Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effects on plasma levels of coagulation and fibrinolysis factors of two currently used "sub-50" oral contraceptive preparations (OCs), one containing 750 micrograms lynestrenol and 37.5 micrograms ethinyl estradiol (LYN-EE) and the other containing 150 micrograms levonorgestrel and 30 micrograms ethinyl estradiol (LNG-EE), in groups of about 25 women aged 21 +/- 2 years. After 3 months, plasminogen levels increased in the two experimental groups (LYN-EE and LNG-EE), by 40% and 32%, respectively. This change was positively correlated with changes in ceruloplasmin levels, indicating that an estrogenic effect might be involved. Histidine-rich glycoprotein concentration decreased by 26% and 16%, respectively. Tissue-type plasminogen activator (t-PA) activity increased by 260% and 167%; t-PA antigen decreased by 12% and 18%, and t-PA inhibitor activity decreased by 31% and 32%, respectively. In the coagulation system, in both groups factor XII increased by 47% and 34%, respectively. The main inhibitor of factor XII, C1-inactivator, decreased slightly, but this was significant only in the LNG-EE group. The von Willebrand factor antigen fell by 8% and 9%, whereas factor VIII activity did not change. Antithrombin III antigen decreased by 14% in both groups. Factor IX activity increased by 15% and 21%. The difference in hormonal effects of both preparations was reflected by the increases in sex hormone binding globulin (by 130% and 21%) and ceruloplasmin (by 98% and 51%), indicating that LYN-EE had a more estrogenic potency than LNG-EE. In a control group of 25 matched subjects, who were observed simultaneously, we found no significant changes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of two low-dose oral contraceptives on circulating components of the coagulation and fibrinolytic systems. 310 29

The effects of hormone replacement therapy (HRT) on thrombosis risk, thrombotic variables, and the inflammatory marker C-reactive protein (CRP) may vary by route of administration (oral versus transdermal). We studied the relationships of 14 thrombotic variables (previously related to cardiovascular risk) and CRP to menopausal status and to use of HRT subtypes in a cross-sectional study of 975 women aged 40-59 years. Our study confirmed previously-reported associations between thrombotic variables and menopausal status. Oral HRT use was associated with increased plasma levels of Factor IX, activated protein C (APC) resistance, and CRP; and with decreased levels of tissue plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI) activity. Factor VII levels were higher in women taking unopposed oral oestrogen HRT. The foregoing associations were not observed in users of transdermal HRT; hence they may be consequences of the "first-pass" effect of oral oestrogens on hepatic protein synthesis. We conclude that different effects of oral and transdermal HRT on thrombotic and inflammatory variables may be relevant to their relative thrombotic risk; and suggest that this hypothesis should be tested in prospective, randomised studies.
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PMID:Different effects of oral and transdermal hormone replacement therapies on factor IX, APC resistance, t-PA, PAI and C-reactive protein--a cross-sectional population survey. 1152 2

A new series of peptide inhibitors of human Factor VIIa (FVIIa) has been identified and affinity matured from naive and partially randomized peptide phage libraries selected against the immobilized tissue factor x Factor VIIa (TF x FVIIa) complex. These "A-series" peptides contain a single disulfide bond and a 13-residue minimal core required for maximal affinity. They are exemplified by peptide A-183 (EEWEVLCWTWETCER), which binds at a newly identified exosite on the FVIIa protease domain, described in the accompanying report [Roberge, M., Santell, L., Dennis, M. S., Eigenbrot, C., Dwyer, M. A., and Lazarus, R. A. (2001) Biochemistry 40, 9522-9531]. A-183 was obtained from a trypsin digest of A-100-Z, a recombinant protein comprising A-183 and the Z domain of protein A. Surprisingly, A-183 was a very potent inhibitor of TF x FVIIa, inhibiting activation of Factor X (FX) and Factor IX and amidolytic activity of Chromozym t-PA with IC50 values of 1.6 +/- 1.2, 3.5 +/- 0.3, and 8.5 +/- 3.5 nM, respectively. Kinetic analysis revealed that A-183 was a partial (hyperbolic) mixed-type inhibitor of FX activation having a Ki of 200 pM as well as a partial competitive inhibitor of amidolytic activity. The A-series peptides were also specific and potent inhibitors of TF-dependent clotting as measured in a prothrombin time (PT) clotting assay and had no effect on the TF-independent activated partial thromboplastin time. At saturating concentrations of peptide, the maximal extent by which A-183 and A-100-Z inhibited the rate of FX activation was 78 +/- 3 and 89 +/- 6%, respectively. The degree of inhibition of the rate of FX activation correlated with a maximum fold prolongation in the PT assay of 1.8-fold for A- 183 and 3.3-fold for A-100-Z. The A-series peptides represent a new class of peptide exosite inhibitors that are capable of attenuating, rather than completely inhibiting, the activity of TF x FVIIa, potentially leading to anticoagulants with an increased therapeutic window.
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PMID:Selection and characterization of a new class of peptide exosite inhibitors of coagulation factor VIIa. 1158 50

Modulation of cytosolic phospholipase A(2) (PLA(2)) expression levels and production of its metabolites have been reported in several tumor types, indicating involvement of arachidonic acid and its derivatives in tumorigenesis. Following our demonstration that the PLA(2) group IV isoform alpha (PLA(2)IV alpha) controls TSH-independent growth of normal thyroid (PCCl(3)) cells, we have investigated the mitogenic role of PLA(2)IV alpha in rat thyroid cells transformed by the RET/PTC oncogenes (PC-PTC cells). We now report that PLA(2)IV alpha acts downstream of the RET/PTC oncogenes in a novel pathway controlling RET-dependent cell proliferation. In addition, we show that PLA(2)IV alpha is in its phosphorylated/active form not only in RET/PTC-transformed cells and in cells derived from human papillary carcinomas but also in lysates from tumor tissues, thus relating constitutive activation of PLA(2)IV alpha to RET/PTC-dependent tumorigenesis. Moreover, p38 stress-activated protein kinase is the downstream effector of RET/PTC that is responsible for PLA(2)IV alpha phosphorylation and activity. In summary, our data elucidate a novel mechanism in the control of thyroid tumor cell growth that is induced by the RET/PTC oncogenes and which is distinguishable from that of other oncogenes, such as BRAF. This mechanism is mediated by PLA(2)IV alpha and should be amenable to targeted pharmacologic intervention.
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PMID:Cytosolic phospholipase A2 alpha regulates cell growth in RET/PTC-transformed thyroid cells. 1808 7