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Spreading of fatigue-related effects from active to inactive parts in the medial gastrocnemius muscle of the cat.

In the medial gastrocnemius muscle of the decerebrate cat, the spatial spread of fatigue between active and inactive muscle parts was studied. Conditioning fatiguing stimulation (CFS) was applied to a part of the muscle to test whether it had an effect on the contraction efficiency in an unstimulated part. To exclude somato-sympathetic reflexes during CFS, a full rhizotomy of the lumbo-sacral spinal cord was performed. The same ipsilateral ventral root, either L7 or S1, was divided into seven filaments, one of which was used for the test stimulation, and four or five for CFS. The CFS consisted of 12 s sessions of distributed stimulation of five (or four) filaments at a rate of 40 s(-1), the sessions were repeated, every 40 s, 15 or more times. The test consisted of 12 s of regular stimulation at a rate of 10 s(-1), preceded and followed by a single stimulus. The tests applied just after CFS showed a strong decline of both tension and electromyogram (EMG), amounting to only [mean (SD)] 0.45 (0.18) and 0.51 (0.19) (n = 15), respectively, of the corresponding values in the tests before CFS. It thus turned out that depressive fatigue-related effects could spread within the muscle. At the same time, control reactions recorded in the lateral gastrocnemius during stimulation of its cut nerve did not change. Subsequent repetitions of the tests usually revealed a tendency towards restoration. The EMG reactions recovered more quickly than tension. The depression of EMG after CFS was accompanied by a slowing of the constituent M-waves; their latencies decreased during restoration. Distinct changes in the systemic blood pressure were observed during CFS. These changes were usually correlated well with muscle tension changes. The factors possibly underlying the observed effects may include diffusion of metabolites from active to inactive muscle fibres, lowering of the efficiency of neuro-muscular transmission due to squeezing of efferent motor terminals and changes in outer metabolite content, as well as local hypoxia due to increases in intramuscular pressure.

Animals↗

Fast imaging in two dimensions resolves extensive sources of Ca2+ sparks in frog skeletal muscle.

Ca2+ sparks were monitored by confocal laser-scanning microscopy of fluo-3 at video rates, in fast twitch muscle fibres, stimulated by exposure to caffeine and/or low [Mg2+]. Scanning was in two spatial dimensions ('2D') or 2D plus time, at 4 ms per image frame. Sparks were identified in 2D images of normalized fluorescence by an automatic procedure, which also evaluated the event's location and morphometric parameters. Most sparks were circular, but some were elongated, especially in caffeine. Separation of the spark from circular symmetry was quantified by its eccentricity (length/width - 1). In an internal solution with 0.4 mM [Mg2+], sparks (989 events in 4 cells) had amplitude 0.73, width 1.94 microm, length 2.12 microm and eccentricity not significantly different from 0. Upon application of 1 mM caffeine, length (of 2578 events in the same cells) increased significantly (by 0.41 microm, or 19 %), width increased by 0.18 microm (9 %) and amplitude decreased slightly. The eccentricity became significantly different from 0, and the sparks' long axis predominantly oriented parallel to the plane of the Z disks. More than 10 % of the events in caffeine had length greater than 4 microm, a relatively flat top, and a sharp termination at both ends of the major axis. Additionally, there was only a weak correlation between eccentricity and amplitude. These properties suggest that the elongated events are produced by simultaneous opening of multiple channels within a junction, rather than anisotropic diffusion of Ca2+ or random overlap of round sparks. Elongated events often increased in eccentricity early in their evolution. Then, most remained elongated during their rise and decay, while others spread spatially in the plane of the Z disks. In 1-2 % of the events, the centre of mass migrated in space, over time, at approximately 0.1 microm x ms(-1). These spatio-temporal features require the involvement of multiple release channels, at spatially resolvable locations. Because sources often spread over distances greater than 1 or 2 microm, and arrays of junctional elements (couplons) are at most 1.2 microm long, it must be possible for activation of release to propagate between neighbouring couplons, especially under the influence of caffeine and/or low [Mg2+].

Aniline Compounds↗

A spatial-frequency dependent quantum accounting diagram and detective quantum efficiency model of signal and noise propagation in cascaded imaging systems.

The detective quantum efficiency (DQE) is a system parameter that can be used to accurately describe image noise transfer characteristics through many imaging systems. A simpler approach used by some investigators, particularly when evaluating new ideas and system designs, is to describe the system as a series of cascaded stages. Each stage may correspond to either an increase in the number of quanta (e.g., conversion from x-ray to optical quanta in a radiographic screen), or a loss (a detection or coupling probability). The number of secondary quanta at each stage per incident primary quantum is given by the product of all preceding gains, and can be displayed graphically for convenient interpretation. The stage with the fewest quanta is called the "quantum sink," limiting the pixel signal-to-noise ratio to less than the square root of the number of quanta per pixel. This conventional zero-spatial-frequency "quantum accounting diagram" (QAD), however, neglects the spatial spreading of secondary quanta and can seriously underestimate image noise. It is shown that this problem is avoided with the introduction of a spatial-frequency dependent QAD, expressed as the product of the gains and squared modulation-transfer functions (MTF) of each stage. A generalized expression is developed for the DQE of a cascaded imaging system that is dependent only on the gain, gain Poisson excess (related to the variance), and MTF, of each stage. A direct relationship is then shown to exist between the DQE and values in the QAD. The QAD of a hypothetical system consisting of a charge-coupled device camera and a scintillating screen is evaluated as an illustrative example. The conventional zero-frequency analysis suggests two quantum sinks occur with approximately equal importance: one in the number of x rays, and one in the number of optical quanta. The spatial-frequency dependent analysis, however, shows the optical quantum sink becomes severe and dominates at nonzero frequencies. The necessary increase in gain or optical numerical aperture required to prevent the optical quantum sink for spatial frequencies of interest is determined from the QAD analysis. The visual impact of this nonzero spatial-frequency quantum sink is shown in images generated using a Monte Carlo simulation of the cascading process.

Algorithms↗

Effects of blur and eccentricity on differential spatial displacement discrimination.

Differential spatial displacement discrimination thresholds were determined for stimuli consisting of blobs with Gaussian spatial and temporal contrast envelopes. The stimuli were presented at detection threshold luminance contrast. The tasks were similar to the two-point discrimination acuity task and the three-dot alignment hyperacuity task. Thresholds were determined as a function of eccentricity along the horizontal meridian of the visual field (from 45 degrees nasal to 65 degrees temporal). The spatial spread or blur parameter of the blobs was adopted as a scale parameter. The results show that the performance of the visual system in differential spatial displacement discrimination tasks becomes progressively more homogeneous for a progressive increase in the blur parameter of the stimuli. Scaling (i) the three-blob alignment results with estimates of the cortical magnification factor and (ii) the two-blob separation discrimination results with their corresponding neural blur parameter shows an impressive isotropy and blur scale-invariance for the mechanisms mediating differential spatial displacement discrimination across the visual field. These results are interpreted in terms of a scaled sampling lattice model of the visual system, in combination with an automatic scale-selection mechanism.

Adult↗

A quantitative study of the lateral spread of Müller cell responses to retinal lesions in the rabbit.

A wide variety of retinal pathology is associated with an increase in Müller glial cell expression of glial fibrillary acidic protein (GFAP). In this study the time course and spatial spread of the Müller cell GFAP response following argon laser photocoagulation lesions was examined in wholemounted rabbit retina. At 24 hours single focal lesions were surrounded by GFAP positive Müller cell end feet which declined in density with distance but extended as far as 2-3 mm from the lesion. The Müller cell reaction reached a maximal spread of 4-5 mm at 14 to 21 days and had started to contract by 30 days, leaving a core of GFAP positive processes immediately around the lesion site at 60 days. This zone of spread was much larger than the area of disrupted pigment epithelium. Isodensity plots did not reveal any correlation with the trajectory of retinal ganglion cell axons. The spread of reaction was more confined for lesions within the visual streak than in the dorsal or ventral retinal periphery. Multiple lesions within a focal region of retina resulted in a greater density of GFAP reactive end feet with a corresponding greater spread. However, when five to ten lesions were made in a horizontal row, the Müller cells over the entire retina became GFAP immunoreactive. This pan-retinal reaction took several days to spread, peaked at 7-14 days, and contracted back to the primary lesion sites by 2 months. This spread of Müller cell reactivity may be triggered by the diffusion of substances released by injury or it may be due to direct cellular communication. The extensive indirect effect on Müller cells of laser irradiation might be an important component of the clinical effect of laser photocoagulation and indicates a long distance communication mechanism between retinal glia which is poorly understood. This study also shows the importance of the time at which the Müller cell response is assessed.

Animals↗

[AIDS epidemic dynamics in the municipality of Rio de Janeiro, Brazil, 1988-1996: Spatial-temporal statistic modeling].

This study uses a spatial-temporal model to analyze the spatial spread of the AIDS epidemic (adult cases) in the municipality of Rio de Janeiro, Brazil, during three periods: 1988-1990, 1991-1993, and 1994-1996. City districts were used as the geographic units of analysis. A spatial analysis was also performed for pediatric AIDS cases due to vertical HIV transmission, according to period of birth, 1985-90 and 1991-96. For total adult AIDS cases, the initial period was characterized by a polygonal cluster located around the harbor area, which expanded from west to east. Among homosexual cases, in situ growth predominated, and a decrease in the intensity of the diffusion process was observed from the second to the final period. Among heterosexual cases, the epidemic displayed a relevant geographic spread, mainly from 1988-1990 to 1991-1993. Among female cases in the final time period, a cluster of high incidence rates was found towards the northwest, including very poor areas. Among pediatric cases in 1991-1996, a significant correlation was found between AIDS incidence rates and poverty levels in the respective municipal districts. The results suggest that a more complete understanding of AIDS spatial-temporal dynamics can make a major contribution to preventive measures.

Acquired Immunodeficiency Syndrome↗

How predation can slow, stop or reverse a prey invasion.

Observations on Mount St Helens indicate that the spread of recolonizing lupin plants has been slowed due to the presence of insect herbivores and it is possible that the spread of lupins could be reversed in the future by intense insect herbivory [Fagan, W. F. and J. Bishop (2000). Trophic interactions during primary sucession: herbivores slow a plant reinvasion at Mount St. Helens. Amer. Nat. 155, 238-251]. In this paper we investigate mechanisms by which herbivory can contain the spatial spread of recolonizing plants. Our approach is to analyse a series of predator-prey reaction-diffusion models and spatially coupled ordinary differential equation models to derive conditions under which predation pressure can slow, stall or reverse a spatial invasion of prey. We focus on models where prey disperse more slowly than predators. We comment on the types of functional response which give such solutions, and the circumstances under which the models are appropriate.

Animals↗

A model for spatiotemporal frequency responses in the X cell pathway of the cat's retina.

A linear model is described for the cat eye's signal-processing pathway, from the visual stimulus at the cornea, to cones, to X-type ganglion cells. The model contains elements representing the eye's optics, phototransduction, gain control, spatiotemporal processing by cell layers, and pure delay. Centre-surround antagonism in the model arises through the presence of a centre element producing a small spatial spread of signals, and an antagonistic element producing a larger spread. Two arrangements were tried, feedforward and feedback, in which the antagonistic element's output was subtracted from the centre element's output, and input, respectively. The model was fitted to empirical spatial and temporal frequency responses collected by Frishman et al. (1987), and accounted qualitatively for these data in the feedback, but not the feedforward, arrangement. The model's centre pathway comprises a cascade of low-pass spatial filters, as does the surround pathway. As a consequence, the spatial frequency responses for these two pathways closely approximate Gaussian functions of spatial frequency, and the spatial frequency response of the complete model at low temporal frequency closely matches that of the difference of Gaussians model.

Adaptation, Ocular↗

Background contrast modulates kinetics and lateral spread of responses to superimposed stimuli in outer retina.

Surround enhancement (sensitization) is a poorly understood form of network adaptation in which the kinetics of the responses of retinal neurons to test stimuli become faster, and absolute sensitivity of the responses increases with increasing level of steady, surrounding light. Surround enhancement has been observed in all classes of retinal neurons in lower vertebrates except cones, in some primate retinal ganglion cells, and in human psychophysical studies. In theory, surround enhancement could be mediated by two broad classes of mechanisms, which are not mutually exclusive: one in which the kinetics of the transduction linking cone voltage to postsynaptic current in second-order neurons is modulated, and another in which the transformation of postsynaptic current to membrane voltage is modulated. We report here that both classes of mechanism play a role in surround enhancement measured in turtle horizontal cells (HCs). We stimulated the retina by modulating sinusoidally the illuminance of a bar placed at various positions in the HC receptive field. The bar was surrounded by either equally luminant or dim, steady light. Interpretation of responses in the context of a model for the cone-HC network led to the conclusion that the speeding up of response kinetics--due to selective increase in response gain at high temporal frequencies--by surround illuminance is almost completely accounted for by the change in the kinetics of the transduction linking cone membrane potential to HC postsynaptic current. However, surround illuminance also had an additional, surprising effect on the transformation between postsynaptic current and voltage: the space constant for signal spread in the HC network for the dim-surround condition was roughly twice as large as that for the bright-surround condition. Thus, increasing surround illuminance had analogous effects in the spatial and temporal domains: it restricted the time course and the spatial spread of signal. Both effects were dependent on the contrast between the mean bar illuminance and that of the surround, rather than on overall light level. When the stimulus with the bright surround was dimmed uniformly by a neutral density filter, the space constant did not increase, and response gain at high temporal frequencies did not decrease. Pharmacological experiments performed with dopamine and various agonists and antagonists indicated that, although exogenous dopamine can influence surround enhancement, endogenous dopamine does not play an important role in surround enhancement. We conclude that contrast in background light modulates the spatiotemporal properties of signal processing in the outer retina, and does so by a non-dopaminergic mechanism.

Adaptation, Physiological↗

Modeling and analysis of stochastic invasion processes.

In this paper we derive spatially explicit equations to describe a stochastic invasion process. Parents are assumed to produce a random number of offspring which then disperse according to a spatial redistribution kernel. Equations for population moments, such as expected density and covariance averaged over an ensemble of identical stochastic processes, take the form of deterministic integro-difference equations. These equations describe the spatial spread of population moments as the invasion progresses. We use the second order moments to analyse two basic properties of the invasion. The first property is 'permanence of form' in the correlation structure of the wave. Analysis of the asymptotic form of the invasion wave shows that either (i) the covariance in the leading edge of the wave of invasion asymptotically achieves a permanence of form with a characteristic structure described by an unchanging spatial correlation function, or (ii) the leading edge of the wave has no asymptotic permanence of form with the length scales of spatial correlations continually increasing over time. Which of these two outcomes pertains is governed by a single statistic, phi which depends upon the shape of the dispersal kernel and the net reproductive number. The second property of the invasion is its patchy structure. Patchiness, defined in terms of spatial correlations on separate short (within patch) and long (between patch) spatial scales, is linked to the dispersal kernel. Analysis shows how a leptokurtic dispersal kernel gives rise to patchiness in spread of a population.

Animals↗

Prognostic significance of primary site after radiotherapy in non-Hodgkin's lymphomata.

In contrast to Hodgkin's lymphomata, non-Hodgkin's lymphomata originate in approximately a fourth of the cases in extranodal organs and sites. The prognosis of patients with primary extranodal organ involvement of the non-Hodgkin's lymphomata is similar to that of patients with primary lumph node involvement of the Hodgkin's and non-Hodgkin's lymphomata, dependent on the special spreading of the disease corresponding to the 4 stages of the Ann Arbor classification. This applies to the primary involvement of a single lymph node region (Stage I) or a single extralymphatic organ or site (stage IE) as well as to further stages of spreading within the lymphatic system (Stages II and III) including secondary localized involvement of an extralymphatic organ and site (Stages IIE and IIIE). The same qualitative dependence of the prognosis of Hodgkin's and non-Hodgkin's lymphomata on the spatial spreading, corresponding to the Ann Arbor concept, legitimizes, in spite of some quantitative differences, the application of the Ann Arbor classification system to all malignant lymphomata.

Hodgkin Disease↗

Global asymptotic stability of a periodic solution to an epidemic model.

In this paper a periodic delay differential equation with spatial spread is investigated. This equation can be used to model the growth of malaria which is transmitted by a mosquito. Using monotone techniques, it is shown that the following bifurcation holds: either the disease dies out or the density of infectious people tends to a spatially homogeneous, time periodic and positive solution.

Epidemiology↗

Multichannel surface EMG: basic aspects and clinical utility.

The generation of the surface electromyogram (sEMG) is described with regard to the properties of the single muscle fiber action potential as source, the physical aspects of volume conduction and recording configuration, and the properties and firing pattern of motor units (MUs). The spatial aspect of the motor unit action potential (MUP) is emphasized in relation to the results of high-density, multichannel sEMG measurements. The endplate zone, depth, size, and position of MUs can be estimated. The use of muscle fiber conduction velocity measurements in channelopathies and the changes in pathological fatigue are described. Using the unique patterns of spatial spread of MUPs over the skin (MU fingerprint), MU classification and the determination of firing moments is done noninvasively. Clinical applications of high-density sEMG measurements are reviewed. Emerging possibilities provided by MUP size and fingerprint measurements in neuromuscular disease and motor control are discussed. We conclude that multichannel sEMG adds unique, and sometimes indispensable, spatial information to our knowledge of the motor unit.

Action Potentials↗

The metapopulation dynamics of an infectious disease: tuberculosis in possums.

An SEI metapopulation model is developed for the spread of an infectious agent by migration. The model portrays two age classes on a number of patches connected by migration routes which are used as host animals mature. A feature of this model is that the basic reproduction ratio may be computed directly, using a scheme that separates topography, demography, and epidemiology. We also provide formulas for individual patch basic reproduction numbers and discuss their connection with the basic reproduction ratio for the system. The model is applied to the problem of spatial spread of bovine tuberculosis in a possum population. The temporal dynamics of infection are investigated for some generic networks of migration links, and the basic reproduction ratio is computed-its value is not greatly different from that for a homogeneous model. Three scenarios are considered for the control of bovine tuberculosis in possums where the spatial aspect is shown to be crucial for the design of disease management operations.

Animal Migration↗

Numerical simulation of Ca2+ "sparks" in skeletal muscle.

A three dimensional (3D) model of Ca(2+) diffusion and binding within a sarcomere of a myofibril, including Ca(2+) binding sites troponin, parvalbumin, sarcoplasmic reticulum Ca(2+) pump, and fluorescent Ca(2+)-indicator dye (fluo-3), was developed to numerically simulate laser scanning confocal microscope images of Ca(2+) "sparks" in skeletal muscle. Diffusion of free dye (D), calcium dye (CaD), and Ca(2+) were included in the model. The Ca(2+) release current was assumed to last 8 ms, to arise within 4 x 10(-5) microm(3) at the triad and to be constant during release. Line scan confocal fluorescence images of Ca(2+) sparks were simulated by 3D convolution of the calculated distribution of CaD with a Gaussian kernel approximating the point spread function of the microscope. Our results indicate that the amplitude of the simulated spark is proportional to the Ca(2+) release current if all other model parameters are constant. For a given release current, the kinetic properties and concentrations of the binding sites and the diffusion parameters of D, CaD, and Ca(2+) all have significant effects on the simulated Ca(2+) sparks. The simulated sparks exhibited similar amplitudes and temporal properties, but less spatial spread than experimentally observed sparks.

Adenosine Triphosphate↗

Ca2+ diffusion and sarcoplasmic reticulum transport both contribute to [Ca2+]i decline during Ca2+ sparks in rat ventricular myocytes.

1. We sought to evaluate the contribution of the sarcoplasmic reticulum (SR) Ca2+ pump (vs. diffusion) to the kinetics of [Ca24]i decline during Ca2+ sparks, which are due to spontaneous local SR Ca2+ release, in isolated rat ventricular myocytes measured using fluo-3 and laser scanning confocal microscopy. 2. Resting Ca2+ sparks were compared before (control) and after the SR Ca2(+)-ATPase was either completely blocked by 5 microM thapsigargin (TG) or stimulated by isoprenaline. Na(+)-Ca2+ exchange was blocked using Na(+)-free, Ca(2+)-free solution (0 Na+, O Ca2+) and conditions were arranged so that the SR Ca2+ content was the same under all conditions when Ca2+ sparks were measured. 3. The control Ca2+ spark amplitude (281 +/- 13 nM) was not changed by TG (270 +/- 21 nM) or isoprenaline (302 +/- 10 nM). However, the time constant of [Ca2+]i decline was significantly slower in the presence of TG (29.3 +/- 4.3 ms) compared with control (21.6 +/- 1.5 ms) and faster with isoprenaline (14.5 +/- 0.9 ms), but in all cases was much faster than the global [Ca2+]i decline during a control twitch (177 +/- 10 ms). 4. The spatial spread of Ca2+ during the Ca2+ spark was also influenced by the SR Ca2+ pump. The apparent 'space constant' of the Ca2+ sparks was longest when the SR Ca2+ pump was blocked, intermediate in control and shortest with isoprenaline. 5. We conclude that while Ca2+ diffusion from the source of Ca2+ release is the dominant process in local [Ca2+]i decline during the Ca2+ spark, Ca2+ transport by the SR contributes significantly to both the kinetics and spatial distribution of [Ca2+]i during the Ca2+ spark.

Adrenergic beta-Agonists↗

Calcium wave evoked by activation of endogenous or exogenously expressed receptors in Xenopus oocytes.

The mRNA encoding the cloned substance K receptor was microinjected into Xenopus laevis oocytes. After expression of the mRNA, Ca2+ was imaged in the oocytes with a digital imaging fluorescence microscopy system using the Ca2(+)-sensitive dyes fura-2 and fluo-3. Application of substance K caused a dose-related wave of Ca2+ mobilization to spread from a focus and to elevate the Ca2+ concentration in the oocyte. Activation of endogenous muscarinic or angiotensin II receptors in noninjected oocytes evoked a similar response. The Ca2+ rise in oocytes induced by substance K was due to internal Ca2+ mobilization and was independent of external Ca2+, since it occurred in Ca2(+)-free medium fortified with 2 mM EGTA. The Ca2+ imaging was well correlated with ion current measurements of voltage-clamped oocytes. Imaging, in addition to detecting the spatial spread of Ca2+ across the cell, was at least as sensitive as voltage clamping and much faster when screening oocytes for the expression of receptor mRNAs that stimulate Ca2+ mobilization. While it is known that fertilization of Xenopus eggs causes a spreading wave of Ca2+ mobilization, we found that activation of either native or newly expressed receptors in oocytes causes a similar change in Ca2+ distribution.

Animals↗

Ca(2+) signals mediated by Ins(1,4,5)P(3)-gated channels in rat ureteric myocytes.

Localized Ca(2+)-release signals (puffs) and propagated Ca(2+) waves were characterized in rat ureteric myocytes by confocal microscopy. Ca(2+) puffs were evoked by photorelease of low concentrations of Ins(1,4,5)P(3) from a caged precursor and by low concentrations of acetylcholine; they were also observed spontaneously in Ca(2+)-overloaded myocytes. Ca(2+) puffs showed some variability in amplitude, time course and spatial spread, suggesting that Ins(1,4,5)P(3)-gated channels exist in clusters containing variable numbers of channels and that within these clusters a variable number of channels can be recruited. Immunodetection of Ins(1,4,5)P(3) receptors revealed the existence of several spots of fluorescence in the confocal cell sections, supporting the existence of clusters of Ins(1,4,5)P(3) receptors. Strong Ins(1,4,5)P(3) photorelease and high concentrations of acetylcholine induced Ca(2+) waves that originated from an initiation site and propagated in the whole cell by spatial recruitment of neighbouring Ca(2+)-release sites. Both Ca(2+) puffs and Ca(2+) waves were blocked selectively by intracellular applications of heparin and an anti-Ins(1,4,5)P(3)-receptor antibody, but were unaffected by ryanodine and intracellular application of an anti-ryanodine receptor antibody. mRNAs encoding for the three subtypes of Ins(1,4,5)P(3) receptor and subtype 3 of ryanodine receptor were detected in these myocytes, and the maximal binding capacity of [(3)H]Ins(1,4,5)P(3) was 10- to 12-fold higher than that of [(3)H]ryanodine. These results suggest that Ins(1,4,5)P(3)-gated channels mediate a continuum of Ca(2+) signalling in smooth-muscle cells expressing a high level of Ins(1,4,5)P(3) receptors and no subtypes 1 and 2 of ryanodine receptors.

Acetylcholine↗