ライフサイエンスコーパス: GPIIb

1 GPIIb peptide-induced inhibition of platelet spreading i

2 GPIIb/IIIa antagonists, such as eptifibatide, interfere

3 GPIIb/IIIa blockers are a new class of compounds that ha

4 Reactions of 24 GPIIb-IIIa-specific antibodies evaluated (12 monoclonal,

5 activation of the integrin alpha IIb beta 3 (GPIIb-IIIa) were strongly reduced in platelets from G al

6 Platelet integrin alpha IIb beta 3 (GPIIb/IIIa) plays a central role in the initiation of ar

7 tail) results in integrin alpha(IIb)beta(3) (GPIIb-IIIa) activation.

8 ancy of platelet integrin alpha(IIb)beta(3) (GPIIb-IIIa) generate biologically important signals: con

9 to the platelet integrin alpha(IIb)beta(3) (GPIIb/IIIa) through confocal fluorescence imaging of pri

10 A GPIIb/IIIa blocking antibody did not alter the blood cel

11 rin, methylprednisolone, and eptifibatide (a GPIIb/IIIa antagonist).

12 ctin and anti-CD154 mAbs, or eptifibatide (a GPIIb/IIIa receptor antagonist), was tested.

13 ognized by D3 represents the expression of a GPIIb-IIIa activation state that participates in full-sc

14 g without clopidogrel pretreatment, use of a GPIIb/IIIa inhibitor produces superior platelet inhibiti

15 In the absence of a GPIIb/IIIa inhibitor, 600 mg clopidogrel provides better

16 To Improve Long-term Outcome with abciximab GPIIb/IIIa Receptor Blockade (EPILOG) trials, abciximab

17 and G(i) pathways is sufficient to activate GPIIb/IIIa in human platelets in a mechanism that involv

18 CD39 was recombinantly fused to an activated GPIIb/IIIa-specific scFv (targ-CD39) and a nonfunctional

19 A9, which bind to both resting and activated GPIIb-IIIa, was normal.

20 Platelet GPIb and activated GPIIb/IIIa expression without added agonist was unchange

21 Expression of P-selectin and activated GPIIb/IIIa in response to high-dose ADP was lower during

22 latelets, which do not yet express activated GPIIb/IIIa.

23 chain antibody (scFv, specific for activated GPIIb/IIIa) for targeting CD39.

24 and-induced binding site (LIBS) of activated GPIIb/IIIa receptors, enabled the efficient detection of

25 Platelet surface expression of activated GPIIb/IIIa, P-selectin, and GPIb was measured with and w

26 of MoAb PAC1, which binds to only activated GPIIb-IIIa, was diminished upon activation with PAF, ade

27 eptor (TRAP-stimulated P-selectin, activated GPIIb-IIIa, and CD42b), independent of platelet count, a

28 nd (iii) fibrinogen binding to the activated GPIIb-IIIa complex.

29 igand-induced binding sites of the activated GPIIb/IIIa receptor (MBDual).

30 Active GPIIb/IIIa expression was inhibited most in the groups t

31 In our efforts to develop orally active GPIIb-IIIa antagonists with improved pharmaceutical prop

32 ry of RWJ-53308 (2), a potent, orally active GPIIb/IIIa antagonist.

33 neous coronary interventions with adjunctive GPIIb/IIIa inhibition, the risk of bleeding, particularl

34 peptide which incorporates two high affinity GPIIb/IIIa receptor-binding domains and a novel 99mTc bi

35 These data suggest that high-affinity GPIIb-IIIa- mediated ligand binding can be separated mec

36 CD36 or GPIb, but not by antibodies against GPIIb/IIIa, von Willebrand factor (VWF), thrombospondin

37 eraction of platelet integrin alphaIIbbeta3 (GPIIb-IIIa) with fibrinogen during platelet aggregation.

38 ding to the platelet integrin alphaIIbbeta3 (GPIIb-IIIa), a prerequisite for platelet thrombus format

39 ho lacked functional integrin alphaIIbbeta3 (GPIIb-IIIa).

40 n of fibrinogen with integrin alphaIIbbeta3 (GPIIb/IIIa), in part mediated by an RGD tripeptide motif

41 Also using SPR analysis, GPIIb/IIIa was found to bind monovalently to immobilized

42 Both GPIIb-Ala5IIIa- and GPIIb-Ala435IIIa-transfected CHO cells also bound more a

43 suggesting that interaction between CIB and GPIIb/IIIa is required for progression from filopodial t

44 he molecular basis of MK differentiation and GPIIb-IIIa function.

45 ice) and increased P-selectin expression and GPIIb/IIIa activation in platelets.

46 mic and nuclear distribution in GPIIb(+) and GPIIb(-) cells derived from CD34(+) cells and in HEL cel

47 decreases of secretion of alpha-granules and GPIIb-IIIa activation induced by adenosine 5'-diphosphat

48 ium; and (iv) independent of the GPIb-IX and GPIIb-IIIa complexes.

49 s-1 binds to proximal regions in the PF4 and GPIIb promoters in vivo.

50 mpaired platelet protein phosphorylation and GPIIb-IIIa activation; (2) proteins regulated by CBFA2 a

51 t activation and trigger granule release and GPIIb/IIIa activation via protein kinase C-alpha.

52 Ib/IIIa and anti-alpha v beta 3), 10E5 (anti-GPIIb/IIIa), or LM609 (anti-alpha v beta 3).

53 e platelets in the presence of mAb 1B5 (anti-GPIIb/IIIa) and platelets from beta3-null mice behaved l

54 ets with monoclonal antibody (mAb) 7E3 (anti-GPIIb/IIIa (alphaIIbbeta3) + alphaVbeta3) or tirofiban (

55 ibodies (mAb) CD42b (anti-GPIb), CD41a (anti-GPIIb/IIIa), and CD62 (anti-P-selectin), with flow cytom

56 l and patient plasma with no detectable anti-GPIIb/IIIa or anti-GPIb autoantibodies.

57 preincubated with antibodies c7E3 Fab (anti-GPIIb/IIIa and anti-alpha v beta 3), 10E5 (anti-GPIIb/II

58 distinct autoantibodies), we identified anti-GPIIb/IIIa antibody-specific phage encoding the peptide

59 aIIbbeta3) + alphaVbeta3) or tirofiban (anti-GPIIb/IIIa) did not prevent platelet adhesion but nearly

60 ound less often, but not in the same PLNs as GPIIb/IIIa.

61 The integrin alphaIIb beta3 (GPIIb-IIIa) is expressed on the surface of platelets in

62 iciency in platelet integrin alphaIIb beta3 (GPIIb-IIIa).

63 of the fibrinogen receptor, alphaIIb beta3 (GPIIb-IIIa).

64 e we demonstrate that an association between GPIIb/IIIa and calcium- and integrin-binding protein (CI

65 ined the intramolecular relationship between GPIIb-IIIa activation and fibrinogen binding, platelet a

66 human alloantibodies have been shown to bind GPIIb-IIIa on the platelet surface and inhibit ADP-induc

67 noclonal antibody fragment (c7E3 Fab) blocks GPIIb/IIIa and alpha v beta 3 receptors, inhibits platel

68 eration, whereas antibody 10E5, which blocks GPIIb/IIIa but not alpha v beta 3 receptors decreased th

69 Both GPIIb-Ala5IIIa- and GPIIb-Ala435IIIa-transfected CHO cel

70 y c7E3 Fab, most likely in part through both GPIIb/IIIa and alpha v beta 3 blockade, and that this ef

71 cessfully bound by fibrinogen cross-bridging GPIIb/IIIa receptors on the platelet surfaces.

72 omotion or inhibition of fibrin formation by GPIIb-IIIa, and could be relevant to the use of specific

73 platelet-stimulated sprouting is mediated by GPIIb/IIIa.

74 ate identification of epitopes recognized by GPIIb-IIIa-specific antibodies, study of the mechanism(s

75 r combined G(i) and G(z) pathways also cause GPIIb/IIIa activation and compared the signaling require

76 e marrow cells for their expression of CD41 (GPIIb-GPIIIa) and CD4 with specific monoclonal antibody

77 These data suggest that formation of the CIB-GPIIb/IIIa complex may be necessary for initiation of do

78 and clinical data now suggest that combining GPIIb/IIIa inhibition with reduced-dose thrombolytic the

79 ific platelet glycoprotein IIb/IIIa complex (GPIIb/IIIa) antagonist.

80 immunoprecipitates of GPIIb-IIIa containing GPIIb with Ala, Val, Lys, or Pro, but not Gly, at positi

81 In contrast, GPIIb expression appears to be independent of GATA-1 in

82 in inside-out signal transduction-dependent GPIIb-IIIa activation due to an upstream defect in the s

83 r the design of highly potent, long-duration GPIIb/IIIa antagonists, the effect of placing lipophilic

84 s) from high-expresser platelets, especially GPIIb and PECAM (CD31).

85 CHO cells expressing GPIIb-Ala5GPIIIa or GPIIb-Ala435IIIa bound well-characte

86 s a first estimate of eta for the fibrinogen-GPIIb/IIIa cross-bridging of platelets.

87 286, located immediately distal to the first GPIIb calcium binding domain, was replaced by Asp and Ph

88 elopment of bleeding complications following GPIIb/IIIa blockade represents a significant limitation

89 uted isoquinolones 2 and 3 have affinity for GPIIb-IIIa and represent leads for further structural ev

90 ructures provide compounds with affinity for GPIIb-IIIa.

91 d and were found to have modest affinity for GPIIb-IIIa.

92 les yielded compounds with high affinity for GPIIb-IIIa.

93 ed the MoAb 7E3, which has high affinity for GPIIb/IIIa.

94 onstrated a selectivity of > 50,000-fold for GPIIb-IIIa versus the most closely related integrin, the

95 eld potent antagonists that are specific for GPIIb-IIIa.

96 t, platelet-reactive antibodies specific for GPIIb/IIIa or GPIb/IX were identified in each case.

97 inding can be separated mechanistically from GPIIb-IIIa-mediated clot retraction and that clot retrac

98 Cultured MKs expressed functional GPIIb-IIIa receptors as assessed by agonist inducible so

99 crossed to an mpl(-/-) background generating GPIIb-tva+mpl(-/-) mice.

100 ibodies against cell-specific glycoproteins (GPIIb-IIIa, GPIb-IX and others) accelerate platelet dest

101 avian retroviral infection; 815 bp of human GPIIb regulatory sequence was used to generate transgeni

102 , from a mouse immunized with purified human GPIIb/IIIa and quinine that recognize the N terminus of

103 atelet factor 4 (PF4), and glycoprotein IIb (GPIIb) as model systems to explore the properties of Ets

104 shown that, when bound to glycoprotein IIb (GPIIb), calcium- and integrin-binding protein (CIB) regu

105 alpha-subunit, also termed glycoprotein IIb (GPIIb), to bind metal ions, we prepared small synthetic

106 ish CD41 cDNA (alpha(IIb), glycoprotein IIb [GPIIb]) and its promoter and have generated transgenic z

107 e fibrinogen receptor glycoprotein IIb-IIIa (GPIIb-IIIa; alphaIIbbeta3) and the vitronectin receptor

108 Glycoprotein IIb/IIIa (GPIIb/IIIa) blockade was associated with lower cardiac m

109 indicate that CIB and glycoprotein IIb/IIIa (GPIIb/IIIa) interact with each other as platelets adhere

110 Glycoprotein IIb/IIIa (GPIIb/IIIa) is the key receptor involved in platelet agg

111 et adhesion receptor, glycoprotein IIb/IIIa (GPIIb/IIIa), also reduced EAE severity in mice.

112 ding to impaired aggregation from defects in GPIIb-IIIa per se to aberrations in signaling mechanisms

113 Platelets deficient in GPIIb-IIIa integrins or with GPIIb-IIIa function inhibit

114 ed a cytoplasmic and nuclear distribution in GPIIb(+) and GPIIb(-) cells derived from CD34(+) cells a

115 thways for calcium and Src family kinases in GPIIb/IIIa activation and thromboxane production.

116 data suggest that the Leu214Pro mutation in GPIIb disrupts the structural conformation, and either d

117 ulation of nuclear factors that synergize in GPIIb promoter regulation.

118 suggesting that the patient's' defect was in GPIIb.

119 s in several megakaryocytic genes, including GPIIb, GPIX, and C-MPL.

120 s with the finding that Mpl ligand increases GPIIb mRNA in megakaryocytes but not the density of the

121 uced MKs remained capable of agonist induced GPIIb-IIIa activation.

122 tibody (D3) specific for GPIIIa that induces GPIIb-IIIa binding to adhesive protein molecules and yet

123 Agents that block the platelet integrin GPIIb-IIIa receptor inhibit the binding of fibrinogen to

124 gregation through activation of the integrin GPIIb-IIIa and subsequent binding of fibrinogen.

125 gnition site of alpha(IIb)/beta(3) integrin (GPIIb/IIIa), thereby preventing the activated integrin f

126 oprotein, usually alpha(IIb)/beta3 integrin (GPIIb/IIIa) when the drug is present.

127 these interactions are mediated by integrins GPIIb/IIIa and alphavbeta3.

128 specific blockade of cell surface integrins GPIIb/IIIa (alphaIIbbeta3) and GPIa/IIa (alpha2beta1), t

129 ndergone normal maturational processing into GPIIb heavy and light chains.

130 8-fold improvement in affinity for isolated GPIIb/IIIa receptors over analogues possessing an isoind

131 e alpha-carbamate substituent of isoxazoline GPIIb/IIIa (alphaIIb beta3) antagonist DMP 754 (7) led t

132 ts with Glanzmann thrombasthenia, who lacked GPIIb/IIIa receptors but had normal or increased alpha v

133 y and internalization of ligands bound to MK GPIIb-IIIa also shared similarities with those observed

134 ity and kinetics of fibrinogen binding to MK GPIIb-IIIa receptors were similar to those described for

135 binding was achieved at approximately 15 nM GPIIb-IIIa.

136 We conclude direct activation of GPIIb-IIIa in the absence of platelet activation results

137 signal transduction-dependent activation of GPIIb-IIIa; and (3) we have documented the first deficie

138 Activation of GPIIb/IIIa is known to require agonist-induced inside-ou

139 ale aggregation and decreased the amounts of GPIIb-IIIa and talin incorporated into the core cytoskel

140 C-1 was diminished despite normal amounts of GPIIb-IIIa on platelets.

141 her known naturally occurring antagonists of GPIIb-IIIa, including the disintegrins from snakes, deco

142 er, unlike the RGD-containing antagonists of GPIIb-IIIa, the RGD sequence of variabilin is not positi

143 any other naturally occurring antagonists of GPIIb-IIIa, variabilin contains the RGD (Arg-Gly-Asp) mo

144 linkage protein mediating the attachment of GPIIb-IIIa to actin filaments, direct binding of GPIIb-I

145 The benefits of GPIIb/IIIa inhibition in reducing death, MI or urgent re

146 b-IIIa to actin filaments, direct binding of GPIIb-IIIa to this cytoskeletal protein has not been dem

147 e results indicate that combined blockade of GPIIb/IIIa and alphavbeta3 affords significant antiangio

148 in this model system, absence or blockade of GPIIb/IIIa receptors interferes with thrombus formation

149 ents in EPIC was due to c7E3 Fab blockade of GPIIb/IIIa receptors.

150 and in vitro activity of this novel class of GPIIb-IIIa antagonists are presented.

151 ing isotherms with varying concentrations of GPIIb-IIIa showed that half-saturation binding was achie

152 at flank the first calcium binding domain of GPIIb affect its folding.

153 tions of the fourth Ca(2+)-binding domain of GPIIb also failed to bind metal ions in a normal manner.

154 sition of the first Ca(2+)-binding domain of GPIIb had no effect on divalent-cation-binding ability w

155 egion of the fourth Ca(2+)-binding domain of GPIIb, with a negatively charged Asp residue resulted in

156 tion of talin with the cytoplasmic domain of GPIIb-IIIa was further investigated using peptide-coated

157 ology between the calcium binding domains of GPIIb and the calcium binding loops of HLH-containing pr

158 near the divalent-cation-binding domains of GPIIb do not necessarily exert their biochemical effects

159 Thus, the engagement of GPIIb/IIIa with anubeta3 integrin interaction mediates t

160 To refine the quantitative estimation of GPIIb/IIIa receptors on resting platelets, we have used

161 main of platelet GPIIb impairs the export of GPIIb-IIIa heterodimers to the platelet surface.

162 is a sensitive indication of the fidelity of GPIIb-IIIa folding, it is not sufficient to account for

163 At saturation, there was 211 +/- 8 fmol of GPIIb-IIIa bound per well containing 117 +/- 10 fmol of

164 A variant form of GPIIb with a deletion of two amino acids at the -1 and X

165 Like Pena, the Penb form of GPIIb-IIIa could undergo conformational changes in respo

166 Both allelic forms of GPIIb-IIIa were expressed on the cell surface and were r

167 IIb, and an abnormally migrating fragment of GPIIb.

168 ne BiP was detected in immunoprecipitates of GPIIb-IIIa containing GPIIb with Ala, Val, Lys, or Pro,

169 study was conducted to assess the impact of GPIIb/IIIa blockade with tirofiban on costs during the i

170 elevant to the use of specific inhibitors of GPIIb-IIIa as antithrombotic agents.

171 pies (P2Y(12) antagonists with inhibitors of GPIIb-IIIa, thrombin or Factor Xa, etc.) to provide addi

172 These antibodies are potent inhibitors of GPIIb/IIIa and alphavbeta3.

173 Moreover, the interaction of GPIIb-IIIa to 8d4-captured talin was blocked by mAb10B2,

174 resent study, we examined the interaction of GPIIb-IIIa with purified talin using a solid-phase bindi

175 treatment reduced the steady-state level of GPIIb mRNA and increased those for glycophorin A and gam

176 let lysates demonstrated decreased levels of GPIIb (approximately 30% to 35% of normal) and GPIIIa (a

177 PIIIa, approximately 30% of normal levels of GPIIb, and an abnormally migrating fragment of GPIIb.

178 ace GPIIb/IIIa number and that the number of GPIIb/IIIa receptors is approximately 80,000 per platele

179 Studies to define precisely the number of GPIIb/IIIa receptors using specific monoclonal antibodie

180 after ischemia, respectively, and numbers of GPIIb/IIIa immunoreactive downstream cerebral microvesse

181 activation involves the proximal promoter of GPIIb within 114 bp upstream of the transcriptional star

182 Fli-1 and Ets-1 occupy the promoters of GPIIb, GPIX, and C-MPL genes in both Meg-01 and CMK11-5

183 enia and structure-function relationships of GPIIb-IIIa.

184 o resulted in the intracellular retention of GPIIb-IIIa, suggesting that interactions between sequenc

185 ro, or Asn caused intracellular retention of GPIIb-IIIa.

186 ompassing the entire cytoplasmic sequence of GPIIb.

187 orresponding to the cytoplasmic sequences of GPIIb (P2b) and GPIIIa (P3a).

188 Direct sequencing of GPIIb exon 6 indicated that the patient is homozygous fo

189 different high-affinity activation states of GPIIb-IIIa, the properties of an antibody (D3) specific

190 w this mutation might alter the structure of GPIIb, G273 was replaced by other amino acids and the re

191 recognize similar antigenic determinants on GPIIb/IIIa, the three phage were tested for binding to f

192 replacement with Ala or Val had no effect on GPIIb-IIIa expression, replacement with Glu, Lys, Pro, o

193 bodies recognize multiple target epitopes on GPIIb/IIIa complexed with the inhibitor to which the pat

194 Recent literature on GPIIb/IIIa inhibitors in acute coronary syndromes was re

195 ected against the fibrinogen binding site on GPIIb-IIIa), and (iv) generation of procoagulant platele

196 inding exposes new antibody binding sites on GPIIb-IIIa (ligand-induced binding sites: LIBS).

197 ctrophoresis (SDS-PAGE) analysis showed only GPIIb and GPIIIa subunits of normal size.

198 CHO cells expressing GPIIb-Ala5GPIIIa or GPIIb-Ala435IIIa bound well-characterized, conformationa

199 e the function of integrin alphaIIbbeta3 (or GPIIb/IIIa), the platelet fibrinogen receptor, is unknow

200 Introduction of anti-CIB antibody or GPIIb cytoplasmic peptide into platelets blocks lamellip

201 Further, anti-CIB- or GPIIb peptide-induced inhibition of platelet spreading c

202 activation decreased after one month of oral GPIIb/IIIa inhibition, levels remained higher than norma

203 CT51464) thus appears to be a promising oral GPIIb-IIIa inhibitor with significantly improved pharmac

204 anticoagulated PRP, and 4 nM in solid-phase GPIIb-IIIa competition binding assay (ELISA).

205 or G(q) signaling pathways activate platelet GPIIb/IIIa when combined with G(i) signaling.

206 ctive activation of G(12/13) causes platelet GPIIb/IIIa activation when combined with G(i) signaling.

207 binds to both human tumor and host platelet GPIIb/IIIa and endothelial alphavbeta3 integrins, thus p

208 the first calcium binding domain of platelet GPIIb impairs the export of GPIIb-IIIa heterodimers to t

209 e the transcriptional regulation of platelet GPIIb integrin (CD41) by ERK during megakaryocyte differ

210 functional reduction or absence of platelet GPIIb/IIIa (alphaIIbbeta3) integrin receptors.

211 oAb) binding, surface expression of platelet GPIIb/IIIa receptors was less than 5.5% of normal, where

212 ies against either platelet GPIb or platelet GPIIb/IIIa in ITP plasma not only are involved in platel

213 eeding events in patients receiving platelet GPIIb/IIIa receptor antagonist include older age, low bo

214 e C4 domain, which also harbors the platelet GPIIb/IIIa-binding RGD sequence.

215 distinguishable from reactions with platelet GPIIb-IIIa.

216 sels was temporally associated with platelet GPIIb/IIIa immunoreactivity within the vessels.

217 eports suggest other platelet polymorphisms (GPIIb, FcgammaRIIa, P-selectin, alpha2 adrenergic recept

218 is currently focused on combining the potent GPIIb/IIIa receptor inhibitors with reduced-dose fibrino

219 each template yielded analogues with potent GPIIb-IIIa inhibitory activity.

220 udies of gamma12 in the presence of purified GPIIb/IIIa (230 kDa) demonstrate that two gamma12 bindin

221 , and binding could be blocked with purified GPIIb/IIIa.

222 bleeding complications in patients receiving GPIIb/IIIa inhibitors are proposed in this article.

223 ck or dysfunction of the fibrinogen receptor GPIIb/IIIa (integrin alphaIIbbeta3), respectively.

224 with platelet glycoprotein integrin receptor GPIIb/IIIa.

225 has good affinity for the platelet receptor GPIIb-IIIa and was chosen for study by 1H NMR techniques

226 Constitutively active platelet receptor GPIIb/IIIa (integrin alphaIIbbeta3) expressed on Chinese

227 ministered antiplatelet fibrinogen receptor (GPIIb/IIIa) antagonists have become established in the a

228 ent platelet glycoprotein IIb-IIIa receptor (GPIIb-IIIa) antagonists is described.

229 m that reported for the fibrinogen receptor, GPIIb-IIIa, and could have profound physiological signif

230 dual cation-binding domains, and recombinant GPIIb poly peptides that encompassed all four Ca(2+)-bin

231 ith either synthetic peptides or recombinant GPIIb polypeptides.

232 n kinase C (PKC), are considered to regulate GPIIb-IIIa activation.

233 cultured MKs (1) express agonist responsive GPIIb-IIIa receptors, (2) are capable of expressing tran

234 In addition to its physiologic role, GPIIb-IIIa also bears a number of clinically important a

235 Sequence analysis of the patient's GPIIb cDNA identified a T to C transition at nucleotide

236 ulfonamide 34b (DMP 802), a highly selective GPIIb/IIIa antagonist, demonstrated a prolonged duration

237 Soluble GPIIb-IIIa bound in a time- and dose-dependent manner to

238 ector P2Bac, we were able to express soluble GPIIb-IIIa complex (srGPIIb-IIIa) lacking cytoplasmic an

239 n of the platelet integrin alphaIIb subunit (GPIIb) only when the drug is present and closely mimic t

240 spite the very low level of platelet surface GPIIb/IIIa expression in this patient raises some intere

241 E3 Fab corresponds most closely with surface GPIIb/IIIa number and that the number of GPIIb/IIIa rece

242 Besides binding to immobilized talin, GPIIb-IIIa also bound to talin captured by the anti-tali

243 cellular Ca2+ levels, the specific role that GPIIb-IIIa may play in both these events remains unresol

244 The GPIIb-IIIa blockers are taking the clinician and patient

245 lity of mild reducing agents to activate the GPIIb-IIIa complex and promote platelet aggregation.

246 PIIIa (approximately 10% of normal), and the GPIIb had undergone normal maturational processing into

247 ptor and vanilloid (TRPV1) channels, and the GPIIb integrin.

248 are dependent on both the FcgammaRII and the GPIIb/IIIa integrin and that may be involved in pathophy

249 es the costimulation of P2Y1, P2Y12, and the GPIIb/IIIa receptors.

250 k the fibrinogen-platelet interaction at the GPIIb/IIIa receptors and inhibit thrombus formation.

251 irin has been shown to be effective, but the GPIIb/IIIa inhibitors offer the potential for more effec

252 case, thrombus formation is inhibited by the GPIIb/IIIa antagonist, G4120.

253 rs of a new class of antiplatelet drugs, the GPIIb-IIIa blockers, targeted at this important receptor

254 e the GPIbalpha and, to a lesser extent, the GPIIb promoter.

255 having high affinity and specificity for the GPIIb/IIIa receptor expressed on activated platelets, fo

256 l transduction mechanisms rather than in the GPIIb-IIIa complex itself.

257 -induced binding sites (LIBS) induced in the GPIIb/IIIa heterodimer when it reacts with a ligand-mime

258 quinine that recognize the N terminus of the GPIIb beta propeller domain only when soluble quinine is

259 on of the entire extracellular region of the GPIIb light chain in the construct.

260 tion appears to confer susceptibility of the GPIIb subunit to proteolysis.

261 egrin, resulted in partial activation of the GPIIb-IIIa complex and spreading.

262 Whether these allelic variants of the GPIIb-IIIa complex differ in the ability to interact wit

263 ding affinity for Fg of the Pena form of the GPIIb-IIIa complex was not significantly different from

264 se C [PKC] substrate), and activation of the GPIIb-IIIa complex.

265 of GPIIIa on the adhesive properties of the GPIIb-IIIa complex.

266 A soluble, recombinant form of the GPIIb-IIIa heterodimer that could be produced in large q

267 sue plasminogen activator (rtPA), and of the GPIIb/IIIa antagonist tirofiban, in a middle cerebral ar

268 ites indicating that ligand had bound to the GPIIb-IIIa receptor.

269 ctor XI antibody, with PAC1 antibody (to the GPIIb/IIIa complex on activated platelets), and with S12

270 the inhibition of fibrinogen binding to the GPIIb/IIIa receptor and an IC50 of 13 microM for the inh

271 binds specifically with high affinity to the GPIIb/IIIa receptor involved in platelet aggregation.

272 ) within several hours of treatment with the GPIIb/IIIa inhibitors tirofiban (4 patients) and eptifib

273 action requires additional signaling through GPIIb-IIIa after ligand binding.

274 PET imaging that binds with high affinity to GPIIb/IIIa receptors and has suitable pharmacokinetic pr

275 est whether this observation also applies to GPIIb, V286, located immediately distal to the first GPI

276 ch certain drugs promote antibody binding to GPIIb-IIIa in drug-induced thrombocytopenia and structur

277 inogen- and von Willebrand factor-binding to GPIIb-IIIa on intact platelets.

278 consequence of its high-affinity binding to GPIIb/IIIa on circulating platelets and suggests that 5

279 FRE Peptides capable of binding to GPIIb/IIIA receptors on activated platelets appear to of

280 platelet spreading but only on Fg binding to GPIIb/IIIa.

281 indicating that the prolongation was due to GPIIb/IIIa blockade.

282 velopment of thrombocytopenia on exposure to GPIIb/IIIa antagonists threatens the utility and economi

283 Binding of (18)F-GP1 to GPIIb/IIIa receptors was investigated in competition bin

284 mal inhibitory concentration of (18)F-GP1 to GPIIb/IIIa was 20 nM.

285 to anubeta3 integrin on melanoma cells or to GPIIb/IIIa significantly reduced melanoma cell adhesion

286 The binding of P748 peptide and [ReO]P748 to GPIIb/IIIa receptors on activated platelets was assessed

287 ibution of the G(12/13) signaling pathway to GPIIb/IIIa activation has not been investigated.

288 t potent inhibition of platelet function via GPIIb/IIIa receptor blockade can decrease ischemic organ

289 suggest that DMP 728, a low-molecular-weight GPIIb/IIIa receptor antagonist, may have therapeutic pot

290 Whereas GPIIb is expressed in both Meg-01 and CMK11-5 cells, GPI

291 Whereas GPIIb, GPIX, and C-MPL are direct target genes for Fli-1

292 la435GPIIIa were capable of associating with GPIIb and were expressed normally on the cell surface wh

293 ng peptide (CQQHHLGGAKQAGDV) that binds with GPIIb/IIIa expressed on activated platelets.

294 levels were similarly reduced compared with GPIIb and Galphaq mRNA levels.

295 n marked contrast to the 5-6-fold found with GPIIb/IIIa antagonists.

296 gamma12 suggest that gamma12 interacts with GPIIb/IIIa primarily through N-terminal residues H400 to

297 ts deficient in GPIIb-IIIa integrins or with GPIIb-IIIa function inhibited by calcium chelation or th

298 Unexpectedly, each of 6 patients with GPIIb/IIIa-specific antibodies was found to have a secon

299 a recognized complication of treatment with GPIIb/IIIa inhibitors whose cause is not yet known.

300 ) and Enoxaparin and TNK-tPA With or Without GPIIb/IIIa Inhibitor as Reperfusion Strategy in STEMI (E