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Sarcolemmal calcium binding sites in heart: II. Mathematical model for diffusion of calcium released from the sarcoplasmic reticulum into the diadic region.

We present a model for predicting the temporal and spatial dependence of [Ca] in the cardiac subsarcolemmal diadic region (cleft), following Ca release from the "feet" of the sarcoplasmic reticulum. This region is modeled as a disc 10 nm thick, 430 nm in radius, with or without Ca binding sites and open at its periphery to the cytosol. [Ca] is computed for three diffusion coefficients (100, 20 and 4% of aqueous diffusion), following release of a 20-msec square pulse sufficient to produce 50% maximal contractile force, or repetitive release (400/min) of such pulses. Numerical solutions are obtained for the general diffusion/binding problem and analytic solutions for the case of no binding sites. For the middle value of diffusion coefficient, and in the absence of binding sites, [Ca] rises to approximately 1.5 mM in 20-msec and then falls to approximately 0.1 microM in less than 3 msec. Adding binding sites reduces peak [Ca] to approximately 0.6 mM but prolongs its decline, requiring approximately 200 msec to reach 20 microM. For repetitive release [Ca] is greater than 100 microM for roughly half of each cycle. Two major implications of the predicted [Ca] are: (i) The effect of Ca binding sites on [Ca] will cause Ca efflux from the cleft via the Na-Ca exchanger (Km(Ca) approximately 20 microM) to continue at a significant level for greater than 200 msec. (ii) The time constant for inactivation of release from the "feet" must be much greater than for activation if Ca-induced Ca release is to continue for greater than 1-2 msec.

Animals↗

The asymptotic transectional/circumferential homogeneity of the solutions of reaction-diffusion systems in/on cylinder-like domains.

It is often reported that an animal with spotty coat markings on its body has a tail with stripe-shaped pattern. In other various biological and chemical phenomena in/on cylinder-like domains, longitudinally periodic band patterns are observed much more often than the other non-uniform patterns. This paper mathematically explains these observations by proving that, in/on a long and narrow cylinder-like domain, any solution of reaction-diffusion system asymptotically loses its spatial dependence in the transectional/circumferential direction.

Animals↗

Mechanics of the transduction of sound in the tympanal organ of adults and larvae of locusts.

The mechanical transmission of sound in the tympanal organ of adults and 5th instar larvae of Locusta migratoria and Schistocerca gregaria has been investigated by means of stroboscopic measurements within a frequency range from 1-20 kHz. Frequency dependent spatial distributions of amplitudes and phases of oscillation on the tympanal membrane and the Müller's organ could be demonstrated. Cuticular structures on the membrane may act as a lever arm (e.g. elevated process) and cause a transformation of the (unidimensional) membrane motion into components of displacements in the Müller's organ perpendicular, as well as even parallel, to the membrane. Sites of maximum relative displacements at distinct frequencies are found to be correlated to the course of the dendrites of the acoustic receptor cells. Differences in morphology of the tympanal organ between the two species as well as between adults and larvae always correspond to differences in the mechanical properties (resonances etc.). Consequently, differences or changes in the neurophysiological response characteristics of the different receptor cells have been found. Based upon these findings a correlation between the anatomical and physiological classification of the receptor cell groups is presented.

Animals↗

Two-dimensional deghosting for EPI.

A residual ghost artefact in echo-planar imaging (EPI) remains after the standard correction procedure based on a 1-dimensional phase-modulation of the spectra of even or odd echoes. A better reduction of this artefact is demonstrated using a 2-dimensional phase correction. The phase correction map is measured inside the ghost-free region of the image, preferably in a reference scan with an increased field of view, as the phase difference between complex images reconstructed separately from even and odd echoes. An extrapolated map consisting of spatial components up to the second order (constant, x, y, xy and x2-y2) is then found by a fit to the measured values. This map is used to correct the phase of even- and odd-reconstructed images before adding them. This procedure may cause some spatially dependent loss of signal, but if the level of the residual artefact is less than 20% of the image intensity, such losses are negligible.

Artifacts↗

Microscopic spin tagging (MiST) for flow imaging.

In this study, a new strategy for slow flow imaging is proposed. The basic idea is to generate flow contrast on a microscopic level below the spatial resolution of an imaging experiment. Since a microscopic spin tagging scheme is used, this concept is called MiST (Microscopic Spin Tagging). MiST is not a single specific measurement sequence, but rather a new flow sensitive preparation concept which is highly flexible and can be carried out in many ways. The common principle in all possible realizations of MiST is a periodic tagging of magnetization in thin planes (100-200 microm) within the imaging voxels by means of spatially selective RF-pulses. Therefore, flow sensitivity occurs via inflow of fresh spins on a microscopic scale. With this approach, short evolution times are sufficient to introduce inflow contrast and a spatial dependence of inflow times is avoided. The flow sensitive preparation and image orientation are also not connected as they are in conventional time-of-flight techniques. Another powerful feature of MiST is that it can be designed as a non-subtraction method, which results in no signal from stationary spins. Here we present a first realization of the MiST concept and its validation in quantitative flow measurements to demonstrate the feasibility of the proposed preparation concept.

Arteries↗

Visual-tactile spatial interaction in saccade generation.

Saccadic reaction times to visual targets tend to be faster when non-visual stimuli are presented in close temporal or spatial proximity even if subjects are instructed to ignore the accessory input. The effect tends to decrease with increasing spatial distance between the stimuli. Multisensory interaction effects measured in neural structures involved in saccade generation have demonstrated a similar spatial dependence. The present study investigated visual-tactile interaction effects on saccadic reaction time using a focused attention paradigm. Compared to unimodal visual targets saccadic reaction time to bimodal stimuli was reduced by up to 30 ms. The effect was larger for ipsi- than for contralateral presentations, and it increased with the eccentricity of the visual target. The results are consistent with attributing part of the facilitation to a multisensory effect of bimodal neurons with overlapping visual and tactile receptive field structures in the deep layers of the superior colliculus.

Adaptation, Physiological↗

Suitability of cerebrospinal fluid as a signal-intensity reference on MRI: evaluation of signal-intensity variations in the lumbosacral dural sac.

The suitability of the cerebrospinal fluid (CSF) in the lumbosacral dural sac as an internal signal-intensity reference was studied on magnetic resonance imaging (MRI) of the lumbar spine using a surface coil and motion artefact suppression technique. A signal-intensity reference is needed when signal is compared between images, studies or subjects. Homogeneity of the CSF was estimated visually on T2-weighted images of 60 subjects at 1.5 T and of another 60 subjects at 0.1 T. Spines with a severely narrowed dural sac or marked scoliosis were excluded from the study to avoid partial volume effect. CSF was homogeneous in 82% and 73% of the examinations at 1.5 T and 0.1 T, respectively. The type and location of the local inhomogeneities did not relate to local narrowings of the dural sac. The signal intensity of CSF was measured in 108 examinations at 0.1 T after correcting the spatially-dependent signal-intensity non-uniformities with a phantom-based method. The signal-intensity difference between the CSF in the upper and lower lumbar dural sac was less than 10% in 73% of the examinations. The CSF in the lumbosacral dural sac can be a useful signal-intensity reference for estimation of the signal of the adjacent structures in patients without severe narrowing of the dural sac or marked scoliosis. It may contribute to assessing spinal disease processes.

Adult↗

A prototype high-resolution animal positron tomograph with avalanche photodiode arrays and LSO crystals.

To fully utilize positron emission tomography (PET) as a non-invasive tool for tissue characterization, dedicated instrumentation is being developed which is specially suited for imaging mice and rats. Semiconductor detectors, such as avalanche photodiodes (APDs), may offer an alternative to photomultiplier tubes for the readout of scintillation crystals. Since the scintillation characteristics of lutetium oxyorthosilicate (LSO) are well matched to APDs, the combination of LSO and APDs seems favourable, and the goal of this study was to build a positron tomograph with LSO-APD modules to prove the feasibility of such an approach. A prototype PET scanner based on APD readout of small, individual LSO crystals was developed for tracer studies in mice and rats. The tomograph consists of two sectors (86 mm distance), each comprising three LSO-APD modules, which can be rotated for the acquisition of complete projections. In each module, small LSO crystals (3.7 x 3.7 x 12 mm3) are individually coupled to one channel within matrices containing 2x8 square APDs (2.6 x 2.6 mm2 sensitive area per channel). The list-mode data are reconstructed with a penalized weighted least squares algorithm which includes the spatially dependent line spread function of the tomograph. Basic performance parameters were measured with phantoms and first experiments with rats and mice were conducted to introduce this methodology for biomedical imaging. The reconstructed field of view covers 68 mm, which is 80% of the total detector diameter. Image resolution was shown to be 2.4 mm within the whole reconstructed field of view. Using a lower energy threshold of 450 keV, the system sensitivity was 350 Hz/MBq for a line source in air in the centre of the field of view. In a water-filled cylinder of 4.6 cm diameter, the scatter fraction at the centre of the field of view was 16% (450 keV threshold). The count rate was linear up to 700 coincidence counts per second. In vivo studies of anaesthetized rats and mice showed the feasibility of in vivo imaging using this PET scanner. The first LSO-APD prototype tomograph has been successfully introduced for in vivo animal imaging. APD arrays in combination with LSO crystals offer new design possibilities for positron tomographs with finely granulated detector channels.

Animals↗

Characterisation of the nucleolar organising regions during the cell cycle in two varieties of Petunia hybrida as visualised by fluorescence in situ hybridisation and silver staining.

The cell cycle-dependent spatial position, morphology and activity of the four nucleolar organising regions (NORs) of the Petunia hybrida cultivar Mitchell and the inbred line V26 have been analysed. Application of the silver staining technique and fluorescence in situ hybridisation on fixed root-tip material revealed that these interspecific hybrids possess four NORs of which only those of chromosome 2 are active during interphase, which implies that the NOR activity is not of parental origin. However, at the end of mitosis, activity of all NOR regions could be detected, suggesting that the high demand for ribosomes at this stage of the cell cycle requires temporal activity of all NORs. Using actin DNA probes as markers in fluorescence in situ hybridisation experiments enabled the identification of the individual petunia chromosomes.

Cell Cycle↗

Radial maze performance in three strains of mice: role of the fimbria/fornix.

Three strains of mice were tested on an 8-arm radial maze, an index of hippocampus-dependent spatial memory. Levels of performance differed between strains with C57Br/cj greater than Balb/cj greater than C57Bl/6j. Lesions of the fimbria/fornix disrupted performance in the C57Br and Balb strains: the C57Bl mice never performed better than chance before or after surgery. Choline acetyltransferase activity in hippocampus was not correlated with radial maze performance. These findings suggest a possible genetic contribution towards radial maze behavior.

Animals↗

Intranigral dynorphin-1-13 suppresses kindled seizures by a naloxone-insensitive mechanism.

Numerous lines of evidence indicate that the substantia nigra (SN) facilitates the propagation of seizures in kindling and in other seizure models. Intranigral injection of dynorphin-1-13 exerted a potent seizure suppressant action in kindled rats. This seizure suppressant action was dose dependent, spatially specific for the area of the SN and was not blocked by naloxone (2 mg/kg i.p.). This finding extends previous work indicating that treatments which reduce SN output exert an anticonvulsant action and further suggests that opioid peptides endogenous to the SN may regulate seizure susceptibility in the kindling model.

Animals↗

Prolonged memory impairment in the absence of hippocampal cell death following traumatic brain injury in the rat.

Prolonged neurological dysfunction that results from an insult to the brain is often attributed to irreversible structural damage such as loss of neurons or axonal degeneration. For example, following cerebral ischemia even partial hippocampal CA1 neuronal loss has been proposed to be sufficient to result in deficits in hippocampal dependent spatial memory. This study examined if hippocampal CA1 neuronal loss and/or axonal injury was necessary to produce prolonged spatial memory deficits resulting from traumatic brain injury (TBI). Prior to TBI Sprague-Dawley rats were trained on an 8-arm radial maze, a task sensitive to detecting specific lesions of the hippocampus or its extrinsic connections. Following a mild, moderate, or sham injury, rats were tested for working and reference memory for 25 days. After 25 days of maze testing, histological cell counts were made from consistent coronal sections of the mid-dorsal hippocampus. Rats subjected to mild or moderate TBI manifested working memory deficits for 5 and 15 days, respectively, after injury in the absence of overt (all brain regions) or quantitative (CA1 only) evidence of neuronal death. The number of CA1 pyramidal neurons of representative sections of the mid-dorsal hippocampi for injured maze-deficit rats and sham control rats were: 1626 (S.E.M. = +/- 66) and 1693 (S.E.M. = +/- 69) per 10(6) micron2, respectively. Additionally, no overt evidence of axonal injury was observed in any forebrain structure including major intrinsic or extrinsic connecting hippocampal pathways. These data strongly suggest that mild to moderate TBI is capable of producing prolonged spatial memory deficits in the rat without evidence of either neuronal cell death in the intrinsic hippocampus or overt axonal injury in hippocampal pathways.

Animals↗

DNA damage caused by ionizing radiation.

A survey is given of continuous-time Markov chain models for ionizing radiation damage to the genome of mammalian cells. In such models, immediate damage induced by the radiation is regarded as a batch-Poisson arrival process of DNA double-strand breaks (DSBs). Enzymatic modification of the immediate damage is modeled as a Markov process similar to those described by the master equation of stochastic chemical kinetics. An illustrative example is the restitution/complete-exchange model. The model postulates that, after being induced by radiation, DSBs subsequently either undergo enzymatically mediated restitution (repair) or participate pairwise in chromosome exchanges. Some of the exchanges make irremediable lesions such as dicentric chromosome aberrations. One may have rapid irradiation followed by enzymatic DSB processing or have prolonged irradiation with both DSB arrival and enzymatic DSB processing continuing throughout the irradiation period. Methods for analyzing the Markov chains include using an approximate model for expected values, the discrete-time Markov chain embedded at transitions, partial differential equations for generating functions, normal perturbation theory, singular perturbation theory with scaling, numerical computations, and certain matrix methods that combine Perron-Frobenius theory with variational estimates. Applications to experimental results on expected values, variances, and statistical distributions of DNA lesions are briefly outlined. Continuous-time Markov chains are the most systematic of those radiation damage models that treat DSB-DSB interactions within the cell nucleus as homogeneous (e.g., ignore diffusion limitations). They contain virtually all other relevant homogeneous models and semiempirical summaries as special cases, limiting cases, or approximations. However, the Markov models do not seem to be well suited for studying spatial dependence of DSB interactions, which is known to be important in some situations.

Animals↗

On the concentration profile of a growth inhibitory factor in multicell spheroids.

A mathematical model is presented for the production of a growth inhibitory factor (GIF) within a multicell spheroid. The main assumption of the model is that the GIF is produced by cells within the spheroid in some prescribed nonlinear, spatially dependent manner. Given that the diffusion of the GIF is known to take place over a much shorter time scale than that of spheroid growth, the steady-state profile of the GIF in various spheroids of differing radii is examined and theoretical results are compared with actual experimental data.

Animals↗

Nonlinear diffusion of a growth inhibitory factor in multicell spheroids.

A mathematical model is presented for the production of a growth inhibitory factor (GIF) within a multicell spheroid. The model is based on the assumption that the GIF diffuses within the spheroid in a nonlinear spatially dependent manner. This is in contrast with previous models, in which the nonlinearity was assumed in the production term. The results of the new model are compared with those of previous models and with experimental data.

Animals↗

The time-course of rod-cone interaction.

The time-course of rod-cone interaction (change of scotopic sensitivity caused by photopic background stimulation) was measured in the presence of briskly exchanged, scotopically matched, 490- and 630-nm background disks. In all conditions, interaction rose and fell quickly with changes of photopic stimulation. When the background was a small 0.6 degree-diameter disk, photopic stimulation produced relatively constant maintained interaction of about 0.6 log units. When the background was a large 7.8 degree-dia disk, photopic stimulation produced larger initial (0.6-1.0 log unit) than maintained (0.2 log unit) interaction. When a 0.6 degree by 7.8 degree annulus was used instead of a background, photopic stimulation produced substantial interaction only at offset, a transitory interaction. Thus, the spatial dependence of transitory interactions differs from that of maintained interaction: transitory interactions can be large even when maintained interaction is small or absent. The results are discussed in terms of a simple center-surround model of rod-cone interaction that unifies both maintained and transient interaction.

Dark Adaptation↗

Polycyclic aromatic hydrocarbon (PAH) concentrations in ambient airborne particles from local traffic and distant sources; variation of the PAH profile.

The temporal and spatial dependence of the PAH profile, i.e. the relative concentrations of polycyclic aromatic hydrocarbons, was investigated for ambient airborne particles during a period with moderate photochemical air pollution. The concentrations of 14 PAH were measured; they differed in volatility, sensitivity to atmospheric chemical conversion and contributing sources. Multivariate analysis (principal-component analysis and factor analysis) revealed that temporal dependence was predominantly determined by five factors clearly linked with volatility, reactivity and sources of the PAH, the first being by far the most important. The results, therefore, indicate that volatilization, conversion and a varying contribution of local sources were the major causes of the variation of the profile with time. The contribution of local sources was investigated by comparison of samples that were taken simultaneously at three different sites, one a background site and two sites downwind of traffic. A marked site dependence was found. The comparison suggested that the differences were not only determined by sources, but also by volatilization and/or conversion during residence of the particles in the air.

Air Pollutants↗

Possible applications of digital analysis of ultrasonic images of the placenta.

Analysis of the digitised ultrasonic images of in vivo placentae at 15-18 weeks gestation has revealed various textural differences. These have been correlated with smoking, visual appearance and the subsequent development of hypertension. The total number of patients included in this study was 98, of which 70 had images suitable for analysis. There were no significant textural differences between the images of the placentae of smokers and non-smokers nor did the spatially dependent co-occurrence matrices correlate with visual appearance. Textural differences were however detected when the placentae of the normotensive group were compared to those of patients who subsequently developed hypertension (latent hypertension) in the third trimester of pregnancy (p less than 0.05 Mann Whitney 'U' test).

Female↗