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Inhibition of platelet receptors involved in neutrophil-platelet interaction in model cardiopulmonary bypass. We investigated the interactions between neutrophils, platelets, and artificial surfaces, and whether blocking of relevant receptors on platelets reduced unwanted activation responses in model cardiopulmonary bypass. Isolated neutrophils and platelets resuspended in heparin-anticoagulated plasma were recirculated with and without blocking antibodies to CD62P, CD42b, or junctional adhesion molecule C (JAM-C) in polyvinyl chloride tubing using a roller pump. Platelet adhesion to the tubing was inhibited by anti-CD42b and anti-CD62P, and adhesion of neutrophils by anti-JAM-C. Formation of platelet-neutrophil and platelet aggregates was reduced by anti-CD62P. Anti-JAM-C decreased platelet-neutrophil aggregation at low concentrations and platelet macroaggregates at high concentrations. Anti-CD62P increased neutrophil CD11b expression but not degranulation. Anti-JAM-C substantially increased neutrophil degranulation and slightly increased CD11b expression. Platelet activation increased when CD62P was blocked and decreased with anti-CD42b antibody. High-dose anti-JAM-C reduced platelet activation. In conclusion, inhibiting platelet and neutrophil-platelet interactions had useful effects but no single blocking antibody seemed capable of inducing only beneficial effects.
17651117 T18 GENE 14 32 platelet receptors
17651117 T5 GENE 465 470 CD62P
17651117 T6 GENE 472 477 CD42b
17651117 T7 GENE 482 512 junctional adhesion molecule C
17651117 T8 GENE 514 519 JAM-C
17651117 T1 CHEMICAL 524 542 polyvinyl chloride
17651117 T9 GENE 625 630 CD42b
17651117 T10 GENE 640 645 CD62P
17651117 T11 GENE 683 688 JAM-C
17651117 T12 GENE 767 772 CD62P
17651117 T13 GENE 779 784 JAM-C
17651117 T14 GENE 907 912 CD62P
17651117 T15 GENE 934 939 CD11b
17651117 T16 GENE 979 984 JAM-C
17651117 T17 GENE 1057 1062 CD11b
17651117 T2 GENE 1110 1115 CD62P
17651117 T3 GENE 1152 1157 CD42b
17651117 T4 GENE 1183 1188 JAM-C
Protein kinase C potentiates homologous desensitization of the beta2-adrenoceptor in bovine tracheal smooth muscle. Preincubation (30 min) of bovine tracheal smooth muscle with various concentrations (0.1, 1 and 10 microM) of fenoterol decreased isoprenaline-induced maximal relaxation (E(max)) of methacholine-contracted preparations in a concentration dependent fashion, indicating desensitization of the beta(2)-adrenoceptor. Preincubation with 1 microM of the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) caused a small but significant decrease in isoprenaline-induced E(max), indicating activated PKC-mediated heterologous beta(2)-adrenoceptor desensitization. To investigate the capacity of activated PKC to regulate homologous desensitization, we incubated the smooth muscle strips with the combination of both 1 microM PMA and 1 microM fenoterol. This combined treatment synergistically decreased the isoprenaline-induced maximal relaxation, as compared to the individual effects of PMA and fenoterol alone, indicating a common pathway for heterologous and homologous desensitization. Moreover, the specific PKC-inhibitor 2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl) maleimide (GF 109203X) markedly increased the potency and E(max) of isoprenaline for all conditions used, including control conditions, and the synergistic effects of PMA and fenoterol were completely prevented. In conclusion, the present study demonstrates that homologous desensitization of the beta(2)-adrenergic receptor can be enhanced by PKC activation. For the first time we have provided evidence that this concept is functionally operative in airway smooth muscle, and it may explain the reduced bronchodilator response to beta(2)-adrenoceptor agonists in patients with asthma during a severe exacerbation.
16324695 T26 GENE 0 16 Protein kinase C
16324695 T27 GENE 63 81 beta2-adrenoceptor
16324695 T2 CHEMICAL 226 235 fenoterol
16324695 T7 CHEMICAL 246 258 isoprenaline
16324695 T8 CHEMICAL 298 310 methacholine
16324695 T20 GENE 407 427 beta(2)-adrenoceptor
16324695 T21 GENE 464 480 protein kinase C
16324695 T22 GENE 482 485 PKC
16324695 T9 CHEMICAL 497 528 phorbol 12-myristate 13-acetate
16324695 T10 CHEMICAL 530 533 PMA
16324695 T11 CHEMICAL 578 590 isoprenaline
16324695 T23 GENE 628 631 PKC
16324695 T24 GENE 654 674 beta(2)-adrenoceptor
16324695 T25 GENE 733 736 PKC
16324695 T12 CHEMICAL 870 879 fenoterol
16324695 T13 CHEMICAL 935 947 isoprenaline
16324695 T14 CHEMICAL 1017 1020 PMA
16324695 T15 CHEMICAL 1025 1034 fenoterol
16324695 T16 GENE 1142 1145 PKC
16324695 T1 CHEMICAL 1156 1227 2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl) maleimide
16324695 T3 CHEMICAL 1229 1239 GF 109203X
16324695 T4 CHEMICAL 1286 1298 isoprenaline
16324695 T5 CHEMICAL 1385 1388 PMA
16324695 T6 CHEMICAL 1393 1402 fenoterol
16324695 T17 GENE 1515 1542 beta(2)-adrenergic receptor
16324695 T18 GENE 1562 1565 PKC
16324695 T19 GENE 1750 1770 beta(2)-adrenoceptor
Interaction of rofecoxib and celecoxib with warfarin. The interaction of celecoxib and rofecoxib with warfarin was studied. Patients stable on warfarin therapy and concurrently taking a cyclooxygenase-2 (COX-2) inhibitor comparator (traditional nonsteroidal antiinflammatory medications, salsalate, or acetaminophen) randomly received celecoxib 200 mg/day or rofecoxib 25 mg/day for three weeks. After a one-week washout period, the patients were crossed over to treatment with the opposite COX-2 inhibitor for three more weeks. The International Normalized Ratio (INR) was measured at baseline and at weeks 1, 2, and 3 of therapy with each COX-2 inhibitor by testing blood samples obtained by finger stick. Data for 16 patients were analyzed. The INR increased by 13%, 6%, and 5% on average in patients taking celecoxib at weeks 1, 2, and 3, respectively, and by 5%, 9%, and 5% in patients taking rofecoxib. Changes in the INR were statistically significant at week 1 for celecoxib and at week 2 for rofecoxib. Of the 12 subjects who had a clinically significant > or = 15% change in the INR while receiving either COX-2 inhibitor, 4 showed this change for both agents. Adverse drug reactions were similar for each COX-2 inhibitor, but the rate of edema requiring medical intervention was higher in the rofecoxib group. Significant increases in the INR were observed in patients who were stable on warfarin therapy after the addition of therapy with rofecoxib or celecoxib.
12901032 T17 CHEMICAL 15 24 rofecoxib
12901032 T18 CHEMICAL 29 38 celecoxib
12901032 T19 CHEMICAL 44 52 warfarin
12901032 T5 CHEMICAL 73 82 celecoxib
12901032 T10 CHEMICAL 87 96 rofecoxib
12901032 T11 CHEMICAL 102 110 warfarin
12901032 T14 CHEMICAL 143 151 warfarin
12901032 T22 GENE 186 202 cyclooxygenase-2
12901032 T23 GENE 204 209 COX-2
12901032 T6 CHEMICAL 288 297 salsalate
12901032 T7 CHEMICAL 302 315 acetaminophen
12901032 T8 CHEMICAL 335 344 celecoxib
12901032 T9 CHEMICAL 359 368 rofecoxib
12901032 T24 GENE 491 496 COX-2
12901032 T25 GENE 641 646 COX-2
12901032 T12 CHEMICAL 811 820 celecoxib
12901032 T13 CHEMICAL 898 907 rofecoxib
12901032 T15 CHEMICAL 973 982 celecoxib
12901032 T16 CHEMICAL 1001 1010 rofecoxib
12901032 T20 GENE 1116 1121 COX-2
12901032 T21 GENE 1216 1221 COX-2
12901032 T1 CHEMICAL 1304 1313 rofecoxib
12901032 T2 CHEMICAL 1399 1407 warfarin
12901032 T3 CHEMICAL 1451 1460 rofecoxib
12901032 T4 CHEMICAL 1464 1473 celecoxib
Chromatin-associated proteins HMGB1/2 and PDIA3 trigger cellular response to chemotherapy-induced DNA damage. The identification of new molecular components of the DNA damage signaling cascade opens novel avenues to enhance the efficacy of chemotherapeutic drugs. High-mobility group protein 1 (HMGB1) is a DNA damage sensor responsive to the incorporation of nonnatural nucleosides into DNA; several nuclear and cytosolic proteins are functionally integrated with HMGB1 in the context of DNA damage response. The functional role of HMGB1 and HMGB1-associated proteins (high-mobility group protein B2, HMGB2; glyceraldehyde-3-phosphate dehydrogenase, GAPDH; protein disulfide isomerase family A member 3, PDIA3; and heat shock 70 kDa protein 8, HSPA8) in DNA damage response was assessed in human carcinoma cells A549 and UO31 by transient knockdown with short interfering RNAs. Using the cell proliferation assay, we found that knockdown of HMGB1-associated proteins resulted in 8-fold to 50-fold decreased chemosensitivity of A549 cells to cytarabine. Western blot analysis and immunofluorescent microscopy were used to evaluate genotoxic stress markers in knocked-down cancer cells after 24 to 72 hours of incubation with 1 micromol/L of cytarabine. Our results dissect the roles of HMGB1-associated proteins in DNA damage response: HMGB1 and HMGB2 facilitate p53 phosphorylation after exposure to genotoxic stress, and PDIA3 has been found essential for H2AX phosphorylation (no gamma-H2AX accumulated after 24-72 hours of incubation with 1 micromol/L of cytarabine in PDIA3 knockdown cells). We conclude that phosphorylation of p53 and phosphorylation of H2AX occur in two distinct branches of the DNA damage response. These findings identify new molecular components of the DNA damage signaling cascade and provide novel promising targets for chemotherapeutic intervention.
19372559 T31 GENE 30 37 HMGB1/2
19372559 T32 GENE 42 47 PDIA3
19372559 T16 GENE 264 293 High-mobility group protein 1
19372559 T18 GENE 295 300 HMGB1
19372559 T3 CHEMICAL 371 382 nucleosides
19372559 T19 GENE 465 470 HMGB1
19372559 T20 GENE 533 538 HMGB1
19372559 T21 GENE 543 548 HMGB1
19372559 T22 GENE 570 600 high-mobility group protein B2
19372559 T23 GENE 602 607 HMGB2
19372559 T4 CHEMICAL 609 635 glyceraldehyde-3-phosphate
19372559 T24 GENE 609 649 glyceraldehyde-3-phosphate dehydrogenase
19372559 T25 GENE 651 656 GAPDH
19372559 T26 GENE 658 703 protein disulfide isomerase family A member 3
19372559 T5 CHEMICAL 666 675 disulfide
19372559 T27 GENE 705 710 PDIA3
19372559 T28 GENE 716 743 heat shock 70 kDa protein 8
19372559 T29 GENE 745 750 HSPA8
19372559 T30 GENE 942 947 HMGB1
19372559 T6 CHEMICAL 1042 1052 cytarabine
19372559 T1 CHEMICAL 1241 1251 cytarabine
19372559 T7 GENE 1286 1291 HMGB1
19372559 T8 GENE 1336 1341 HMGB1
19372559 T9 GENE 1346 1351 HMGB2
19372559 T10 GENE 1363 1366 p53
19372559 T11 GENE 1423 1428 PDIA3
19372559 T12 GENE 1458 1462 H2AX
19372559 T13 GENE 1483 1493 gamma-H2AX
19372559 T2 CHEMICAL 1559 1569 cytarabine
19372559 T14 GENE 1573 1578 PDIA3
19372559 T15 GENE 1633 1636 p53
19372559 T17 GENE 1660 1664 H2AX
The role of 5-HT(1A) and 5-HT(1B/1D) receptors on the modulation of acute fluoxetine-induced changes in extracellular 5-HT: the mechanism of action of (+/-)pindolol. Some clinical evidence has suggested that (+/-)pindolol can be effective at producing a shortened time to onset of antidepressant activity when co-administered with a serotonin specific reuptake inhibitor (SSRI). This effect has been attributed to the antagonist effects of pindolol at the 5-HT(1A) receptor. In the present study, we compared the pharmacology of (+/-)pindolol, WAY-100635 (a 5-HT(1A) antagonist), GR127935 (a 5-HT(1B/1D) antagonist), and isamoltane (a 5-HT(1B) antagonist), when given acutely in combination with fluoxetine, using in vivo microdialysis in the frontal cortex of the freely moving rat. We have determined that the acute fluoxetine-induced increases in extracellular 5-HT can be augmented by (+/-)pindolol, WAY100635, GR127935 and isamoltane with maximum increases of 216+/-32%, 235+/-49%, 240+/-18% and 171+/-47% of preinjection control levels, respectively. Combination of both 5-HT(1A) and 5-HT(1B/1D) autoreceptor antagonists with fluoxetine produced additive increases in extracellular 5-HT (i.e. WAY100635+GR127935+fluoxetine and WAY100635+isamoltane+fluoxetine produced a four- and five-fold potentiation, respectively), suggesting that this strategy may be useful in further augmenting the action of a SSRI in the treatment of depression. In addition, by comparing the combined administration of (+/-)pindolol with either WAY100635, GR127935 or isamoltane, we have determined that (+/-)pindolol produces much of its acute potentiation of fluoxetine-induced increases in extracellular 5-HT via its action at the 5-HT(1B/D) receptor in addition to any activity it has at the presynaptic 5-HT(1A) receptor.
10727715 T42 GENE 12 20 5-HT(1A)
10727715 T43 GENE 25 46 5-HT(1B/1D) receptors
10727715 T32 CHEMICAL 74 84 fluoxetine
10727715 T30 CHEMICAL 118 122 5-HT
10727715 T31 CHEMICAL 151 164 (+/-)pindolol
10727715 T20 CHEMICAL 208 221 (+/-)pindolol
10727715 T15 CHEMICAL 333 342 serotonin
10727715 T16 CHEMICAL 440 448 pindolol
10727715 T36 GENE 456 464 5-HT(1A)
10727715 T17 CHEMICAL 529 542 (+/-)pindolol
10727715 T18 CHEMICAL 544 554 WAY-100635
10727715 T37 GENE 558 566 5-HT(1A)
10727715 T19 CHEMICAL 580 588 GR127935
10727715 T38 GENE 592 603 5-HT(1B/1D)
10727715 T21 CHEMICAL 621 631 isamoltane
10727715 T39 GENE 635 643 5-HT(1B)
10727715 T22 CHEMICAL 696 706 fluoxetine
10727715 T23 CHEMICAL 818 828 fluoxetine
10727715 T24 CHEMICAL 864 868 5-HT
10727715 T25 CHEMICAL 889 902 (+/-)pindolol
10727715 T26 CHEMICAL 904 913 WAY100635
10727715 T27 CHEMICAL 915 923 GR127935
10727715 T28 CHEMICAL 928 938 isamoltane
10727715 T40 GENE 1077 1085 5-HT(1A)
10727715 T41 GENE 1090 1101 5-HT(1B/1D)
10727715 T29 CHEMICAL 1132 1142 fluoxetine
10727715 T1 CHEMICAL 1188 1192 5-HT
10727715 T2 CHEMICAL 1199 1208 WAY100635
10727715 T3 CHEMICAL 1209 1217 GR127935
10727715 T4 CHEMICAL 1218 1228 fluoxetine
10727715 T5 CHEMICAL 1233 1242 WAY100635
10727715 T6 CHEMICAL 1243 1253 isamoltane
10727715 T7 CHEMICAL 1254 1264 fluoxetine
10727715 T8 CHEMICAL 1501 1514 (+/-)pindolol
10727715 T9 CHEMICAL 1527 1536 WAY100635
10727715 T10 CHEMICAL 1538 1546 GR127935
10727715 T11 CHEMICAL 1550 1560 isamoltane
10727715 T12 CHEMICAL 1586 1599 (+/-)pindolol
10727715 T13 CHEMICAL 1643 1653 fluoxetine
10727715 T14 CHEMICAL 1689 1693 5-HT
10727715 T33 GENE 1716 1726 5-HT(1B/D)
10727715 T34 GENE 1716 1735 5-HT(1B/D) receptor
10727715 T35 GENE 1790 1798 5-HT(1A)
Common and specific determinants for fibroblast growth factors in the ectodomain of the receptor kinase complex. The assembly and activation of oligomeric complexes of FGF, the transmembrane receptor kinase (FGFR), and heparan sulfate transmit intracellular signals regulating growth and function of cells. An understanding of the structural relationships between the three subunits and their redundancy and specificity is essential for understanding the ubiquitous FGF signaling system in health and disease. Previously, we reported that a primary heparin or heparan sulfate binding site resides in a distinct sequence in immunoglobulin (Ig)-like module II of the three modules of FGFR. Here we report that in the absence of flanking sequences, isolated Ig module II of FGFR1 supports the binding of FGF-1, FGF-2, and FGF-7 in respective order of affinity. None of the three FGFs detectably bind Ig module I or the IIIb and IIIc splice variants of Ig module III in the absence of flanking sequences. Ig module I and the C-terminus of Ig module III are dispensable for high-affinity binding of FGF-1, FGF-2, and FGF-7. Alterations in highly conserved Ig module II in the heparin binding domain and substitution of individual sequence domains spanning the entire sequence of Ig module II with those from Ig module I obliterated FGF binding. Addition of a specific number of FGFR sequences to the C-terminus of Ig module II resulted in a gain in affinity for FGF-7. Several site-specific alterations in the C-terminus of full-length FGFR1IIIc, an isoform that otherwise absolutely rejects FGF-7, resulted in gain of FGF-7 binding. These results suggest that a complex of Ig module II and heparan sulfate is the base common active core of the FGFR ectodomain and that flanking structural domains modify FGF affinity and determine specificity.
9890894 T39 GENE 37 62 fibroblast growth factors
9890894 T40 GENE 88 103 receptor kinase
9890894 T22 GENE 168 171 FGF
9890894 T25 GENE 177 206 transmembrane receptor kinase
9890894 T35 GENE 208 212 FGFR
9890894 T1 CHEMICAL 227 234 sulfate
9890894 T20 GENE 466 469 FGF
9890894 T5 CHEMICAL 568 575 sulfate
9890894 T21 GENE 623 657 immunoglobulin (Ig)-like module II
9890894 T23 GENE 682 686 FGFR
9890894 T24 GENE 755 767 Ig module II
9890894 T26 GENE 771 776 FGFR1
9890894 T27 GENE 801 806 FGF-1
9890894 T28 GENE 808 813 FGF-2
9890894 T29 GENE 819 824 FGF-7
9890894 T30 GENE 876 880 FGFs
9890894 T31 GENE 897 929 Ig module I or the IIIb and IIIc
9890894 T32 GENE 949 962 Ig module III
9890894 T33 GENE 1001 1012 Ig module I
9890894 T6 CHEMICAL 1021 1022 C
9890894 T34 GENE 1035 1048 Ig module III
9890894 T36 GENE 1094 1099 FGF-1
9890894 T37 GENE 1101 1106 FGF-2
9890894 T38 GENE 1112 1117 FGF-7
9890894 T7 GENE 1151 1163 Ig module II
9890894 T8 GENE 1274 1286 Ig module II
9890894 T9 GENE 1303 1314 Ig module I
9890894 T10 GENE 1327 1330 FGF
9890894 T11 GENE 1373 1377 FGFR
9890894 T2 CHEMICAL 1395 1396 C
9890894 T12 GENE 1409 1421 Ig module II
9890894 T13 GENE 1457 1462 FGF-7
9890894 T3 CHEMICAL 1505 1506 C
9890894 T14 GENE 1531 1540 FGFR1IIIc
9890894 T15 GENE 1587 1592 FGF-7
9890894 T16 GENE 1614 1619 FGF-7
9890894 T17 GENE 1669 1681 Ig module II
9890894 T4 CHEMICAL 1694 1701 sulfate
9890894 T18 GENE 1740 1755 FGFR ectodomain
9890894 T19 GENE 1800 1803 FGF
Pharmacokinetic and pharmacodynamic modeling of hedgehog inhibitor TAK-441 for the inhibition of Gli1 messenger RNA expression and antitumor efficacy in xenografted tumor model mice. 6-Ethyl-N-[1-(hydroxyacetyl)piperidin-4-yl]-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-3-(2,2,2-trifluoroethoxy)-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-2-carboxamide (TAK-441) is a potent, selective hedgehog signaling pathway inhibitor that binds to Smo and is being developed for the treatment of cancer. The objectives of these studies were to explore the possibility of establishing of a link between the pharmacokinetics of TAK-441 and the responses of Gli1 mRNA in tumor-associated stromal or skin cells and the antitumor effect of hedgehog inhibition. To this end, we built pharmacokinetic and pharmacodynamic models that describe the relationship of the concentrations of TAK-441 plasma to the responses of Gli1 mRNA in the tumor (target) and skin (surrogate) and to tumor growth inhibition in mice bearing xenografts of human pancreatic tumors (PAN-04). The responses of Gli1 mRNA and tumor growth were described by an indirect response model and an exponential tumor growth model, respectively. The IC50 values for Gli1 mRNA inhibition in the tumor and skin by TAK-441 were estimated to be 0.0457 and 0.113 μg/ml, respectively. The IC90 value for tumor growth inhibition was estimated to be 0.68 μg/ml. These results suggest that a >83% inhibition of Gli1 mRNA expression in the skin or a >94% inhibition of Gli1 mRNA expression in the tumor would be required to sufficiently inhibit (>90%) hedgehog-related tumor growth in the xenografted model mice. We conclude that Gli1 mRNA expression in the tumor and skin could be a useful biomarker for predicting the antitumor effect of hedgehog inhibitors.
23298863 T19 GENE 48 56 hedgehog
23298863 T6 CHEMICAL 67 74 TAK-441
23298863 T20 GENE 97 101 Gli1
23298863 T1 CHEMICAL 183 343 6-Ethyl-N-[1-(hydroxyacetyl)piperidin-4-yl]-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-3-(2,2,2-trifluoroethoxy)-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-2-carboxamide
23298863 T3 CHEMICAL 345 352 TAK-441
23298863 T13 GENE 377 385 hedgehog
23298863 T14 GENE 428 431 Smo
23298863 T4 CHEMICAL 606 613 TAK-441
23298863 T15 GENE 635 639 Gli1
23298863 T16 GENE 715 723 hedgehog
23298863 T5 CHEMICAL 857 864 TAK-441
23298863 T17 GENE 892 896 Gli1
23298863 T18 GENE 1057 1061 Gli1
23298863 T7 GENE 1202 1206 Gli1
23298863 T2 CHEMICAL 1248 1255 TAK-441
23298863 T8 GENE 1438 1442 Gli1
23298863 T9 GENE 1495 1499 Gli1
23298863 T10 GENE 1578 1586 hedgehog
23298863 T11 GENE 1656 1660 Gli1
23298863 T12 GENE 1766 1774 hedgehog
Proto-oncogene PIM-1 is a novel estrogen receptor target associating with high grade breast tumors. We searched ERα cistromes of MCF-7 breast cancer cells for previously unrecognized ERα targets and identified proto-oncogene PIM-1 as a novel potential target gene. We show that the expression of PIM-1 is induced in response to estradiol in MCF-7 cells and that the induction is mediated by ERα-regulated enhancers located distally upstream from the gene. In keeping with the growth-promoting role of the PIM-1, depletion of the PIM-1 attenuated the proliferation of the MCF-7 cells, which was paralleled with up-regulation of cyclin-dependent protein kinase inhibitor CDKN1A and CDKN2B expression. Analysis of PIM-1 expression between invasive breast tumors and benign breast tissue samples showed that elevated PIM-1 expression is associated with malignancy and a higher tumor grade. In sum, identification of PIM-1 as an ERα target gene adds a novel potential mechanism by which estrogens can contribute to breast cancer cell proliferation and carcinogenesis.
23142699 T19 GENE 0 14 Proto-oncogene
23142699 T20 GENE 15 20 PIM-1
23142699 T3 CHEMICAL 32 40 estrogen
23142699 T21 GENE 32 49 estrogen receptor
23142699 T5 GENE 112 115 ERα
23142699 T18 GENE 183 186 ERα
23142699 T4 GENE 210 224 proto-oncogene
23142699 T6 GENE 225 230 PIM-1
23142699 T7 GENE 296 301 PIM-1
23142699 T1 CHEMICAL 328 337 estradiol
23142699 T8 GENE 391 394 ERα
23142699 T9 GENE 505 510 PIM-1
23142699 T10 GENE 529 534 PIM-1
23142699 T11 GENE 627 668 cyclin-dependent protein kinase inhibitor
23142699 T12 GENE 669 675 CDKN1A
23142699 T13 GENE 680 686 CDKN2B
23142699 T14 GENE 711 716 PIM-1
23142699 T15 GENE 813 818 PIM-1
23142699 T16 GENE 912 917 PIM-1
23142699 T17 GENE 924 927 ERα
23142699 T2 CHEMICAL 982 991 estrogens
Nonthrombolytic intervention in acute myocardial infarction. Alternative interventions are available for patients in whom thrombolytic therapy is inappropriate after an acute myocardial infarction. Administration of a beta blocker within the first 24 hours of the patient's admission to the coronary care unit can reduce overall morbidity and mortality within the first 7 days by about 15%. Maintenance therapy with an oral beta blocker can reduce mortality within the succeeding 3 years by about 25%. Esmolol, a unique cardioselective beta 1-adrenergic receptor blocker with a half-life of 9 minutes, can enable some patients with relative contraindications to beta blockers to nevertheless benefit from early beta-blocking therapy. It also is useful in screening patients for subsequent therapy with beta blockers. Those who tolerate the esmolol infusion can be given a long-acting beta blocker. For patients who exhibit intolerance to esmolol, the infusion can be terminated with rapid return to baseline hemodynamics.
2568748 T1 CHEMICAL 502 509 Esmolol
2568748 T4 GENE 536 562 beta 1-adrenergic receptor
2568748 T2 CHEMICAL 840 847 esmolol
2568748 T3 CHEMICAL 938 945 esmolol