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101.
抑癌基因PTEN与食管癌 总被引:3,自引:0,他引:3
PTEN是近年发现的一种与细胞信号传导途径有关的具有双特异性磷酸酶活性的新型抑癌基因。研究表明,该基因的突变与人类多种恶性肿瘤的发生发展密切相关。近年来国内外的学者在食管癌组织中发现,虽然该基因发生突变的频率较低,但其蛋白表达却普遍下降,表达程度与食管癌的恶性程度及预后密切相关。因此,PTEN的低表达可能参与了食管癌的发生发展过程。 相似文献
102.
H. Degens J. M. Sanchez Horneros Y. F. Heijdra P. N. R. Dekhuijzen M. T. E. Hopman 《Acta physiologica (Oxford, England)》2005,184(3):235-242
Aim: Peripheral muscle dysfunction often occurs in patients with chronic obstructive pulmonary disease (COPD). The muscle dysfunction may be caused by a loss of force‐generating capacity, resulting from a loss of muscle mass, as well as by other alterations in contractile properties of skeletal muscle. Methods: The maximal isometric voluntary strength and fatigability were determined in hand‐grip and quadriceps muscles from nine male COPD patients (FEV1 30–50% predicted) and control subjects matched for fat‐free mass (FFM), physical activity level and age. Contractile properties and fatigability of the quadriceps muscle were also studied with electrically evoked isometric contractions. Results: The maximal voluntary force (MVC) and fatigability of the handgrip muscle did not differ between the COPD patients and control subjects. Also the MVC of the quadriceps muscle and the rate of force rise, contraction time, force–frequency relationship and fatigability, as determined with electrically evoked contractions, were similar in patients with COPD and control subjects. Conclusion: Skeletal muscle strength, contractile properties and fatigability are preserved in patients with moderate COPD and a normal FFM and activity level. This suggests that skeletal muscle dysfunction does not take place during moderate COPD until cachexia and/or a decline in physical activity occur. 相似文献
103.
食管癌三维适形放射治疗疗效的Meta分析 总被引:6,自引:0,他引:6
目的分析三维适形放射治疗技术(3-DCRT)治疗食管癌的疗效和放射毒性反应。方法检索国内有关数据库查找符合条件的临床随机对照试验,采用Meta分析方法,对国内公开发表的有关3-DCRT治疗食管癌的临床随机对照试验研究文献进行综合分析,在RevMan4.2.7软件中统计分析相应的研究指标。结果有8项独立的临床随机对照试验研究进入了本次meta分析。3-DCRT组的近期疗效,1、2、3年局控率及1、2、3年生存率均优于对照组(p〈0.01)。两组毒副反应的差异无统计学显著性意义。结论3-DCRT治疗食管癌的近期疗效优于常规放射治疗方法,远期疗效和毒副反应有待进一步观察随访和研究。 相似文献
104.
J. Gordon C. Ghez 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1984,55(1):167-171
Summary We studied the EMG activity of biceps and triceps in human subjects during isometric force adjustments at the elbow. Rapid targeted force pulses exhibited stereotyped trajectories in which peak force was a linear function of the derivatives of force and the time to peak force was largely independent of its amplitude. These responses were associated with an alternating triphasic pattern of EMG bursts in agonist and antagonist muscles similar to that previously described for rapid limb movements. When the instructions demanded rapid force pulses, initial agonist bursts were of constant duration, and their magnitude was strongly related to peak force achieved. The timing of EMG bursts in antagonist pairs was closely coupled to the dynamics of the force trajectory, and the rising phase of the force was determined by both agonist and antagonist bursts. When peak force was kept constant and rise time systematically varied, the presence and magnitude of antagonist and late agonist bursts were dependent on the rate of rise of force, appearing at a threshold value and then increasing in proportion to this parameter. It is proposed that antagonist activity compensates for nonlinearity in muscle properties to enable the linear scaling of targeted forces which characterizes performance in this task.Supported by the Dystonia Medical Research Foundation and NS 19205 相似文献
105.
G. J. M. Stienen K. Güth J. C. Rüegg 《Pflügers Archiv : European journal of physiology》1983,397(4):272-276
A freeze-drying method is described by which single skinned skeletal muscle fibres or fibre bundles can readily be obtained. Skinned fibre segments of the ileofibularis and semitendinous muscles of the frog — activated by means of a rapid increase in the Ca-concentration — showed very stable and reproducible contractions. Complete activation occurred at a Ca-concentration of 1.6·10–6 M and the mid-point of the pCa-tension curve occurred at 6.3·10–7 M. Addition of phosphate (10–2 M) had a depressing effect on the speed of the Ca-activated tension development as well as on the maximum tension reached.Addition of caffeine (10–2 M) had no effect on the tension generation, indicating that the sarcoplasmic reticulum, if present, was not active. The force responses due to rapid length changes applied to the Ca-activated fibre preparations were found to be qualitatively similar to the force responses on intact tissue. This skinning technique might be employed on human biopsies, enabling the measurement of physiological parameters such as for example force and shortening velocity. 相似文献
106.
Patrick Gonzalez De La Fuente Jean -Pierre Savineau Roger Marthan 《Pflügers Archiv : European journal of physiology》1995,429(5):617-624
The effect of thapsigargin (TG) and cyclopiazonic acid (CPA) on the mechanical activity of the rat pulmonary artery were investigated. In chemically (-escin)-skinned arterial strips, application of TG (0.1–1 M) or CPA (0.5–10 M) prior and throughout the loading procedure of the internal Ca2+ stores (0.3 M free Ca2+ ions for 8–10 min) concentration dependently inhibited the subsequent contractile response induced by noradrenaline (NA, 10 M) or caffeine (25 mM). In intact strips repeatedly incubated in a Ca2+-containing solution (2.5 mM for 10 min), followed by incubation in a Ca2+-free solution 12 min before NA-stimulation, TG and CPA not only inhibited the NA-induced contraction but also increased the tension which appeared during the exposure time to Ca2+. The two phenomena developed with similar time courses. The increase in tension during the readmission of Ca2+ ions was not antagonized by verapamil (10 M) or nifedipine (1 M) but was blocked by La3+ (50 M) and Co2+ (1 mM) ions. The amplitude of the verapamil-insensitive TG (or CPA)-induced contraction was dependent on the external [Ca2+] [0.1–10 mM, concentration for half maximal effect (EC50) =0.85 mM], not modified by the reduction of the external [Na+] (from 130 to 10 mM) and decreased by depolarization of the strip using K+-rich (30–120 mM) solutions. Under the latter condition, 38±9 and 83±4% reduction (n=5) was observed in the presence of 60 and 120 mM K+ respectively. This contraction was also concentration dependently inhibited by the tyrosine kinase inhibitors genistein (0.5–50 M) and tyrphostin (2–50 M). Sr2+ ions, which contracted both depolarized intact and skinned strips, failed to replace Ca2+ ions in the verapamil-insensitive contraction induced by TG or CPA (n=4). Finally, TG (1 M) and CPA (10 M) did not modify the pCa tension relationship in skinned strips (n=5). These results show that the main action of TG and CPA in rat pulmonary artery is to prevent the refilling of the internal Ca2+ store. TG and CPA also seem to facilitate a Ca2+ influx through a specific verapamil-insensitive pathway. The biophysical and molecular characteristics of this pathway remain to be elucitated, although it appears to involve a tyrosine kinase activity. 相似文献
107.
108.
T. CLAUSEN 《Acta physiologica (Oxford, England)》1996,156(3):227-235
In skeletal muscle, the Na+, K+ pump is predominantly situated in the sarcolemma (1000–3500 pumps per μm2). The total concentration can be determined in fresh or frozen biopsies (1–5 mg) using a 3H-ouabain binding assay. The values obtained have been confirmed by measurements of maximum ouabain suppressible Na+, K+-transport capacity in intact muscles as well as Na+, K+-ATPase-related enzyme activity in muscle homogenates. In the mature organism, the concentration of Na+, K+ pumps varies with muscle type and species in the range 150–600 pmol (g wet wt)-1. In rat and human muscle, the concentration increases markedly with thyroid status. Semi-starvation and untreated diabetes reduce the concentration by 20–48%. K+ deficiency leads to a downregulation of up to 75%. Both in animals and in humans, training increases the concentration of Na+, K+ pumps in muscle, and inactivity leads to a downregulation. High-frequency stimulation elicits up to a 20-fold increase in the net efflux of Na+ within 10 s This is the major activation mechanism for the Na+, K+ pump, utilizing its entire capacity and possibly represents a drive on de novo synthesis of Na+, K+ pumps. A variety of hormones (insulin, insulin-like growth factor I, adrenaline, noradrenaline, calcitonin gene-related peptide, calcitonin, amylin) increase the rate of active Na+, K+ transport by 60–120% within a few minutes. This leads to a decrease in intracellular Na+ and hyperpolarization. In isolated muscles, where contractility is inhibited by high extracellular K+, such agents produce rapid force recovery, which is entirely suppressed by ouabain and closely correlated to the stimulation of K+ uptake and the decline in intracellular Na+. The observations support the conclusion that the Na+, K+ pump plays a central role in the acute recovery and maintenance of excitability during contractile activity. 相似文献
109.
Recombinant troponin I substitution and calcium responsiveness in skinned cardiac muscle 总被引:1,自引:0,他引:1
John D. Strauss Jennifer E. Van Eyk Zacharias Barth Lan Kluwe Rudolf J. Wiesner K. Maéda J. Caspar Rüegg 《Pflügers Archiv : European journal of physiology》1996,431(6):853-862
Using treatment with vanadate solutions, we extracted native cardiac troponin I and troponin C (cTnI and cTnC) from skinned
fibers of porcine right ventricles. These proteins were replaced by exogenously supplied TnI and TnC isoforms, thereby restoring
Ca2+-dependent regulation. Force then depended on the negative logarithm of Ca2+ concentration (pCa) in a sigmoidal manner, the pCa for 50% force development, pCa50, being about 5.5. For reconstitution we used fast-twitch rabbit skeletal muscle TnI and TnC (sTnI and sTnC), bovine cTnI
and cTnC or recombinant sTnIs that were altered by site-directed mutagenesis. Incubation with TnI inhibited isometric tension
in TnI-extracted fibers in the absence of Ca2+, but restoration of Ca2+ dependence required incubation with both TnI and TnC. Relaxation at low Ca2+ levels and the steepness of the force/pCa relation depended on the concentration of exogenously supplied TnI in the reconstitution
solution (range 20–150 μM), while Ca2+ sensitivity, i.e. the pCa50, was dependent on the isoform, and also on the concentration of TnC in the reconstitution solution. At pH 6.7, skinned fibers
reconstituted with optimal concentrations of sTnC and sTnI (120 μM and 150 μM, respectively) were more sensitive to Ca2+ than those reconstituted with cTnC and cTnI (difference in pCa50 approx. 0.2 units). Rabbit sTnI was cloned and expressed in Escherichia coli using a high yield expression plasmid. We introduced point mutations into the TnI inhibitory region comprising the sequence
of the minimal common TnC/actin binding site (-G104-K-F-K-R-P-P-L-R-R-V-R115-). The four mutants produced by substitution of T for P110, G for P110, G for L111, and G for K105 were chosen, based on previous work with synthetic peptides showing that single amino acid substitution in this region diminished
the capacity of these peptides to inhibit acto-S1 ATPase or contraction of skinned fibers. Therefore, all amino acid residues of the inhibitory region are thought to contribute
to biological activity of TnI. However, each of the recombinant TnIs could substitute for endogenous TnI. In combination with
exogenous TnC, Ca2+ dependence could be restored when gly110sTnI, thr110sTnI or gly111sTnI was used for reconstitution. The mutant gly105sTnI, on the other hand, reduced the ability of skinned fibers to relax at low Ca2+ concentrations and it caused an increase in Ca2+ sensitivity.
Received: 5 October 1995/Received after revision and accepted: 1 December 1995 相似文献
110.
D. G. Allen 《Acta physiologica (Oxford, England)》2001,171(3):311-319
Pain and weakness are prominent symptoms which occur after a delay in muscles which have been stretched during contraction (eccentric contraction). These symptoms are particularly severe when the exercise is unaccustomed and when the stretch occurs in muscles on the descending limb of the force–length relation, i.e. at long muscle lengths. It is known that sarcomeres are potentially unstable on the descending limb and it has been proposed by Morgan that uncontrolled elongation of some sarcomeres occurs during eccentric contractions on the descending limb. In this article, the evidence that this mechanism leads to the reduced force is considered. If overextended sarcomeres persist after the eccentric exercise it will cause a shift in the peak of the force–length curve. There is also evidence that in some types of muscle, excitation–contraction coupling is impaired and contributes to the muscle weakness. Cytoskeletal proteins stabilize the sarcomeric structure and may be injured either by the overextended sarcomeres or by activation of proteases. The potential of these mechanisms to contribute to the effects of muscle training and to the symptoms of muscle disease, such as muscular dystrophy, is considered. 相似文献