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

We adopted the technique and method of integrating the morphology with function to select the effective acupoints for treatment of deafness. The results show that: (1) Tinggong (SI 19), Yifeng (TE 17), Waiguan (TE 5), Shenshu (UB 23), Sanyinjiao (SP 6) and Zhubin (KI 9) etc. are the effectine acupoints for the treatment of ototoxic auditory damage caused by drug, especially, the effect of Tinggong, Sanyinjiao and Zhubin etc, is much better; (2) electroacupuncture can promote audibility, improve SDH activity and relieve progressing injury of auditory hair cells, (3) FFR method has an important significance in the determination of ototoxic damage caused by drug.
 ...
PMID:[Treatment of ototoxic auditory damage caused by kanamycin with electroacupuncture at different acupoints]. 875 32

Des (1-38)- and des(1-44)-factor VIIa (fVIIa) were inhibited with Phe-Phe-Arg-chloromethyl ketone (FFR-cmk). Des(1-38)-FFR-fVIIa inhibited tissue factor (TF)-enhanced fVIIa amidolytic activity with an IC50 value of 15 nM, whereas 3- and 6-fold higher values were obtained with des(1-44)-FFR-fVIIa using soluble and full-length TF, respectively. The value for FFR-fVIIa was 8-10 nM. Clotting time was prolongated with IC50 values for inactivated des(1-38)- and des(1-44)-fVIIa of 50 nM and 1 mu M, respectively, whereas FFR-fVIIa yielded a value of 10 nM. From binding experiments in a BIA-core instrument, dissociation constants for the complexes between TF1-218 and fVIIa, des(1-38)-fVIIa and des(1-44)-fVIIa of about 3, 20 and 70 nM, respectively, could be estimated.
 ...
PMID:Influence of the gamma-carboxyglutamic acid-rich domain and hydrophobic stack of factor VIIa on tissue factor binding. 890 70

To study how diet composition affects exercise endurance and body composition, 48 male Sprague-Dawley rats were treadmill trained for 8 wk while consuming either a high-fat (F) diet or high-carbohydrate (C) diet. The diets were switched for one-half the number of rats in each group 3 days before the animals were killed, during which feeding time the rats did not exercise. One-half of rats receiving each of the four diet combinations were taken at rest (R) or exhaustion (E), resulting in eight groups: CCR, CFR, FFR, FCR, CCE CFE, FFE, and FCE. An analysis of variance revealed that resting glycogen in the FCR group was enhanced in muscle (19-33%) and liver (23%) compared with controls. Each F group's exercise time to exhaustion [CFE, 322.9 +/- 25.0; FFE, 356.8 +/- 37.8; FCE, 467.0 +/- 32.6 (SE) min] was different (P < 0.05) from control (CCE, 257.5 +/- 29.2 min). Postexercise glycogen was equivalent among all dietary groups, were muscle triglycerides. The FF and FC groups had higher 3-hydroxyacyl-CoA dehydrogenase activity in soleus muscle than either CC or CF animals. After training, body weights were similar between the two dietary groups; however, percent body fat was 17% greater after the F diet, even though F diet animals voluntarily consumed 12% less energy than did C diet animals. These data suggest that exercise endurance time is optimized in trained rats that receive a carbohydrate load after adaptation to a F diet. However, despite intense exercise training, the F diet promotes body fat deposition, and the health consequences of following such a regimen are still unknown.
 ...
PMID:Body fat and exercise endurance in trained rats adapted to a high-fat and/or high-carbohydrate diet. 892 43

Thrombotic thrombocytopenic purpura (TTP) is characterized by micro-angiopathic hemolytic anemia (MAHA), thrombocytopenia, neurological symptoms, renal involvement, and fever. We describe our experience in 70 serially encountered TTP patients in the last decade who were treated with a standard therapeutic plasma exchange (TPE) protocol. Seventy percent of the patients were females. The median age of the patients was 43 years (range: 8-80). Sixty patients (85.7%) had a complete response to TPE therapy. This represented 91% of 66 who received at least one TPE. Ten patients died, two patients died before and two during the first plasma exchange. The median number of TPEs performed was nine (range: 1-85). Thirty-five (58%) out of 60 responded to 3-9 TPEs, and 25 (42%) required 10-34 TPEs for the response. The median total plasma volume exchanged was 28 liters (range: 2.7-250 L) and the mean plasma volumes exchanged during each procedure was 3.2 (SD +/- 1.09 L). The patients were classified into early responders (ER) and late responders (LR). ERs had a mean platelet count of 180 x 10(9)/L by Day 5, mean LDH of 643 IU/L by Day 7, and required median of seven TPEs. LRs had a mean platelet count of 122 x 10(9)/L by Day 5, mean LDH of 885 IU/L by Day 7, and required median of 19 TPEs (P = 0.001). The platelet counts were significantly higher (P = 0.01-0.03) in ERs on Days 1, 3, and 5 as compared to LRs but the LDH did not differ significantly. Seventy-seven percent of LRs had exacerbation of TTP and 18% had relapse as compared to 7% each in ERs. Thirteen patients were in coma/semicoma at presentation. Out of these, six died, making coma a bad prognostic indicator. Five of the seven survivors in coma had received two single-plasma volume exchanges on Day 1. In conclusion, 91% of TTP patients had an excellent response to plasma exchange therapy with FFR Coma/ semicoma appears to be a bad prognostic indicator. LRs needed prolonged treatment with a greater number of patients experiencing exacerbation and relapse of TTP as compared to ERs.
 ...
PMID:Thrombotic thrombocytopenic purpura: early and late responders. 903 83

The enhancement of force of contraction (FOC) following increasing frequencies of stimulation is an important mechanism of positive inotropy in human myocardium. The present study aimed to investigate the influence of alterations in Na+ influx on FFR in human myocardium. Isometric FOC of electrically stimulated right auricular trabeculae (AUT, n = 12) from human non-failing hearts (n = 8) was measured at different stimulation rates (0.5-3 Hz) under control conditions, after increasing Na+ influx by the addition of (+/-)BDF 9148 (BDF, 3 mumol l-1) and after decreasing Na+ influx by the addition of lidocaine (LIDO, 10 mumol l-1). Additionally, the rate dependent changes in diastolic tension (DT) were measured in all experiments. Under control conditions FOC increased with increasing frequencies of stimulation. The rate at which maximal FOC was observed (SFmax) was 2.0 +/- 0.2 Hz and maximal increase in FOC (PIEmax) by increasing frequency of stimulation was +1.5 +/- 0.5 mN. After increase of Na+ influx by BDF (3 mumol l-1) SFmax was decreased to 0.8 +/- 0.1 Hz (p < 0.05 versus control) and PIEmax was +0.1 +/- 0.3 mN (p < 0.05). When Na+ influx was diminished by LIDO (10 mumol l-1) SFmax and PIEmax were increased compared to control (2.4 +/- 0.1 Hz and +4.1 +/- 0.9 mN, p < 0.05 versus control). The diastolic tension (DT) of AUT at 3 Hz was not changed at higher rates in the control group and after application of LIDO (10 mumol l-1), whereas after enhancement of Na+ influx by BDF there was an increase in DT of +0.7 +/- 0.2 at 3 Hz (p < 0.05 versus control and LIDO). An enhanced Na+ influx leads to a decrease in the optimal frequency and to a smaller force potentiation by higher stimulation rates which could be at least partly due to incomplete relaxation at higher frequencies, whereas a reduced Na+ influx is followed by opposite alterations. It is concluded that besides Ca2+ handling also Na+ influx and Na+ homeostasis might determine the frequency-induced force potentiation in human myocardium. Thus, the negative FFR in diseased human myocardium might result from changes in cellular Ca2+ or Na+ regulatory sites.
 ...
PMID:Na+ channel modulation and force-frequency relationship in human myocardium. 920 57

Active site-inactivated factor VIIa has potential as an antithrombotic agent. The effects of D-Phe-L-Phe-L-Arg-chloromethyl ketone-treated factor VIIa (FFR-FVIIa) were evaluated in a cell-based system mimicking in vivo initiation of coagulation. FFR-FVIIa inhibited platelet activation (as measured by expression of P-selectin) and subsequent large-scale thrombin generation in a dose-dependent manner with IC50 values of 1.4 +/- 0.8 nM (n = 8) and 0.9 +/- 0.7 nM (n = 7), respectively. Kd for factor VIIa binding to monocytes and Ki for FFR-FVIIa competing with factor VIIa were similar (11.4 +/- 0.8 pM and 10.6 +/- 1.1 pM, respectively), showing that FFR-FVIIa binds to tissue factor in the tenase complex with the same affinity as factor VIIa. Using platelets from volunteers before and after ingestion of aspirin (1.3 g), there were no significant differences in the IC50 values of FFR-FVIIa [after aspirin ingestion, the IC50 values were 1.7 +/- 0.9 nM (n = 8) for P-selectin expression, p = 0.37, and 1.4 +/- 1.3 nM (n = 7) for thrombin generation, p = 0.38]. This shows that aspirin treatment of platelets does not influence the inhibition of tissue factor-initiated coagulation by FFR-FVIIa, probably because thrombin activation of platelets is not entirely dependent upon expression of thromboxane A2.
 ...
PMID:The effect of active site-inhibited factor VIIa on tissue factor-initiated coagulation using platelets before and after aspirin administration. 936 85

The binding of the multidomain protein factor VIIa (fVIIa) to tissue factor provides the interprotein communication necessary to make fVIIa an efficient catalyst of the initial event in the extrinsic pathway of blood coagulation. We have investigated the stability of individual domains in fVIIa and the influence of Ca2+ and an irreversible active-site inhibitor (FFR-chloromethyl ketone). Equilibrium guanidine hydrochloride (GuHCl)-induced unfolding monitored by tryptophan fluorescence and far-UV circular dichroism (CD) demonstrated that the gamma-carboxyglutamic acid (Gla) domain unfolds at 0.3 M GuHCl and the serine protease (SP) domain at 3 M GuHCl and that Ca2+ is a prerequisite for the formation of an ordered, compact structure in the Gla domain. The loss of amidolytic activity coincides with the first transition, which is stabilized by the active-site inhibitor, and a change in the environment of the active site is demonstrated using a fluorescent inhibitor (DEGR-chloromethyl ketone). Thermal unfolding monitored by differential scanning calorimetry (DSC) reveals that Ca2+ stabilizes the SP domain slightly, increasing the unfolding temperature by 2.7 degrees C. In addition, Ca2+ is required for a large enthalpy change concomitant with unfolding of the Gla domain, and this unfolding enthalpy is only detectable in the presence of the SP domain, indicating some kind of interaction between these domains. Thermal unfolding measured by CD indicates secondary structural changes at the same temperature as the heat absorption in the DSC but only when both the Gla domain and the SP domain are present together with Ca2+ ions. Taken together, these results indicate a Ca2+-dependent interaction between the Gla domain and the SP domain, implying a high degree of flexibility of the domains in free fVIIa. It is also shown that the epidermal growth factor-like domains are stable at elevated temperatures and high GuHCl concentrations. Moreover, already at physiological temperature, subtle structural changes take place which influence the overall shape of fVIIa and are detrimental to its enzymatic activity.
 ...
PMID:Conformational stability of factor VIIa: biophysical studies of thermal and guanidine hydrochloride-induced denaturation. 958 32

The importance of activated factor VII (FVIIa) in coagulation initiated by tissue factor (TF) was illustrated by competition of active site-inhibited FVIIa (FFR-FVIIa; FVIIa treated with D-Phe-Phe-Arg-chloromethyl ketone) with FVIIa in various cell-based assays mimicking TF-initiated coagulation. FFR-FVIIa inhibited the overall initiation process as measured by platelet activation and large-scale thrombin generation on the activated platelet surface. When the individual steps in the initiation process were separated, FFR-FVIIa affected only the reactions taking place on TF-bearing cells, demonstrating that FVIIa takes part only in the very first step in the initiation process. The dissociation constant (Kd) for FVIIa binding to TF and the inhibition constant (Ki) for FFR-FVIIa competing with FVIIa in binding to TF, measured in a factor X activation assay, were both around 10 pmol/l, showing that FVIIa and FFR-FVIIa bound to TF in the extrinsic pathway tenase complex with the same affinity.
 ...
PMID:The effects of activated factor VII in a cell-based model for tissue factor-initiated coagulation. 981 25

We have examined the mechanism whereby C-type natriuretic peptide (CNP), an agonist acting through the second messenger cGMP, enhances NaCl secretion in the rectal gland of Squalus acanthias. Single rectal gland tubules (RGT) were dissected manually, perfused in vitro and equivalent short-circuit current [Isc=transepithelial voltage/transepithelial resistance (Rte)] as well as basolateral membrane voltage (Vbl) were measured. CNP was added to luminal and basolateral perfusates at concentrations between 1 and 1000 nmol/l and its effects on the above parameters were compared to those of a "stimulation cocktail" (Stim, containing dibutyryl cAMP, adenosine and forskolin) that maximally enhances cytosolic cAMP, and other agonists and hormones such as guanylin, vasoactive intestinal peptide (VIP), and adenosine. CNP had no effect from the luminal side (n=6). Its effects from the basolateral side consisted of a substantial increase in Isc (-31.6+/-7.7 to -316+/-82.2 microA/cm2, n=15). CNP significantly depolarized the luminal membrane from -87. 4+/-1.0 to -82.3+/-2.6 mV (n=12). Vbl was not changed (n=12) but the fractional conductance for K+ was increased (n=3). These effects were qualitatively and even quantitatively comparable to those of other agonists acting via cytosolic cAMP, but were less marked than those caused by Stim (n=64). The effects of VIP and CNP on Isc were not additive (n=5). The cytosolic Ca2+ concentration ([Ca2+]i) was monitored using the fura-2 fluorescence ratio (FFR 340/380 nm) and it was found that CNP, like agonists acting via cAMP, enhances FFR significantly from 1.02+/-0.05 to 1.32+/-0.05 (n=8) with a time constant in the 1-2 min in range. Our data suggest that CNP, acting via the second messenger cGMP, induces a marked increase in Isc in the rectal gland. The concomitant fall in Rte corresponds to increases in the luminal membrane Cl- conductance and in the basolateral membrane K+ conductance. The latter effect is probably due to an increase in [Ca2+]i.
 ...
PMID:The cellular mechanisms of Cl- secretion induced by C-type natriuretic peptide (CNP). Experiments on isolated in vitro perfused rectal gland tubules of Squalus acanthias. 1037 82

The aim of this study was to examine the role of muscle fiber composition in insulin resistance and the effect of a calcium channel antagonist on insulin sensitivity in fructose-induced insulin resistant and hypertensive rats. Six-week-old male Sprague-Dawley rats were fed either normal rat chow (control) or fructose-rich diet (FFR). For the last 2 weeks of a 6-week period of either diet, the rats were treated, by gavage, with gum arabic solution (control or FFR) or a dihydropyridine calcium channel antagonist, benidipine hydrochloride (3 mg/kg/day: FFR + Ca), then the euglycemic hyperinsulinemic glucose clamp technique was performed to evaluate insulin sensitivity. Blood pressure was measured weekly for 6 weeks. At the end of the glucose clamp, the soleus muscle was dissected out for determination of muscle fiber composition by ATPase methods. Blood pressure was elevated at 2 weeks after the start of fructose-rich chow feeding and persisted thereafter throughout the study. Blood pressure at the glucose clamp in the FFR was significantly higher than that in the control group (142 +/- 2 v 155 +/- 2 mm Hg, P < .01) and the calcium antagonist significantly lowered blood pressure of FFR (136 +/- 6 mm Hg for FFR +/- Ca, P < .05). The average rate of glucose infusion during glucose clamp, as a measure of insulin sensitivity (M value), was significantly lower in the FFR than in the control (15.4 +/- 0.4 v 10.9 +/- 0.6 mg/kg/min, P < .01). The calcium channel antagonist partially improved the M value compared to that of FFR (13.4 +/- 0.7 mg/kg/min in FFR +/- Ca, P < .01 compared to FFR, P < .05 compared to control). The composite ratio of type I fiber in soleus muscle was significantly decreased in FFR compared to control (81.7 +/- 1.5% v 75.0 +/- 1.7%, P < .01), and the composite ratio of type I fiber in rats treated with the calcium channel antagonist (FFR +/- Ca) recovered to the control level (79.9 +/- 1.1%, P < .05 compared to FFR). The M value was significantly correlated with the compositions of type I and type II fibers (for type I fibers, r = 0.80, P < .01; for type II fibers, r = -0.81, P < .01). These results suggest that fiber composition of skeletal muscle links insulin resistance and that a calcium channel antagonist may modulate muscle fiber composition in hypertensive animal model, fructose-fed rats.
 ...
PMID:Alteration of muscle fiber composition linking to insulin resistance and hypertension in fructose-fed rats. 1037 69


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>