Relevant bibliographies by topics / Antithrombin

Contents

  1. Journal articles
  2. Dissertations / Theses
  3. Books
  4. Book chapters
  5. Conference papers

Academic literature on the topic 'Antithrombin'

Author: Grafiati
Published: 4 June 2021
Last updated: 11 March 2023

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'Antithrombin.'

Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.

You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.

Journal articles on the topic "Antithrombin"

1

Izaguirre, Gonzalo, Richard Swanson, Srikumar M. Raja, Alireza R. Rezaie, and Steven T. Olson. "Mechanism by Which Exosites Promote the Inhibition of Blood Coagulation Proteases by Heparin-activated Antithrombin." Journal of Biological Chemistry 282, no. 46 (September 17, 2007): 33609–22. http://dx.doi.org/10.1074/jbc.m702462200.

Full text
Abstract:
Heparin activates the serpin, antithrombin, to inhibit its target blood-clotting proteases by generating new protease interaction exosites. To resolve the effects of these exosites on the initial Michaelis docking step and the subsequent acylation and conformational change steps of antithrombin-protease reactions, we compared the reactions of catalytically inactive S195A and active proteases with site-specific fluorophore-labeled antithrombins that allow monitoring of these reaction steps. Heparin bound to N,N′-dimethyl-N-(acetyl)-N′-(7-nitrobenz-3-oxa-1,3-diazol-4-yl)ethylenediamine (NBD)-fluorophore-labeled antithrombins and accelerated the reactions of the labeled inhibitor with thrombin and factor Xa similar to wild type. Equilibrium binding of NBD-labeled antithrombins to S195A proteases showed that exosites generated by conformationally activating antithrombin with a heparin pentasaccharide enhanced the affinity of the serpin for S195A factor Xa minimally 100-fold. Moreover, additional bridging exosites provided by a hexadecasaccharide heparin activator enhanced antithrombin affinity for both S195A factor Xa and thrombin at least 1000-fold. Rapid kinetic studies showed that these exosite-mediated enhancements in Michaelis complex affinity resulted from increases in kon and decreases in koff and caused antithrombin-protease reactions to become diffusion-controlled. Competitive binding and kinetic studies with exosite mutant antithrombins showed that Tyr-253 was a critical mediator of exosite interactions with S195A factor Xa; that Glu-255, Glu-237, and Arg-399 made more modest contributions to these interactions; and that exosite interactions reduced koff for the Michaelis complex interaction. Together these results show that exosites generated by heparin activation of antithrombin function both to promote the formation of an initial antithrombin-protease Michaelis complex and to favor the subsequent acylation of this complex.
APA, Harvard, Vancouver, ISO, and other styles
2

Zhou, Aiwu, James A. Huntington, and Robin W. Carrell. "Formation of the Antithrombin Heterodimer In Vivo and the Onset of Thrombosis." Blood 94, no. 10 (November 15, 1999): 3388–96. http://dx.doi.org/10.1182/blood.v94.10.3388.422k20_3388_3396.

Full text
Abstract:
Antithrombin is shown to undergo a slow spontaneous conversion to its inactive latent conformation with readily discernible amounts present in plasma on incubation at 37°C for 72 hours. More rapid conversion occurs on incubation of isolated antithrombin at 41°C or 50°C, but the appearance on electrophoresis of free latent antithrombin is preceded by the formation, in reciprocal proportions, of a new slow band. This slow component is shown to be a heterodimer of active and latent antithrombin. It can be isolated as a single stable band either by incubation of antithrombin or by mixing equimolar proportions of active and latent antithrombin under the same conditions that give overnight crystallization of the active/latent antithrombin heterodimer. Similarly, equimolar addition of latent antithrombin to plasma results electrophoretically in a quantitative shift to the slower heterodimer mobility. Clinically, the presence of latent antithrombin is potentially deleterious, because its linkage to form the heterodimer results in inactivation of the otherwise normal molecule linked to the latent antithrombin. In the case of -antithrombin, because the dimer readily dissociates, there is only a 11% additive loss of activity, but with β-antithrombin the dimer appears more stable, with the additive loss of activity from the normal β component being 21%, increasing to 33% on stabilization of the dimer with heparin. This linked and selective loss of activity of β-antithrombin provides an explanation for the unexpected severity of thrombotic episodes in heterozygotes with conformationally unstable antithrombins.
APA, Harvard, Vancouver, ISO, and other styles
3

Chang, Wun-Shaing W., and Paul L. Harper. "Commercial Antithrombin Concentrate Contains Inactive L-forms of Antithrombin." Thrombosis and Haemostasis 77, no. 02 (1997): 323–28. http://dx.doi.org/10.1055/s-0038-1655962.

Full text
Abstract:
SummaryThe preparation of antithrombin concentrate for clinical use requires a viral inactivation step. In most commercial preparations this is achieved by heat pasteurisation. This process would be expected to alter the conformation of antithrombin from the active native species to an inactive latent (L-form) state (1, 2). To determine if this occurs during commercial preparation and to identify the proportion of the product in the inactive state, we examined the various antithrombin conformations within a therapeutic concentrate. The antithrombin concentrate was separated into five fractions by heparin-Sepharose chromatography. The fraction with the highest heparin affinity retained full activity, whereas the four fractions with reduced heparin affinity (~40% of the total antithrombin) had lost their inhibitory function. These inactive antithrombins were intact, monomeric, thermostable and resistant to unfolding in 8 M urea. Moreover, the protein patterns on isoelectric focusing and non-denaturing-PAGE showed that there were at least two different L-forms with isoelectric points separate from the native active species. Our findings demonstrate that approximately 40% of the antithrombin preparation examined exists as inactive l-forms. The clinical significance of administering this altered material is uncertain.
APA, Harvard, Vancouver, ISO, and other styles
4

Zhang, Weiqing, Yung-Jen Chuang, Richard Swanson, Juan Li, Kyunga Seo, Lawrence Leung, Lester F. Lau, and Steven T. Olson. "Antiangiogenic antithrombin down-regulates the expression of the proangiogenic heparan sulfate proteoglycan, perlecan, in endothelial cells." Blood 103, no. 4 (February 15, 2004): 1185–91. http://dx.doi.org/10.1182/blood-2003-08-2920.

Full text
Abstract:
Abstract Antithrombin, a key serpin family regulator of blood coagulation proteases, is transformed into a potent antiangiogenic factor by limited proteolysis or mild heating. Here, we show by cDNA microarray, semiquantitative reverse transcriptase–polymerase chain reaction (RT-PCR), Northern blotting, and immunoblotting analyses that the expression of the proangiogenic heparan sulfate proteoglycan (HSPG), perlecan, but not other HSPGs, is dramatically down-regulated in human umbilical vein endothelial cells (HUVECs) treated with antiangiogenic cleaved and latent forms of antithrombin but not with the native form. Down-regulation of perlecan expression by cleaved and latent antithrombins was observed in both basic fibroblast growth factor (bFGF)–stimulated and unstimulated cells, whereas the antiangiogenic antithrombins inhibited the proliferation of only bFGF-stimulated HUVECs by arresting cells at the G1 cell cycle phase. The importance of perlecan expression levels in mediating the antiproliferative effect of the antiangiogenic antithrombins was suggested by the finding that transforming growth factor-β1, a potent stimulator of perlecan expression in endothelial cells, blocked the down-regulation of perlecan expression and antiproliferative activity of cleaved antithrombin on endothelial cells. The previously established key role of perlecan in mediating bFGF stimulation of endothelial cell proliferation and angiogenesis suggests that a primary mechanism by which antiangiogenic antithrombins exert their effects is through the down-regulation of perlecan expression.
APA, Harvard, Vancouver, ISO, and other styles
5

Kaneider, Nicole C., Christina M. Reinisch, Stefan Dunzendorfer, Jürgen Römisch, and Christian J. Wiederman. "Syndecan-4 mediates antithrombin-induced chemotaxis of human peripheral blood lymphocytes and monocytes." Journal of Cell Science 115, no. 1 (January 1, 2002): 227–36. http://dx.doi.org/10.1242/jcs.115.1.227.

Full text
Abstract:
Antithrombin inhibits chemokine-induced migration of neutrophils by activating heparan sulfate proteoglycan-dependent signaling. Whether antithrombin affects migration of other types of leukocytes is not known. We investigated the effects of antithrombin on spontaneous and chemokine-triggered migration of lymphocytes and monocytes from human peripheral blood in modified Boyden chamber micropore filter assays. Lymphocyte and monocyte populations from human peripheral blood were purified using magnetic antibody cell sorting. The signaling mechanisms required for antithrombin-dependent migration were studied using signaling enzyme blockers. Expression of heparan sulfate proteoglycan core protein was studied by RT-PCR and flow cytometry. The antithrombins used were Kybernin®P from human plasma and a monoclonal-antibody-purified preparation from this plasma. Pretreatment of lymphocytes and monocytes with antithrombin inhibited chemotaxis toward optimal concentrations of interleukin-8 or Rantes (regulated upon activation normal T-cell expressed and activated) at concentrations of antithrombin as low as 10 nU/ml. In the absence of the chemokines, direct exposure of cells to gradients of antithrombin stimulated migration. Effects of antithrombin were abolished by pretreating cells with heparinase-1, chondroitinase, sodium chlorate and anti-syndecan-4 antibodies. Expression of syndecan-4 mRNA and protein in monocytes and lymphocytes was demonstrated in RT-PCR and anti-syndecan-4 immunoreactivity assays, respectively. In the presence of pentasaccharide, antithrombin lost its effect on cells. Data indicate that antithrombin directly inhibits chemokine-stimulated migration of monocytes and lymphocytes via the effects of its heparin-binding site on cell surface syndecan-4 by activation of protein kinase C and Rho signaling.
APA, Harvard, Vancouver, ISO, and other styles
6

George, PM, P. Pemberton, IC Bathurst, RW Carrell, HL Gibson, S. Rosenberg, RA Hallewell, and PJ Barr. "Characterization of antithrombins produced by active site mutagenesis of human alpha 1-antitrypsin expressed in yeast." Blood 73, no. 2 (February 1, 1989): 490–96. http://dx.doi.org/10.1182/blood.v73.2.490.490.

Full text
Abstract:
Abstract Both congenital and acquired antithrombin-III (AT-III) deficiencies are amenable to replacement therapy. We describe two antithrombins produced by recombinant DNA techniques from human alpha 1-antitrypsin (alpha 1AT) cDNA in yeast. Alteration of the alpha 1AT active site, replacing methionine 358 with arginine, results in a thrombin inhibition rate similar to that of heparin-activated AT-III. Alteration of two further residues, to give a five-residue sequence identical to AT-III, does not increase this rate further. Neither antithrombin is activated by heparin; both are unglycosylated and have shorter in vivo half-lives (t1/2) than human alpha 1AT. These antithrombins should be suitable for therapeutic replacement of AT-III in cases of congenital deficiency and in conditions associated with acquired AT-III deficiency, such as disseminated intravascular coagulation.
APA, Harvard, Vancouver, ISO, and other styles
7

George, PM, P. Pemberton, IC Bathurst, RW Carrell, HL Gibson, S. Rosenberg, RA Hallewell, and PJ Barr. "Characterization of antithrombins produced by active site mutagenesis of human alpha 1-antitrypsin expressed in yeast." Blood 73, no. 2 (February 1, 1989): 490–96. http://dx.doi.org/10.1182/blood.v73.2.490.bloodjournal732490.

Full text
Abstract:
Both congenital and acquired antithrombin-III (AT-III) deficiencies are amenable to replacement therapy. We describe two antithrombins produced by recombinant DNA techniques from human alpha 1-antitrypsin (alpha 1AT) cDNA in yeast. Alteration of the alpha 1AT active site, replacing methionine 358 with arginine, results in a thrombin inhibition rate similar to that of heparin-activated AT-III. Alteration of two further residues, to give a five-residue sequence identical to AT-III, does not increase this rate further. Neither antithrombin is activated by heparin; both are unglycosylated and have shorter in vivo half-lives (t1/2) than human alpha 1AT. These antithrombins should be suitable for therapeutic replacement of AT-III in cases of congenital deficiency and in conditions associated with acquired AT-III deficiency, such as disseminated intravascular coagulation.
APA, Harvard, Vancouver, ISO, and other styles
8

Navarro-Fernández, José, María Morena-Barrio, José Padilla, Antonia Miñano, Nataliya Bohdan, Sonia Águila, Irene Martínez-Martínez, et al. "Antithrombin Dublin (p.Val30Glu): a relatively common variant with moderate thrombosis risk of causing transient antithrombin deficiency." Thrombosis and Haemostasis 116, no. 07 (January 2016): 146–54. http://dx.doi.org/10.1160/th15-11-0871.

Full text
Abstract:
SummaryThe key haemostatic role of antithrombin and the risk of thrombosis associated with its deficiency support that the low incidence of antithrombin deficiency among patients with thrombosis might be explained by underestimation of this disorder. It was our aim to identify mutations in SERPINC1 causing transient antithrombin deficiency. SERPINC1 was sequenced in 214 cases with a positive test for antithrombin deficiency, including 67 with no deficiency in the sample delivered to our laboratory. The p.Val30Glu mutation (Antithrombin Dublin) was identified in five out of these 67 cases, as well as in three out of 127 cases with other SERPINC1 mutations. Genotyping in 1593 patients with venous thrombosis and 2592 controls from two populations, revealed a low prevalent polymorphism (0.3 %) that moderately increased the risk of venous thrombosis (OR: 2.9; 95 % CI: 1.07–8.09; p= 0.03) and identified one homozygous patient with an early thrombotic event. Carriers had normal anti-FXa activity, and plasma antithrombin was not sensitive to heat stress or proteolytic cleavage. Analysis of one sample with transient deficit revealed a type I deficiency, without aberrant or increased latent forms. The recombinant variant, which lacked the two amino-terminal residues, had reduced secretion from HEK-EBNA cells, formed hyperstable disulphidelinked polymers, and had negligible activity. In conclusion, p.Val30Glu by affecting the cleavage of antithrombin’s signal peptide, results in a mature protein lacking the N-terminal dipeptide with no functional consequences in normal conditions, but that increases the sensitivity to be folded intracellularly into polymers, facilitating transient antithrombin deficiency and the subsequent risk of thrombosis.
APA, Harvard, Vancouver, ISO, and other styles
9

KOIDE, Takehiko. "Antithrombin." Journal of Japan Atherosclerosis Society 23, no. 10 (1996): 573–79. http://dx.doi.org/10.5551/jat1973.23.10_573.

Full text
APA, Harvard, Vancouver, ISO, and other styles
10

Roemisch, J., E. Gray, J. N. Hoffmann, and C. J. Wiedermann. "Antithrombin." Blood Coagulation& Fibrinolysis 13, no. 8 (December 2002): 657–70. http://dx.doi.org/10.1097/00001721-200212000-00001.

Full text
APA, Harvard, Vancouver, ISO, and other styles
More sources

Dissertations / Theses on the topic "Antithrombin"

1

Skinner, Richard. "Structural biology of antithrombin." Thesis, University of Cambridge, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627475.

Full text
APA, Harvard, Vancouver, ISO, and other styles
2

Bruce, David. "Antithrombin : structural variants and thrombosis." Thesis, Open University, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.386084.

Full text
APA, Harvard, Vancouver, ISO, and other styles
3

Fitton, Hazel Louise. "Modulation of antithrombin by heparin." Thesis, University of Cambridge, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.624993.

Full text
APA, Harvard, Vancouver, ISO, and other styles
4

Jin, L. "Antithrombin structures and the heparin pentasaccharide." Thesis, University of Cambridge, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.605606.

Full text
Abstract:
Antithrombin, the major inhibitor of blood coagulation, is relatively inactive until it binds to, and is achieved by the heparan sidechains that line the microvasculature. The binding specifically occurs to a core pentasaccharide, present both in the heparans and in their therapeutic derivative heparin. This specific binding can cause antithrombin's conformational change which is required for activation. The crystal structure of a dimer of inhibitory(I) and latent(I) antithrombin, each in complex with the high-affinity pentasaccharide, was solved at 2.9A resolution. To achieve this, a new approach to the effective crystallisation of antithrombin was developed involving equal-molar mixing of inhibitory and latent antithrombin, in this case, in the additional presence of the heparin pentasaccharide. The structure elucidated, for the first time, the binding details and accompanying conformational change of antithrombin which is fundamental for activation. The pentasaccharide binds to antithrombin by hydrogen-bonding or salt-bridging of its sulphates and carboxylates to Arg129 and Lys125 on the D-helix, to Asn45, Arg46 and Arg47 on the A-helix, to Lys114 and Glu113 on the new induced P-helix and to LKys11 and Arg13 in a cleft formed by the amino-terminus. Inhibitory activation results from a shift in the main β-sheet of the molecule(the A-sheet) from a partially six-stranded to a five-stranded form with extrusion of the reactive loop to give a more exposed orientation. There is a tilting and elongation of the D-helix with the formation of a new 2-turn P-helix between the C and D helices. Comparing the concomitant conformational changes at the heparin binding site of the I and L molecules also explains structurally both the initial tight binding of antithrombin to the heparans and the subsequent release of the antithrombin/protease complex into the circulation. The clear definition of the binding site and interaction details has given a new insight into the molecular pathology of antithrombin deficiency and provides a structural basis for developing heparin analogues which are more specific towards their intended target, antithrombin, and therefore less likely to exhibit side-effects.
APA, Harvard, Vancouver, ISO, and other styles
5

Christey, Peter B. "Heparin binding and activation of antithrombin." Thesis, University of Cambridge, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.315820.

Full text
APA, Harvard, Vancouver, ISO, and other styles
6

CORNO, ANNA ROSA. "CARENZA CONGENITA DI ANTITROMBINA E DIAGNOSI DI LABORTORIO: QUALE TEST FUNZIONALE?" Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/233996.

Full text
Abstract:
Introduzione - La carenza congenita di Antitrombina (AT), che espone a rischio trombotico di tipo prevalentemente venoso, viene classificata in tipo I (difetto quantitativo) o tipo II (difetto qualitativo). I difetti qualitativi possono interessare il sito reattivo (Reactive Site, RS) o il sito di legame dell’AT con l’eparina (Heparin Binding Site, HBS), oppure possono avere effetto pleiotropico (PE). I test di screening, che misurano la capacità dell’AT, presente nel plasma, di neutralizzare la trombina (attività anti-IIa) o il Fattore Xa (attività anti-Xa) in presenza di eparina, sono in grado di evidenziare la maggior parte dei difetti dell’AT; tuttavia, sono stati osservati risultati discrepanti (valore normale vs. valore patologico) con i due differenti metodi. Scopo della tesi è quello di valutare la concordanza tra un test AT anti-Xa e un test AT anti-IIa e di valutare la relativa capacità di individuare le carenze di AT. Materiali e Metodi – La popolazione in studio è costituita dal gruppo “routine e trombofilici” (493 soggetti con prescrizione del test AT) e dal gruppo “carenti noti” (23 soggetti con carenza nota di AT e 18 familiari). I dosaggi dell’attività dell’AT sono stati effettuati con i metodi AT anti-Xa (HemosIL, Instrumentation Laboratory) e AT anti-IIa (home-made). Una popolazione di controllo (n= 100) è stata utilizzata per definire i relativi intervalli di riferimento. In 21 soggetti con carenza di AT è stata effettuata la ricerca di mutazioni nel gene SERPINC1 (Universitair Ziekenhuis di Bruxelles). Risultati – I risultati di AT% ottenuti con i due metodi sono altamente correlati (rho di Spearman >0.70); tuttavia, sono stati riscontrati 8 dati discordanti (3 nel gruppo “routine e trombofilici”, 5 nel gruppo “carenti noti”). L’analisi genetica ha identificato la presenza di mutazioni nel gene SERPINC1 in 18/21 soggetti studiati, 5 dei quali con valori di attività AT discordanti. Infatti, valori normali di AT anti-Xa si sono ottenuti per il difetto Cambridge II (II RS), mentre il test AT anti-IIa ha fornito valori normali per un difetto HBS. Valori di AT patologici concordi sono stati ottenuti per 5 carenze di tipo I, mentre si sono ottenuti risultati di AT normali con entrambi i metodi per altre 2 carenze HBS. Nella popolazione indagata la sensibilità del test AT anti-Xa è 61.1%, quella del test AT anti-IIa è 55.6%. Se si considerano entrambi i test la sensibilità diventa 72.2%. Se si utilizza in aggiunta anche il rapporto tra l’attività AT anti-IIa e l’attività anti-Xa, la sensibilità aumenta a 88.9%. Conclusioni – I metodi funzionali attualmente a disposizione per il dosaggio dell’AT non sono in grado di individuare tutti i tipi di difetti molecolari dell’AT. L’utilizzo combinato di un test anti-Xa e di un test anti-IIa e del rapporto AT anti-IIa/AT anti-Xa potrebbe aumentare la capacità diagnostica dei dosaggi. I risultati dei test di laboratorio vanno comunque considerati alla luce della storia clinica personale e familiare del soggetto.
Introduction – Antithrombin (AT) deficiency, associated with an increased risk for venous thrombosis, is classified into type I (quantitative defect) and type II (qualitative defect). Qualitative defects may affect the reactive site (RS), the heparin binding site (HBS) of AT, or they may have a pleiotropic effect (PE). Screening tests, which measure the ability of AT, in the presence of heparin, to inhibits either thrombin (anti-IIa activity) or FXa (anti-Xa activity), are able to detect most AT deficiencies; however, few cases of discrepancies have been described (i.e. normal vs. pathological value) with the two different methods. Aim of the study was the evaluation of agreement between an anti-Xa assay and an anti-IIa assay for AT, and the evaluation of their ability in detecting AT defects. Materials and Methods – The study population consisted of the “routine and thrombophilic” group (493 patients for which AT test was required) and the “historical deficiencies” group (23 subjects with known AT deficiency and 18 relatives). Anti-Xa HemosIL Antithrombin kit (from Instrumentation Laboratory) and a home-made anti-IIa method were used to measure AT activities. A control group (n= 100) was used to determine AT reference ranges. SERPINC1 gene analysis was carried out for 21 patients (Universitair Ziekenhuis in Bruxelles). Results – The results provided by the two methods showed a high correlation (Spearman rho>0.70); however, 8 discrepant results were observed (3 in the “routine and thrombophilia” group and 5 in the “historical deficiencies” group). Gene analysis confirmed the presence of a molecular defect in 18/21 subjects, 5 of which had also descrepant AT results. In fact, normal anti-Xa AT values were obtained for Cambridge II defect (RS), whereas anti-IIa test provided normal values for a HBS defect. Both methods provided pathological AT values for 5 type I deficiencies but normal AT values for other 2 HBS defects. In the study population AT anti-Xa and AT anti-IIa sensitivity was 61.1% and 55.6%, respectively; when both tests were used, sensitivity increased to 72.2%. When the ratio between AT anti-IIa and AT anti-Xa was added, sensitivity increased to 88.9%. Conclusions – Currently avaible screening tests are not able to detect all molecular defects. However, when anti-Xa assay is carried out together with anti-IIa method, and the ratio between the results provided by both is considered, the diagnostic power is increased. Anyway, laboratory test results should be considered together with personal and familiar clinical history of the single subject under evaluation.
APA, Harvard, Vancouver, ISO, and other styles
7

Chen, Iris Ye Wu. "The interactions between human antithrombin and heparin." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0005/NQ42731.pdf.

Full text
APA, Harvard, Vancouver, ISO, and other styles
8

Perry, David James. "The genetic basis of human antithrombin deficiency." Thesis, University of Cambridge, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283014.

Full text
APA, Harvard, Vancouver, ISO, and other styles
9

Belzar, Klara Jane. "The allosteric activation of antithrombin by heparin." Thesis, University of Cambridge, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.621213.

Full text
APA, Harvard, Vancouver, ISO, and other styles
10

Bourti, Yasmine. "Evaluation d'un variant d'antithrombine dans différentes indications thérapeutiques." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS404/document.

Full text
Abstract:
Notre équipe s’intéresse à la relation structure-fonction d’une protéine, l’antithrombine (AT), un inhibiteur physiologique de la coagulation, en vue d’un développement thérapeutique. Cette protéine anticoagulante, capable de lier un motif pentasaccharidique sur les dérivés hépariniques, possède en outre, à fortes concentrations (500%), des propriétés anti-inflammatoires médiées par sa liaison aux héparan-sulfates cellulaires. Ce profil a mené à l’évaluation de l’AT dans des situations associant un emballement de la coagulation et de l’inflammation, comme c’est le cas au cours du sepsis sévère et d’autres situations d’ischémie-reperfusion (I/R). Cependant, les fortes concentrations utilisées dans les études précliniques nécessiteraient d’administrer des doses d’AT incompatibles avec le profil de sécurité de cette protéine anticoagulante.Dans ce contexte, nous avons, au cours de ce travail, caractérisé un variant d’AT (AT-N135Q-Pro394) dépourvu d’activité anticoagulante et doué d’une affinité augmentée pour l’héparine. Ce variant est capable de piéger des dérivés hépariniques et apparait comme un candidat idéal pour une utilisation comme antidote en cas de surdosage en héparine non fractionnée (HNF), héparines de bas poids moléculaire (HBPM) ou fondaparinux. Par ailleurs, ce variant pourrait être utilisé à des doses cytoprotectrices, sans risque hémorragique.Afin de tester cette dernière hypothèse, nous avons développé un modèle d’I/R rénale chez la souris, qui s’accompagne d’une augmentation significative de marqueurs de dysfonction rénale (Urée, Créatinine, Kim-1) et de l’inflammation (expression tissulaire de cxcl-1, il-6). L’AT avait déjà été montrée protectrice (Mizutani et al, Blood 2003) dans un modèle murin comparable. De façon surprenante, nous n’avons observé aucun des effets protecteurs décrits, ni sur l’inflammation ni sur la fonction rénale, et que ce soit avec de l’AT plasmatique, de l’AT recombinante ou encore avec un mélange équimolaire d’AT latente et native. Ce même modèle nous a pourtant permis de mettre en évidence les effets nephroprotecteurs et anti-inflammatoires d’une autre protéine anticoagulante, la protéine C activée. Ces résultats décevants font écho à la rétractation pour fraude de l’article de Mizutani et al. en 2013. Le travail approfondi que nous avons mené nous permet de clarifier la littérature et d’affirmer que l’AT, d’origine plasmatique ou recombinante, ne possèdent pas d’effet protecteur dans l’I/R rénale chez la souris. Dans ces conditions, le variant AT-N135Q-Pro394 n’a pas été testé.Concernant la seconde indication, l’AT-N135Q-Pro394 avait déjà été évaluée in vivo comme antidote aux dérivés hépariniques, HNF, HBPM et fondaparinux, avec d’excellents résultats. Néanmoins, cet effet antidote a été exploré spécifiquement par mesure de l’activité anti-facteur Xa alors que l’AT inhibe plusieurs enzymes de la cascade de coagulation tel que les facteurs VIIa, IXa et IIa. Nous avons donc exploré cet effet antidote dans un test plus global de la coagulation, le test de génération de thrombine (TGT) pour pouvoir le comparer aux autres stratégies non spécifiques utilisées pour antagoniser les dérivés hépariniques (facteur VII activé recombinant, concentré de complexes prothrombiques activés ou protamine). De façon intéressante, dans un plasma mimant un surdosage, notre variant présente un effet antidote supérieur aux agents hémostatiques et au sulfate de protamine vis-à-vis du fondaparinux et des HBPMs, respectivement, et équivalent au sulfate de protamine vis-à-vis de l’HNF. Enfin, dans du plasma en l’absence d’anticoagulant, l’AT-N135Q-Pro394 ne montre aucun effet sur la génération de thrombine contrairement aux agents hémostatiques et au sulfate de protamine qui, ajoutés seuls dans du plasma, modifient significativement le profil des TGT
Our team topic focuses on the structural-function relationship of a natural anticoagulant, antithrombin (AT), in order to develop potential therapeutic agents. AT inhibits several serine proteases of the coagulation cascade and its inhibitory activity is increased when AT binds to a pentasaccharidic motif contained within in the heparin derivatives. At high concentrations (500%), AT also exerts anti-inflammatory and cytoprotective properties through its binding to heparan sulfate proteoglycans, making it a good candidate for supportive therapy in clinical settings associating inflammation and coagulation activation. Indeed, AT has already been evaluated in vivo in various models of ischemia-reperfusion injury (IRI) and AT even reached a large-scale clinical trial in severe sepsis. However, the high concentrations of AT that are needed to exert anti-inflammatory properties are inconsistent with the safety profile of this anticoagulant protein.In this context we have further characterized an AT variant (AT-N135Q-Pro394) with increased affinity to heparin but devoid of anticoagulant activity. Indeed, this variant was described to be able to trap heparin derivatives and our work was to pursue the characterization of this variant as an antidote toward heparin derivatives in clinical situations of overdosing. In addition, this AT variant binds to heparan sulfate proteoglycans with higher affinity, as compared to native AT, and appears as a promising cytoprotective agent whose administration would not be associated with any bleeding risk.To test the latter hypothesis, we developed a murine model of renal IRI in which the renal function was severely impaired, as attested by increased kidney injury markers (urea, creatinine, kim-1) and local kidney inflammation (renal gene expression of il-6 and cxcl-1). Indeed, in 2003, Mizutani et al. reported a protective effect of AT in a similar murine model of renal IRI. Surprisingly, we observed none of the described protective effects, neither on inflammation nor renal function, with plasma AT, recombinant AT and an equimolar mixture of native and latent AT. Nevertheless, the same model enabled us to highlight the nephroprotective and anti-inflammatory properties of another anticoagulant protein, activated protein C (APC), as previously reported. These disappointing results coincided with the withdrawal in 2013 of the study of Mizutani et al., and our work allowed us to clarify the literature and to claim that neither recombinant nor plasma-derived native nor latent forms of AT exhibit a protective effect in renal IRI in mice. Under these conditions, AT-N135Q-Pro394 variant has not been tested in our model.AT-N135Q-Pro394 has also been previously shown to efficiently neutralise the anticoagulant activity of heparin derivatives, including unfractionated heparin (UFH), low molecular weight heparins (LMWH) and fondaparinux in vivo. Nevertheless, this reversal effect was only explored by anti-factor Xa assays whereas AT inhibits a number of coagulation proteases, including factors VIIa, IXa and IIa. Therefore, we explored AT-N135Q-Pro394 variant in a more global coagulation assay, the thrombin-generation assay (TGA), in order to compare its activity with non-specific reversal agents used toward heparin derivative overdose (recombinant-activated factor VII, activated prothrombin-complex concentrate or protamine). Interestingly, in plasma mimicking an overdose, our variant demonstrated greater reversal efficiency as compared to hemostatic agents and protamine sulfate toward fondaparinux and LMWH, respectively, and was as efficient as protamine sulfate toward UFH. Finally, when added to native plasma (in the absence of heparin derivative), AT-N135Q-Pro394 showed no effect on thrombin generation unlike hemostatics and protamine sulfate that all significantly affect the TGA profile
APA, Harvard, Vancouver, ISO, and other styles
More sources

Books on the topic "Antithrombin"

1

Sas, Géza. The biology of antithrombins. Boca Raton, Fla: CRC Press, 1990.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
2

Weilemann, L. S., and H. Schinzel, eds. Antithrombin — Diagnostik und Therapie. Berlin, Heidelberg: Springer Berlin Heidelberg, 1998. http://dx.doi.org/10.1007/978-3-642-60305-1.

Full text
APA, Harvard, Vancouver, ISO, and other styles
3

Sas, Géza. The biology of antithrombins. Boca Raton, Fla: CRC Press, 1990.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
4

Lantbruksuniversitet, Sveriges, ed. Why does Heparin bind antithrombin? Uppsala: Sveriges Lantbruksuniversitet, 1988.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
5

Ramirez, Pablo Antonio Rivera. Messung der Antithrombin III-aktivität bei der Katze: Referenzbereich und Veränderung bei verschiedenen Erkrankungen. Hannover: s.n., 1997.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
6

Sharma, Anupama. A comparison of the binding abilities of human kidney heparan sulphate and heparin glycosaminoglycans for antithrombin III. Manchester: University of Manchester, 1995.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
7

Grebe, Susanne. Pharmakokinetik von intravenös und subkutan verabreichtem niedermolekularen Heparin beim Hund: Wirkung auf Thrombinzeit, aktivierte partielle Thromboplastinzeit, Resonanzthrombogramm und Antithrombin-III-Aktivität. Hannover: [s.n.], 1999.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
8

Jacobs, Christina. Pharmakokinetik von intravenös und subkutan verabreichtem unfraktionierten Heparin beim Hund: Wirkung auf aktivierte partielle Thromboplastinzeit, Thrombinzeit, Resonanzthrombogramm und Antithrombin-III-Aktivität. Hannover: [s.n.], 1999.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
9

Roque, Pifarré, ed. New anticoagulants for the cardiovascular patient. Philadelphia: Hanley & Belfus, 1997.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
10

Weilemann, L. S., and H. Schinzel. Antithrombin - Diagnostik und Therapie. Springer Berlin / Heidelberg, 1997.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
More sources

Book chapters on the topic "Antithrombin"

1

Björk, Ingemar, and Steven T. Olson. "Antithrombin." In Advances in Experimental Medicine and Biology, 17–33. Boston, MA: Springer US, 1997. http://dx.doi.org/10.1007/978-1-4615-5391-5_3.

Full text
APA, Harvard, Vancouver, ISO, and other styles
2

Hepner, Mirta, and Vasiliki Karlaftis. "Antithrombin." In Haemostasis, 355–64. Totowa, NJ: Humana Press, 2013. http://dx.doi.org/10.1007/978-1-62703-339-8_28.

Full text
APA, Harvard, Vancouver, ISO, and other styles
3

Ness, SallyAnne L., and Marjory B. Brooks. "Antithrombin." In Interpretation of Equine Laboratory Diagnostics, 141–42. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2017. http://dx.doi.org/10.1002/9781118922798.ch21.

Full text
APA, Harvard, Vancouver, ISO, and other styles
4

Schuster, H. P., and S. Knaub. "Antithrombin III." In Intensivtherapie bei Sepsis und Multiorganversagen, 191–208. Berlin, Heidelberg: Springer Berlin Heidelberg, 2000. http://dx.doi.org/10.1007/978-3-662-07962-1_8.

Full text
APA, Harvard, Vancouver, ISO, and other styles
5

Stief, T. "Antithrombin-3." In Lexikon der Medizinischen Laboratoriumsdiagnostik, 1–2. Berlin, Heidelberg: Springer Berlin Heidelberg, 2017. http://dx.doi.org/10.1007/978-3-662-49054-9_253-1.

Full text
APA, Harvard, Vancouver, ISO, and other styles
6

Stief, T. "Antithrombin-3." In Springer Reference Medizin, 177–79. Berlin, Heidelberg: Springer Berlin Heidelberg, 2019. http://dx.doi.org/10.1007/978-3-662-48986-4_253.

Full text
APA, Harvard, Vancouver, ISO, and other styles
7

Brown, James P. R., and Joanne Douglas. "Antithrombin Deficiency." In Consults in Obstetric Anesthesiology, 39–40. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-59680-8_10.

Full text
APA, Harvard, Vancouver, ISO, and other styles
8

Scharnagl, Hubert, Winfried März, Markus Böhm, Thomas A. Luger, Federico Fracassi, Alessia Diana, Thomas Frieling, et al. "Antithrombin Deficiency." In Encyclopedia of Molecular Mechanisms of Disease, 109–10. Berlin, Heidelberg: Springer Berlin Heidelberg, 2009. http://dx.doi.org/10.1007/978-3-540-29676-8_122.

Full text
APA, Harvard, Vancouver, ISO, and other styles
9

Riess, H. "Hereditärer Antithrombin-Mangel." In Antithrombin — Diagnostik und Therapie, 21–29. Berlin, Heidelberg: Springer Berlin Heidelberg, 1998. http://dx.doi.org/10.1007/978-3-642-60305-1_3.

Full text
APA, Harvard, Vancouver, ISO, and other styles
10

Pindur, G. "Antithrombin und Sepsis." In Antithrombin — Diagnostik und Therapie, 31–38. Berlin, Heidelberg: Springer Berlin Heidelberg, 1998. http://dx.doi.org/10.1007/978-3-642-60305-1_4.

Full text
APA, Harvard, Vancouver, ISO, and other styles

Conference papers on the topic "Antithrombin"

1

Knoller, S., and N. Savion. "MODULATION OF ANTITHROMBIN III ACTIVITY AND ANTITHROMBIN III-THROMBIN COMPLEXES BINDING TO CULTURED CELLS BY MONOCLONAL ANTIBODIES AGAINST ANTITHROMBIN III." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644361.

Full text
Abstract:
Two monoclonal antibodies (mAb's) against antithrombin III (ATIII) were characterized with respect to their ability to interfere with ATIII activity. AT III activity was measured by its ability to inhibit the amidolitic activity of thrombin on the substrate BCP-100. Incubation of 150 ng of ATIII with 28pg mAb A36R2 prior to addition of 50 ng thrombin totally abolishes the inhibitory effect of ATIII on thrombin. Incubation of 200ng of ATIII with 10 μg of mAb B26R4 prior to addition of 75 ng thrombin raises the inhibitory effects of ATIII from 37% to 100%. We examined the effect of these mAb's on binding of antithrombin III-thrombin (ATIII-Th) complexes to bovine corneal endothelial cells. 120 pg/ml mAb's are reacted with 2 μg/ml ATIII-Th complexes prior to their addition to the cells. mAb A36R2 completely blocks ATIII-Th complexes binding. In contrast, mAb B26R4 enhances binding up to 250% of the control binding.We conclude that mAb A36R2 prevents binding of thrombin to ATIII by recognizing an epitope on ATIII close to thrombin binding site or that its binding to ATIII induces a conformational change in the thrombin binding site thus it no longer recognizes thrombin. mAb B26R4 has a heparin-like effect on ATIII: Its binding to ATIII induces conformational changes which improve thrombin binding to ATIII. There is a correlation between inhibition and enhancement of thrombin binding to ATIII and of ATIII-Th complexes binding to cells by the two mAb's. These mAb's may provide a new tool to control the activity of ATIII and to identify the cellular binding site on the ATIII-Th complex.This research was supported by a grant from the National Council for Research and Development, Israel and G.S.F. München, Germany.
APA, Harvard, Vancouver, ISO, and other styles
2

Samama, J. P., M. Delarue, D. Moras, M. Petitou, J. C. Lormeau, and J. Choay. "CRYSTALLOGRAPHIC INVESTIGATION OF ANTITHROMBIN III." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643765.

Full text
Abstract:
The plasma protein inhibitor anti thrombin III in its native form has been crystallized using standard techniques.The crystals diffract to about and belong to space group P41212 with cell parameters:a = b = 90.6<, c = 380.7<.The asymmetric unit contains three molecules of anti thrombin III.The self rotation function computed with the native data set indicates the presence of a non crystallographic three fold axis. Cross rotation function calculations using themodel of the cleaved α1,-antitrypsin (H. Loebermann at.,J. Mol. Biol.(1985) 177, 531) suggests tertiary structuresimilarities between the two plasma proteins.This is in agreement with the already described primary sequence homology of these glycoproteins but at variance with the model of active α1-anti trypsin inferred from the previous studies on the cleaved molecule.The technical assistance of M. Maman is deeply appreciated.
APA, Harvard, Vancouver, ISO, and other styles
3

de Moerloose, Ph, G. Reber, Ph Minazio, and C. A. Bouvier. "ANTITHROMBIN III GENEVA : AN HEREDITARY ABNORMAL ANTITHROMBIN III (AT III) WITH DEFECTIVE HEPARIN COFACTOR ACTIVITY." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644367.

Full text
Abstract:
A 43-year old man presented a pulmonary embolism. Despite a negative family history for thromboembolic disorders, the unusual circumstances of apparition and the relatively young age of the patient prompted us to study carefully the coagulation parameters. Routine coagulation tests, as well as plasminogen, alpha-2-anti-plasmin, protein C and protein S were all within normal range. Biological and immunological assays of AT III were performed on 12 members of the family and showed a low AT III activity in the propositus and other members of this family (mean 50%), but normal immunologic levels. Crossed immunoelectrophoresis in absence of heparin showed a normal pattern, but in presence of heparin showed an abnormal peak as compared with controls. Kinetics experiments showed a normal inhibition of Xa and 11a in absence of heparin, but abnormal in presence of heparin. An affinity chromatography on heparin Sepharose revealed two populations of AT III, one of which was devoid of heparin cofactor activity.The toponym AT III Geneva is proposed for this new familial abnormal AT III with defective heparin cofactor activity. This family confirms the low incidence of thromboembolic events reported in this type of AT III variant.
APA, Harvard, Vancouver, ISO, and other styles
4

Asakura, S., N. Yoshida, and M. Matsuda. "MONOCLONAL ANTIBODIES AGAINST THROHBIN-ANTITHROMBIN III COMPLEX: EPITOPE SPECIFICITY AND EFFECT ON THROMBIN-ANTITHROMBIN III INTERACTION." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643673.

Full text
Abstract:
Among monoclonal antibodies (MCA´s) raised against human thrombin (T)-antithrombin m (AT) complex (TAT), two MCA´s designated as JITAT-16 and 17 with high affinity, Kd = 4.6nMand 4.1 nfi, respectively, were selected and characterized for specificity and functions. Their respective immunoglobulin subclasses are IgGi and IgG2a, and epitopes were found to be different from each Dther as shown by crisscross inhibition experiments. Immuno-alotting of normal plasma and serum electrophoresed on non-SDS aolyacrylamide gel showed that these antibodies reacted with normal serum but not with plasma. This was verified by an anzyme-linked differential antibody immunosorbent assay using aither one of the MCA´s as the first antibody and the other MCA labeled with peroxidase as the second one. By immunoblotting after SDS-PAGE, we found that both antibodies reacted with TAT, nut not with its respective nascent constituent, AT or T. However, they reacted with reactive site-cleaved AT (or thrombin-nodified AT, ATM) and also a complex of AT with activated factor K (Xa-AT). These results indicate that both of these antibodies recognize enzyme-treated forms of AT, including AT molecules :omplexed with enzymes reversibly or irreversibly as well as ATM. Jpon incubation of T with AT in the presence of JITAT-16, T activity remained nearly unchanged and formation of irreversible rAT did not proceed as expected. Moreover, AT was preferentially :onverted to ATM. When JITAT-16 was added after completion of FAT formation, however, neither recovery of T activity nor generation of ATM was observed. These findings were not obtained vhen JITAT-17 had been substituted for JITAT-16. These data suggest that JITAT-16 may have converted AT from an inhibitor to a substrate for T after having recognized a possible intermediate reversible complex of AT with T. Undoubtedly, in the presence of a polyclonal antibody against AT, neither TAT formation nor ATM neneration was observed at all. The mechanism of the unique Function of JITAT-16 has not been fully clarified as yet, but this antibody seems to give us new information on the kinetic study of TAT formation and ATM generation when AT was allowed to react with enzymes.
APA, Harvard, Vancouver, ISO, and other styles
5

Baruch, D., J. Franssen, H. C. Hemker, and T. Lindhout. "THE ROLE OF HEPARIN CHARGE DENSITY IN THE ANTITHROMBIN III-DEPENDENT AND ANTITHROMBIN III-INDEPENDENT INACTIVATION OF THROMBIN." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644357.

Full text
Abstract:
The dependence of the anticoagulant properties of heparin upon charge density may reflect structural factors that are important in anti-thrombin effect. We have previously demonstrated that in the absence of antithrombin III (AT III) unfractionated heparin inhibits the catalytic effect of thrombin upon platelet activation. In the present study we evaluated the thrombin-binding properties of heparin fractions obtained by ion-exchange chromatography on DEAE-Sephacei. We found that these fractions were able to bind to thrombin with an affinity that increased with their charge density. This was shown by their inhibitory effect in the absence of AT III on thrombin-catalyzed platelet factor Va formation and by the ability of active site blocked thrombin to prevent the heparin-dependent inactivation of thrombin by AT III. However, their increase in charge density and thus affinity for thrombin was found to go along with an increase in AT III-binding sites, as measured by the heparin-dependent increase of the intrinsic fluorescence of AT III. Moreover all heparin fractions showed the same specific antithrombin activity when the molar concentration of AT III-binding heparin was taken into account. We also investigated the thrombin-binding properties of two heparin fractions obtained by affinity chromatography on AT III-Sepharose. The AT III low affinity fraction was practically devoid of any inhibitory effect on the rate of the thrombin-catalyzed factor Va formation, indicating a low, if any, affinity for thrombin. In contrast the AT III-independent inhibition of thrombin was completely recovered from the AT III high affinity fraction. In addition, we also established that when the heparin fraction from the DEAE-Sephacel column, with the lowest charge density and very low in AT III binding material, was modified by the incorporation of sulfate groups so as to achieve a higher charge density, it obtained a higher affinity for thrombin but this modification caused the loss of half the AT III binding sites. In conclusion, it is apparent that fractionation of crude heparin on a DEAE-Sephacel column or on an AT III-Sepharose column does not result exclusively in a separation of either the thrombin-binding or the AT III-binding heparin fractions.
APA, Harvard, Vancouver, ISO, and other styles
6

Jordan, R. E., J. Kilpatrick, J. Nelson, J. O. New gren, and M. A. Fournel. "HEPARIN DIRECTS THE INACTIVATION OF ANTITHROMBIN BY ELASTASE." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643770.

Full text
Abstract:
In apparent contradiction to its anticoagulant activity, we have observed a previously undetected, and potentially opposing function for heparin: a distinct heparin-dependency for the in vitro inactivation of highly-purified human antithrombin by neutrophil elastase. Similar to its ability to accelerate antithrombin-mediated inhibition of coagulation enzymes, anticoagulantly-active heparin was also found to stimulate the rate of inactivation of antithrombin by the neutrophil enzyme.In the absence of heparin, or in the presence of the heparin antagonists platelet factor 4 or polybrene, little or no inactivation of antithrombin occurred. Catalytic amounts of heparin and elastase caused the complete inactivation of antithrombin (approximate molar ratio of 1:1:400 respectively) in 5-10 minutes. The loss of heparin binding affinity by the elastase-cleaved form of antithrombin permitted its separation from active antithrombin by heparin-agarose chromatography.The purified elastase-inactivated antithrombin was injected into rabbits for determination of its comparative clearance behavior. In contrast to intact, functional antithrombin (t 1/2 >30 hours) and the thrombin-antithrombin (T-AT) complex (t 1/2 previously shown to be minutes), elastase-inactivated antithrombin circulated for approximately 13 hours. This prolonged clearance relative to the T-AT complex may suggest an alternative explanation for the circulating, non-functional antithrombin observed in certain coagulopathic states. In summary, these results point to a potential and unexpected role for heparin in directing the inactivation of antithrombin and suggest a possible in vivo mechanism for neutralizing the usually non-thrombogenic nature of the vascular lining.
APA, Harvard, Vancouver, ISO, and other styles
7

Schober, S., C. Deppisch, U. Holzer, R. Handgretinger, U. Ernemann, N. Kaiser, V. Icheva, and G. Wiegand. "Congenital Antithrombin Deficiency Type II: A Case Report." In 63rd Annual Meeting of the Society of Thrombosis and Haemostasis Research. Georg Thieme Verlag KG, 2019. http://dx.doi.org/10.1055/s-0039-1680210.

Full text
APA, Harvard, Vancouver, ISO, and other styles
8

Goto, T., D. Kudo, R. Uchimido, K. Yamakawa, M. Hayakawa, S. Kushimoto, and H. Yasunaga. "Sepsis Phenotypes and the Effect of Antithrombin III." In American Thoracic Society 2020 International Conference, May 15-20, 2020 - Philadelphia, PA. American Thoracic Society, 2020. http://dx.doi.org/10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a6006.

Full text
APA, Harvard, Vancouver, ISO, and other styles
9

Karges, H. E., G. Zettlemeiβl, H. Naumann, U. Eberhard, and M. Bröker. "PURIFICATION AND CHARACTERIZATION OF GENTECHNOLOGICALLY PREPARED ANTITHROMBIN III." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643684.

Full text
Abstract:
Isolation and purification of antithrombin III (AT III) by affinity chromatography on immobilized heparin is a standard method for the large scale preparation of this protein from human or animal plasma. Hence, after AT III became available by gentechnological methods, we tried to adapt this procedure for the isolation of AT III from supernatants of mammalian- and yeast-cells. Indeed, it was possible to use this method also for the isolation of the recombinant gene products. Since, however, the cell growth media contain heterologous protein or peptide mixtures like fetal calf serum, the method had to be improved to avoid the adsorption of non human proteins or peptides. We are now able to purify AT III from CHO-cell-superna-tants to more than 95 % purity. The characterization of this AT III-product by double immuno diffusion revealed that it is immunologically totally identical with the authentic material from plasma. AT III antigen content, progressive inhibitor activity and heparin cofactor activity compare very well in the final product; hence, it is totally active compared to AT III from plasma.In polyacrylamidegel electrophoresis most of the material migrated differently to the authentic material showing 9 bands in equal distance to each other, instead four in the At III from plasma. After degradation with sialinidase from both AT III preparations identical cleavage products were obtained migrating predominantly as a single band. Hence, the electrophoretic heterogeneity seems to be due to a different degree of sialinyla-tion of the products.
APA, Harvard, Vancouver, ISO, and other styles
10

soons, H., T. Jansen-claessen, G. C. Tans, and H. C. Hemker. "HEPARIN CATALYZED FACTOR XIa INHIBITION BY ANTITHROMBIN III." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643768.

Full text
Abstract:
The inactivation of human factor XIa by human antithrombin III (AT III) was studied under pseudo-first order reaction conditions (excess AT III) both in the absence and presence of heparin. The time course of inhibition was followed using SDS-PAGE. After electrophoresis proteins were blotted onto nitrocellulose and stained either for glycoprotein or for AT III using antibodies against AT III. Concomittant with factor XIa inactivation two new slower migrating bands became visible on the blots. One of these, representing the intermediate complex consisting of one AT III complexed with one of the active sites present in factor XIa, appeared as a transient band. Complete inactivation resulted in a single band representing the complex of factor XIa with two AT III molecules. This indicates that inhibition of factor XIa by AT III can be described as:Quantitative analysis of the time course of inactivation was accomplished by measurement of the disappearance of factor XIa amidolytic activity towards the chromogenic substrate S2366. Pseudo first order reaction kinetics were observed throughout. The time course of inactivation and the distribution of the reaction products observed upon gelelectrophoresis are best explained assuming a mechanism of inactivation in which the two active sites present in factor XIa are inhibited in random order (i.e. independent of each other) with the same rate constant of inhibition (k1= k2)- The rate constant of inactivation for the active sites in factor XIa was found to be 1,000 M-1 s-1 in the absence of heparin and 34,900 M-1 s-1 in the presence of saturating amounts of heparin.- From the kinetic data a binding constant Kd of 0.11 uM was inferred for the binding of AT III to heparin. Experiments with four well characterized heparin fractions indicate, that the actual magnitude of the rate enhancement of factor XIa inactivation is, however, not only due to the binding of AT III to heparin, but also depends on the type of heparin to which the AT III is bound.
APA, Harvard, Vancouver, ISO, and other styles
You might also be interested in the extended bibliographies on the topic 'Antithrombin' for particular source types:
Journal articles Dissertations / Theses Books
We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!

To the bibliography