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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have performed thin-section electron microscopy on muscle fibers fixed in different mechanically monitored states, in order to identify structural changes in myosin crossbridges associated with force production and maintenance. Tension and stiffness of fibers from glycerinated Lethocerus flight muscle were monitored during a sequence of conditions using AMPPNP and then AMPPNP plus increasing concentrations of ethylene glycol, which brought fibers through a graded sequence from rigor relaxation. Two intermediate crossbridge forms distinct from the rigor or relaxed forms were observed. The first was produced by AMPPNP at 20 degrees C, which reduced isometric tension 60 to 70% below rigor level without reducing rigor stiffness. Electron microscopy of these fibers showed that, in spite of the drop in tension, no obvious change from the 45 degrees crossbridge angle characteristic of rigor occurred. However, the thick filament ends of the crossbridges were altered from their rigor positions, so that they now marked a 14.5 nm repeat, and formed four separate origins at each crossbridge level. The bridges were also less slewed and bent than rigor bridges, as seen in transverse sections. The second crossbridge form was seen in glycol-AMPPNP at 4 degrees C, just below the glycol concentration that produced mechanical relaxation. These fibers retained 90% of rigor stiffness at 40 Hz oscillation, but would not bear sustained tension. Stiffness was also high in the presence of calcium at room temperature under similar conditions. Electron microscopy showed crossbridges projecting from the thick filaments at an angle that centered around 90 degrees, rather than the 45 degree angle familiar from rigor. This coupling of relaxed appearance with persistent stiffness suggests that the 90 degree form may represent a weakly attached crossbridge state like that proposed to precede force development in current models of the crossbridge power stroke.
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PMID:Two attached non-rigor crossbridge forms in insect flight muscle. 322 90

The relationship between the mechanical and biochemical states of the muscle cross-bridge cycle and the control of contraction were investigated by using the nucleotide analogs adenosine 5'-[gamma-thio]triphosphate (ATP[gamma S]) and caged ATP[gamma S] [the O-1(2-nitrophenyl)ethyl P3-ester of ATP[gamma S]]. ATP[gamma S] interacts with actomyosin in a manner similar to ATP but is hydrolyzed (by a factor of 500) more slowly. Generation of ATP[gamma S] by photolysis of caged ATP[gamma S] within a permeabilized fiber in rigor in the absence of Ca2+ relaxed tension and stiffness as occurs with ATP. The transient rise in tension prior to final relaxation observed with photolysis of caged ATP was absent with caged ATP[gamma S]. This result suggests that following detachment of a cross-bridge, ATP is normally hydrolyzed before force generation. In the presence of Ca2+, photolysis of caged ATP[gamma S] within rigor fibers caused tension to relax fully but significant stiffness remained. Stiffness also developed without concomitant tension when Ca2+ concentration was raised from less than 1 nM to 30 microM in the presence of ATP[gamma S]. The amplitude of the tension response to ramp stretches in the presence of Ca2+ and ATP[gamma S] increased with ramp stretch velocity, suggesting that the cross-bridges have detachment rate constants extending into the 10(3) s-1 range. The results provide evidence that the Ca2+-regulatory system can directly control attachment of cross-bridges into states before the power stroke.
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PMID:Relaxation of muscle fibers with adenosine 5'-[gamma-thio]triphosphate (ATP[gamma S]) and by laser photolysis of caged ATP[gamma S]: evidence for Ca2+-dependent affinity of rapidly detaching zero-force cross-bridges. 341 19

Stiffness of aortic walls has been shown to be a marker of coronary and cerebrovascular diseases in patients with myocardial infarction or stroke. However, its value for predicting preclinical atherosclerosis has not been demonstrated. Therefore, this study tested the association of aortic wall stiffness and coronary and extracoronary atherosclerosis in the absence of clinical cardiovascular disease. In 190 asymptomatic men at cardiovascular risk, carotid-to-femoral pulse wave velocity (PWV) was measured mechanographically and the compliance of the aorta (C), as well as the intrinsic compliance (Ci), was deduced after correction for the effect of blood pressure. Also determined noninvasively were 1) the degree of coronary calcium deposit coded as grade 0, 1, 2, or 3 using ultrafast computed tomography; 2) the extent of extracoronary plaque detected by B-mode echography at three different sites (carotid, abdominal aorta, and femoral) coded as 0, 1, 2, or 3 diseased sites; and 3) the estimated Framingham coronary risk. The grade of coronary calcium was not associated with any aortic elastic parameter. The number of extracoronary diseased sites was not associated with PWV and C but correlated negatively with Ci before but not after age adjustment. The coronary risk correlated positively with PWV and negatively with C before but not after age adjustment and was not associated with Ci. In symptom-free subjects aortic stiffening does not predict the presence of coronary and extracoronary atheroma and therefore cannot be considered as a useful surrogate marker of early atherosclerosis.
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PMID:Aortic stiffening does not predict coronary and extracoronary atherosclerosis in asymptomatic men at risk for cardiovascular disease. 954 69

Ultrasound densitometry has been measured in the os calcis of 31 stroke patients (14 women, 17 men), ages 46-87 years, to determine whether bone density is lower than expected for normal subjects at this site, and to investigate whether or not the stroke side has lower values than the nonstroke side. We have also measured a large control group of 268(39 men, 228 women) subjects who showed similar values to other published data. Immobility is a known precursor to bone loss and so we also compared ultrasound Stiffness Index with an index of mobility in 22 of the stroke patients. In healthy subjects, ultrasound densitometry (measured as Stiffness) fell by 25% in females from 48-52 to 68-72 years. Stiffness (expressed as z-score) in patients with stroke was low in females (P < 0.02) but not in males, but both stroke side and nonstroke side were equally low. Stiffness did not decline with time since stroke, but did correlate with mobility after stroke, on the stroke (r = 0.73) and nonstroke (r = 0.62) side. The data suggest that stroke patients, particularly females, have low bone density before the stroke event. The greater ultrasound Stiffness with increasing mobility after stroke may suggest that active rehabilitation after stroke may produce denser bone.
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PMID:Ultrasound densitometry of the os calcis in patients with hemiparesis following a cerebrovascular accident. 1059 61

The present study was undertaken to assess the effect of hyperthyroidism on stiffness in the common carotid artery (CCA) in patients with Graves' disease (GD) and elucidate the mechanism by which arterial stiffness is increased in hyperthyroidism. The arterial stiffness index beta (stiffness beta) was evaluated in the CCA using an ultrasonic phase-locked echo-tracking system. Stiffness beta was defined as the logarithm of the ratio of systolic to diastolic blood pressure divided by the fractional diameter increase during the cardiac cycle and thus established as a measure of arterial stiffness uninfluenced by the change in blood pressure. Seventy euthyroid GD patients were measured for CCA stiffness beta to determine its relationship to retinal blood flow and plasma levels of vascular injury markers. To investigate the effect of hyperthyroidism, 27 GD patients were measured for changes during antithyroid drug (ATD) therapy in stiffness beta and in hemodynamic parameters, retinal blood flow and plasma vascular injury markers. In euthyroid GD patients, stiffness beta in the CCA showed a significant and positive correlation with systolic blood pressure and pulse pressure, but not with peripheral blood flow in the central retinal artery. ATD therapy significantly reduced stiffness beta from 5.23 +/- 2.10 to 4.36 +/- 1.48. The fractional reduction of stiffness beta during ATD therapy correlated significantly with reductions in pulse pressure and retinal blood flow, but not with the reductions in systolic and mean blood pressure, or any of the plasma injury markers. In summary, the significant increase in stiffness beta in the hyperthyroid state may reflect the harmful effect of hyperthyroidism on the arterial wall, which may in turn result from increased stroke volume.
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PMID:Increased stiffness in common carotid artery in hyperthyroid Graves' disease patients. 1219 23

Epidemiological studies have demonstrated that pulse pressure and arterial stiffness are strong independent risk factors for all-cause and cardiovascular mortality, primary coronary heart disease (CHD) and stroke. Thus, treatment of hypertension and congestive heart failure (CHF) should aim to reduce arterial stiffness in order to lower afterload and pulse pressure, promote regression of left ventricular and arterial wall hypertrophy and, in CHF, increase cardiac output. Elevation of diastolic blood pressure appears to be beneficial to coronary perfusion and this may be particularly relevant in the setting of CHD. In patients with essential hypertension, numerous studies have shown a decrease in arterial stiffness with various pharmacological classes of antihypertensive agents (including beta-blockers, diuretics, ACE inhibitors, angiotensin II receptor antagonists and calcium antagonists), either acutely or during long-term studies. Their efficacy is not surprising, since blood pressure reduction unloads the stiff components of the arterial wall, such as collagen. However, it seems likely that pharmacological treatment has the capacity to decrease arterial stiffness beyond blood pressure reduction, because long-term drug administration can modify the wall components, including a reduction in collagen density or changes in the spatial arrangement of the wall materials. Whether classes of antihypertensive agents vary in their efficacy to affect arterial structure and thus influence arterial stiffness via a pressure-independent mechanism is more controversial and has yet to be evaluated in large-scale trials. A Consensus Conference on the 'Clinical Applications of Arterial Stiffness', held in Paris, June 17, 2000, recommended guidelines for further pharmacological and therapeutic studies on arterial stiffness. Among them were the following: 'To reach full normalisation of arterial stiffness, pharmacological and therapeutic trials should aim at lowering systolic and diastolic blood pressure to a larger extent than in previous studies and giving treatments for a longer duration than in most previous studies;Mainly, studies designed to demonstrate the prognostic value of the reduction of arterial stiffness are urgently needed. They should be performed in patients at high cardiovascular risk, on a large scale and a long-term basis, and include all-cause and cardiovascular mortality and cardiovascular morbidity'.
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PMID:[Drugs and arterial stiffness in hypertensive patients]. 1270 78

Hypertonia of the elbow joint complex is common in individuals with stroke and is related to the magnitude of the torque response (described by position dependent parameters) during constant velocity extensions. The objective of this study was to model position and velocity dependent characteristics of hypertonia. For both the more and less affected arms in 17 persons with chronic stroke, we measured the torque response to constant velocity stretches (30-180 degrees/s). The responses were combined in position-velocity space and parameters of stiffness, damping, and offset angle were determined from a linear spring-damper model of the torque profile. The model was assessed at three levels: (1) ability to describe the combined torque profile variance, (2) reliability of parameters, and (3) validity of parameters (i.e. clinical correlation). Model parameters fit the torque profiles of both arm groups well and exhibited day-to-day reliability. Stiffness (r=0.820), damping (r=0.816), and 'viscoelasticity' (r=0.909), a composite parameter index developed posthoc, were highly correlated to a manual assessment of hypertonia (Modified Ashworth Scale). Mechanically determined parameters of hypertonia graded along a continuum may have better discriminatory power than manual assessments and thus, may be better at tracking recovery and evaluating interventions.
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PMID:Linear spring-damper model of the hypertonic elbow: reliability and validity. 1294 55

Recent studies provide strong evidence that single myosin class V molecules transport vesicles and organelles processively along F-actin, taking several 36-nm steps, 'hand over hand', for each diffusional encounter. The mechanisms regulating myosin-V's processivity remain unknown. Here, we have used an optical-tweezers-based transducer to measure the effect of load on the mechanical interactions between rabbit skeletal F-actin and a single head of mouse brain myosin-V, which produces its working stroke in two phases. We found that the lifetimes of the first phase of the working stroke changed exponentially and about 10-fold over a range of pushing and pulling forces of +/- 1.5 pN. Stiffness measurements suggest that intramolecular forces could approach 3.6 pN when both heads are bound to F-actin, in which case extrapolation would predict the detachment kinetics of the front head to slow down 50-fold and the kinetics of the rear head to accelerate respectively. This synchronizing effect on the chemo-mechanical cycles of the heads increases the probability of the trail head detaching first and causes a strong increase in the number of forward steps per diffusional encounter over a system with no strain dependence.
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PMID:Load-dependent kinetics of myosin-V can explain its high processivity. 1613 83

Relatively little is known about the functional expression of cardiovascular angiotensin type 2 (AT2)-receptors in healthy young adult humans. We performed a randomised, placebo-controlled crossover study of the effects of intravenous administration of the selective AT2-receptor antagonist PD 123319 on haemodynamics and arterial stiffness in normal volunteers. Sixteen normal subjects aged 29.9+/-13.8 years (range 18-30 years) received an intravenous infusion of PD 123319 (10 mcg/minute for 5 minutes) and placebo, separated by one week. Haemodynamics (cardiac index, stroke index and systemic vascular resistance) were measured non-invasively using a BioZ.com thoracic impedance detection system. Blood pressure was measured from an arm cuff using oscillometry. Stiffness index, a measure of arterial stiffness, was measured using a Pulse Trace recorder. No significant changes in blood pressure (p=0.92), cardiac index (p=0.52), stroke index (p=0.61), systemic vascular resistance index (p=0.32) or stiffness index (p=0.57) was demonstrated following PD 123319 infusion, compared with placebo. The results of this study do not support the functional presence of cardiovascular AT2-receptors that mediate acute haemodynamic effects in healthy young adults. It remains possible that higher doses of PD 123319 may be required to demonstrate functional cardiovascular AT2-receptors in this population, if they are present.
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PMID:Effects of intravenous PD 123319 on haemodynamic and arterial stiffness indices in healthy volunteers. 1647 Apr 90

Structural changes in myosin motors and filaments during relaxation from short tetanic contractions of intact single fibres of frog tibialis anterior muscles at sarcomere length 2.14 mum, 4 degrees C were investigated by X-ray diffraction. Force declined at a steady rate for several hundred milliseconds after the last stimulus, while sarcomere lengths remained almost constant. During this isometric phase of relaxation the intensities of the equatorial and meridional M3 X-ray reflections associated with the radial and axial distributions of myosin motors also recovered at a steady rate towards their resting values, consistent with progressive net detachment of myosin motors from actin filaments. Stiffness measurements confirmed that the fraction of motors attached to actin declined at a constant rate, but also revealed a progressive increase in force per motor. The interference fine structure of the M3 reflection suggested that actin-attached myosin motors are displaced towards the start of their working stroke during isometric relaxation. There was negligible recovery of the intensities of the meridional and layer-line reflections associated with the quasi-helical distribution of myosin motors in resting muscle during isometric relaxation, and the 1.5% increase in the axial periodicity of the myosin filament associated with muscle activation was not reversed. When force had decreased to roughly half its tetanus plateau value, the isometric phase of relaxation abruptly ended, and the ensuing chaotic relaxation had an exponential half-time of ca 60 ms. Recovery of the equatorial X-ray intensities was largely complete during chaotic relaxation, but the other X-ray signals recovered more slowly than force.
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PMID:Structural changes in myosin motors and filaments during relaxation of skeletal muscle. 1965 65


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