and the foetus. HPA incompatibility accounts for a majority of severe thrombocytopaenic cases in neonates, and delayed diagnosis and treatment of such a condition often lead to intracranial haemorrhage. The risk in neonates diagnosed with FMAIT becomes increasingly significant in cases where intra-uterine (during pregnancy) platelet transfusion is the only effective therapeutic option. There are currently no antenatal screening programs for this condition, and laboratory diagnosis of FMAIT relies on the detection of maternal alloantibodies and parental HPA typing. For these reasons a significant amount of research is currently being invested into the isolation of recombinant antibodies with specific reactivity against FMAIT-related platelet antigens. Stable and specific recombinant platelet antibodies have great potential as a diagnostic agent in antenatal screening and broad-scale HPA typing of blood donors for platelet transfusion. Further characterisation of the isolated antibody may lead to a possible therapeutic agent. Studies by previous researchers have shown that the traditional methods (ie. Mouse monoclonal and EBV transformation) of obtaining monoclonal antibodies against FMAIT-related antigens have proven unsuccessful. The continuing progress in the discipline of phage display has produced several novel antibodies against self and non-self antigens. A further advantage in the application of phage display technology for the isolation of novel antibodies is the easy transition from bacterial to mammalian expression for the characterisation of glycosylated antibodies. The main focus of this project was to create and isolate a recombinant human anti-HPA-3a antibody using phage display for its possible application as a therapeutic or diagnostic agent.

Style APA, Harvard, Vancouver, ISO itp.

49

Nunez, Danielle. "Étude de la plaquette sanguine : phosphorylation des proteines et recepteur du platelet activating factor (paf)". Paris 7, 1990. http://www.theses.fr/1990PA077072.

Pełny tekst źródła

Streszczenie:

I) Effet du PAF sur les réactions de phosphorylation dans la plaquette. Le PAF, après s'être lie a son récepteur, stimule, comme la thrombine, la phosphorylation de la chaine légère de la Myosine (P20) et celle d'une protéine de poids moléculaire apparent 47 KD (P47) dont la nature et la fonction restent discutées. Nous avons montré que la P47 n'est pas l'actine dont elle diffère par le point isoélectrique. La phosphorylation de la p47 est en relation avec la sécrétion: en présence de l'Ionophore A23187 et l'EDTA l'agrégation est inhibée alors que la sécrétion et la phosphorylation de la p47 ne l'est pas. Ii. Spécificité du récepteur du PAF: études des effets du zinc et de divers antagonistes sur la liaison du PAF aux plaquettes et l'agrégation plaquettaire. 1. Le PAF se lie a un petit nombre de sites de haute affinité dont le KD (0,4-0,6 nm) est de même ordre de grandeur que la concentration seuil de PAF (0,1 nm) agrégeant les plaquettes. 2. Le zinc bloque la liaison du PAF et l'agrégation aux concentrations de ce cation trouvées dans le plasma (10-20 m). Cette action est spécifique car elle n'est pas reproduite par d'autres cations divalents ni observée avec d'autres agonistes plaquettaires. Elle pourrait expliquer les effets anti-inflammatoires du zinc. 3. Un Ginkgolide, le BN 52021, inhibe spécifiquement et a des concentrations de l'ordre du m, l'agrégation induite par le PAF. Une même relation structure-fonction a été trouvée pour une série d'analogues du BN 52021 entre la liaison du PAF et ses effets sur l'agrégation plaquettaire. D'autres antagonistes sont spécifiques (Kadsurenone) ou non (CV 3988) du PAF

Style APA, Harvard, Vancouver, ISO itp.

50

Herd, Caroline Mary. "Inflammatory mediators : the involvement of histamine, serotonin and platelet activating factor in anaphylactoid-type reactions". Title page, summary and table of contents only, 1990. http://hdl.handle.net/2440/19111.

Pełny tekst źródła

Streszczenie:

1v.
Title page, contents and abstract only. The complete thesis in print form is available from the University Library.
Thesis (Ph.D.)--University of Adelaide, 1990
Thesis (Ph.D.)--University of Adelaide, Dept. of Clinical and Experimental Pharmacology, 1990

Style APA, Harvard, Vancouver, ISO itp.

Rozprawy doktorskie na temat „Platelet activating factor”

Utwórz poprawne odniesienie w stylach APA, MLA, Chicago, Harvard i wielu innych