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 ffinity and blockade activity for its ligand activated protein C.

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

4 heparan-sulfate-accelerated antithrombin and 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 matory activity of rTMD23 was independent of activated protein C.

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

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

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

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

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

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

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

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

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

17 istration of 40-fold more (0.45 mg/kg bolus) activated protein C.

18 ts protein C into the natural anticoagulant, activated protein C.

19 ween observational and randomized studies of activated protein C.

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

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

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

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

24 ike serine proteases thrombin, factor Xa, or 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 by generating pharmacological quantities of activated protein C and effectively diagnoses protein C

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

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

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

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

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

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

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

42 g by a different mechanism), factor XIIa and activated protein C; and group C (no binding), factor VI

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

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

45 a inactivation by the anticoagulant factors, activated protein C (APC) and protein S.

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

47 Activated protein C (APC) anticoagulant activity and the

48 Activated protein C (APC) anticoagulant activity involve

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

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

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

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

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

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

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

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

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

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

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

60 The serine protease domain of activated protein C (APC) contains a Na+ and a Ca2+ site

61 Activated protein C (APC) contributes to systemic antico

62 Activated protein C (APC) exerts endothelial cytoprotect

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

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

65 Activated protein C (APC) has endothelial barrier protec

66 ve outcome of a recent phase III study using activated protein C (APC) has led to a renewed optimism

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

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

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

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

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

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

73 its cleavage by the anticoagulant proteinase activated protein C (APC) inactivates it.

74 Activated protein C (APC) inhibits thrombin generation a

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

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

77 Activated protein C (APC) is a natural anticoagulant in

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

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

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

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

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

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

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

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

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

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

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

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

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

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

92 Activated protein C (APC) possesses profibrinolytic, ant

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

115 psin numbering) in the catalytic function of activated protein C (APC) was investigated by expressing

116 3K3A-APC is a recombinant analog of activated protein C (APC) which is an endogenous proteas

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

138 e if these carbohydrate moieties altered the activated protein C (APC)-catalyzed cleavage and inactiv

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

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

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

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

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

144 thrombin, including decreased generation of activated protein C (APC).

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

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

147 of glycolipids on anticoagulant response to activated protein C (APC):protein S in modified prothrom

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

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

150 We discuss the potential of activated protein C as a unique system modulator for the

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

152 Recombinant human activated protein C attenuated ALI after smoke inhalatio

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

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

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

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

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

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

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

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

161 he, Val559Ala, Asp560Ala, Gln565Arg, and the activated protein C cleavage site mutant Arg562Ala.

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

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

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

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

166 Plasma activated protein C concentrations in activated protein

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

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

169 e protein C system in regulating thrombosis, activated protein C does not serve as a primary regulato

170 ed the only surface for thrombin generation, activated protein C dose-dependently decreased thrombin

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

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

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

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

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

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

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

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

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

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

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

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

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

184 ssion suppressed TM and subsequently reduced activated protein C generation.

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

186 Activated protein C had essentially no effect on thrombi

187 Activated protein C has anticoagulant and anti-inflammat

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

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

190 cogin alfa (activated), or recombinant human activated protein C, has antithrombotic, antiinflammator

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 nalysis includes a discussion of the role of activated protein C in directly modulating cell system b

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

217 Activated protein C levels were then measured directly b

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 Replacement with recombinant human activated protein C offers a system-modulating approach

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

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

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

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

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

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

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

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

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

236 Activated protein C overexpressing mice demonstrated enh

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

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

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

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

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

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

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

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 with activated partial thromboplastin time, activated protein C resistance, hematocrit, or factor VI

256 splantation with subsequent normalization of activated protein C resistance.

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

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

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

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

261 festations presented with a markedly reduced activated protein C-sensitivity ratio (APC-SR).

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

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

264 Activated protein C significantly decreased neutrophil a

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

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

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

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