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Acioly, Marcus André, Marina Liebsch, Carlos Henrique Carvalho, Alireza Gharabaghi, and Marcos Tatagiba. "Transcranial Electrocortical Stimulation to Monitor the Facial Nerve Motor Function During Cerebellopontine Angle Surgery." Operative Neurosurgery 66, suppl_2 (June 1, 2010): ons354—ons362. http://dx.doi.org/10.1227/01.neu.0000369654.41677.b7.
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Abstract OBJECTIVE This study was conducted to investigate the success rate of using the facial motor evoked potential (FMEP) of orbicularis oculi and oris muscles for facial nerve function monitoring with use of a stepwise protocol, and its usefulness in predicting facial nerve outcome during cerebellopontine angle (CPA) surgeries. METHODS FMEPs were recorded intraoperatively from 60 patients undergoing CPA surgeries. Transcranial electrocortical stimulation (TES) was performed using corkscrew electrodes positioned at hemispheric montage (C3/C4 and CZ). The contralateral abductor pollicis brevis muscle was used as the control response. Stimulation was always applied contralaterally to the affected side using 1, 3, or 5 rectangular pulses ranging from 200 to 600 V with 50 μs of pulse duration and an interstimulus interval of 2 ms. Facial potentials were recorded from needles placed in the orbicularis oculi and oris muscles. RESULTS FMEP from the orbicularis oris and oculi muscles could be reliably monitored in 86.7% and 85% of the patients, respectively. The immediate postoperative facial function correlated significantly with the FMEP ratio in the orbicularis oculi muscle at 80% amplitude ratio (P = .037) and orbicularis oris muscle at 35% ratio (P = .000). FMEP loss was always related to postoperative facial paresis, although in different degrees. CONCLUSION FMEPs can be obtained reliably by using TES with 3 to 5 train pulses. Stable intraoperative FMEPs can predict a good postoperative outcome of facial function. However, further refinements of this technique are necessary to minimize artifacts and to make this method more reliable.
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Hardian, Ridzky Firmansyah, Tetsuya Goto, Yu Fujii, Kohei Kanaya, Tetsuyoshi Horiuchi, and Kazuhiro Hongo. "Intraoperative facial motor evoked potential monitoring for pontine cavernous malformation resection." Journal of Neurosurgery 132, no. 1 (January 2020): 265–71. http://dx.doi.org/10.3171/2018.8.jns181199.
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OBJECTIVEThe aim of this study was to predict postoperative facial nerve function during pontine cavernous malformation surgery by monitoring facial motor evoked potentials (FMEPs).METHODSFrom 2008 to 2017, 10 patients with pontine cavernous malformations underwent total resection via the trans–fourth ventricle floor approach with FMEP monitoring. House-Brackmann grades and Karnofsky Performance Scale (KPS) scores were obtained pre- and postoperatively. The surgeries were performed using one of 2 safe entry zones into the brainstem: the suprafacial triangle and infrafacial triangle approaches. Six patients underwent the suprafacial triangle approach, and 4 patients underwent the infrafacial triangle approach. A cranial peg screw electrode was used to deliver electrical stimulation for FMEP by a train of 4 or 5 pulse anodal constant current stimulation. FMEP was recorded from needle electrodes on the ipsilateral facial muscles and monitored throughout surgery by using a threshold-level stimulation method.RESULTSFMEPs were recorded and analyzed in 8 patients; they were not recorded in 2 patients who had severe preoperative facial palsy and underwent an infrafacial triangle approach. Warning signs appeared in all patients who underwent the suprafacial triangle approach. However, after temporarily stopping the procedures, FMEP findings during surgery showed recovery of the thresholds. FMEPs in patients who underwent the infrafacial triangle approach were stable during the surgery. House-Brackmann grades were unchanged postoperatively in all patients. Postoperative KPS scores improved in 3 patients, decreased in 1, and remained the same in 6 patients.CONCLUSIONSFMEPs can be used to monitor facial nerve function during surgery for pontine cavernous malformations, especially when the suprafacial triangle approach is performed.
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Tawfik, Kareem O., Zoe A. Walters, Gavriel D. Kohlberg, Noga Lipschitz, Joseph T. Breen, Kelly O’Neal, Mario Zuccarello, and Ravi N. Samy. "Impact of Motor-Evoked Potential Monitoring on Facial Nerve Outcomes after Vestibular Schwannoma Resection." Annals of Otology, Rhinology & Laryngology 128, no. 1 (October 20, 2018): 56–61. http://dx.doi.org/10.1177/0003489418803969.
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Objectives: Assess the utility of intraoperative transcranial facial motor-evoked potential (FMEP) monitoring in predicting and improving facial function after vestibular schwannoma (VS) resection. Study Design: Retrospective chart review. Methods: Data were obtained from 82 consecutive VS resections meeting inclusion criteria. Sixty-two cases were performed without FMEP and 20 with FMEP. Degradation of FMEP response was defined as a final-to-baseline amplitude ratio of 0.5 or less. House-Brackmann (HB) grade was assessed preoperatively, postoperatively, at follow-up assessments, and it was compared between pre- and post-FMEP cohorts. Positive predictive value (PPV) and negative predictive value (NPV), sensitivity, and specificity of FMEP degradation in predicting facial weakness were calculated. Results: In the pre-FMEP group, at length of follow-up (LOF) ⩾9 months, 83.9% (52/62) of patients exhibited HB 1-2 outcome. In the post-FMEP cohort, 75.0% (15/20) exhibited HB 1-2 function at LOF ⩾9 months. There was no difference in rates of HB 1-2 outcomes between groups in the immediate postoperative period ( P = .35) or at long-term follow-up ( P = 1.0). With respect to predicting immediate postoperative facial function, FMEP demonstrated high specificity (88.9%) and moderate sensitivity (54.5%). The PPV and NPV for immediate postoperative facial function were 85.7% and 61.5%, respectively. With respect to long-term (⩾9 months LOF) facial function, intraoperative FMEP was moderately sensitive (71.4%) and highly specific (84.6%); PPV was moderate (71.4%), and NPV was high (84.6%). Conclusions: Intraoperative FMEP is highly specific and moderately sensitive in predicting postoperative facial function for patients undergoing VS resection, but its use may not be associated with improved facial nerve outcomes. Level of Evidence: 4
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Matsuoka, Ryuta, Yasuhiro Takeshima, Hironobu Hayashi, Tsunenori Takatani, Fumihiko Nishimura, Ichiro Nakagawa, Yasushi Motoyama, Young-Su Park, Masahiko Kawaguchi, and Hiroyuki Nakase. "Feasibility of adjunct facial motor evoked potential monitoring to reduce the number of false-positive results during cervical spine surgery." Journal of Neurosurgery: Spine 32, no. 4 (April 2020): 570–77. http://dx.doi.org/10.3171/2019.9.spine19800.
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OBJECTIVEFalse-positive intraoperative muscle motor evoked potential (mMEP) monitoring results due to systemic effects of anesthetics and physiological changes continue to be a challenging issue. Although control MEPs recorded from the unaffected side are useful for identifying a true-positive signal, there are no muscles on the upper or lower extremities to induce control MEPs in cervical spine surgery. Therefore, this study was conducted to clarify if additional MEPs derived from facial muscles can feasibly serve as controls to reduce false-positive mMEP monitoring results in cervical spine surgery.METHODSPatients who underwent cervical spine surgery at the authors’ institution who did not experience postoperative neurological deterioration were retrospectively studied. mMEPs were induced with transcranial supramaximal stimulation. Facial MEPs (fMEPs) were subsequently induced with suprathreshold stimulation. The mMEP and subsequently recorded fMEP waveforms were paired during each moment during surgery. The initial pair was regarded as the baseline. A significant decline in mMEP and fMEP amplitude was defined as > 80% and > 50% decline compared with baseline, respectively. All mMEP alarms were considered false positives. Based on 2 different alarm criteria, either mMEP alone or both mMEP and fMEP, rates of false-positive mMEP monitoring results were calculated.RESULTSTwenty-three patients were included in this study, corresponding to 102 pairs of mMEPs and fMEPs. This included 23 initial and 79 subsequent pairs. Based on the alarm criterion of mMEP alone, 17 false-positive results (21.5%) were observed. Based on the alarm criterion of both mMEP and fMEP, 5 false-positive results (6.3%) were observed, which was significantly different compared to mMEP alone (difference 15.2%; 95% CI 7.2%–23.1%; p < 0.01).CONCLUSIONSfMEPs might be used as controls to reduce false-positive mMEP monitoring results in cervical spine surgery.
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An, Sung Chan, Sang Don Lee, Jung Ho Son, and Yong Joo Cho. "Friction Power Loss Reduction for a Marine Diesel Engine Piston." Journal of the Korean Society of Tribologists and Lubrication Engineers 32, no. 4 (August 31, 2016): 132–39. http://dx.doi.org/10.9725/kstle.2016.32.4.132.
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Lodi, Faisal, Ali Zare, Priyanka Arora, Svetlana Stevanovic, Mohammad Jafari, Zoran Ristovski, Richard J. Brown, and Timothy Bodisco. "Engine Performance and Emissions Analysis in a Cold, Intermediate and Hot Start Diesel Engine." Applied Sciences 10, no. 11 (May 31, 2020): 3839. http://dx.doi.org/10.3390/app10113839.
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Presented in this paper is an in-depth analysis of the impact of engine start during various stages of engine warm up (cold, intermediate, and hot start stages) on the performance and emissions of a heavy-duty diesel engine. The experiments were performed at constant engine speeds of 1500 and 2000 rpm on a custom designed drive cycle. The intermediate start stage was found to be longer than the cold start stage. The oil warm up lagged the coolant warm up by approximately 10 °C. During the cold start stage, as the coolant temperature increased from ~25 to 60 °C, the brake specific fuel consumption (BSFC) decreased by approximately 2% to 10%. In the intermediate start stage, as the coolant temperature reached 70 °C and the injection retarded, the indicated mean effective pressure (IMEP) and the brake mean effective pressure (BMEP) decreased by approximately 2% to 3%, while the friction mean effective pressure (FMEP) decreased by approximately 60%. In this stage, the NOx emissions decreased by approximately 25% to 45%, while the HC emissions increased by approximately 12% to 18%. The normalised FMEP showed that higher energy losses at lower loads were most likely contributing to the heating of the lubricating oil.
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Quillen, Kris, Rudolf H. Stanglmaier, Luke Moughon, Rosalind Takata, Victor Wong, Ed Reinbold, and Rick Donahue. "Friction Reduction by Piston Ring Pack Modifications of a Lean-Burn Four-Stroke Natural Gas Engine: Experimental Results." Journal of Engineering for Gas Turbines and Power 129, no. 4 (January 11, 2007): 1088–94. http://dx.doi.org/10.1115/1.2719262.
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A project to reduce frictional losses from natural gas engines is currently being carried out by a collaborative team from Waukesha Engine Dresser, Massachusetts Institute of Technology (MIT), and Colorado State University (CSU). This project is part of the Advanced Reciprocating Engine System (ARES) program led by the U.S. Department of Energy. Previous papers have discussed the computational tools used to evaluate piston-ring/cylinder friction and described the effects of changing various ring pack parameters on engine friction. These computational tools were used to optimize the ring pack of a Waukesha VGF 18-liter engine, and this paper presents the experimental results obtained on the engine test bed. Measured reductions in friction mean effective pressure (FMEP) were observed with a low tension oil control ring (LTOCR) and a skewed barrel top ring (SBTR). A negative twist second ring (NTSR) was used to counteract the oil consumption increase due to the LTOCR. The LTOCR and SBTR each resulted in a ∼0.50% improvement in mechanical efficiency (ηmech).
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Meng, Zhen, Linfeng Zhang, and Tian Tian. "Study of Break-In Process and its Effects on Piston Skirt Lubrication in Internal Combustion Engines." Lubricants 7, no. 11 (November 2, 2019): 98. http://dx.doi.org/10.3390/lubricants7110098.
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The piston skirt is one of the main contributors to the total mechanical loss in internal combustion engines. Usually, the skirt friction experiences a rapid change during the break-in period largely due to the wear of the machine marks or roughness against soft coatings. It is thus important to consider the effect of the change of the roughness for a realistic prediction of the piston skirt friction and system optimization. In this work, an existing model of piston skirt lubrication was improved with the consideration of a breaking in process for the most commonly used triangle machine marks. A new set of flow factors in the averaged Reynolds equation were analytically derived for the trapezoid shape formed after wear of the original triangle shape. A new asperity contact model was developed for the trapezoid shape. The calculation results reflect the trend of friction mean effective pressure (FMEP) during break-in in an engine test and showed quantitative agreement under the same amount of wear.
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Abdul Jalal, Rifqi Irzuan, M. A. Mohd Yusoff, H. M. Abid Hasan, and M. N. Yahya. "Simulation of bypass electric water pump to reduce the engine warm-up time." Journal of Mechanical Engineering and Sciences 15, no. 3 (September 19, 2021): 8241–52. http://dx.doi.org/10.15282/jmes.15.3.2021.03.0647.
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There are several strategies have been developed in the automotive cooling system to improve engine thermal management. Basically, these designs use controllable actuators and mechatronic components such as electric water pump, controllable thermostat, and controllable electric fan to improve engine temperature control on most operating ranges. Most of the strategies are complicated and costly. This paper introduced a different approach to improve coolant temperature warm-up during cold start. The new strategy was by promoting a higher coolant flow rate inside the engine block by just installing an electric water pump in the bypass hose. The new approach’s cold start performance was studied using GT-SUITE on a transient model, complete with finite-element of engine block design, lubrication system, components friction model, engine with combustion model and vehicle system. The proposed strategy clearly showed faster coolant temperature increase (18 seconds faster compared to the conventional cooling system). The strategy not only increase the coolant temperature faster, but also increases the oil temperature faster, lower Friction Mean Effective Pressure (FMEP), and lower fuel consumption at certain condition during the warm-up period.
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Park, Jae Sung, Seunghoon Lee, Sang-Ku Park, Jeong-A. Lee, and Kwan Park. "Facial motor evoked potential with paired transcranial magnetic stimulation: prognostic value following microvascular decompression for hemifacial spasm." Journal of Neurosurgery 131, no. 6 (December 2019): 1780–87. http://dx.doi.org/10.3171/2018.8.jns18708.
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OBJECTIVEMicrovascular decompression (MVD) is widely considered the treatment of choice for hemifacial spasm (HFS), but not all patients immediately benefit from it. Numerous electrophysiological tests have been employed to monitor the integrity of the facial nerve prior to, during, and after MVD treatment. The authors sought to verify if facial motor evoked potential (FMEP) with paired transcranial magnetic stimulation (pTMS) can be utilized as a tool to predict prognosis following MVD for HFS.METHODSFMEP using pTMS was performed preoperatively and postoperatively for 527 HFS patients who underwent an MVD treatment. Various interstimuli intervals (ISIs), which included 2, 10, 20, 25, 30, 75, and 100 msec, were applied for each paired stimulation and pTMS(%) was obtained. A graph of pTMS(%) versus each ISI was drawn for every patient and its pattern was analyzed in accordance with patients’ clinical outcomes.RESULTSWith ISIs of 75 and 100 msec, pTMS(%) was physiologically further inhibited, whereas it was relatively facilitated under ISIs of 20, 25, and 30 msec; loss of this specific pattern, that is, further inhibition-relative facilitation, indicated impaired integrity of the facial nerve. Those patients who immediately benefited from an MVD and experienced no relapse tended to show proper restoration of this further inhibition-relative facilitation pattern (p = 0.01). Greater resemblance between the physiological pattern of pTMS(%) and postoperative pTMS(%) was correlated to better outcome (p = 0.019).CONCLUSIONSA simple linear graph of pTMS(%) versus each ISI may be a helpful tool to predict prognosis for HFS following an MVD.
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Chang, Stephano, Serge Makarenko, Ivan Despot, Charles Dong, Brian D. Westerberg, and Ryojo Akagami. "Differential Recovery in Early- and Late-Onset Delayed Facial Palsy Following Vestibular Schwannoma Resection." Operative Neurosurgery 18, no. 1 (May 7, 2019): 34–40. http://dx.doi.org/10.1093/ons/opz083.
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AbstractBACKGROUNDDelayed facial palsy (DFP) after resection of vestibular schwannomas (VS) is worsening of facial nerve function after an initially normal postoperative result.OBJECTIVETo characterize different types of DFP, compare recovery rates, and review of series of outcomes in patients following resection of VS.METHODSBetween 2001 and 2017, 434 patients (51% female) with VS underwent resection. We categorized the patients who developed facial palsy into groups based on timing of onset after surgery, immediate facial palsy (IFP), early-onset DFP (within 48 h), and late-onset DFP (after 48 h). Introduction of facial nerve motor-evoked potentials (fMEP) in 2002 and a change of practice utilizing perioperative minocycline in 2005 allowed for historical analysis of these interventions.RESULTSMean age of study cohort was 49.1 yr (range 13-81 yr), with 19.8% developing facial palsy. The late-onset DFP group demonstrated a significantly faster recovery than the early-onset DFP group (2.8 ± 0.5 vs 47 ± 8 wk, P < .0001), had prolonged latency to palsy onset after initiating perioperative minocycline (7.3 vs 12.5 d, P = .001), and had a nonsignificant trend towards faster recovery from facial palsy with use of minocycline (2.6 vs 3.4 wk, P = .11).CONCLUSIONGiven the timings, it is likely axonal degeneration is responsible for early-onset DFP, while demyelination and remyelination lead to faster facial nerve recovery in late-onset DFP. Reported anti-apoptotic properties of minocycline could account for the further delay in onset of DFP, and possibly reduce the rate and duration of DFP in the surgical cohort.
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Chen, Ling-Yu, Astrid Doerner, Paul F. Lehmann, Shuang Huang, Guangming Zhong, and Zhixing K. Pan. "A Novel Protein Kinase C (PKCϵ) Is Required for fMet-Leu-Phe-induced Activation of NF-κB in Human Peripheral Blood Monocytes." Journal of Biological Chemistry 280, no. 23 (April 4, 2005): 22497–501. http://dx.doi.org/10.1074/jbc.m413033200.
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We have reported that the chemoattractant, fMet-Leu-Phe (fMLP), induces the activation of NF-κB in human peripheral blood monocytes and that this requires the activity of small GTPase, RhoA (Huang, S., Chen, L.-Y., Zuraw, B. L., Ye, R. D., and Pan, Z. K. (2001) J. Biol. Chem. 276, 40977-40981). Here we showed that the novel protein kinase C isozyme, PKCϵ, associates functionally with RhoA in fMLP-stimulated monocytes and that PKCϵ acted as a signaling component downstream of the GTPase RhoA during fMLP-induced activation of NF-κB. Stimulation of monocytes with fMLP resulted in activation of both PKCϵ and NF-κB. This latter activation was largely blocked by specific inhibitors of PKCϵ by transient expression of a dominant-negative form of PKCϵ and by PKCϵ-specific short interfering RNA. These findings demonstrate, for the first time, that fMLP-induced activation of NF-κB utilizes a signaling pathway, which requires activity of PKCϵ, and that PKCϵ acts as a signaling component downstream of RhoA in cytokine gene transcription stimulated by a chemoattractant. The specificity of this response suggests an important role for the Rho GTPase-PKCϵ-NF-κB pathway in host defense and represents a novel and potentially important mechanism through which fMLP not only attracts leukocytes but may also contribute directly to inflammation.
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Chetty, Sylvie, Masoud Karami, and Oscar Martín Martín. "Opportunity Discovery and Creation as a Duality: Evidence from Small Firms’ Foreign Market Entries." Journal of International Marketing 26, no. 3 (September 2018): 70–93. http://dx.doi.org/10.1509/jim.17.0005.
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Little research addresses the likely enabling character of the discovery and creation of opportunities during the internationalization of small firms or how international opportunities are found and constructed during the process of foreign market entry (FME). This article therefore studies how opportunities become connected during small firms’ FME. By incorporating the concept of duality, this article conceives of the discovery and creation of opportunity as mutually enabling rather than opposed. From this duality perspective, opportunity discovery and creation facilitate each other during internationalization processes. This case study involves five high-tech Australian firms and 30 FMEs. The findings show that knowledge, networks, and capabilities enable opportunities in the FME context. International opportunities are connected and nested in different levels of generality and specificity. The FME opportunities may be based on opportunity embeddedness, because each opportunity has implications for other opportunities. The findings lead to a model and propositions to explain the relationships between opportunity discovery and creation in FME.
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Thibault, Nathalie, Danielle Harbour, Pierre Borgeat, Paul H. Naccache, and Sylvain G. Bourgoin. "Adenosine receptor occupancy suppresses chemoattractant-induced phospholipase D activity by diminishing membrane recruitment of small GTPases." Blood 95, no. 2 (January 15, 2000): 519–27. http://dx.doi.org/10.1182/blood.v95.2.519.
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Adenosine (Ado) is an important autocrine modulator of neutrophil functions. In this study, we determined the effects of endogenous Ado on fMet-Leu-Phe (fMLP)–induced phospholipase D (PLD) activity in neutrophils. The removal of extracellular Ado by Ado deaminase (ADA) or the blockade of its action by the A2a receptor antagonists 8-(3-chlorostyryl) caffeine (CSC) or CGS15943 markedly increased fMLP-induced PLD activation. The concentration-dependent stimulatory effects of CSC and CGS15943 were abolished by a pretreatment of neutrophil suspensionswith ADA. In contrast, the selective A2a receptor agonist CGS21680 suppressed fMLP-induced PLD activation. Furthermore, inhibition by CGS21680 of fMLP-induced PLD activity was reversed by CSC or CGS15943. The removal of Ado by ADA or the blockade of its action by CSC or CGS15943, markedly increased the membrane recruitment of cytosolic protein kinase C (PKC), RhoA, and ADP-ribosylation factor (ARF) in response to fMLP. As shown for PLD activity, the stimulatory effect of Ado receptor antagonists on PLD cofactors translocation was abolished by a pretreatment of the cells with ADA. Moreover, the membrane translocation of both PKC, RhoA, and ARF in response to fMLP was attenuated by CGS21680 and this effect of the A2a receptor agonist was antagonized by CSC or CGS15943. These data demonstrate that Ado released by neutrophils in the extracellular milieu inhibits PLD activation by blocking membrane association of ARF, RhoA, and PKC through Ado A2a receptor occupancy.
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Haines, K. A., K. N. Giedd, A. M. Rich, H. M. Korchak, and G. Weissmann. "The leukotriene B4 paradox: neutrophils can, but will not, respond to ligand-receptor interactions by forming leukotriene B4 or its ω-metabolites." Biochemical Journal 241, no. 1 (January 1, 1987): 55–62. http://dx.doi.org/10.1042/bj2410055.
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Leukotriene B4 (5S,12R-dihydroxy-6,14-cis,8,10-trans-eicosatetraenoic acid, LTB4) is released from neutrophils exposed to calcium ionophores. To determine whether LTB4 might be produced by ligand-receptor interactions at the plasmalemma, we treated human neutrophils with serum-treated zymosan (STZ), heat-aggregated IgG and fMet-Leu-Phe (fMLP), agonists at the C3b, Fc and fMLP receptors respectively. STZ (10 mg/ml) provoked the formation of barely detectable amounts of LTB4 (0.74 ng/10(7) cells); no omega-oxidized metabolites of LTB4 were found. Adding 10 microM-arachidonate did not significantly increase production of LTB4 or its metabolites. Addition of 50 microM-arachidonate (an amount which activates protein kinase C) before STZ caused a 40-fold increase in the quantity of LTB4 and its omega-oxidation products. Neither phorbol myristate acetate (PMA, 200 ng/ml) nor linoleic acid (50 microM), also activators of protein kinase C, augmented generation of LTB4 by cells stimulated with STZ. Neither fMLP (10(-6) M) nor aggregated IgG (0.3 mg/ml) induced LTB4 formation (less than 0.01 ng/10(7) cells). Moreover, cells exposed to STZ, fMLP, or IgG did not form all-trans-LTB4 or 5-hydroxyeicosatetraenoic acid; their failure to make LTB4 was therefore due to inactivity of neutrophil 5-lipoxygenase. However, adding 50 microM-arachidonate to neutrophil suspensions before fMLP or IgG triggered LTB4 production, the majority of which was metabolized to its omega-oxidized products (fMLP, 20.2 ng/10(7) cells; IgG, 17.1 ng/10(7) cells). The data show that neutrophils exposed to agonists at defined cell-surface receptors produce significant quantities of LTB4 only when treated with non-physiological concentrations of arachidonate.
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BOUTI, ABDELKADER, and DAOUD AIT KADI. "A STATE-OF-THE-ART REVIEW OF FMEA/FMECA." International Journal of Reliability, Quality and Safety Engineering 01, no. 04 (December 1994): 515–43. http://dx.doi.org/10.1142/s0218539394000362.
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The Failure Mode and Effects Analysis (FMEA) documents single failures of a system, by identifying the failure modes, and the causes and effects of each potential failure mode on system service and defining appropriate detection procedures and corrective actions. When extended by Criticality Analysis procedure (CA) for failure modes classification, it is known as Failure Mode Effects and Criticality Analysis (FMECA). The present paper presents a literature review of FME(C)A, covering the following aspects: description and review of the basic principles of FME(C)A, types, enhancement of the method, automation and available computer codes, combination with other techniques and specific applications. We conclude with a discussion of various issues raised as a result of the review.
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Geijsen, Niels, Sanne van Delft, Jan A. M. Raaijmakers, Jan-Willem J. Lammers, John G. Collard, Leo Koenderman, and Paul J. Coffer. "Regulation of p21rac Activation in Human Neutrophils." Blood 94, no. 3 (August 1, 1999): 1121–30. http://dx.doi.org/10.1182/blood.v94.3.1121.415k04_1121_1130.
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The small guanosine triphosphate (GTPase) p21rac is highly expressed in human neutrophils where it is thought to play a role in cytoskeletal reorganization and superoxide production. Using the p21rac binding domain of PAK (PAK-RBD) as an activation-specific probe, we have investigated agonist-stimulated activation of p21rac. Stimulation of neutrophils with the chemoattractants fMet-Leu-Phe (fMLP) or platelet-activating factor (PAF) induced an extremely rapid and transient p21rac activation, being optimal within 5 seconds. This activation correlates with the rapid changes of intracellular free Ca2+ ([Ca2+]i) stimulated by fMLP; however, changes in [Ca2+]i were neither sufficient nor required for p21rac activation. Furthermore, fMLP-induced p21rac activation was not inhibited by broad tyrosine kinase inhibitors or specific inhibitors of ERK, p38 mitogen activated protein kinase, Src, or phosphatidylinositol 3-kinases. Surprisingly, the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor- did not cause p21rac activation or modulate fMLP-induced p21rac activation. AlF−, a potent activator of heterotrimeric G-protein -subunits, however, was found to activate p21rac. Stimulation of neutrophils with phorbol myristate acetate (PMA) strongly activated the respiratory burst, but did not induce p21rac activation, suggesting that superoxide production per se can occur independently of p21rac activation. These data suggest that in human granulocytes, G-protein coupled receptors, but not cytokine receptors, activate p21rac via a rapid, novel exchange-mechanism independently of changes in [Ca2+]i, tyrosine phosphorylation, or PI3K.
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Lang, J., F. Boulay, P. Parker, P. Gierschik, and C. B. Wollheim. "Regulation of cytosolic calcium and insulin secretion by galanin and ATP receptors: interactions of pertussis-toxin-sensitive and -insensitive signalling pathways." Biochemical Journal 303, no. 3 (November 1, 1994): 885–91. http://dx.doi.org/10.1042/bj3030885.
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In a previous study it was found that the expression of the exogenous fMet-Leu-Phe-receptor (NFPR) in the insulin-secreting cell line RINm5F mediates inhibition of hormone release and additionally raises cytosolic calcium concentration ([Ca2+]i) by activating phospholipase C (PLC) in a pertussis-toxin (PTX)-sensitive manner. We investigated whether an endogenous receptor could elicit similar effects and examined the interaction with PTX-insensitive signalling pathways. The hormone galanin inhibited insulin release at subnanomolar concentrations and increased [Ca2+]i, mainly by a PTX-sensitive mechanism with an EC50 (50 nM) comparable with that for hyperpolarization of membrane potential. The effect of galanin or fMet-Leu-Phe on [Ca2+]i was inhibited by pre-activation of the P2-receptor by ATP, which mobilizes calcium in a PTX-insensitive fashion. Simultaneous activation of the P2- and peptide receptors caused additive increases in [Ca2+]i saturating at a calcium concentration corresponding to the optimal ATP response. This suggests a specific convergence of PTX-sensitive and -insensitive pathways. In contrast, galanin and FMLP inhibited the insulin secretion induced by ATP (1-100 microM), but only when added prior to the nucleotide. In permeabilized cells, FMLP added after the calcium stimulus still inhibited secretion, indicating that the inefficacy observed in intact cells was not due to the rapid ATP-evoked rise in [Ca2+]i. Thus, (i) insulin-secreting cells possess an endogenous PTX-sensitive pathway mobilizing [Ca2+]i, (ii) inhibitory hormones preferentially activate different effectors depending on the agonist concentration and (iii) activation of NFPR or galanin receptor reveals an unusual dissociation between [Ca2+]i rises and insulin secretion, pointing towards an overriding inhibitory control of exocytosis.
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Merritt, J. E., K. E. Moores, A. T. Evans, P. Sharma, F. J. Evans, and C. H. MacPhee. "Involvement of calcium in modulation of neutrophil function by phorbol esters that activate protein kinase C isotypes and related enzymes." Biochemical Journal 289, no. 3 (February 1, 1993): 919–26. http://dx.doi.org/10.1042/bj2890919.
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In this study, the effects of a series of phorbol esters with different spectra of biological activities and different patterns of activation of the isoenzymes of protein kinase C (PKC) have been studied in human neutrophils. The aim was to gain more information on which isoenzymes of PKC are involved in neutrophil activation, specifically inhibition of fMet-Leu-Phe (fMLP)-stimulated bivalent cation influx and stimulation of O2-. release (either alone or potentiation of the response to fMLP). Prior addition of both phorbol 12-myristate 13-acetate (PMA) and sapintoxin A (SAPA) inhibited fMLP-stimulated Mn2+ influx. Higher concentrations of resiniferatoxin (RX) were also inhibitory, inhibition being more apparent at longer preincubation times. However, 12-deoxyphorbol 13-O-phenylacetate (DOPPA) showed only a slight inhibitory effect and required a prolonged preincubation. PMA, SAPA and RX, but not DOPPA, stimulated O2-. release by themselves. Lower concentrations of PMA, SAPA and RX, which were ineffective alone, considerably potentiated O2-. release stimulated by fMLP, whereas DOPPA had little or no effect. These results rule out a major role for PKC-delta (not activated by SAPA) and PKC-beta 1 (activated by DOPPA), but suggest the involvement of RX kinase in addition to PKC in the inhibition of fMLP-stimulated Mn2+ influx and potentiation of fMLP-stimulated O2-. release. However, when the cytosolic free Ca2+ concentration ([Ca2+]i) was elevated with the Ca2+ ionophore ionomycin, DOPPA was able to stimulate O2-. release, which probably reflects the known Ca2+ requirement for activation of PKC-beta 1 by DOPPA in vitro. The effects of the other phorbols were also enhanced when [Ca2+]i was elevated; all of the phorbols synergize, to variable extents, with Ca2+ to activate PKC in vitro. Enhancement of RX-stimulated O2- release by elevation of [Ca2+]i was unexpected, since RX kinase has been reported to be inhibited by high concentrations of Ca2+ in vitro. Finally, use of fura-2 and SK&F 96365 to manipulate the fMLP-stimulated rise in [Ca2+]i showed that when fMLP was able to evoke its normal rise in [Ca2+]i (to a peak of 700-900 nM), O2-. release was potentiated by PMA, SAPA and RX. However, when fMLP was only able to evoke a small increase in [Ca2+]i (to a peak of 400 nM), potentiation by PMA was unaffected but potentiation by SAPA and RX was considerably reduced. This observation agrees with published data demonstrating that activation of PKC in vitro by SAPA is more Ca(2+)-dependent than activation by PMA.(ABSTRACT TRUNCATED AT 400 WORDS)
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Naccache, PH, AC Caon, C. Gilbert, G. Chouinard, and SR McColl. "Pertussis toxin selectively interferes with the responses of the HL-60 human promyelocytic cell line to dimethylsulfoxide." Blood 78, no. 10 (November 15, 1991): 2534–41. http://dx.doi.org/10.1182/blood.v78.10.2534.2534.
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Abstract The effects of pertussis toxin (PT) on the growth and dimethylsulfoxide (Me2SO4)-induced differentiation of the HL-60 human promyelocytic leukemia cell line were tested. Cell growth was quantified by direct cell counts. Cell differentiation was estimated by measuring the expression of myeloid-specific cell-surface antigens (Mo-1 and fMet-Leu- Phe [fMLP] receptors), the ability of the cells to produce superoxide anions on stimulation with fMLP, the calcium ionophore A23187 and phorbol 12-myristate 13-acetate (PMA), and by monitoring the level of expression of messenger RNA (mRNA) for tumor necrosis factor alpha (TNF alpha). By itself, PT did not affect the proliferation of HL-60 cells in serum-containing medium. In contrast, PT (but not its B-oligomer) dose-dependently inhibited the Me2SO4-induced expression of Mo-1, fMLP receptors, and the oxidative responses to the chemotactic factor and to A23187, but not to PMA. The addition of Me2SO4 induced a significant increase in the steady-state levels of TNF alpha mRNA, and this effect was strongly inhibited by PT. Finally, the bacterial toxin did not reverse the block of cell division that follows the addition of Me2SO4. These results provide evidence for the involvement of a PT substrate (presumably a guanine nucleotide-binding protein) in the regulation of the maturation of the excitation-response coupling sequence in human myeloid cell precursors and show that the regulation of cell division and maturation of HL-60 cells are under distinct sets of control mechanisms.
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Naccache, PH, AC Caon, C. Gilbert, G. Chouinard, and SR McColl. "Pertussis toxin selectively interferes with the responses of the HL-60 human promyelocytic cell line to dimethylsulfoxide." Blood 78, no. 10 (November 15, 1991): 2534–41. http://dx.doi.org/10.1182/blood.v78.10.2534.bloodjournal78102534.
Full textAbstract:
The effects of pertussis toxin (PT) on the growth and dimethylsulfoxide (Me2SO4)-induced differentiation of the HL-60 human promyelocytic leukemia cell line were tested. Cell growth was quantified by direct cell counts. Cell differentiation was estimated by measuring the expression of myeloid-specific cell-surface antigens (Mo-1 and fMet-Leu- Phe [fMLP] receptors), the ability of the cells to produce superoxide anions on stimulation with fMLP, the calcium ionophore A23187 and phorbol 12-myristate 13-acetate (PMA), and by monitoring the level of expression of messenger RNA (mRNA) for tumor necrosis factor alpha (TNF alpha). By itself, PT did not affect the proliferation of HL-60 cells in serum-containing medium. In contrast, PT (but not its B-oligomer) dose-dependently inhibited the Me2SO4-induced expression of Mo-1, fMLP receptors, and the oxidative responses to the chemotactic factor and to A23187, but not to PMA. The addition of Me2SO4 induced a significant increase in the steady-state levels of TNF alpha mRNA, and this effect was strongly inhibited by PT. Finally, the bacterial toxin did not reverse the block of cell division that follows the addition of Me2SO4. These results provide evidence for the involvement of a PT substrate (presumably a guanine nucleotide-binding protein) in the regulation of the maturation of the excitation-response coupling sequence in human myeloid cell precursors and show that the regulation of cell division and maturation of HL-60 cells are under distinct sets of control mechanisms.
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Huang, RiYun, Jian P. Lian, Dwight Robinson, and John A. Badwey. "Neutrophils Stimulated with a Variety of Chemoattractants Exhibit Rapid Activation of p21-Activated Kinases (Paks): Separate Signals Are Required for Activation and Inactivation of Paks." Molecular and Cellular Biology 18, no. 12 (December 1, 1998): 7130–38. http://dx.doi.org/10.1128/mcb.18.12.7130.
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ABSTRACT Activation of the p21-activated protein kinases (Paks) was compared in neutrophils stimulated with a wide variety of agonists that bind to receptors coupled to heterotrimeric G proteins. Neutrophils stimulated with sulfatide, a ligand for the L-selectin receptor, or the chemoattractant fMet-Leu-Phe (fMLP), platelet-activating factor, leukotriene B4, interleukin-8, or the chemokine RANTES exhibited a rapid and transient activation of the 63- and 69-kDa Paks. These kinases exhibited maximal activation with each of these agonists within 15 s followed by significant inactivation at 3 min. In contrast, neutrophils treated with the chemoattractant and anaphylatoxin C5a exhibited a prolonged activation (>15 min) of these Paks even though the receptor for this ligand may activate the same overall population of complex G proteins as the fMLP receptor. Addition of fMLP to neutrophils already stimulated with C5a resulted in the inactivation of the 63- and 69-kDa Paks. Optimal activation of Paks could be observed at concentrations of these agonists that elicited only shape changes and chemotaxis in neutrophils. While all of the agonists listed above triggered quantitatively similar activation of the 63- and 69-kDa Paks, fMLP was far superior to the other stimuli in triggering activation of the c-Jun N-terminal kinase (JNK) and the p38 mitogen-activated protein kinase (MAPK). These data indicate that separate signals are required for activation and inactivation of Paks and that, in contrast to other cell types, activated Pak does not trigger activation of JNK or p38-MAPK in neutrophils. These results are consistent with the recent hypothesis that G-protein-coupled receptors may initiate signals independent of those transmitted by the α and βγ subunits of complex G proteins.
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Magnusson, Karl Eric, Claes Dahlgren, and Anita Sj�Olander. "Effect ofN-formylated methionyl-phenylalanine (FMP) and methionyl-leucyl-phenylalanine (FMLP) on gut permeability." Inflammation 9, no. 4 (December 1985): 365–73. http://dx.doi.org/10.1007/bf00916336.
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M’Rabet, Laura, Paul Coffer, Fried Zwartkruis, Barbara Franke, Anthony W. Segal, Leo Koenderman, and Johannes L. Bos. "Activation of the Small GTPase Rap1 in Human Neutrophils." Blood 92, no. 6 (September 15, 1998): 2133–40. http://dx.doi.org/10.1182/blood.v92.6.2133.
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Abstract The small GTPase Rap1 is highly expressed in human neutrophils, but its function is largely unknown. Using the Rap1-binding domain of RalGDS (RalGDS-RBD) as an activation-specific probe for Rap1, we have investigated the regulation of Rap1 activity in primary human neutrophils. We found that a variety of stimuli involved in neutrophil activation, including fMet-Leu-Phe (fMLP), platelet-activating factor (PAF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IgG-coated particles, induce a rapid and transient Rap1 activation. In addition, we found that Rap1 is normally activated in neutrophils from chronic granulomatous disease patients that lack cytochrome b558 or p47phox and have a defective NADPH oxidase system. From these results we conclude that in neutrophils Rap1 is activated independently of respiratory burst induction. Finally, we found that Rap1 is activated by both the Ca2+ ionophore ionomycin and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), indicating that phospholipase C (PLC) activation leading to elevated levels of intracellular free Ca2+ and diacylglycerol (DAG) can mediate Rap1 activation. However, inhibition of PLC and Ca2+ depletion only marginally affected fMLP-induced Rap1 activation, suggesting that additional pathways may control Rap1 activation. © 1998 by The American Society of Hematology.
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M’Rabet, Laura, Paul Coffer, Fried Zwartkruis, Barbara Franke, Anthony W. Segal, Leo Koenderman, and Johannes L. Bos. "Activation of the Small GTPase Rap1 in Human Neutrophils." Blood 92, no. 6 (September 15, 1998): 2133–40. http://dx.doi.org/10.1182/blood.v92.6.2133.418k19_2133_2140.
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The small GTPase Rap1 is highly expressed in human neutrophils, but its function is largely unknown. Using the Rap1-binding domain of RalGDS (RalGDS-RBD) as an activation-specific probe for Rap1, we have investigated the regulation of Rap1 activity in primary human neutrophils. We found that a variety of stimuli involved in neutrophil activation, including fMet-Leu-Phe (fMLP), platelet-activating factor (PAF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IgG-coated particles, induce a rapid and transient Rap1 activation. In addition, we found that Rap1 is normally activated in neutrophils from chronic granulomatous disease patients that lack cytochrome b558 or p47phox and have a defective NADPH oxidase system. From these results we conclude that in neutrophils Rap1 is activated independently of respiratory burst induction. Finally, we found that Rap1 is activated by both the Ca2+ ionophore ionomycin and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), indicating that phospholipase C (PLC) activation leading to elevated levels of intracellular free Ca2+ and diacylglycerol (DAG) can mediate Rap1 activation. However, inhibition of PLC and Ca2+ depletion only marginally affected fMLP-induced Rap1 activation, suggesting that additional pathways may control Rap1 activation. © 1998 by The American Society of Hematology.
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MARCIL, Josée, Danielle HARBOUR, Martin G. HOULE, Paul H. NACCACHE, and Sylvain BOURGOIN. "Monosodium urate-crystal-stimulated phospholipase D in human neutrophils." Biochemical Journal 337, no. 2 (January 8, 1999): 185–92. http://dx.doi.org/10.1042/bj3370185.
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Protein kinase Cα (PKCα) and small GTPases of the Rho and ADP-ribosylation factor (Arf) family are implicated in the regulation of phospholipase D1 (PLD1) activity. Although they are involved in fMet-Leu-Phe (fMLP)-mediated PLD activation, their role in monosodium urate (MSU)-stimulated PLD1 activity in human neutrophils is not clear. The translocation of PKCα, RhoA and Arf from the cytosol to the membranes was monitored. fMLP induced a cytochalasin B (CB)-dependent recruitment of Arf, RhoA and PKCα to neutrophil membranes. CB also increased the activation of PLD 10-fold. In contrast with fMLP, MSU stimulated a sustained and time-dependent relocalization of Arf and PKCα, but not of RhoA, to the membrane fraction. MSU-stimulated PLD was activated with a time course preceding membrane recruitment of Arf and PKCα in the absence of CB. Furthermore, MSU-induced PLD activation and the membrane recruitment of PKCα, but not that of Arf, were inhibited by CB. An anti-FcγRIIIB antibody, VIFcRIII, prevented the membrane relocalization of Arf and PKCα and the stimulation of the levels of tyrosine phosphorylation and of PLD activity induced by MSU. Erbstatin and ST-638, two inhibitors of tyrosine kinases, inhibited the MSU-induced translocation of Arf and PKCα but not MSU-induced tyrosine phosphorylation and PLD activation. Furthermore MSU crystals did not cause the tyrosine phosphorylation of PLD1. The present study indicates that soluble and particulate agonists show selectivity in inducing the translocation of RhoA in neutrophils and that the ability of MSU to increase PLD activation was independent of the membrane relocalization of Arf and PKCα.
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McKay, D. A., J. R. Kusel, and P. C. Wilkinson. "Studies of chemotactic factor-induced polarity in human neutrophils. Lipid mobility, receptor distribution and the time-sequence of polarization." Journal of Cell Science 100, no. 3 (November 1, 1991): 473–79. http://dx.doi.org/10.1242/jcs.100.3.473.
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Differences in membrane composition between the anterior and posterior poles of human blood neutrophils on exposure to chemoattractant were studied using a laser microscope, and the effects of attractant concentration and time on the ability of neutrophils to polarize were determined. The findings were as follows. (1) The fluorescein-labelled chemotactic hexapeptide fLeu-Norleu-Phe-Norleu-Tyr-Lys was asymmetrically distributed on polarized cells with the highest concentration at the anterior pole of the cell. (2) Differences in membrane lipid behaviour were studied by fluorescence recovery after photobleaching (FRAP) using the probe 5-N-(octadecanoyl)-aminofluorescein. Recovery curves suggested that the proportion of mobile lipid probe at the anterior pole of the cell was higher than at the posterior. However, no difference was found in the rate of recovery between the two poles. (3) Studies of the time-course of polarization were undertaken using neutrophils in suspension exposed to different isotropic concentrations of fMet-Leu-Phe (fMLP). At low concentrations (less than or equal to 10(−9) M), the cells polarized immediately on exposure to the attractant. At a high concentration (10(−7) M) they assumed multipolar morphologies and polarized very poorly, suggesting that ligand binding was too rapid for the cells to form a dominant pole. At the optimal concentration, 10(−8) M fMLP, the cells assumed irregular, ruffled, morphologies after 30s, but showed an increasing proportion of polarized forms over the next 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)
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Rosenbaum, Gitte O. "Female entrepreneurial networks and foreign market entry." Journal of Small Business and Enterprise Development 24, no. 1 (February 20, 2017): 119–35. http://dx.doi.org/10.1108/jsbed-07-2016-0113.
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Purpose The purpose of this paper is to explore the role of networks in the 116 foreign market entries (FMEs) of women-owned small businesses. Design/methodology/approach A multiple case study based on semi-structured interviews with eight female entrepreneurs in the Danish fashion design industry. Findings The results show that contrary to the traditional emphasis placed on the role of networks in the internationalization literature, the focal female entrepreneurs only spartanly used networks to expand into new foreign markets. Indeed, networks were used in only 24 of the 116 FMEs. The respondents largely attributed this reluctance to use networks to work-life balance issues and misgivings about knowledge misappropriation. In contrast, the focal entrepreneurs strongly attested to the decisive role played by information and communication technology (ICT) in allowing firms to enter foreign markets without incurring the costs of network membership or compromising their work-life balance. Research limitations/implications The present study’s findings suggest that ICT has a much stronger role in the FME of firms than previously envisioned. Practical implications The study’s findings also have important implications for policymakers and practitioners charged with promoting the international growth of female entrepreneurial ventures. Originality/value This study is the first of its kind to explore the way in which female entrepreneurs enter new foreign markets.
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Dasgupta, Dalia, Prasanta Chakraborty, and Mukul K. Basu. "fMLP Receptor Stimulated Activation of Macrophage: Its Effect on Killing of Intracellular Leishmania donovani." Bioscience Reports 20, no. 5 (October 1, 2000): 345–54. http://dx.doi.org/10.1023/a:1010325916675.
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The fMLP receptor of peritoneal macrophages stimulated by fMLP graftedliposomes as ligand, was analysed and compared with respective controlsfor its ability to promote killing of intracellular Leishmaniaparasites. fMLP grafted liposomes show greater efficacy in killingintracellular L. donovani (MHOM/IN/1983/AG83) parasites in a timedependent manner than free fMLP. fMLP grafted liposomes also releasemore active oxygen intermediates and reactive nitrogen intermediates(O−2, H2O2, NO) than free fMLP. The key enzymes PKCand PTK for the respiratory burst and nitric oxide generation werefound to be important in this fMLP receptor mediated signaling processas the enzyme specific inhibitors viz. staurosporine, genistein andAG126 suppressed the leishmanicidal effect of fMLP graftedliposomes. The above findings suggest that the fMLP receptorof macrophages activates PKC and PTK mediated signalling thatis responsible for the intracellular parasite killing.
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Kim, Miri, Michel Bellini, and Stephanie Ceman. "Fragile X Mental Retardation Protein FMRP Binds mRNAs in the Nucleus." Molecular and Cellular Biology 29, no. 1 (October 20, 2008): 214–28. http://dx.doi.org/10.1128/mcb.01377-08.
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ABSTRACT The fragile X mental retardation protein FMRP is an RNA binding protein that associates with a large collection of mRNAs. Since FMRP was previously shown to be a nucleocytoplasmic shuttling protein, we examined the hypothesis that FMRP binds its cargo mRNAs in the nucleus. The enhanced green fluorescent protein-tagged FMRP construct (EGFP-FMRP) expressed in Cos-7 cells was efficiently exported from the nucleus in the absence of its nuclear export sequence and in the presence of a strong nuclear localization sequence (the simian virus 40 [SV40] NLS), suggesting an efficient mechanism for nuclear export. We hypothesized that nuclear FMRP exits the nucleus through its bound mRNAs. Using silencing RNAs to the bulk mRNA exporter Tap/NXF1, we observed a significantly increased number of cells containing EGFP-FMRP in the nucleus, which was further augmented by removal of FMRP's nuclear export sequence. Nuclear-retained SV40-FMRP could be released upon treatment with RNase. Further, Tap/NXF1 coimmunoprecipitated with EGFP-FMRP in an RNA-dependent manner and contained the FMR1 mRNA. To determine whether FMRP binds pre-mRNAs cotranscriptionally, we expressed hemagglutinin-SV40 FMRP in amphibian oocytes and found it, as well as endogenous Xenopus FMRP, on the active transcription units of lampbrush chromosomes. Collectively, our data provide the first lines of evidence that FMRP binds mRNA in the nucleus.
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Мирошников, Вячеслав, Vyacheslav Miroshnikov, Олег Горленко, Oleg Gorlenko, Николай Борбаць, and Nikolay Borbats. "QUALITY MANAGEMENT IN DESIGN-TECHNOLOGICAL PREPARATION OF ENGINEERING PRODUCE MANUFACTURING BASED ON COMPLEX FMEA-ANALYSIS." Bulletin of Bryansk state technical university 2016, no. 1 (March 31, 2016): 178–87. http://dx.doi.org/10.12737/18313.
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Under presentday conditions the main constituent in the competitiveness of any enterprise – a capaci-ty for ensuring ever-growing requirements of a con-sumer market and concrete customers to produce quality. One of the ways to solve this not simple problem is the development and introduction of an ever-improving system of quality management (SQM) meeting the highest international requirements. A significant requirement of international standards is the application in SQM a procedure of the FMEA-analysis of kinds and consequences of failures which is used for more than half a century abroad at the creation of complex engineering systems.
To date a considerable urgency gains the introduction of the complex FMEA-methodology including the fulfillment of a product design analysis, the PFMEA-analysis of the product manufacturing method and the MFMEA-analysis of equipment (rigging). The peculiarity of such a complex analysis consists in the hierarchy and consistency of the ful-fillment various kinds of FMEA: FMEA of product – FMEA of an assembly (A) – FMEA of a part. All kinds of FMEA are connected and depend on each other. The FMEA result of product and assembly design is a basis for the FMEA of product and unit assembly. It is evident that the last should be carried out after the introduction of changes in the design of a unit according to the FMEA results of design. The FMEA of equipment should be carried out after the introduction of changes in an engineering procedure according to the FMEA results of a process. Taking into account this, first should be carried out the FMEA of a design and the FMEA of a process and the FMEA of equipment should complete the consistency of tests. The paper reports thoroughly the first two stages of the complex FMEA-analysis.
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Wang, Houping, Jason B. Dictenberg, Li Ku, Wen Li, Gary J. Bassell, and Yue Feng. "Dynamic Association of the Fragile X Mental Retardation Protein as a Messenger Ribonucleoprotein between Microtubules and Polyribosomes." Molecular Biology of the Cell 19, no. 1 (January 2008): 105–14. http://dx.doi.org/10.1091/mbc.e07-06-0583.
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The fragile X mental retardation protein (FMRP) is a selective RNA-binding protein that regulates translation and plays essential roles in synaptic function. FMRP is bound to specific mRNA ligands, actively transported into neuronal processes in a microtubule-dependent manner, and associated with polyribosomes engaged in translation elongation. However, the biochemical relationship between FMRP–microtubule association and FMRP–polyribosome association remains elusive. Here, we report that although the majority of FMRP is incorporated into elongating polyribosomes in the soluble cytoplasm, microtubule-associated FMRP is predominantly retained in translationally dormant, polyribosome-free messenger ribonucleoprotein (mRNP) complexes. Interestingly, FMRP–microtubule association is increased when mRNPs are dynamically released from polyribosomes as a result of inhibiting translation initiation. Furthermore, the I304N mutant FMRP that fails to be incorporated into polyribosomes is associated with microtubules in mRNP particles and transported into neuronal dendrites in a microtubule-dependent, 3,5-dihydroxyphenylglycine-stimulated manner with similar kinetics to that of wild-type FMRP. Hence, polyribosome-free FMRP–mRNP complexes travel on microtubules and wait for activity-dependent translational derepression at the site of function. The dual participation of FMRP in dormant mRNPs and polyribosomes suggests distinct roles of FMRP in dendritic transport and translational regulation, two distinct phases that control local protein production to accommodate synaptic plasticity.
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Zhou, Xuelian, and Yongchuan Tang. "Modeling and Fusing the Uncertainty of FMEA Experts Using an Entropy-Like Measure with an Application in Fault Evaluation of Aircraft Turbine Rotor Blades." Entropy 20, no. 11 (November 9, 2018): 864. http://dx.doi.org/10.3390/e20110864.
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As a typical tool of risk analysis in practical engineering, failure mode and effects analysis (FMEA) theory is a well known method for risk prediction and prevention. However, how to quantify the uncertainty of the subjective assessments from FMEA experts and aggregate the corresponding uncertainty to the classical FMEA approach still needs further study. In this paper, we argue that the subjective assessments of FMEA experts can be adopted to model the weight of each FMEA expert, which can be regarded as a data-driven method for ambiguity information modeling in FMEA method. Based on this new perspective, a modified FMEA approach is proposed, where the subjective uncertainty of FMEA experts is handled in the framework of Dempster–Shafer evidence theory (DST). In the improved FMEA approach, the ambiguity measure (AM) which is an entropy-like uncertainty measure in DST framework is applied to quantify the uncertainty degree of each FMEA expert. Then, the classical risk priority number (RPN) model is improved by aggregating an AM-based weight factor into the RPN function. A case study based on the new RPN model in aircraft turbine rotor blades verifies the applicable and useful of the proposed FMEA approach.
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Didiot, Marie-Cécile, Murugan Subramanian, Eric Flatter, Jean-Louis Mandel, and Hervé Moine. "Cells Lacking the Fragile X Mental Retardation Protein (FMRP) have Normal RISC Activity but Exhibit Altered Stress Granule Assembly." Molecular Biology of the Cell 20, no. 1 (January 2009): 428–37. http://dx.doi.org/10.1091/mbc.e08-07-0737.
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The fragile X mental retardation protein (FMRP) is an RNA-binding protein involved in the mRNA metabolism. The absence of FMRP in neurons leads to alterations of the synaptic plasticity, probably as a result of translation regulation defects. The exact molecular mechanisms by which FMRP plays a role in translation regulation have remained elusive. The finding of an interaction between FMRP and the RNA interference silencing complex (RISC), a master of translation regulation, has suggested that both regulators could be functionally linked. We investigated here this link, and we show that FMRP exhibits little overlap both physically and functionally with the RISC machinery, excluding a direct impact of FMRP on RISC function. Our data indicate that FMRP and RISC are associated to distinct pools of mRNAs. FMRP, unlike RISC machinery, associates with the pool of mRNAs that eventually goes into stress granules upon cellular stress. Furthermore, we show that FMRP plays a positive role in this process as the lack of FMRP or a point mutant causing a severe fragile X alter stress granule formation. Our data support the proposal that FMRP plays a role in controlling the fate of mRNAs after translation arrest.
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Tanaka, H., J. D. Bradley, L. J. Baudendistel, and T. E. Dahms. "Mechanisms of increased pulmonary microvascular permeability induced by FMLP in isolated rabbit lungs." Journal of Applied Physiology 73, no. 5 (November 1, 1992): 2074–82. http://dx.doi.org/10.1152/jappl.1992.73.5.2074.
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We observed that the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L- phenylalanine (FMLP) induced pulmonary edema when polymorphonuclear leukocytes (PMNs) were added to isolated constant-flow buffer-perfused rabbit lungs. This study was designed to test the hypothesis that PMNs activated by FMLP induced lung injury by the modulation of reactive oxygen species (ROS), cyclooxygenase products, or cysteinyl leukotrienes (LTs). Addition of FMLP alone did not increase microvascular permeability (Kf). When PMNs were added to the isolated lung, FMLP caused an 80% increase in Kf. Wet-to-dry weight ratio was also significantly increased with PMNs + FMLP compared with FMLP only. There was a significant positive correlation between total myeloperoxidase activity in lung tissue and Kf values after FMLP (30 min). Pretreatment with two dissimilar cyclooxygenase inhibitors, meclofenamate or ibuprofen, had no effect on the PMN + FMLP-induced increase in Kf. However, the ROS inhibitor catalase and the nonantioxidant LT synthesis blocker MK 886 inhibited the PMN + FMLP increase in Kf. Perfusate levels of LTs (LTC4, -D4, and -E4) were significantly increased from baseline values 30 min after FMLP. Both MK 886 and catalase suppressed the elevation of LTs after PMN + FMLP. These results indicate that FMLP increased a pulmonary microvascular permeability in isolated buffer-perfused rabbit lungs that is PMN dependent and mediated by LT produced possibly by a result of ROS production.
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Carlson, Ryan M., Stephan R. Vavricka, Jyrki J. Eloranta, Mark W. Musch, Donna L. Arvans, Keri A. Kles, Margaret M. Walsh-Reitz, Gerd A. Kullak-Ublick, and Eugene B. Chang. "fMLP induces Hsp27 expression, attenuates NF-κB activation, and confers intestinal epithelial cell protection." American Journal of Physiology-Gastrointestinal and Liver Physiology 292, no. 4 (April 2007): G1070—G1078. http://dx.doi.org/10.1152/ajpgi.00417.2006.
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Sustained expression of cytoprotective intestinal epithelial heat shock proteins (Hsps), particularly Hsp27, depends on stimuli derived from bacterial flora. In this study, we examined the role of the bacterial chemotactic peptide fMLP in stimulating colonic epithelial Hsp expression at concentrations encountered in a physiological milieu. Treatment of the polarized human intestinal epithelial cell line Caco2bbe with physiological concentrations of fMLP (10–100 nM) induced expression of Hsp27, but not Hsp72, in a time- and concentration-dependent manner. Induction of Hsp27 by fMLP was specific since the fMLP analogs MRP and MLP were not effective. Hsp27 induction by fMLP was blocked by the fMLP-receptor antagonist BOC-FLFLF and was blocked when the dipeptide transporter PepT1, an entry pathway for fMLP, was silenced. fMLP activated both the p38 and ERK1/2 MAP kinase pathways in Caco2bbe cells, but not the SAPK/JNK pathway. The p38 inhibitor SB203580, but not the MEK-1 inhibitor PD98059, blocked Hsp27 induction by fMLP. fMLP treatment inhibited actin depolymerization and decreased transepithelial resistance caused by the oxidant monochloramine, and this inhibition was reversed by silencing Hsp27 expression. fMLP pretreatment also inhibited activation of proinflammatory transcription factor NF-κB by TNF-α in Caco2bbe cells, reducing induction of NF-κB target genes by TNF-α both in human intestinal biopsies and Caco2bbe cells. In conclusion, fMLP may contribute to the maintenance of intestinal homeostasis by mediating physiological expression of Hsp27, enhancing cellular protection, and negatively regulating the inflammatory response.
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Karnad, AB, KL Hartshorn, J. Wright, JB Myers, JH Schwartz, and AI Tauber. "Priming of human neutrophils with N-formyl-methionyl-leucyl- phenylalanine by a calcium-independent, pertussis toxin-insensitive pathway." Blood 74, no. 7 (November 15, 1989): 2519–26. http://dx.doi.org/10.1182/blood.v74.7.2519.2519.
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Abstract Resting neutrophils may be “primed” to augmented effector function, eg, superoxide (O2-) production in the respiratory burst, upon a second stimulation with a variety of soluble agonists including formylated methionyl-leucyl-phenylalanine (FMLP) and phorbol myristate acetate (PMA). At priming concentrations of FMLP (5 x 10(-9) mol/L) that did not initiate O2- generation, two metabolic activities were noted: (1) approximately a threefold increase in the baseline intracellular calcium (Ca++i) level, that was not dependent on extracellular Ca++, and (2) a rapid rise in intracellular pH that was blocked by 5-(N,N- dimethyl) amiloride (DA), that had no effect on the Ca++i response to priming. Furthermore, there were no significant increases in inositol metabolites in cells primed and stimulated with FMLP compared with cells receiving the stimulating dose of FMLP alone and pretreatment with pertussis toxin (PT) (before the addition of the priming -5 x 10(- 9) mol/L dose of FMLP), whereas abolishing the response to FMLP during the second stage of stimulation, had (1) no effect on FMLP-primed cells subsequently stimulated with PMA, and (2) only partially ablated the rise in Ca++i initiated with FMLP. That FMLP priming involved distinctive processes to those of the well characterized FMLP-coupled Ca++-dependent activation cascade was shown by the full priming effect attained in a Ca++-free buffer, which did not sustain an O2- response to a second-stage FMLP stimulation, but sustained a primed response to PMA. These data demonstrate that FMLP primes human neutrophils by a Ca++-independent and PT-insensitive pathway, offering a functional model for studying heterogeneous FMLP receptor-coupled reactions.
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Karnad, AB, KL Hartshorn, J. Wright, JB Myers, JH Schwartz, and AI Tauber. "Priming of human neutrophils with N-formyl-methionyl-leucyl- phenylalanine by a calcium-independent, pertussis toxin-insensitive pathway." Blood 74, no. 7 (November 15, 1989): 2519–26. http://dx.doi.org/10.1182/blood.v74.7.2519.bloodjournal7472519.
Full textAbstract:
Resting neutrophils may be “primed” to augmented effector function, eg, superoxide (O2-) production in the respiratory burst, upon a second stimulation with a variety of soluble agonists including formylated methionyl-leucyl-phenylalanine (FMLP) and phorbol myristate acetate (PMA). At priming concentrations of FMLP (5 x 10(-9) mol/L) that did not initiate O2- generation, two metabolic activities were noted: (1) approximately a threefold increase in the baseline intracellular calcium (Ca++i) level, that was not dependent on extracellular Ca++, and (2) a rapid rise in intracellular pH that was blocked by 5-(N,N- dimethyl) amiloride (DA), that had no effect on the Ca++i response to priming. Furthermore, there were no significant increases in inositol metabolites in cells primed and stimulated with FMLP compared with cells receiving the stimulating dose of FMLP alone and pretreatment with pertussis toxin (PT) (before the addition of the priming -5 x 10(- 9) mol/L dose of FMLP), whereas abolishing the response to FMLP during the second stage of stimulation, had (1) no effect on FMLP-primed cells subsequently stimulated with PMA, and (2) only partially ablated the rise in Ca++i initiated with FMLP. That FMLP priming involved distinctive processes to those of the well characterized FMLP-coupled Ca++-dependent activation cascade was shown by the full priming effect attained in a Ca++-free buffer, which did not sustain an O2- response to a second-stage FMLP stimulation, but sustained a primed response to PMA. These data demonstrate that FMLP primes human neutrophils by a Ca++-independent and PT-insensitive pathway, offering a functional model for studying heterogeneous FMLP receptor-coupled reactions.
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De Diego Otero, Yolanda, Lies-Anne Severijnen, Gert van Cappellen, Mariëtte Schrier, Ben Oostra, and Rob Willemsen. "Transport of Fragile X Mental Retardation Protein via Granules in Neurites of PC12 Cells." Molecular and Cellular Biology 22, no. 23 (December 1, 2002): 8332–41. http://dx.doi.org/10.1128/mcb.22.23.8332-8341.2002.
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ABSTRACT Lack of fragile X mental retardation protein (FMRP) causes fragile X syndrome, a common form of inherited mental retardation. FMRP is an RNA binding protein thought to be involved in translation efficiency and/or trafficking of certain mRNAs. Recently, a subset of mRNAs to which FMRP binds with high affinity has been identified. These FMRP-associated mRNAs contain an intramolecular G-quartet structure. In neurons, dendritic mRNAs are involved in local synthesis of proteins in response to synaptic activity, and this represents a mechanism for synaptic plasticity. To determine the role of FMRP in dendritic mRNA transport, we have generated a stably FMR1-enhanced green fluorescent protein (EGFP)-transfected PC12 cell line with an inducible expression system (Tet-On) for regulated expression of the FMRP-GFP fusion protein. After doxycycline induction, FMRP-GFP was localized in granules in the neurites of PC12 cells. By using time-lapse microscopy, the trafficking of FMRP-GFP granules into the neurites of living PC12 cells was demonstrated. Motile FMRP-GFP granules displayed two types of movements: oscillatory (bidirectional) and unidirectional anterograde. The average velocity of the granules was 0.19 μm/s with a maximum speed of 0.71 μm/s. In addition, we showed that the movement of FMRP-GFP labeled granules into the neurites was microtubule dependent. Colocalization studies further showed that the FMRP-GFP labeled granules also contained RNA, ribosomal subunits, kinesin heavy chain, and FXR1P molecules. This report is the first example of trafficking of RNA-containing granules with FMRP as a core constituent in living PC12 cells.
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Yoo, Jae Min, Dong Geun Ahn, and Joong Soon Jang. "Review of FMEA." Journal of Applied Reliability 19, no. 4 (December 31, 2019): 318–33. http://dx.doi.org/10.33162/jar.2019.12.19.4.318.
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Pistone, Cheryl. "FMEA & SCHMEMEA." Gastroenterology Nursing 29, no. 2 (March 2006): 167. http://dx.doi.org/10.1097/00001610-200603000-00073.
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Widianti, Tri, and Himma Firdaus. "PENGUJIAN SUHU LEMARI ES DENGAN METODE TERINTEGRASI FUZZYFAILURE MODE AND EFFECT ANALYSIS (FUZZY-FMEA)." Jurnal Standardisasi 18, no. 1 (May 9, 2018): 9. http://dx.doi.org/10.31153/js.v18i1.693.
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Failure Mode and Effect Analysis (FMEA) banyak diimplementasikan untuk analisis risiko baik di bidang manufaktur maupun jasa. Permasalahan yang sering timbul pada implementasi FMEA yaitu sulitnya menentukan peringkat risiko karena kesamaan nilai RPN. Samanya nilai RPN menimbulkan kesulitan bagi pengambil keputusan untuk memprioritisasi risiko yang harus ditindaklanjuti. Logika fuzzy merupakan logika matematis yang dapat digunakan untuk memperbaiki kelemahan FMEA. Sehingga, tujuan penelitian ini adalah integrasi FMEA dengan logika fuzzy sebagai upaya perbaikan terhadap metode FMEA. Tujuan lainnya adalah implementasi integrasi Fuzzy-FMEA pada lingkup pengujian suhu lemari es. Implementasi Fuzzy-FMEA pada pengujian ini dilakukan sebagai tindakan pencegahan terhadap risiko kegagalan pada pengujian yang dipersyaratkan oleh SNI ISO/IEC 17025:2008. Studi kasus pengujian suhu pada lemari es ini dipilih karena lemari es merupakan salah satu produk yang diwajibkan untuk memperoleh Sertifikat Produk Penggunaan Tanda SNI (SPPT-SNI) yang mengacu pada standar SNI IEC 60335-2-7:2009. Selain itu, penerapan Fuzzy-FMEA pada konteks pengujian sampai saat ini belum ditemukan. Hasil analisis dengan Fuzzy-FMEA menunjukkan bahwa risiko kegagalan paling tinggi pada proses pengujian suhu lemari es paling tinggi terjadi pada mode kegagalan: power source tibatiba shut down dengan nilai RPN 5,8887.
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Aoki, Hiroyuki, Lizhu Ke, Susan M. Poppe, Toni J. Poel, Elizabeth A. Weaver, Robert C. Gadwood, Richard C. Thomas, Dean L. Shinabarger, and M. Clelia Ganoza. "Oxazolidinone Antibiotics Target the P Site on Escherichiacoli Ribosomes." Antimicrobial Agents and Chemotherapy 46, no. 4 (April 2002): 1080–85. http://dx.doi.org/10.1128/aac.46.4.1080-1085.2002.
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ABSTRACT The oxazolidinones are a novel class of antimicrobial agents that target protein synthesis in a wide spectrum of gram-positive and anaerobic bacteria. The oxazolidinone PNU-100766 (linezolid) inhibits the binding of fMet-tRNA to 70S ribosomes. Mutations to oxazolidinone resistance in Halobacterium halobium, Staphylococcus aureus, and Escherichia coli map at or near domain V of the 23S rRNA, suggesting that the oxazolidinones may target the peptidyl transferase region responsible for binding fMet-tRNA. This study demonstrates that the potency of oxazolidinones corresponds to increased inhibition of fMet-tRNA binding. The inhibition of fMet-tRNA binding is competitive with respect to the fMet-tRNA concentration, suggesting that the P site is affected. The fMet-tRNA reacts with puromycin to form peptide bonds in the presence of elongation factor P (EF-P), which is needed for optimum specificity and efficiency of peptide bond synthesis. Oxazolidinone inhibition of the P site was evaluated by first binding fMet-tRNA to the A site, followed by translocation to the P site with EF-G. All three of the oxazolidinones used in this study inhibited translocation of fMet-tRNA. We propose that the oxazolidinones target the ribosomal P site and pleiotropically affect fMet-tRNA binding, EF-P stimulated synthesis of peptide bonds, and, most markedly, EF-G-mediated translocation of fMet-tRNA into the P site.
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Peters, M. J., K. Panaretto, L. Kemsley, A. B. Breslin, and N. Berend. "Effect of neutral endopeptidase inhibition of f-Met-Leu-Phe-induced bronchoconstriction in the rabbit." Journal of Applied Physiology 70, no. 2 (February 1, 1991): 877–81. http://dx.doi.org/10.1152/jappl.1991.70.2.877.
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Inhalation of f-Met-Leu-Phe (FMLP) produces dose-dependent increases in pulmonary resistance (RL) in rabbits. We hypothesized that inhibition of neutral endopeptidase (NEP), which has high affinity for FMLP, would augment the response to FMLP inhalation. We found the increase in RL above baseline in response to FMLP to be reduced from 56 +/- 18 to 8 +/- 10% (P less than 0.01) by phosphoramidon (1 mg/kg) and to 15 +/- 6% (P less than 0.02) by thiorphan (3 mg/kg). The geometric mean dose of FMLP producing a 20% rise in RL (PC20RL FMLP) was increased by phosphoramidon from 1.1 to 4.5 mg/ml (P less than 0.05). Enkephalins, which are also NEP substrates, modulate cholinergic neurotransmission in the airway. Inhibition of the FMLP response by phosphoramidon was reversed by coadministration of naloxone (0.1 mg/kg); after atropine (2 mg/kg) the change in RL in response to FMLP was reduced to 7 +/- 4% (P less than 0.01), whereas morphine (0.15 mg/kg) increased PC20RL FMLP to 5.1 mg/ml (P less than 0.05). FMLP-induced bronchoconstriction in the rabbit is vagally mediated, and reduced responses after NEP inhibition may reflect modulation of cholinergic bronchoconstriction by enkephalins. Changes in airway NEP activity may influence the activity of a wide range of its substrates, of which some are bronchoconstrictors and others bronchodilators.
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Yazdanbakhsh, M., CM Eckmann, L. Koenderman, AJ Verhoeven, and D. Roos. "Eosinophils do respond to fMLP." Blood 70, no. 2 (August 1, 1987): 379–83. http://dx.doi.org/10.1182/blood.v70.2.379.379.
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Abstract Eosinophils were isolated from normal human blood by separation over Percoll gradients, which resulted in eosinophil suspensions of a purity higher than 95% and recoveries of about 65%. Normal human eosinophils were found to respond to formyl-methionyl-leucyl-phenylalanine (fMLP) at concentrations greater than 10(-7) mol/L with an increase in the concentration of intracellular free calcium, oxygen consumption, nitroblue tetrazolium reduction, and chemiluminescence. The maximal response of eosinophils to fMLP was lower than that of neutrophils isolated from the same blood samples and required at least ten times as much fMLP as was needed for neutrophils. Low fMLP concentrations (approximately 10(-8) mol/L), which in themselves did not stimulate O2 consumption by either eosinophils or neutrophils, primed these cells to respond to a suboptimal concentration of another stimulus. Purification of eosinophils after treatment of whole blood with fMLP showed that these eosinophils had lost their ability to respond to fMLP. We conclude that normal eosinophils do respond to fMLP and that therefore fMLP should not be used to isolate eosinophils.
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Yazdanbakhsh, M., CM Eckmann, L. Koenderman, AJ Verhoeven, and D. Roos. "Eosinophils do respond to fMLP." Blood 70, no. 2 (August 1, 1987): 379–83. http://dx.doi.org/10.1182/blood.v70.2.379.bloodjournal702379.
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Eosinophils were isolated from normal human blood by separation over Percoll gradients, which resulted in eosinophil suspensions of a purity higher than 95% and recoveries of about 65%. Normal human eosinophils were found to respond to formyl-methionyl-leucyl-phenylalanine (fMLP) at concentrations greater than 10(-7) mol/L with an increase in the concentration of intracellular free calcium, oxygen consumption, nitroblue tetrazolium reduction, and chemiluminescence. The maximal response of eosinophils to fMLP was lower than that of neutrophils isolated from the same blood samples and required at least ten times as much fMLP as was needed for neutrophils. Low fMLP concentrations (approximately 10(-8) mol/L), which in themselves did not stimulate O2 consumption by either eosinophils or neutrophils, primed these cells to respond to a suboptimal concentration of another stimulus. Purification of eosinophils after treatment of whole blood with fMLP showed that these eosinophils had lost their ability to respond to fMLP. We conclude that normal eosinophils do respond to fMLP and that therefore fMLP should not be used to isolate eosinophils.
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Berkow, RL, and RW Dodson. "Purification and functional evaluation of mature neutrophils from human bone marrow." Blood 68, no. 4 (October 1, 1986): 853–60. http://dx.doi.org/10.1182/blood.v68.4.853.853.
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Abstract Human myeloid maturation proceeds within the bone marrow and results in a mature neutrophil that is released into the peripheral circulation. Previous reports have indicated that neutrophils from bone marrow demonstrate decreased adherence, impaired phagocytosis, and decreased nitroblue tetrazolium dye reduction when stimulated. Due to lack of a suitable method for isolating purified bone marrow neutrophils, these studies have been performed by microscopic techniques. We now report a method for isolating 1 X 10(8) neutrophils [bands plus polymorphonuclear leukocytes (PMNs)] from 10 mL of bone marrow aspirate sample. By means of a discontinuous Percoll-gradient centrifugation through densities of 1.085, 1.095, and 1.10 g/mL a leukocyte-rich suspension of bone marrow can be separated into three leukocyte layers. By combining the lower two leukocyte layers (M2/3), a population of neutrophils consisting of 26% bands and 63% PMNs is seen. When compared with peripheral blood PMNs, these bone marrow neutrophils had a lower alkaline phosphatase activity, decreased ingestion of Oil Red O-coated particles, impaired superoxide release on stimulation with the chemotactic peptide Fmet-leu-phe (FMLP) or the tumor promotor phorbol myristate acetate (PMA), and less activity of the NADPH-dependent oxidase. These results indicate that morphologically mature neutrophilic cells within the bone marrow exist in a still functionally immature state.
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Berkow, RL, and RW Dodson. "Purification and functional evaluation of mature neutrophils from human bone marrow." Blood 68, no. 4 (October 1, 1986): 853–60. http://dx.doi.org/10.1182/blood.v68.4.853.bloodjournal684853.
Full textAbstract:
Human myeloid maturation proceeds within the bone marrow and results in a mature neutrophil that is released into the peripheral circulation. Previous reports have indicated that neutrophils from bone marrow demonstrate decreased adherence, impaired phagocytosis, and decreased nitroblue tetrazolium dye reduction when stimulated. Due to lack of a suitable method for isolating purified bone marrow neutrophils, these studies have been performed by microscopic techniques. We now report a method for isolating 1 X 10(8) neutrophils [bands plus polymorphonuclear leukocytes (PMNs)] from 10 mL of bone marrow aspirate sample. By means of a discontinuous Percoll-gradient centrifugation through densities of 1.085, 1.095, and 1.10 g/mL a leukocyte-rich suspension of bone marrow can be separated into three leukocyte layers. By combining the lower two leukocyte layers (M2/3), a population of neutrophils consisting of 26% bands and 63% PMNs is seen. When compared with peripheral blood PMNs, these bone marrow neutrophils had a lower alkaline phosphatase activity, decreased ingestion of Oil Red O-coated particles, impaired superoxide release on stimulation with the chemotactic peptide Fmet-leu-phe (FMLP) or the tumor promotor phorbol myristate acetate (PMA), and less activity of the NADPH-dependent oxidase. These results indicate that morphologically mature neutrophilic cells within the bone marrow exist in a still functionally immature state.
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Reeves, Emer P., Nessa Banville, Dorothy M. Ryan, Niamh O’Reilly, David A. Bergin, Kerstin Pohl, Kevin Molloy, et al. "Intracellular Secretory Leukoprotease Inhibitor Modulates Inositol 1,4,5-Triphosphate Generation and Exerts an Anti-Inflammatory Effect on Neutrophils of Individuals with Cystic Fibrosis and Chronic Obstructive Pulmonary Disease." BioMed Research International 2013 (2013): 1–18. http://dx.doi.org/10.1155/2013/560141.
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Secretory leukoprotease inhibitor (SLPI) is an anti-inflammatory protein present in respiratory secretions. Whilst epithelial cell SLPI is extensively studied, neutrophil associated SLPI is poorly characterised. Neutrophil function including chemotaxis and degranulation of proteolytic enzymes involves changes in cytosolic calcium (Ca2+) levels which is mediated by production of inositol 1,4,5-triphosphate (IP3) in response to G-protein-coupled receptor (GPCR) stimuli. The aim of this study was to investigate the intracellular function of SLPI and the mechanism-based modulation of neutrophil function by this antiprotease. Neutrophils were isolated from healthy controls (n=10), individuals with cystic fibrosis (CF) (n=5) or chronic obstructive pulmonary disease (COPD) (n=5). Recombinant human SLPI significantly inhibited fMet-Leu-Phe (fMLP) and interleukin(IL)-8 induced neutrophil chemotaxis (P<0.05) and decreased degranulation of matrix metalloprotease-9 (MMP-9), hCAP-18, and myeloperoxidase (MPO) (P<0.05). The mechanism of inhibition involved modulation of cytosolic IP3production and downstream Ca2+flux. The described attenuation of Ca2+flux was overcome by inclusion of exogenous IP3in electropermeabilized cells. Inhibition of IP3generation and Ca2+flux by SLPI may represent a novel anti-inflammatory mechanism, thus strengthening the attractiveness of SLPI as a potential therapeutic molecule in inflammatory airway disease associated with excessive neutrophil influx including CF, non-CF bronchiectasis, and COPD.
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Adayev, Tatyana, Giuseppe LaFauci, Weimin Xu, Carl Dobkin, Richard Kascsak, W. Ted Brown, and Jeffrey H. Goodman. "Development of a Quantitative FMRP Assay for Mouse Tissue Applications." Genes 12, no. 10 (September 26, 2021): 1516. http://dx.doi.org/10.3390/genes12101516.
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Fragile X syndrome results from the absence of the FMR1 gene product—Fragile X Mental Retardation Protein (FMRP). Fragile X animal research has lacked a reliable method to quantify FMRP. We report the development of an array of FMRP-specific monoclonal antibodies and their application for quantitative assessment of FMRP (qFMRPm) in mouse tissue. To characterize the assay, we determined the normal variability of FMRP expression in four brain structures of six different mouse strains at seven weeks of age. There was a hierarchy of FMRP expression: neocortex > hippocampus > cerebellum > brainstem. The expression of FMRP was highest and least variable in the neocortex, whereas it was most variable in the hippocampus. Male C57Bl/6J and FVB mice were selected to determine FMRP developmental differences in the brain at 3, 7, 10, and 14 weeks of age. We examined the four structures and found a developmental decline in FMRP expression with age, except for the brainstem where it remained stable. qFMRPm assay of blood had highest values in 3 week old animals and dropped by 2.5-fold with age. Sex differences were not significant. The results establish qFMRPm as a valuable tool due to its ease of methodology, cost effectiveness, and accuracy.