Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UID3 (FFR)
 233 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Binding of the fibrinolytic proteinase plasmin (Pm) to streptokinase (SK) in a tight stoichiometric complex transforms Pm into a potent proteolytic activator of plasminogen. SK binding to the catalytic domain of Pm, with a dissociation constant of 12 pm, is assisted by SK Lys(414) binding to a Pm kringle, which accounts for a 11-20-fold affinity decrease when Pm lysine binding sites are blocked by 6-aminohexanoic acid (6-AHA) or benzamidine. The pathway of SK.Pm catalytic complex formation was characterized by stopped-flow kinetics of SK and the Lys(414) deletion mutant (SKDeltaK414) binding to Pm labeled at the active site with 5-fluorescein ([5F]FFR-Pm) and the reverse reactions by competitive displacement of [5F]FFR-Pm with active site-blocked Pm. The rate constants for the biexponential fluorescence quenching caused by SK and SKDeltaK414 binding to [5F]FFR-Pm were saturable as a function of SK concentration, reporting encounter complex affinities of 62-110 nm in the absence of lysine analogs and 4900-6500 and 1430-2200 nm in the presence of 6-AHA and benzamidine, respectively. The encounter complex with SKDeltaK414 was approximately 10-fold weaker in the absence of lysine analogs but indistinguishable from that of native SK in the presence of 6-AHA and benzamidine. The studies delineate for the first time the sequence of molecular events in the formation of the SK.Pm catalytic complex and its regulation by kringle ligands. Analysis of the forward and reverse reactions supports a binding mechanism in which SK Lys(414) binding to a Pm kringle accompanies near-diffusion-limited encounter complex formation followed by two slower, tightening conformational changes.
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PMID:Rapid-reaction kinetic characterization of the pathway of streptokinase-plasmin catalytic complex formation. 1865 46

The suitability of five maturity group (MG) III and five MG IV soybean, Glycine max, cultivars as hosts for Meloidogyne incognita and M. arenaria was evaluated in a greenhouse. 'Forrest', a MG V cultivar, was used as the standard of comparison for M. incognita resistance. With M. incognita, root-gall and egg-mass indices and reproductive factors for 'Asgrow 3307', 'FFR 398', and 'Pioneer 9442' were comparable with those found on Forrest. Meloidogyne arenaria reproduction was lower (P </= 0.05) on 'Stevens' than on the other cultivars studied except 'TN4-86'. When grown in a field infested with M. incognita, the relative ranking of the cultivars was similar to the greenhouse results.
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PMID:Host Suitability of Soybean Cultivars for Meloidogyne incognita and M. arenaria. 1928 69

Prostasin or human channel-activating protease 1 has been reported to play a critical role in the regulation of extracellular sodium ion transport via its activation of the epithelial cell sodium channel. Here, the structure of the extracellular portion of the membrane associated serine protease has been solved to high resolution in complex with a nonselective d-FFR chloromethyl ketone inhibitor, in an apo form, in a form where the apo crystal has been soaked with the covalent inhibitor camostat and in complex with the protein inhibitor aprotinin. It was also crystallized in the presence of the divalent cation Ca(+2). Comparison of the structures with each other and with other members of the trypsin-like serine protease family reveals unique structural features of prostasin and a large degree of conformational variation within specificity determining loops. Of particular interest is the S1 subsite loop which opens and closes in response to basic residues or divalent ions, directly binding Ca(+2) cations. This induced fit active site provides a new possible mode of regulation of trypsin-like proteases adapted in particular to extracellular regions with variable ionic concentrations such as the outer membrane layer of the epithelial cell.
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PMID:Active site conformational changes of prostasin provide a new mechanism of protease regulation by divalent cations. 1938 54

To evaluate the accuracy of myocardial perfusion SPECT (MPI) in the detection and allocation of vessel specific perfusion defects (PD) using standard distribution territories in a routine clinical procedure of patients with multivessel disease (MVD). Combined quantitative coronary angiography and fractional flow reserve (QCA/FFR) measurements were used as invasive reference standard. 216 vessels in 72 MVD patients (67 +/- 10 years, 28 female) were investigated using MPI and QCA. FFR of 93 vessels with intermediate stenoses was determined. MPI detected significant stenoses according to QCA/FFR findings with a sensitivity of 85%. However, vessel-based evaluation using standard myocardial distribution territories delivered a sensitivity of only 62% (28 MPI+ out of 45 (QCA/FFR)+ findings), with specificity, PPV and NPV of 90, 62 and 90%. 7/17 false positive and 7/17 false negative findings (41%) could be attributed to incorrect allocation of reversible PD to their respective coronary arteries. 6/17 (35%) perfusion territories were classified as false negative when additional fixed PD were present. MPI had reasonable sensitivity for the detection of significant coronary artery disease in patients with multivessel disease. However, sensitivity decreased markedly, when the significance of each individual stenosis was evaluated using standard myocardial supplying territories. In this setting, 41% of false negative and false positive MPI findings resulted from incorrect allocation of reversible perfusion defects to their determining supplying vessel.
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PMID:Tc-99m sestamibi single photon emission computed tomography for guiding percutaneous coronary intervention in patients with multivessel disease: a comparison with quantitative coronary angiography and fractional flow reserve. 2003 85

Over the last 15 years, the use of invasive coronary physiology in the catheterization laboratory has demonstrated favorable outcomes for decision making in patients with intermediate single-vessel stenoses, complex bifurcation and ostial branch stenoses, multivessel coronary artery disease, and left main stenoses. A recent large multicenter study (FAME [FFR versus Angiography for Multivessel Evaluation]) found that a physiologically-guided approach was superior to the standard angiographically-guided approach for percutaneous revascularization in patients with multivessel coronary artery disease. This review addresses selected pertinent concepts and studies supporting the integration of coronary physiology in the catheterization laboratory for optimal patient outcomes.
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PMID:Current concepts of integrated coronary physiology in the catheterization laboratory. 2011 97

We previously reported a novel drug delivery system, drug-linker-Phe-Phe-Arg-methylketone (FFR-mk)-factor VIIa (fVIIa). The method utilizes tissue factor (TF), which is aberrantly and abundantly expressed on many cancer cells. The advantage of this delivery system is its ability to furnish a potent anticancer drug specifically to the tumor vasculature and cancer cells. In this paper, we describe the synthesis of paclitaxel (PTX)-Phe-Phe-Arg-chloromethyl ketone (FFR-ck), followed by coupling with fVIIa to form PTX-FFR-mk-fVIIa. FFRck was separately linked to the OH groups at the C2' or C7 positions of PTX (C2'- or C7-PTX-FFRck), the C2' analogue exhibiting better activity against human head and neck squamous KB 3-1 cells. The activity order against PTX-sensitive KB 3-1 cells is C2'-PTX-FFRmk-fVIIa > PTX > C2'-PTX-FFRck. The C2' complex shows an IC(50) of 12 nM against the PTX-sensitive cell line and 130 nM against PTX-resistant cells.
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PMID:Targeted delivery of paclitaxel to tumor cells: synthesis and in vitro evaluation. 2030 3

(-)-Epigallocatechin gallate, Abafungin, ACE-031, Adapalene/benzoyl peroxide, AE-37, Aflibercept, AGS-003, Albiglutide, Alemtuzumab, Aliskiren fumarate, ALT-801, AN-2728, Anacetrapib, API, Aprepitant, ARQ-197, Ascorbic acid, Atazanavir sulfate, ATN-224, AVI-4658, Azacitidine, Azelnidipine; Belinostat, Bevacizumab, BI-2536, Biphasic insulin aspart, Bortezomib, Bovine lactoferrin, Bryostatin 1, Budesonide/formoterol fumarate; cAC10, Canfosfamide hydrochloride, Cediranib, Clofarabine, Cocaine conjugate vaccine; Darbepoetin alfa, Dasatinib, Denosumab, Disomotide, Doripenem, Dovitinib Lactate, Dronedarone hydrochloride, Drospirenone/estradiol, Dutasteride; Ecogramostim, Entinostat, Enzastaurin hydrochloride, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe, Ezetimibe/simvastatin; Fampridine, Fenretinide LXS, FFR-factor VIIa, Fingolimod hydrochloride, Frovatriptan; Gefitinib, Gimatecan, GP-2/GM-CSF; Iloperidone, Imatinib mesylate, Indibulin, Ipilimumab, Ivabradine hydrochloride; Lactobacillus rhamnosus, Lapatinib ditosylate, LC-07, Lenalidomide, Linifanib, Liposomal doxorubicin, Liposomal vincristine, Litenimod, Lutein; M-118, MDX-1401, MEDI-528, Midostaurin, Miglustat, MK-0657; Natalizumab, Nesiritide, NGR-TNF, Niacin/simvastatin; Obatoclax mesylate, Olaparib, Omacetaxine mepesuccinate; Paclitaxel nanoparticles, Paclitaxel-eluting stent, Palonosetron hydrochloride, Pazopanib hydrochloride, Pegfilgrastim, Pemetrexed disodium, PER.C-flu, Perifosine, PF-02341066, Pimecrolimus, Pitrakinra, Plerixafor hydrochloride, Posaconazole; Rasburicase, Recombinant human relaxin H2, ReoT3D, Retaspimycin hydrochloride, Riferminogene pecaplasmid, Rindopepimut, Romiplostim, Ronacaleret hydrochloride, Rosuvastatin calcium, Rotigotine; Sagopilone, sALP-FcD10, SAR-245409, SCH-697243, Selumetinib, Sirolimus-eluting stent, SIR-Spheres, Sitagliptin phosphate monohydrate, Sitaxentan sodium, Sorafenib, Sunitinib malate; Tadalafil, Tandutinib, Tasimelteon, Temsirolimus, Teriparatide, Tiotropium bromide, TIV, Trabectedin, Tremelimumab, TRU-016; Vadimezan, Val8-GLP-1(7-37)OH, Vandetanib, Vernakalant hydrochloride, Voreloxin, Voriconazole, Vorinostat, Yttrium 90 (90Y) ibritumomab tiuxetan; Zeaxanthin, Ziprasidone hydrochloride, Zosuquidar trihydrochloride.
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PMID:Gateways to clinical trials. 2038 46

Adenosine monophosphate-activated protein kinase (AMPK) mediates metabolic responses of muscle to exercise and is involved in improvement of insulin resistance by endurance exercise. Recent studies have suggested that the renin-angiotensin system might negatively modulate insulin-mediated actions, but there has been little investigation of the correlation between the renin-angiotensin system and AMPK. To determine this correlation, we performed studies with glucose clamp in vivo, and glucose uptake by skeletal muscle ex vivo using 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR). Six-week-old male Sprague-Dawley rats were fed standard chow (standard-diet rats; SD) or fructose-rich chow (fructose-fed rats; FFR) for 6 weeks. At the age of 12 weeks, SD and FFR were treated by oral gavage, either with angiotensin II (Ang II) receptor blockade (ARB; valsartan 30 mg/kg) or vehicle. Thirty minutes after the treatment, we performed glucose clamp studies to measure glucose infusion rates during infusion of insulin (GIR(I)) and of AICAR (GIR(A)), which stimulates AMPK, and studied the effect of ARB on either GIR(I) or GIR(A). In an ex vivo study, we used bilateral fresh soleus muscles from 3-week-old male Sprague-Dawley rats to examine the glucose uptake (measured by (3)H-2-deoxyglucose uptake) of one side of soleus muscle incubated with AICAR with or without Ang II, or with tumor necrosis factor-alpha, in comparison with that of the other (untreated control) side of the muscle. Blood pressure of FFR was significantly higher than that of SD rats. GIR(I) was significantly lower in FFR than in SD, and treatment with ARB did not change GIR(I). GIR(A) of FFR was significantly lower than that of SD, but GIR(A) of FFR treated with ARB was significantly increased compared with that of FFR treated with vehicle. In the ex vivo study, incubation with AICAR significantly increased glucose uptake of soleus muscles, Ang II significantly decreased AICAR-activated glucose uptake in a dose-dependent manner, and ARB canceled the effect of Ang II. The results suggest that acute inhibition of the angiotensin 1 receptor improves glucose metabolism via not insulin but AMPK pathway through the angiotensin 1 receptor in FFR.
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PMID:Angiotensin II inhibits glucose uptake of skeletal muscle via the adenosine monophosphate-activated protein kinase pathway. 2040 57

Fractional flow reserve is a simple and efficient tool to assess the severity of an intermediate lesion in order to determine the optimal therapy. However there are some limitations to its use. We observed that in patients with an occluded artery, FFR measurements in the vessel supplying collaterals can be underestimated leading to inappropriate therapy.
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PMID:A pitfall of fractional flow reserve measurement. 2051 16

Strategies during elective PCI procedures in patients with stable angina and multivessel disease are in the majority of catheterisation laboratories, more often than not based, solely on the angiographic analysis on the spur of the moment. This despite the knowledge that angiographic images are often lacking the discriminating power to predict accurately the exact physiologic impact of individual lesions. Evidence is however accumulating telling us that routine stenting of non significant lesion is at best of no additional benefit for the patient. the introduction of dedicated angioplasty guidewires equipped at the tip with a miniature pressure-sensor has greatly expanded the possibilities to accurately evaluate the functional importance of any lesion during diagnostic coronary angiogram by measuring the FFR index. Ths index, based on the measurements of the trans-stenotic coronary gradient during maximal vasodilatation, is accurate, and easy to implement. Results from several important trials (e.g.,DEFER) have brought to our attention the fact that non significant coronary lesion sas documented by FFR measurements, in patients with single vessel disease can safely be left untreated. Recently, the remarkable results from the FAME trial have made a strong case for integrating functional evaluation as a routine work up especially in the presence of angiographic ambiguous lesions referred for PCI in patients with multivessel disease.
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PMID:Is functional assessment necessary in patients with stable angina? 2054 15


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