ライフサイエンスコーパス: activated protein C

1 calfactant) and yet to be described effects (activated protein C).

2 slower time scale, spontaneously converts to activated protein C.

3 ike serine proteases thrombin, factor Xa, or activated protein C.

4 s anti-inflammatory properties when bound by activated protein C.

5 were independent of its ability to generate activated protein C.

6 associated with the use of recombinant human activated protein C.

7 GH patterns, and GH modulated resistance to activated protein C.

8 ty-three patients received recombinant human activated protein C.

9 agulant versus anti-inflammatory function of activated protein C.

10 inflammatory and anti-apoptotic functions of activated protein C.

11 or Va partially resistant to inactivation by activated protein C.

12 rombin, factors VIIa, Xa, XIa, and XIIa, and activated protein C.

13 tor for the thrombin-dependent generation of activated protein C.

14 ffinity and blockade activity for its ligand activated protein C.

15 heparan-sulfate-accelerated antithrombin and activated protein C.

16 al myosin provides membrane-like support for activated protein C.

17 matory activity of rTMD23 was independent of activated protein C.

18 cell could be prevented by recombinant human activated protein C.

19 phase III clinical trial was human recumbent activated protein C.

20 ween observational and randomized studies of activated protein C.

21 d in patients treated with recombinant human activated protein C.

22 hanced enzymatic activity of factor VIIa and activated protein C.

23 presence of tissue factor, thrombomodulin or activated protein C.

24 als and the recent withdrawal of recombinant activated protein C.

25 associated with the use of recombinant human activated protein C (108/311 [34.7%] vs. 254/622 [40.8%]

26 ombin-thrombomodulin-dependent generation of activated protein C, a natural anticoagulant, binds to a

27 Furthermore, treatment with activated protein C, a serine protease effective in sept

28 odulin-protein C pathway are consistent with activated protein C activation and systemic anticoagulat

29 with the institution of a recombinant human activated protein C administration policy from the first

30 rodents, we now show that administration of activated protein C alone or in combination with tissue

31 vy chain, pt-FV is functionally resistant to activated protein C, an anticoagulant.

32 Early treatment with an activated protein C analog restored BSCB integrity that

33 TM catalyzes thrombin-mediated generation of activated protein C and binds to circulating RBCs withou

34 Ill Patients with Septic Shock) and $30,911 (Activated Protein C and Corticosteroids for Human Septic

35 ritically Ill Patients with Septic Shock and Activated Protein C and Corticosteroids for Human Septic

36 ritically Ill Patients with Septic Shock and Activated Protein C and Corticosteroids for Human Septic

37 Per Activated Protein C and Corticosteroids for Human Septic

38 by generating pharmacological quantities of activated protein C and effectively diagnoses protein C

39 s factor, which suppresses the generation of activated protein C and increases TF, augmented FX activ

40 able model assessing the association between activated protein C and mortality resulted in a 9% shift

41 ic children and adults for human recombinant activated protein C and protein C concentrate.

42 d to endothelial cell protein C receptor) to activated protein C and this generates antiinflammatory

43 cing cofactor for the coagulation inhibitors activated protein C and tissue factor pathway inhibitor

44 older drugs, newer drugs, drotrecogin alpha (activated protein C) and activated factor VII concentrat

45 arameters, including soluble thrombomodulin, activated protein C, and disseminated intravascular coag

46 Anti-histone IgG, recombinant activated protein C, and heparin were equally effective

47 Cytoprotection by activated protein C (aPC) after ischemia-reperfusion inj

48 In addition to an anticoagulant activity, activated protein C (APC) also exhibits anti-inflammator

49 n of protease-activated receptor 1 (PAR1) by activated protein C (APC) and thrombin elicits paradoxic

50 Activated protein C (APC) anticoagulant activity and the

51 Activated protein C (APC) anticoagulant activity involve

52 neration both in the absence and presence of activated protein C (APC) anticoagulant activity.

53 nflammatory and cytoprotective properties of activated protein C (APC) are mediated through its endot

54 The cytoprotective effects of activated protein C (aPC) are well established.

55 is revealed that FVII, FVIIa, protein C, and activated protein C (APC) bound to EPCR with similar aff

56 Activated protein C (APC) breaks down the complex that p

57 protein, accelerates in vitro generation of activated protein C (APC) by soluble thrombin/thrombomod

58 hrough 2 mechanisms: decreased generation of activated protein C (APC) by thrombin, and resistance to

59 antibodies are able to inhibit generation of activated protein C (aPC) by thrombin/thrombomodulin (II

60 n, which results in suppressed generation of activated protein C (APC) by TM-thrombin complex and in

61 ion of PS by purified CK1 did not affect its activated protein C (APC) cofactor activity in activated

62 xamination of the structure of Gla domain of activated Protein C (APC) complexed with soluble endothe

63 ontained in the 39-, 60-, and 70-80-loops of activated protein C (APC) comprise an exosite that contr

64 The coagulation protease activated protein C (aPC) confers cytoprotective effects

65 Activated protein C (APC) exerts endothelial cytoprotect

66 Activated protein C (APC) exerts endothelial protein C r

67 WE thrombin acts as an anticoagulant through activated protein C (APC) generation, the observed limit

68 Activated protein C (APC) has anti-inflammatory and vasc

69 Activated protein C (APC) has endothelial barrier protec

70 Activated protein C (APC) has potent anticoagulant and a

71 Pharmacologic infusion of activated protein C (APC) improves survival in severe se

72 Recombinant activated protein C (aPC) improves the survival of patie

73 A recently published X-ray structure of activated protein C (APC) inactivated bovine factor Va(i

74 Activated protein C (APC) inactivates factor Va (fVa) by

75 Activated Protein C (APC) inactivates factor VIIIa by cl

76 Activated protein C (APC) inhibits thrombin generation a

77 Activated protein C (APC) is a blood protease with antic

78 Activated protein C (APC) is a multifunctional serine pr

79 Activated protein C (APC) is a natural anticoagulant ser

80 Activated protein C (aPC) is a natural anticoagulant wit

81 Activated protein C (APC) is a plasma serine protease wi

82 Activated protein C (APC) is a protease with anticoagula

83 Activated protein C (APC) is a serine protease with anti

84 Activated protein C (APC) is a signaling protease with a

85 Activated protein C (APC) is a systemic anti-coagulant a

86 Activated protein C (APC) is a vitamin K-dependent plasm

87 al. report that the endogenous anticoagulant activated protein C (APC) is able to cross the blood-spi

88 Activated protein C (APC) is an anticoagulant enzyme tha

89 Activated protein C (APC) is an anticoagulant protease t

90 Human activated protein C (APC) is an antithrombotic, antiinfl

91 Recent studies have indicated that activated protein C (APC) may exert its cytoprotective a

92 The direct cytoprotective activities of activated protein C (APC) on cells convey therapeutic, r

93 d EPCR, as well as in enhanced generation of activated protein C (APC) on endothelial cells.

94 Here we identify the thrombomodulin (Thbd)-activated protein C (aPC) pathway as a new mechanism for

95 Activated protein C (APC) possesses profibrinolytic, ant

96 Administration of activated protein C (APC) protects from renal dysfunctio

97 The anticoagulant activated protein C (APC) protects neurons and vascular

98 sm of protease-activated receptor (PAR) 1 by activated protein C (APC) provides neuro- and vasculopro

99 ssue of Blood, Sinha et al demonstrated that activated protein C (APC) reduced the severity of pulmon

100 Activated protein C (APC) reduces mortality in severe se

101 Activated protein C (APC) reduces mortality in severe se

102 Activated protein C (APC) reduces mortality of severe se

103 Endothelial barrier protective effects of activated protein C (APC) require the endothelial protei

104 n (FV Trp1920-->Arg, FVNara) associated with activated protein C (APC) resistance and a severe thromb

105 we measured factor V Leiden, HR2 haplotype, activated protein C (APC) resistance, and plasma factor

106 Activated protein C (APC) resistance, often associated w

107 tion of PAR1 with the anticoagulant protease activated protein C (APC) results in activation of Ras-r

108 Thrombin and activated protein C (APC) signaling can mediate opposite

109 Activated protein C (APC) signals in endothelial cells e

110 mmatory signaling, whereas its activation by activated protein C (APC) stimulates cytoprotective and

111 els provide a microenvironment enriched with activated protein C (aPC) that retains EPCR(+) LT-HSCs b

112 Activated protein C (aPC) therapy reduces mortality in a

113 ammation or reducing sepsis lethality due to activated protein C (aPC) therapy.

114 Binding of activated protein C (APC) to cells triggers multiple ben

115 hat Zn(2+) enhanced the binding of protein C/activated protein C (APC) to endothelial cell protein C

116 hesion and compared the protective effect of activated protein C (APC) to that of the Food and Drug A

117 Activated protein C (APC) treatment is now used for pati

118 nd Procrs/+ mice generated similar levels of activated protein C (APC) upon thrombin infusion.

119 To discuss the potential use of recombinant activated protein C (aPC) variants with altered bioactiv

120 3K3A-APC is a recombinant analog of activated protein C (APC) which is an endogenous proteas

121 3K3A-activated protein C (APC), a cell-signaling analogue of

122 Activated protein C (APC), a natural anticoagulant prote

123 Here we report that activated protein C (APC), a plasma serine protease with

124 Activated protein C (APC), a serine protease critically

125 Activated protein C (APC), a serine protease with antico

126 Activated protein C (APC), a serine protease with antico

127 Recombinant activated protein C (APC), a well-defined anticoagulant

128 Activated protein C (APC), administered to colitic WT mi

129 Activated protein C (APC), an anti-coagulant protease, a

130 In contrast, activated protein C (APC), an anticoagulant protease, ac

131 on newly discovered biological properties of activated protein C (APC), an endogenous plasma protease

132 wever, factor Va is prone to inactivation by activated protein C (APC), an important serine protease

133 The homeostatic blood protease, activated protein C (APC), can function as (1) an antith

134 r molecule of the natural protein C pathway, activated protein C (aPC), exerts pleiotropic effects on

135 anticoagulant human plasma serine protease, activated protein C (APC), inhibits blood coagulation by

136 In addition, otaplimastat, 3K3A-activated protein C (APC), intra-arterial verapamil and

137 ks the contact system, but also thrombin and activated protein C (APC), making it an unattractive can

138 anticoagulant and anti-inflammatory enzyme, activated protein C (APC), naturally controls thrombosis

139 hough ProS is known to act as a cofactor for activated Protein C (aPC), plasma from Pros1+/- heterozy

140 The anticoagulant, activated protein C (aPC), possesses antithrombotic, pro

141 rectly precede the Arg-506 cleavage site for activated protein C (APC), the 499-505(VIII) FVa mutant

142 Activated protein C (APC), the only FDA-approved biother

143 Protein S (PS) is a cofactor for activated protein C (APC), which inactivates coagulation

144 eceptor, accelerates the conversion of PC to activated protein C (APC), which leads to the down-regul

145 ity toward cleavage of plasma protein C into activated protein C (APC), which opposes its thrombotic

146 s discovered to play a key role in mediating activated protein C (APC)-induced cytoprotective effects

147 The effect of glucosylceramide (GlcCer) on activated protein C (APC)-phospholipid interactions was

148 cardiovascular disease by binding protein C/activated protein C (APC).

149 agulant function by acting as a cofactor for activated protein C (APC).

150 ctor VIIIa (FVIIIa) inactivating property of activated protein C (APC).

151 armacologically by antibody to histone or by activated protein C (APC).

152 several mechanisms, including production of activated protein C (APC).

153 peptide at PR(221) downward arrow results in activated protein C (APC; residues 222-461).

154 several serine proteases (such as thrombin, activated protein C [APC], and plasmin) involved in hemo

155 leaved by the anticoagulant serine protease, activated protein C, at two cleavage sites, Arg(336) in

156 Recombinant human activated protein C attenuated ALI after smoke inhalatio

157 ia isolates was sufficient to interfere with activated protein C-barrier protective activities in hum

158 , in patients who received recombinant human activated protein C before 24 hrs there was a reduction

159 Factor VIIa (FVIIa) or activated protein C binding to EPCR promoted the interna

160 Overall, our results show that FVIIa or activated protein C binding to EPCR promotes EPCR endocy

161 Blocking protein C/activated protein C binding to the receptor inhibits not

162 EPCR), a cellular receptor for protein C and activated protein C, but the physiologic significance of

163 ding Bcl-2, fibroblast growth factor 21, and activated protein C can reduce injury.

164 t-derived FVa was 2-3-fold more resistant to activated protein C-catalyzed inactivation than purified

165 factor VIIIa, we engineered mutations of the activated protein C cleavage sites into the disulfide bo

166 To isolate the effects of the individual activated protein C cleavage sites on factor VIIIa, we e

167 Recombinant human activated protein C cleaved HeH and PfH3 and abrogated t

168 As a result, in the presence of both activated protein C cofactors, Arg(336) cleavage is only

169 Plasma activated protein C concentrations in activated protein

170 ed protein C, it functions as a cofactor for activated protein C-dependent proteolytic inactivation o

171 oviding the surface for thrombin generation, activated protein C did increase the time until the burs

172 With the lipid surface, activated protein C dose-dependently reduced thrombin ge

173 lar treatment benefit from recombinant human activated protein C (drotrecogin alfa [activated]) as no

174 Recombinant human activated protein C (drotrecogin alfa [activated]) has b

175 Recombinant human activated protein C (drotrecogin alfa [activated]) was s

176 endotoxin trial evaluating recombinant human activated protein C (drotrecogin alfa [activated]).

177 ndomized controlled trial, recombinant human activated protein C (drotrecogin alfa) reduced mortality

178 and mortality resulted in a 9% shift in the activated protein C effect estimate toward the null (odd

179 generates antiinflammatory signals along the activated protein C-endothelial cell protein C receptor-

180 cogin alfa (activated) (or recombinant human activated protein C) excluded patients with specific bas

181 ) or at the level of factor V proteolysis by activated protein C (factor V Leiden mice), were employe

182 Specific interventions such as activated protein C for patients with severe sepsis have

183 eatment, low VT ventilation for ALI/ARDS and activated protein C for severe sepsis (the leading cause

184 e FVL mutation accelerates thrombin and APC (activated protein C) formation in carriers without a his

185 Once in the circulation, activated protein C functions as an anticoagulant, anti-

186 s, the group that received recombinant human activated protein C had a significantly reduced associat

187 Activated protein C had essentially no effect on thrombi

188 Activated protein C has anticoagulant and anti-inflammat

189 A serine protease activated protein C has been shown to be a powerful neur

190 Drotrecogin alfa (activated, human activated protein C) has been shown to be a safe and eff

191 Constitutively enhanced expression of activated protein C impairs host defense during severe G

192 for the administration of recombinant human activated protein C in adult severe sepsis.

193 ding the administration of recombinant human activated protein C in adult severe sepsis.

194 ecommendation against the use of recombinant activated protein C in children (1B).

195 ications to treatment with recombinant human activated protein C in current product labeling.

196 ecently completed trial of recombinant human activated protein C in patients with septic shock.

197 id and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and c

198 We have examined the activity of activated protein C in several tissue factor-initiated m

199 the efficacy and safety of human recombinant activated protein C in severe sepsis is limited, especia

200 +), and neither mutant clotted fibrinogen or activated protein C in the presence of TM.

201 In two studies using recombinant human activated protein C in the setting of human endotoxemia,

202 recent investigations have attributed novel activated protein C-independent functions of protein S t

203 n proteases, such as fXa (factor Xa) or aPC (activated protein C), independently modulate intracellul

204 ms "activated protein C," "recombinant human activated protein C," "inflammation," "leukocyte adhesio

205 F), and the importance of the thrombomodulin-activated protein C inhibitory pathway.

206 effector protease of the protein C pathway, activated protein C, interacts with the endothelial cell

207 Activated protein C is a trypsin-like protease with anti

208 In sepsis, activated protein C is also deficient, potentiating the

209 luated phase II and III trials assuming that activated protein C is truly effective; they showed that

210 In the absence of activated protein C, it demonstrates anticoagulant activ

211 s anticoagulant activity; in the presence of activated protein C, it functions as a cofactor for acti

212 an activation of pathways recruiting stress-activated protein/c-Jun NH(2)-terminal kinases.

213 ction and/or endocytosis, viz., receptor for activated protein C kinase 1 (RACK1), muscle integrin bi

214 omplex starch solutions to recombinant human activated protein C, large multicenter randomized contro

215 investigate the effect of sustained elevated activated protein C levels on the host response during m

216 ated with protein C had significantly higher activated protein C levels than children receiving place

217 aPL+) compared to healthy controls, but anti-activated protein C levels were not increased in these p

218 Activated protein C limits excessive coagulation activat

219 Activated protein C, low-dose heparin, and low-dose hepa

220 ting with septic shock, early treatment with activated protein C may be associated with reduced hospi

221 Thus, activated protein C may be useful as a new stand-alone t

222 A chimeric activated protein C mutant containing the Gla domain of

223 The anticoagulant activity of the activated protein C mutant was nearly eliminated as dete

224 In the case of the activated protein C mutant, similar to factor Xa, pentas

225 across the spectrum of ineffective therapy (activated protein C), novel therapeutic ideas (statins a

226 We could not find a clear effect of activated protein C on nucleosome levels in these patien

227 y contrast, whenever platelets were present, activated protein C only minimally affected the amount o

228 or VIIIa, because proteolysis at Arg(336) by activated protein C or factor IXa is inactivating.

229 reports on the efficacy of recombinant human activated protein C, or drotrecogin alfa (activated) (Dr

230 neutralizing agents such as antihistone IgG, activated protein C, or heparin prevented this effect.

231 ssue factor, endothelial protein C receptor, activated protein C, or thrombin.

232 al administration rates of recombinant human activated protein C over the same timeline (p<.001), wit

233 Wild type and activated protein C overexpressing C57BL/6 mice.

234 Plasma activated protein C concentrations in activated protein C overexpressing mice (median 18.1 ng/

235 Activated protein C overexpressing mice demonstrated enh

236 Additionally, at this time point, activated protein C overexpressing mice showed elevated

237 on of coagulation, were measured in lungs of activated protein C overexpressing mice.

238 urthermore, activation of the thrombomodulin-activated protein C pathway in the regions between sites

239 Activated protein C (PC) is an anticoagulant involved in

240 Similarly, there is preferential binding of activated protein C (PC) to Gr1(high)CD11b(high)VLA-3(hi

241 uences were tested for binding to protein C, activated protein C, plasmin, factor VIIa (FVIIa), FIX,

242 ate that the natural anticoagulant protease, activated protein C, potently inhibits polyP-mediated pr

243 , activated factor VII, factor IX, factor X, activated protein C, protein S, and protein Z.

244 tural anticoagulants (low antithrombin, high activated protein C, protein S, and tissue factor pathwa

245 tithrombin complex, antithrombin, protein C, activated protein C, protein S, soluble endothelial prot

246 On univariable analysis, fibrinogen, low activated protein C ratio, D-dimer, tissue plasminogen a

247 th administration rates of recombinant human activated protein C reaching 9.2% in the last quarter.

248 tro data and a MEDLINE search for the terms "activated protein C," "recombinant human activated prote

249 ivo administration of hirudin or recombinant activated protein C reduced disease severity in experime

250 Recently, treatment with recombinant human activated protein C reduced mortality 6% compared with c

251 Activated protein C resistance as a result of a single g

252 Activated protein C resistance due to factor V Leiden (F

253 dermal hormone-replacement therapy increases activated protein C resistance independently of the pres

254 authors suggest that functional testing for activated protein C resistance is cheaper and more clini

255 splantation with subsequent normalization of activated protein C resistance.

256 Currently, recombinant human activated protein C (rhAPC [Xigris; Eli Lilly]) is licen

257 Recombinant human activated protein C (rhAPC) has been shown to protect pa

258 A recombinant form of human activated protein C (rhAPC) has shown cytoprotective and

259 Recombinant human activated protein C (rhAPC) is a natural anticoagulant w

260 g for thrombomodulin-dependent generation of activated protein C's (APC) anticoagulant, anti-inflamma

261 ctivation efficiency, and down-regulation by activated protein C showed similar results for the two v

262 dministration of mutant forms of recombinant activated protein C showed that both its anticoagulant a

263 Activated protein C significantly decreased neutrophil a

264 have shown improved outcome with the use of activated protein C, steroid replacement and aggressive

265 her putative mechanisms of recombinant human activated protein C, such as inhibition of apoptosis and

266 growth factor-A (VEGF-A)/VEGF receptor-2 and activated protein C systems, among others.

267 trials, for example, studies of recombinant activated protein C, talactoferrin, interleukin-1 recept

268 ere more likely to receive recombinant human activated protein C than patients in South America (4.2%

269 re of two of these proteins, factor VIIa and activated protein C, than did equivalent bilayers contai

270 those who did not receive recombinant human activated protein C, the reduction in the adjusted hospi

271 esuscitate status on the association between activated protein C therapy and mortality, an associatio

272 Thus, in the absence of activated protein C, this variant has stable activity fo

273 receptor (EPCR) is crucial for signaling by activated protein C through PAR1, but EPCR may have addi

274 hrombin, factor X, activated factor VII, and activated protein C to seven different binary lipid comp

275 the patients who received recombinant human activated protein C to those who did not receive recombi

276 ptic shock who received early treatment with activated protein C to those who did not.

277 with a component of the coagulation system (activated protein C) to treat patients with severe sepsi

278 gher proteolytic activity by factor VIIa and activated protein C toward their natural substrates (fac

279 Four activated protein C-treated patients (0.25%) had hemorrh

280 Compared to the entire cohort, the 1576 activated protein C-treated patients included in the mat

281 Recombinant human activated protein C use was associated with a significan

282 goals; corticosteroids and human recombinant activated protein C use) (all I2 > or = 67%, p < .002).

283 Recombinant human activated protein C was administered within 24 hrs of th

284 all covariates achieved balance, receipt of activated protein C was associated with reduced hospital

285 septic shock, early use of recombinant human activated protein C was associated with reduced mortalit

286 Activated protein C was demonstrated to attenuate the ha

287 Recently, recombinant activated protein C was shown to reduce the mortality of

288 Scenarios 2B and 3B assumed that activated protein C was truly ineffective; they showed t

289 Serum levels of antithrombin and anti-activated protein C were compared in 32 patients with AP

290 Thrombin, Factor VIIa, Factor Xa, and activated protein C were not effective.

291 rombin and the anticoagulant serine protease-activated protein C were replaced with the corresponding

292 cenarios based on three published studies on activated protein C were used as real examples for stati

293 novel treatments, such as recombinant human activated protein C, which improves survival in patients

294 e micelle corona for the local generation of activated protein C, which inhibits the formation of thr

295 ical and structural analyses on thrombin and activated protein C, which suggested that residue 192 ma

296 severe sepsis who received recombinant human activated protein C with baseline bleeding precautions a

297 on endothelium that binds both protein C and activated protein C with similar affinity.

298 n 2001 on the basis of the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsi

299 placebo-controlled trial (human recombinant activated Protein C Worldwide Evaluation of Severe Sepsi

300 ing for how much bias in favor of or against activated protein C would be observed in single-arm stud