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21.
K Schesser AK Spiik JM Dukuzumuremyi MF Neurath S Pettersson H Wolf-Watz 《Canadian Metallurgical Quarterly》1998,28(6):1067-1079
22.
S Chasserot-Golaz P Hubert D Thiersé S Dirrig CJ Vlahos D Aunis MF Bader 《Canadian Metallurgical Quarterly》1998,70(6):2347-2356
Several lines of evidence suggest that phosphorylated products of phosphatidylinositol play critical functions in the regulation of membrane trafficking along the secretory pathway. To probe the possible involvement of phosphatidylinositol 3-kinase (PI 3-kinase) in regulated exocytosis, we have examined its subcellular distribution in cultured chromaffin cells by immunoreplica analysis and confocal immunofluorescence. We found that the PI 3-kinase heterodimer consisting of the regulatory and catalytic subunits was associated essentially with the subplasmalemmal cytoskeleton in both resting and nicotine-stimulated chromaffin cells. Attempts to immunoprecipitate PI 3-kinase with anti-phosphotyrosine antibodies failed, suggesting that the activity of PI 3-kinase was not modulated by tyrosine phosphorylation and/or physical interaction with SH2-containing proteins in stimulated chromaffin cells. LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one], a potent inhibitor of PI 3-kinase, produced a dose-dependent inhibition of catecholamine secretion evoked by various secretagogues. Furthermore, cytochemical experiments with rhodamine-labeled phalloidin revealed that LY294002 blocked the disassembly of cortical actin in chromaffin cells stimulated by a depolarizing concentration of potassium. Our results suggest that PI 3-kinase may be one of the important regulatory exocytotic components involved in the signaling cascade controlling actin rearrangements required for catecholamine secretion. 相似文献
23.
G Isenberg S Han A Schiefer MF Wendt-Gallitelli 《Canadian Metallurgical Quarterly》1993,27(10):1800-1809
OBJECTIVE: The aim was to examine whether mitochondrial Ca2+ fluxes are high enough to change mitochondrial and cytosolic calcium concentration during the contraction cycle. METHODS: Isolated guinea pig ventricular myocytes were stimulated with paired voltage clamp pulses until contractions were maximal (2 mM [Ca2+]o, 36 degrees C). At defined times of diastole or systole, the cells were shock frozen. Electron-probe microanalysis measured the concentration of total calcium in mitochondria (sigma Ca(mito)) and surrounding cytosol (sigma Cac). Other experiments were performed to evaluate DNP sensitive mitochondrial Ca2+ uptake from depolarisation induced [Ca2+]c transients (K5indo-1 fluorescence). RESULTS: At end of diastole, sigma Ca(mito) was 446 mumol.litre-1. During systole, sigma Ca(mito) increased with a 20 ms delay. A peak sigma Ca(mito) of 1050 mumol.litre-1 was measured 40 ms after start of systole, while 95 ms after start of systole sigma Ca(mito) had fallen to 530 mumol.litre-1. From the changes in sigma Ca(mito) the rates of net mitochondrial Ca2+ flux were estimated at 100 nmol.s-1 x mg-1 protein for Ca2+ influx and 36 nmol.s-1 x mg-1 protein for Ca2+ egress. Decay of sigma Ca(mito) was coupled to a rise in sigma Na(mito). sigma Cl(mito) and sigma K(mito) rose and fell in parallel with sigma Ca(mito), suggesting Ca2+ activation of mitochondrial anion and cation channels. Activation of the non-specific permeability can be excluded. Block of mitochondrial Ca2+ uptake with DNP (100 microM) or FCCP (10 microM) increased the amplitude of the [Ca2+]c transients for 1-3 min by about 50%; evaluation of mitochondrial Ca2+ uptake from DNP sensitive difference signals, however, was hampered by sequestration of mitochondrial Ca2+ into the sarcoplasmic reticulum. CONCLUSIONS: Mitochondrial calcium content changes during each individual contraction cycle; a substantial amount of calcium is taken up during the systole and released during later systole and diastole. 相似文献
24.
Estimates of loudness balance were obtained for acoustically and electrically presented 250 Hz sine signals from a patient who uses the Ineraid multichannel cochlear implant. Acoustic and electric loudness matching was possible because the patient evidenced a 25 dB HL threshold at 250 Hz in his nonimplanted ear. The level of the electrical stimulus in microamperes required for a balance of loudness grew linearly with equal increments in decibels for the acoustic stimulus. These data, in concert with the very limited data from previous studies, provide a rationale for using a logarithmic transformation of acoustic to electric intensity in signal processors for cochlear implants. 相似文献
25.
JM Karski SJ Teasdale P Norman J Carroll K VanKessel P Wong MF Glynn 《Canadian Metallurgical Quarterly》1995,110(3):835-842
This prospective, double-blind, randomized trial assessed the effectiveness of high-dose tranexamic acid given in the preoperative period on blood loss in patients undergoing cardiopulmonary bypass. One hundred fifty patients scheduled to undergo cardiac operations with cardiopulmonary bypass were randomized into three groups of equal size. The first group received 10 gm of tranexamic acid intravenously over 20 minutes before sternotomy and a placebo infusion over 5 hours. The second group received 10 gm of tranexamic acid over 20 minutes and then another 10 gm infused intravenously over 5 hours. The control group received a placebo bolus and a placebo infusion over 5 hours (0.9% normal saline solution). The blood loss after the operation was measured at 6 hours and 24 hours. The homologous blood and blood products given during and up to 48 hours after operation were recorded. Eighteen percent of the control group patients shed more than 750 ml blood in 6 hours compared with only 2% in both tranexamic acid groups. Patients who shed more than 750 ml blood required 93% more red blood cell transfusions than patients without excessive bleeding. Tranexamic acid (10 gm) given intravenously in the period before cardiopulmonary bypass reduced blood loss over 6 hours by 50% and over 24 hours by 35%. Continued tranexamic acid infusion (10 gm over 5 hours) did not reduce bleeding further. There was no difference in the coagulation profile before operation between patients with and without excessive bleeding. However, coagulation tests done in the postoperative period indicated ongoing fibrinolysis and platelet dysfunction in patients with excessive bleeding. 相似文献
26.
N Cherradi MF Rossier MB Vallotton AM Capponi 《Canadian Metallurgical Quarterly》1996,271(42):25971-25975
In adrenal glomerulosa cells, angiotensin II (Ang II) stimulates aldosterone synthesis through rises of cytosolic calcium ([Ca2+]c). The rate-limiting step in this process is the transfer of cholesterol to the inner mitochondrial membrane, where it is converted to pregnenolone by the P450 side chain cleavage enzyme. The aim of the present study was to examine the effect of changes in [Ca2+]c and of Ang II on intramitochondrial cholesterol distribution. Freshly prepared bovine zona glomerulosa cells were submitted to a cytosolic Ca2+ clamp (600 nM) or stimulated with Ang II (10 nM). Mitochondria were isolated and subfractionated into outer membranes (OM), inner membranes (IM), and contact sites (CS). Cholesterol content was determined by the cholesterol oxidase assay. Stimulation of intact cells with Ca2+ led to a marked decrease in cholesterol content of OM (to 54 +/- 24% of controls, n = 5) and to a concomitant increase of cholesterol in CS and IM (to 145 +/- 14%, n = 5). When glomerulosa cells were exposed to Ang II, a marked increase of cholesterol in CS occurred (to 172 +/- 16% of controls, n = 5). No significant changes were detected in OM cholesterol, suggesting a stimulation of cholesterol supply to the mitochondria in response to Ang II. Cycloheximide specifically and significantly reduced Ca2+-activated cholesterol transfer to CS and IM. In conclusion, our data indicate that one of the main functions of the Ca2+ messenger is to increase cholesterol supply to the P450 side chain cleavage enzyme by enhancing endogenous intermembrane cholesterol transfer to a mitochondrial site containing the enzymes responsible for the initial steps of the steroidogenic cascade. 相似文献
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30.
A Gil-Villarino MI Torres MF Zafra E García-Peregrín 《Canadian Metallurgical Quarterly》1997,117(3):243-250
PURPOSE OF THE STUDY: Impaction in pertrochanteric fracture sites is a well known phenomenon; the screw-plate system is designed to stabilise the fracture. Although easier to use, the risk with the nail-plate system is postoperative penetration of the nail into the joint. The present study was conducted to determine the exact conditions of the impaction, and to identify possible ways to improve the nail-plate system. MATERIAL-METHOD: The study included 129 cases of pertrochanteric fracture, excluding sub-trochanteric fractures. All fractures were fixed with a 130 degrees angulated nail-plate. In all cases, consolidation was uneventful after 8 to a 12 weeks. The anatomical type of fracture, i.e. stable or unstable, was determined according to the size of the intermediary fragment, including the trochanter minor. The displacement was measured as the difference between the length of the nail and the length of the femoral head and neck measured along the axis of the femoral neck. The parameters examined were: fracture stability degree, bony mineralisation (Singh Index), nail length, femoral neck, length nail position in the femoral head, and above all, fracture reduction. All these parameters were computerised and compared using Stat View statistics software. RESULTS: Impaction was observed in 43 per cent of cases. Among these, 25 per cent were rated as slight (1 to 5 mm), 18 per cent as moderate (over 5 mm) and 9 per cent as marked (10 to 25 mm). Impaction was associated with demineralisation of the bone tissue (p = 0.001). The anatomical classification of the fracture was not a determining factor (p = 0.19), as marked displacements were also recorded in stable fractures. A posterior and inferior position of the intramedullary nail in the femoral head is one of displacement determining factors (p = 0.004, two-sided 1 test). Valgus over-correction is the most important factor, especially when it is associated with bony demineralisation (p = 0.02) and an inadequately centred intramedullary pin (p = 0.02). Shorter the femoral neck, and shorter the nail, greater was the frequency of nail articular penetration. DISCUSSION: The risk of articular penetration therefore reaches 15 per cent in petrochanteric fractures repaired with a nail plate, set at an angle of 130 degrees. A short neck, a cervicodiaphyseal angle superior to 140 degrees, and demineralisation are the three determining parameters. Stable or unstable fracture has in fact little effect on displacement incidence, and therefore does not, on its own, warrant the use of a prosthesis in comminuted fractures. The authors compared their results to literature on progressive sliding system: the incidence of complications associated with this type of fracture treatment is identical, but the determining parameters are different. CONCLUSION: The study shows that the nail-plate is efficient and provides simple and solid fracture fixation. However, this osteosynthesis material needs to be modified in order to improve its fixation in the femoral head. 相似文献