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PubMed2000

Female pelvic organ prolapse: a comparison of triphasic dynamic MR imaging and triphasic fluoroscopic cystocolpoproctography.

OBJECTIVE: This study compared dynamic MR imaging with fluoroscopic cystocolpoproctography for the detection and measurement of prolapse of pelvic organs. SUBJECTS AND METHODS: Ten patients underwent triphasic dynamic MR imaging and triphasic fluoroscopic cystocolpoproctography with identical amounts of contrast material to opacify the bladder, vagina, and rectum. The dynamic MR imaging procedure included cine-loop presentation. Each examination was analyzed to determine the presence and extent of prolapse of pelvic organs based on specific measurements. RESULTS: Both dynamic MR imaging and fluoroscopic cystocolpoproctography revealed 10 rectoceles (mean extents, 2.85 and 2.45 cm, respectively). Nine cystoceles were revealed by both dynamic MR imaging (mean extent, 4.05 cm) and fluoroscopy (mean extent, 4.55 cm). Seven enteroceles were revealed, one of which was initially not seen on dynamic MR imaging. Two sigmoidoceles were revealed, one of which was not seen on fluoroscopy. The mean extent of the enteroceles and sigmoidoceles on dynamic MR imaging was 3.50 cm, and the mean extent on fluoroscopy was 4.25 cm. Nine of the 10 patients were able to defecate in the supine position on the MR imaging table. Patients were divided equally in their preference for dynamic MR imaging or fluoroscopic cystocolpoproctography. CONCLUSION: Triphasic dynamic MR imaging and triphasic fluoroscopic cystocolpoproctograpy show similar detection rates for prolapse of pelvic organs. Although dynamic MR imaging underestimates the extent of cystoceles and enteroceles, it has the advantage of revealing all pelvic organs and the pelvic floor musculature in a multiplanar cine-loop presentation.

Adult↗
PubMed1996

Dynamical Cell Assembly Hypothesis - Theoretical Possibility of Spatio-temporal Coding in the Cortex.

This paper is an attempt to understand how knowledge and events are represented and processed in the brain. An important point is the question of what carries information in the brain - the mean firing rate or the timing of spikes? The idea we want to pursue is that, contrary to the traditional view, the brain might use higher order statistics, which means in essence that timing of spikes plays a critical role in encoding, representing, and processing knowledge and events in the brain.A recently revealed salient nature of cortical pyramidal cells, i.e., the high variability of inter-spike intervals suggests that a cortical neuron may function effectively as a coincidence detector. At the same time, non-classical experimental phenomena of task-related, short time-scaled dynamical modulations of temporal correlations between neurons suggest a non-classical view on the dynamics working in the brain. In response to contexts or external events, a group of neurons, a dynamical cell assembly, spontaneously organizes, linked temporarily by coincident timing of incident spikes, showing correlated firing with each other. This is an emergent property of neuronal populations in the cortex.We make a theoretical exploration on issues as (1) the description of such emergent dynamics of dynamical cell assemblies based on the working hypothesis that a cortica neuron functions effectively as a coincidence detector, and (2) the principle of spatio-temporal coding based on the hypothetical emergent dynamics. Note that the conventional rate coding hypothesis does not give satisfactory answers to fundamental questions on the representation and processing of knowledge or events in the brain, e.g., the questions of cross-modular integration of information or the binding problem, and representation of hierarchical knowledge etc.The first goal is to give a non-encyclopedic review on (1) the temporal structure of spike sequences, focusing on the question of the basic code in the brain; (2) the paradigms on representation of knowledge and events proposed from a theoretical or experimental basis. The classical paradigms of Hebb and Barlow with their experimental and theoretical critiques, and more recently proposed experiment-based paradigms are reviewed. Also a review is given on (3) the experimentally observed spatio-temporal structure of spike dynamics.The second goal is to give a description of the dynamical cell assembly - the central concept in this paper. Aside from the question of physiological basis, we make a theoretical study, under a working hypothesis that a cortical neuron functions effectively as a coincidence detector, on the emergent dynamics of cell assemblies, and also examine how the observed experimental data could be explained within this theoretical setting.We also try to give the principle of spatio-temporal coding based on the dynamical cell assembly framework. A key concept is the internal mechanism of "dialogue" among neuronal pools in the brain. This provides a dynamical foundation of bi-directional interactions for the linkage of distant modules to create integrated information. We present a simple model in order to illustrate the working principle of coincidence detector systems. Relations with other temporal coding paradigms are also discussed. Copyright 1996 Elsevier Science Ltd.

Journal Article↗
PubMed2003

Suppression of microtubule dynamics by epothilone B is associated with mitotic arrest.

The epothilones are a group of novel microtubule-targeted, antimitotic compounds that have a paclitaxel-like, assembly enhancing effect on tubulin in vitro as well as in cultured cells. We hypothesize that epothilones induce mitotic arrest by suppressing microtubule dynamics. To test this hypothesis, we used MCF7 cells stably transfected with GFP-alpha-tubulin to analyze microtubule dynamics at three concentrations of epothilone B, one that induced no mitotic arrest (0.2 nM, 20 h), one that induced one-third maximal mitotic arrest (IC(33,) 2 nM, 20 h), and one that induced half-maximal mitotic arrest (IC(50,) 3.5 nM, 20 h). We found that epothilone B suppressed microtubule dynamics in a concentration-dependent manner coincident with mitotic block. At 0.2 nM epothilone B, dynamics were not significantly altered. At 2 nM epothilone B (IC(33)), the mean growth and shortening rates were decreased by 38 and 27%, respectively. Dynamicity was decreased by 47%. At the IC(50), 80% of the cells had nearly complete stabilization of microtubule dynamics, and no anaphase or telophase figures were observed. Comparison of the effects of epothilone B on microtubule dynamics with those of paclitaxel indicated that both drugs alter the same microtubule dynamic parameters to a similar extent. At the IC(50) for mitotic arrest, dynamicity was reduced by 54% by paclitaxel compared with 62% for epothilone B. In 65% of the cells treated with paclitaxel, the microtubules were completely stabilized. Thus, the effects of epothilone B on microtubule dynamics are remarkably similar to those of paclitaxel, suggesting that both drugs induce mitotic block by a similar mechanism.

Anaphase↗
PubMedDate not supplied

Usefulness of contrast-enhanced ultrasonography with dynamic flow imaging to evaluate therapeutic effects for hepatocellular carcinoma.

BACKGROUND/AIMS: To examine the usefulness of dynamic flow imaging in identifying the therapeutic effects for hepatocellular carcinoma, we performed contrast-enhanced ultrasonography with Levovist. METHODOLOGY: Tumor vascularity of 48 hepatocellular carcinoma nodules in 27 patients infected with hepatitis C virus was assessed before and after radiofrequency ablation therapy by dynamic flow imaging with a wide-band power Doppler technology. RESULTS: All patients showed hypervascular enhancement of hepatocellular carcinoma on contrast-enhanced ultrasonography and/or dynamic computed tomography. The dynamic flow was obtained as vascular and perfusion images of hepatic tumors. The diameters of tumors were 1.1-2.0 cm in 12 nodules, 2.1-3.0 cm in 28, and 3.1-5.0 cm in 8, respectively. We were able to assess the tumor vascularities in 45 of 48 nodules before radiofrequency ablation by the dynamic flow. Three nodules showed insufficient dynamic flow which was located approximately 9 cm in depth from the body surface. The dynamic flow study for the therapeutic efficacy indicated that the tumor vessels disappeared in 43 of the 45 visible nodules. The tumor vascularities were noted in the remaining 2 nodules, and they were successfully retreated by radiofrequency ablation. The frequencies detecting positive enhancement in pretreatment and post-treatment were almost equivalent between vascular phase of dynamic flow on ultrasonography and early phase on helical dynamic computed tomography, although 5 nodules gave different findings; 2 were positive only on ultrasonography, and 3 were positive only on computed tomography. A major complication of radiofrequency ablation procedure was noted in only one case associated with intestinal edema, but it was cured by medical treatment. CONCLUSIONS: The results indicated that contrast-enhanced dynamic flow imaging on ultrasonography is a reliable tool to evaluate intratumoral vascularity both before and after radiofrequency ablation treatment in patients with hepatocellular carcinoma.

Aged↗
PubMed1983

[Static and dynamic responses of mechanoreceptors within gastric wall to intragastric pressure changes].

Adult cats were used under sodium pentobarbital anesthesia in order to investigate static and dynamic responses of mechanoreceptors within gastric wall to intragastric pressure changes caused by air inflation of the stomach. By means of tungsten microelectrodes, 17 afferent activities in response to gastric inflation were recorded from cervical vagal nerve trunk. Two modes of gastric inflation were applied (a) intermittent type for studying static response and (b) staircase one for studying dynamic response. The following results were obtained: Static response: An exponential relation was observed between intragastric pressure and frequency of gastric afferent activity, so maximal estimated frequency (fmax) and pressure constant could be calculated using method of extrapolation and method of least squares. Pressure constant is defined as an intragastric pressure at which frequency response is about 63% of fmax. Only one peak was seen in histogram of pressure constants of 17 afferent activities. Their average mean was 24 +/- 3 cmH2O. Dynamic response: A linear relation was observed between dynamic index and rate of pressure change. Dynamic index is defined as the net increment of frequency on dynamic phase of gastric inflation obtained by the difference between the maximal frequency and the frequency at three seconds after dynamic inflation. Dynamic constant which is considered to indicate the sensitivity of the receptor is defined by the slope of the regression line of dynamic index and rate of pressure change. Histogram of dynamic constant revealed two peaks, the large one with a mean of 10.2 +/- 4.0 imp divided by s/cmH2O divided by s and the small one with a mean of 2.5 +/- 0.5 imp divided by s/cmH2O divided by s.

Action Potentials↗
PubMedDate not supplied

Cervical carcinoma: dynamic MR imaging with a turbo-FLASH technique.

The purpose of this study was to evaluate the characteristic findings of cervical carcinoma in dynamic MR imaging with a turbo-FLASH technique and to investigate the cause of the hyperintense rim surrounding the tumor on dynamic MR images by comparing them with the pathological findings in the resected specimens. Sixty consecutive patients with cervical carcinoma were included in this study. Dynamic MR imaging was performed with the rapid administration of Gd-DTPA using the turbo-FLASH technique. After dynamic MR imaging, T1-weighted spin echo (SE) images were obtained. Dynamic patterns of the lesions were investigated from images acquired in the early and late phases of dynamic MR imaging. The causes of the hyperintense rim were investigated by comparing dynamic MR images with the pathological findings. Most of the cervical carcinomas showed higher signal intensity than normal cervical stroma in the early phase of dynamic MR imaging. The pathological findings of the hyperintense rim on dynamic MR images differed according to the time of appearance of the hyperintense rim. Dynamic MR imaging with the turbo-FLASH technique, which shows high contrast between the lesion and normal cervical stroma, should be performed before obtaining contrast-enhanced T1-weighted SE images in patients with cervical carcinoma.

Adult↗
PubMed2002

Changes in actin and myosin structural dynamics due to their weak and strong interactions.

Figure 3 summarizes the effects of actomyosin binding on the internal and global dynamics of either protein, as discussed in this chapter. These effects depend primarily on the strength of the interaction; which in turn depends on the state of the nucleotide at the myosin active site. When either no nucleotide or ADP is bound, the interaction is strong and the effect on each protein is maximal. When the nucleotide is ATP or ADP.Pi, or the equivalent nonhydrolyzable analogs, the interaction is weak and the effect on molecular dynamics of each protein is minimal. The weaker effects in weak-binding states are not simply the reflection of lower occupancy of binding sites--the molecular models in Fig. 3 illustrate the effects of the formation of the ternary complex, after correction for the free actin and myosin in the system. Thus EPR on myosin (Berger and Thomas 1991; Thomas et al. 1995) and pyrene fluorescence studies on actin (Geeves 1991) have shown that the formation of a ternary complex has a negligible effect on the internal dynamics of both [figure: see text] proteins (left side of Fig. 3, white arrows). As shown by both EPR (Baker et al. 1998; Roopnarine et al. 1998) and phosphorescence (Ramachandran and Thomas 1999), both domains of myosin are dynamically disordered in weak-binding states, and this is essentially unaffected by the formation of the ternary complex (left side of Fig. 3, indicated by disordered myosin domains). The only substantial effect of the formation of the weak interaction that has been reported is the EPR-detected (Ostap and Thomas 1991) restriction of the global dynamics of actin upon weak myosin binding (left column of Fig. 3, gray arrow). The effects of strong actomyosin formation are much more dramatic. While substantial rotational dynamics, both internal and global, exist in both myosin and actin in the presence of ADP or the absence of nucleotides, spin label EPR, pyrene fluorescence, and phosphorescence all show dramatic restrictions in these motions upon formation of the strong ternary complex (right column of Fig. 3). One implication of this is that the weak-to-strong transition is accompanied by a disorder-to-order transition in both actin and myosin, and this is itself an excellent candidate for the structural change that produces force (Thomas et al. 1995). Another clear implication is that the crystal structures obtained for isolated myosin and actin are not likely to be reliable representations of structures that exist in ternary complexes of these proteins (Rayment et al. 1993a and 1993b; Dominguez et al. 1998; Houdusse et al. 1999). This is clearly true of the strong-binding states, since the spectroscopic studies indicate consistently that substantial changes occur in both proteins upon strong complex formation. For the weak complexes, the problem is not that complex formation induces large structural changes, but that the structures themselves are dynamically disordered. This is probably why so many different structures have been obtained for myosin S1 with nucleotides bound--each crystal is selecting one of the many different substates represented by the dynamic ensemble. Finally, there is the problem that the structures of actomyosin complexes are probably influenced strongly by their mechanical coupling to muscle protein lattice (Baker at al. 2000). Thus, even if co-crystals of actin and myosin are obtained in the future, an accurate description of the structural changes involved in force generation will require further experiments using site-directed spectroscopic probes of both actin and myosin, in order to detect the structural dynamics of these ternary complexes under physiological conditions.

Actins↗
PubMed2005

Nonlinear dynamical analysis of EEG and MEG: review of an emerging field.

Many complex and interesting phenomena in nature are due to nonlinear phenomena. The theory of nonlinear dynamical systems, also called 'chaos theory', has now progressed to a stage, where it becomes possible to study self-organization and pattern formation in the complex neuronal networks of the brain. One approach to nonlinear time series analysis consists of reconstructing, from time series of EEG or MEG, an attractor of the underlying dynamical system, and characterizing it in terms of its dimension (an estimate of the degrees of freedom of the system), or its Lyapunov exponents and entropy (reflecting unpredictability of the dynamics due to the sensitive dependence on initial conditions). More recently developed nonlinear measures characterize other features of local brain dynamics (forecasting, time asymmetry, determinism) or the nonlinear synchronization between recordings from different brain regions. Nonlinear time series has been applied to EEG and MEG of healthy subjects during no-task resting states, perceptual processing, performance of cognitive tasks and different sleep stages. Many pathologic states have been examined as well, ranging from toxic states, seizures, and psychiatric disorders to Alzheimer's, Parkinson's and Cre1utzfeldt-Jakob's disease. Interpretation of these results in terms of 'functional sources' and 'functional networks' allows the identification of three basic patterns of brain dynamics: (i) normal, ongoing dynamics during a no-task, resting state in healthy subjects; this state is characterized by a high dimensional complexity and a relatively low and fluctuating level of synchronization of the neuronal networks; (ii) hypersynchronous, highly nonlinear dynamics of epileptic seizures; (iii) dynamics of degenerative encephalopathies with an abnormally low level of between area synchronization. Only intermediate levels of rapidly fluctuating synchronization, possibly due to critical dynamics near a phase transition, are associated with normal information processing, whereas both hyper-as well as hyposynchronous states result in impaired information processing and disturbed consciousness.

Animals↗
PubMed2005

Physiological modelling of agitation-sedation dynamics including endogenous agitation reduction.

Sedation administration and agitation management are fundamental activities in any intensive care unit. A lack of objective measures of agitation and sedation, as well as poor understanding of the underlying dynamics, contribute to inefficient outcomes and expensive healthcare. Recent models of agitation-sedation pharmacodynamics have enhanced understanding of the underlying dynamics and enable development of advanced protocols for semi-automated sedation administration. However, these initial models do not capture all observed dynamics, particularly periods of low sedative infusion. A physiologically representative model that incorporates endogenous agitation reduction (EAR) dynamics is presented and validated using data from 37 critical care patients. High median relative average normalised density (RAND) values of 0.77 and 0.78 support and minimum RAND values of 0.51 and 0.55 for models without and with EAR dynamics respectively show that both models are valid representations of the fundamental agitation-sedation dynamics present in a broad spectrum of intensive care unit (ICU) patients. While the addition of the EAR dynamic increases the ability of the model to capture the observed dynamics of the agitation-sedation system, the improvement is relatively small and the sensitivity of the model to the EAR dynamic is low. Although this may represent a limitation of the model, the inclusion of EAR is shown to be important for accurately capturing periods of low, or no, sedative infusion, such as during weaning prior to extubation.

Biomedical Engineering↗
PubMed2002

Non-linear dynamics models characterizing long-term virological data from AIDS clinical trials.

Human immunodeficiency virus (HIV) dynamics represent a complicated variant of the text-book case of non-linear dynamics: predator-prey interaction. The interaction can be described as naturally reproducing T-cells (prey) hunted and killed by virus (predator). Virus reproduce and increase in number as a consequence of successful predation; this is countered by the production of T-cells and the reaction of the immune system. Multi-drug anti-HIV therapy attempts to alter the natural dynamics of the predator-prey interaction by decreasing the reproductive capability of the virus and hence predation. These dynamics are further complicated by varying compliance to treatment and insurgence of resistance to treatment. When following the temporal progression of viral load in plasma during therapy one observes a short-term (1-12 weeks) decrease in viral load. In the long-term (more than 12 weeks from the beginning of therapy) the reduction in viral load is either sustained, or it is followed by a rebound, oscillations and a new (generally lower than at the beginning of therapy) viral load level. Biomathematicians have investigated these dynamics by means of simulations. However the estimation of the parameters associated with the dynamics from real data has been mostly limited to the case of simplified, in particular linearized, models. Linearized model can only describe the short-term changes of viral load during therapy and can only predict (apparent) suppression. In this paper we put forward relatively simple models to characterize long-term virus dynamics which can incorporate different factors associated with resurgence: (Fl) the intrinsic non-linear HIV-1 dynamics, (F2) drug exposure and in particular compliance to treatment, and (F3) insurgence of resistant HIV-1 strains. The main goal is to obtain models which are mathematically identifiable given only measurements of viral load, while retaining the most crucial features of HIV dynamics. For the purpose of illustration we demonstrate an application of the models using real AIDS clinical trial data involving patients treated with a combination of anti-retroviral agents using a model which incorporates compliance data.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Visibility of the environmental noise modulating population dynamics.

Characterizing population fluctuations and their causes is a major theme in population ecology. The debate is on the relative merits of density-dependent and density-independent effects. One paradigm (revived by the research on global warming and its relation to long-term population data) states that fluctuations in population densities can often be accounted for by external noise. Several empirical models have been suggested to support this view. We followed this by assuming a given population skeleton dynamics (Ricker dynamics and second-order autoregressive dynamics) topped off with noise composed of low- and high-frequency components. Our aim was to determine to what extent the modulated population dynamics correlate with the noise signal. High correlations (with time-lag -1) were observed with both model categories in the region of stable dynamics, but not in the region of periodic or complex dynamics. This finding is not very sensitive to low-frequency noise. High correlations throughout the entire range of dynamics are only achievable when the impact of the noise is very high. Fitted parameter values of skeleton dynamics modulated with noise are prone to err substantially. This casts doubt as to what degree the underlying dynamics are any more recognizable after being modulated by the external noise.

Animals↗
PubMed2001

Ansatz for dynamical hierarchies.

Complex, robust functionalities can be generated naturally in at least two ways: by the assembly of structures and by the evolution of structures. This work is concerned with spontaneous formation of structures. We define the notion of dynamical hierarchies in natural systems and show the importance of this particular kind of organization for living systems. We then define a framework that enables us to formulate, investigate, and manipulate such dynamical hierarchies. This framework allows us to simultaneously investigate different levels of description together with their interrelationship, which is necessary to understand the nature of dynamical hierarchies. Our framework is then applied to a concrete and very simple formal, physicochemical, dynamical hierarchy involving water and monomers at level one, polymers and water at level two, and micelles (polymer aggregates) and water at level three. Formulating this system as a simple two-dimensional molecular dynamics (MD) lattice gas allows us within one dynamical system to demonstrate the successive emergence of two higher levels (three levels all together) of robust structures with associated properties. Second, we demonstrate how the framework for dynamical hierarchies can be used for realistic (predictive) physicochemical simulation of molecular self-assembly and self-organization processes. We discuss the detailed process of micellation using the three-dimensional MD lattice gas. Finally, from these examples we can infer principles about formal dynamical hierarchies. We present an ansatz for how to generate robust, higher-order emergent properties in formal dynamical systems that is based on a conjecture of a necessary minimal complexity within the fundamental interacting structures once a particular simulation framework is chosen.

Chemical Phenomena↗
PubMed1999

Smoluchowski dynamics of the vnd/NK-2 homeodomain from Drosophila melanogaster: first-order mode-coupling approximation.

This work is the first in a series devoted to applying mode coupling diffusion theory to the derivation of local dynamics properties of proteins in solution. The first-order mode-coupling approximation, or optimized Rouse-Zimm local dynamics (ORZLD), is applied here to derive the rotational dynamics of the bonds and compare the calculated with the experimental nmr 15N spin-lattice relaxation time behavior of the vnd/NK-2 homeodomain from Drosophila melanogaster. The starting point for the calculations is the experimental three-dimensional structure of the homeodomain determined by multidimensional nmr spectroscopy. The results of the computations are compared with experimentally measured 15N spin-lattice relaxation times T1, at 34.5 and 60.8 MHz, to check the first-order approximation. To estimate the relative importance of internal and overall rotation, both rigid and fluctuating dynamic models are examined, with fluctuations evaluated using molecular dynamics (MD) simulations. The correlation times for the fundamental bond vector time correlation function and for the second-order bond orientational TCF are obtained as a function of the residue number for vnd/NK-2. The stability of the corresponding local dynamics pattern for the fluctuating structure as a function of the length of the MD trajectory is presented. Diffusive dynamics, which is essentially free of model parameters even at first order in the mode-coupling diffusion approach, confirm that local dynamics of proteins can be described in terms of rotational diffusion of a fluctuating quasi-rigid structure. The comparison with the nmr data shows that the first-order mode coupling diffusion approximation accounts for the correct order of magnitude of the results and of important qualitative aspects of the data sensitive to conformational changes. Indications are obtained from this study to efficiently extend the theory to higher order in the mode-coupling expansion. These results demonstrate the promise of the mode-coupling approach, where the local dynamics of proteins is described in terms of rotational diffusion of a fluctuating quasi-rigid structure, to analyze nmr spin-lattice relaxation behavior.

Animals↗
PubMed2006

Dynamic mechanical properties of 3D fiber-deposited PEOT/PBT scaffolds: an experimental and numerical analysis.

Mechanical properties of three-dimensional (3D) scaffolds can be appropriately modulated through novel fabrication techniques like 3D fiber deposition (3DF), by varying scaffold's pore size and shape. Dynamic stiffness, in particular, can be considered as an important property to optimize the scaffold structure for its ultimate in vivo application to regenerate a natural tissue. Experimental data from dynamic mechanical analysis (DMA) reveal a dependence of the dynamic stiffness of the scaffold on the intrinsic mechanical and physicochemical properties of the material used, and on the overall porosity and architecture of the construct. The aim of this study was to assess the relationship between the aforementioned parameters, through a mathematical model, which was derived from the experimental mechanical data. As an example of how mechanical properties can be tailored to match the natural tissue to be replaced, articular bovine cartilage and porcine knee meniscus cartilage dynamic stiffness were measured and related to the modeled 3DF scaffolds dynamic stiffness. The dynamic stiffness of 3DF scaffolds from poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT) copolymers was measured with DMA. With increasing porosity, the dynamic stiffness was found to decrease in an exponential manner. The influence of the scaffold architecture (or pore shape) and of the molecular network properties of the copolymers was expressed as a scaffold characteristic coefficient alpha, which modulates the porosity effect. This model was validated through an FEA numerical simulation performed on the structures that were experimentally tested. The relative deviation between the experimental and the finite element model was less than 15% for all of the constructs with a dynamic stiffness higher than 1 MPa. Therefore, we conclude that the mathematical model introduced can be used to predict the dynamic stiffness of a porous PEOT/PBT scaffold, and to choose the biomechanically optimal structure for tissue engineering applications.

Animals↗
PubMed1999

Periosteum responds to dynamic fluid pressure by proliferating in vitro.

Periosteum provides a source of undifferentiated chondrocyte precursor cells for fracture healing that can also be used for cartilage repair. The quantity of cartilage that can be produced, which is a determining factor in fracture healing and cartilage repair, is related to the number of available stem cells in the cambium layer. Cartilage formation during both of these processes is enhanced by motion of the fracture or joint in which periosteum has been transplanted. The effect of dynamic fluid pressure on cell proliferation in periosteal tissue cultures was determined in 452 explants from 60 immature (2-month-old) New Zealand White rabbits. The explants were cultured in agarose suspension for 1-14 days. One group was subjected to cyclic hydrostatic pressure, which is referred to as dynamic fluid pressure, at 13 kPa and a frequency of 0.3 Hz. Control explants were cultured in similar chambers without application of pressure. DNA synthesis ([3H]thymidine uptake) and total DNA were measured. The temporal pattern and distribution of cell proliferation in periosteum were evaluated with autoradiography and immunostaining with proliferating cell nuclear antigen. Dynamic fluid pressure increased proliferation of periosteal cells significantly, as indicated by a significant increase in [3H]thymidine uptake at all time points and a higher amount of total DNA compared with control values. On day 3, when DNA synthesis reached a peak in periosteal explants, [3H]thymidine uptake was 97,000+/-5,700 dpm/microg DNA in the group exposed to dynamic fluid pressure and 46,000+/-6,000 dpm/microg in the controls (p < 0.001). Aphidicolin, which blocks DNA polymerase alpha, inhibited [3H]thymidine uptake in a dose-dependent manner in the group subjected to dynamic fluid pressure as well as in the positive control (treated with 10 ng/ml of transforming growth factor-beta1) and negative control (no added growth factors) groups, confirming that [3H]thymidine measurements represent proliferation and dynamic fluid pressure stimulates DNA synthesis. Total DNA was also significantly higher in the group exposed to dynamic fluid pressure (5,700+/-720 ng/mg wet weight) than in the controls (3,700+/-630) on day 3 (p < 0.01). Autoradiographs with [3H]thymidine revealed that one or two cell cycles of proliferation took place in the fibrous layer prior to proliferation in the cambium layer (where chondrocyte precursors reside). Proliferating cell nuclear antigen immunophotomicrographs confirmed the increased proliferative activity due to dynamic fluid pressure. These findings suggest either a paracrine signaling mechanism between the cells in these two layers of the periosteum or recruitment/migration of proliferating cells from the fibrous to the cambium layer. On the basis of the data presented in this study, we postulate that cells in the fibrous layer respond initially to mechanical stimulation by releasing growth factors that induce undifferentiated cells in the cambium layer to divide and differentiate into chondrocytes. These data indicate that cell proliferation in the early stages of chondrogenesis is stimulated by mechanical factors. These findings are important because they provide a possible explanation for the increase in cartilage repair tissue seen in joints subjected to continuous passive motion. The model of in vitro periosteal chondrogenesis under dynamic fluid pressure is valuable for studying the mechanisms by which mechanical factors might be involved in the formation of cartilage in the early fracture callus and during cartilage repair.

Aging↗
PubMed2004

Ultrafast dynamics of a solution in spatially restricted environments studied by photothermal spectroscopies.

The ultrafast dynamics of a solution in spatially restricted environments was studied by using the ultrafast transient lens (UTL) method. The UTL method is used to monitor the molecular dynamics of a solution by means of a change in the refractive index, which is advantageous for investigating the molecular dynamics of restricted systems. We investigated the photoisomerization of azobenzene derivatives in cyclodextrin nanocavities and revealed how the confinement affects the photoisomerization dynamics and yields. We also studied the relaxation dynamics of photo-excited auramine O (AuO) in a water/aerosol-OT/n-heptane reversed micelle. Both the perturbed properties of the included water and the interactions between AuO and the interface of the reversed micelle strongly appeared to affect the relaxation dynamics. At the same time, we observed a change in the refractive index suggesting a structural change of the micelles in the picosecond region that could not be detected by transient absorption spectroscopy. In addition, we developed the total internal reflection UTL (TIR-UTL) method to monitor the ultrafast molecular dynamics at the liquid interface. The relaxation dynamics of photoexcited AuO at the silica/water interface were observed with subpicosecond time resolution, and it was revealed that the interaction with the interface strongly inhibited the relaxation process. These results demonstrated the advantages of the UTL method for investigating the molecular dynamics of a solution in spatially restricted environments.

Azo Compounds↗
PubMed1989

Learning and recall in a dynamic theory of coordination patterns.

A dynamic theory of learning and recall of coordination patterns is developed in the context of relative timing skills. Characterizing the coordination patterns in such skills by the collective variable, relative phase, we choose a model system in which the intrinsic pattern dynamics as well as the influence of environmental and memorized information are well understood from previous experimental and theoretical work. To describe learning we endow memorized information with dynamics which is determined by a phenomenological strategy. Similarly, additional degrees of freedom must be introduced to understand recall. As such recall variables we choose the relative strengths with which each memorized pattern acts on the pattern dynamics and model their dynamics phenomenologically. The resulting dynamical system that resembles models used in pattern recognition theory is shown to adequately describe the learning and recall processes. Moreover, due to the operational character of the theory, several predictions emerge that are open to experimental test. In particular, we show under which conditions phase transitions occur in the dynamics of the coordination patterns during learning and during recall. Considering different time scales and their relations we demonstrate how these phase transitions can be identified and observed. Other predictions include the influence of the intrinsic pattern dynamics on the recall process and the existence of history and hysteresis effects in recall. We discuss different forms of "forgetting" and differentiation of memorized information. The results show how a new theoretical view of learning and recall as change of behavioral dynamics can lead to a different understanding of these processes by providing testable predictions.

Extremities↗
PubMed1998

Dynamic nonlinear vago-sympathetic interaction in regulating heart rate.

Although the characteristics of the static interactions between the sympathetic and parasympathetic nervous systems in regulating heart rate have been well established, how the dynamic interaction modulates the heart rate response remains unknown. Thus, we investigated the dynamic interaction by estimating the transfer function from nerve stimulation to heart rate, using band-limited Gaussian white noise, in anesthetized rabbits. Concomitant tonic vagal stimulation at 5 and 10 Hz increased the gain of the transfer function relating dynamic sympathetic stimulation to heart rate by 55.0%+/-40.1% and 80.7%+/-50.5%, respectively (P < 0.05). Concomitant tonic sympathetic stimulation at 5 and 10 Hz increased the gain of the transfer function relating dynamic vagal stimulation to heart rate by 18.2%+/-17.9% and 24.1%+/-18.0%, respectively (P < 0.05). Such bidirectional augmentation was also observed during simultaneous dynamic stimulation of the sympathetic and vagal nerves independent of their stimulation patterns. Because of these characteristics, changes in sympathetic or vagal tone alone can alter the dynamic heart rate response to stimulation of the other nerve. We explained this phenomenon by assuming a sigmoidal static relationship between autonomic nerve activity and heart rate. To confirm this assumption, we identified the static and dynamic characteristics of heart rate regulation by a neural network analysis, using large-amplitude Gaussian white noise input. To examine the mechanism involved in the bidirectional augmentation, we increased cytosolic adenosine 3',5'-cyclic monophosphate (cAMP) at the postjunctional effector site by applying pharmacological interventions. The cAMP accumulation increased the gain of the transfer function relating dynamic vagal stimulation to heart rate. Thus, accumulation of cAMP contributes, at least in part, to the sympathetic augmentation of the dynamic vagal control of heart rate.

Animals↗