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Effects of uniform and non-uniform synaptic 'activation-distributions' on the cable properties of modeled cortical pyramidal neurons.

Knowledge of the resting potential and input resistance reveal little about the electrotonic structure of nerve cells since that structure is governed by the background distribution of activated conductances. The background distribution of activated conductances (or 'activation-distribution') is commonly assumed to be uniform, but there is much evidence to suggest that the 'activation-distribution' of cortical pyramidal cells in non-uniform. We investigated effects of uniform and non-uniform activation-distributions with simulations employing passive cable models of an HRP-injected cortical pyramidal neuron. The consequences of 5 different activation-distributions on the effectiveness of synaptic inputs and the electrophysiological properties of the neuron were compared. With non-uniform activation-distributions, (i) the resting membrane potential was non-uniform (with difference of 10-15 mV or more found between soma and distal dendrites), (ii) the electrotonic distances to distal synapses were smaller than with a uniform distribution, and (iii) a two-fold range of variation was seen in the effectiveness of distal synaptic inputs. Differences in time constants, tau 0 and tau 1, obtained from an analysis of transients and in electrotonic length, L, were also found with different activation-distributions. These differences were difficult to assess due to the inherent difficulty in estimating tau 1 (as demonstrated here) and the inappropriateness of the usual formula for L for these cells. Reducing afferent activity (as might happen in tissue slice) increased the effectiveness of distal inputs and reduced the differences in resting potential seen in the neuron. It is concluded that the effectiveness of synaptic inputs and the electrophysiological properties of a neuron can be quite different when the activation-distribution is non-uniform rather than uniform.

Animals↗

A Monte-Carlo program converting activity distributions to absorbed dose distributions in a radionuclide treatment planning system.

In systemic radiation therapy, the absorbed dose distribution must be calculated from the individual activity distribution. A computer code has been developed for the conversion of an arbitrary activity distribution to a 3-D absorbed dose distribution. The activity distribution can be described either analytically or as a voxel based distribution, which comes from a SPECT acquisition. Decay points are sampled according to the activity map, and particles (photons and electrons) from the decay are followed through the tissue until they either escape the patient or drop below a cut off energy. To verify the calculated results, the mathematically defined MIRD phantom and unity density spheres have been included in the code. Also other published dosimetry data were used for verification. Absorbed fractions and S-values were calculated. A comparison with simulated data from the code with MIRD data shows good agreement. The S values are within 10-20% of published MIRD S values for most organs. Absorbed fractions for photons and electrons in spheres (masses between 1 g and 200 kg) are within 10-15% of those published. Radial absorbed dose distributions in a necrotic tumor show good agreement with published data. The application of the code in a radionuclide therapy dose planning system, based on quantitative SPECT, is discussed.

Absorption↗

Optimization of activity distribution in brachytherapy.

We investigated the problem of how to minimize the dose rate outside a spherical target volume for a given minimal dose rate inside the sphere for 1/r2 photon emitters. An integral equation for an activity distribution is derived from the demand that the dose rate is constant inside the sphere. The solution of this equation is given and it is proven that the resulting activity distribution gives the smallest dose rate at every point outside the target volume. Some other activity distributions are discussed; they are assessed by the required integral activity, which is proportional to the dose rate at some distance from the target volume. Compared with a single point source at the center of the sphere, one can save 50% of the total activity when using the optimal activity distribution. The benefit reduces to about 30% for the other continuous activity distributions and to a few % for symmetrical arrangements of a few point sources.

Brachytherapy↗

Attending to eye movements and retinal eccentricity: evidence for the activity distribution model of attention reconsidered.

When testing between spotlight and activity distribution models of visual attention, D. LaBerge, R. L. Carlson, J. K. Williams, and B. G. Bunney (1997) used an experimental paradigm in which targets are embedded in 3 brief displays. This paradigm, however, may be confounded by retinal eccentricity effects and saccadic eye movements. When the retinal eccentricities of the targets are equated and eye position is monitored, the pattern of results reported by LaBerge et al., which supported the activity distribution model, is not found. This result underscores the importance of considering targets' eccentricity and people's inclination to make saccadic eye movements in certain types of visual cognition tasks. ((c) 2005 APA, all rights reserved).

Attention↗

Microelectrode measurements of the activity distribution in nitrifying bacterial aggregates.

Microelectrodes for ammonium, oxygen, nitrate, and pH were used to study nitrifying aggregates grown in a fluidized-bed reactor. Local reactant fluxes and distribution of microbial activity could be determined from the microprofiles. The interfacial fluxes of the reactants closely reflected the stoichiometry of bacterial nitrification. Both ammonium consumption and nitrate production were localized in the outer shells, with a thickness of approximately 100 to 120 mum, of the aggregates. Under conditions in which ammonium and oxygen penetrated the whole aggregate, nitrification was restricted to this zone; oxygen was consumed in the central parts of the aggregates as well, probably because of oxidation of dead biomass. A sudden increase of the oxygen concentration to saturation (pure oxygen) was inhibitory to nitrification. The pH profiles showed acidification in the aggregates, but not to an inhibitory level. The distribution of activity was determined by the penetration depth of oxygen during aggregate development in the reactor. Mass transfer was significantly limited by the boundary layer surrounding the aggregates. Microelectrode measurements showed that the thickness of this layer was correlated with the diffusion coefficient of the species. Determination of the distribution of nitrifying activity required the use of ammonium or nitrate microelectrodes, whereas the use of oxygen microelectrodes alone would lead to erroneous results.

Journal Article↗

Theoretical study of the influence of a heterogeneous activity distribution on intratumoral absorbed dose distribution.

Radioimmunotherapy of hematopoeitic cancers and micrometastases has been shown to have significant therapeutic benefit. The treatment of solid tumors with radionuclide therapy has been less successful. Previous investigations of intratumoral activity distribution and studies on intratumoral drug delivery suggest that a probable reason for the disappointing results in solid tumor treatment is nonuniform intratumoral distribution coupled with restricted intratumoral drug penetrance, thus inhibiting antineoplastic agents from reaching the tumor's center. This paper describes a nonuniform intratumoral activity distribution identified by limited radiolabeled tracer diffusion from tumor surface to tumor center. This activity was simulated using techniques that allowed the absorbed dose distributions to be estimated using different intratumoral diffusion capabilities and calculated for tumors of varying diameters. The influences of these absorbed dose distributions on solid tumor radionuclide therapy are also discussed. The absorbed dose distribution was calculated using the dose point kernel method that provided for the application of a three-dimensional (3D) convolution between a dose rate kernel function and an activity distribution function. These functions were incorporated into 3D matrices with voxels measuring 0.10 x 0.10 x 0.10 mm3. At this point fast Fourier transform (FFT) and multiplication in frequency domain followed by inverse FFT (iFFT) were used to effect this phase of the dose calculation process. The absorbed dose distribution for tumors of 1, 3, 5, 10, and 15 mm in diameter were studied. Using the therapeutic radionuclides of 131I, 186Re, 188Re, and 90Y, the total average dose, center dose, and surface dose for each of the different tumor diameters were reported. The absorbed dose in the nearby normal tissue was also evaluated. When the tumor diameters exceed 15 mm, a much lower tumor center dose is delivered compared with tumors between 3 and 5 mm in diameter. Based on these findings, the use of higher beta-energy radionuclides, such as 188Re and 90Y is more effective in delivering a higher absorbed dose to the tumor center at tumor diameters around 10 mm.

Algorithms↗

Nitrate reductase activity, distribution, and response to nitrate in two contrasting Phaseolus species inoculated with Rhizobium spp.

The nitrate reductase activity distribution and response of two nodulated species of Phaseolus (Phaseolus vulgaris-common bean, and Phaseolus lunatus-lima bean) to different exogenous nitrate levels were studied during the vegetative period. These Phaseolus species showed to be very contrasting in respect to the pattern of nitrate reductase (NR) activity distribution thought the plant. The highest level of NR activity in P. vulgaris was clearly shown to occur in leaves in contrast with the lowest one detected in roots and nodules as widely seen for other tropical species of the Phaseoleae tribe. Conversely, P. lunatus had higher NR activity in the nodules, whereas its leaves exhibited a steadily decrease during the plant development. Indeed, at 32 days after emergence (pre-flowering stage), the nodulated P. vulgaris had approximately 95% of the total NR activity localized in its leaves, whereas in P. lunatus it was equally distributed in the nodules and in the leaves. Under long-term exposure to increasing exogenous level of nitrate, the leaf-NR activity of nodulated P. vulgaris presented a positive response, whereas the enzyme activity was very low and unresponsive in P. lunatus. In contrast, the nodule-NR activity showed a reverse response to the increasing NO(3)(-) level. The nodule-NR activity of P. lunatus significantly increased whereas in the P. vulgaris nodules it was very low and unresponsive. This present study suggests that P. lunatus inoculated with Rhizobium tropici presents a singular pattern of nitrate reduction distribution among leaves and nodules during the vegetative development. It is speculated that the nodulated Phaseolus lunatus may have different NR isoforms in their leaves (at least a constitutive type) and an inducible form in their nodules, responsive to long-term exposure to nitrate.

Journal Article↗

Assessment of accuracy of PET utilizing a 3-D phantom to simulate the activity distribution of [18F]fluorodeoxyglucose uptake in the human brain.

A three-dimensional brain phantom has been developed to simulate the activity distributions found in human brain studies currently employed in positron emission tomography (PET). The phantom has a single contiguous chamber and utilizes thin layers of lucite to provide apparent relative concentrations of 5, 1, and 0 for gray matter, white matter, and CSF structures, respectively. The phantom and an ideal image set were created from the same set of data. Thus, the user has a basis for comparing measured images with an ideal set that allows a quantitative evaluation of errors in PET studies with an activity distribution similar to that found in patients. The phantom was employed in a study of the effect of deadtime and scatter on accuracy in quantitation on a current PET system. Deadtime correction factors were found to be significant (1.1-2.5) at count rates found in clinical studies. Deadtime correction techniques were found to be accurate to within 5%. Scatter in emission and attenuation correction data consistently caused 5-15% errors in quantitation, whereas correction for scatter in both types of data reduced errors in accuracy to less than 5%.

Brain↗

Activity distribution of a cobalt-60 teletherapy source.

In the course of quantifying the effect of radiation source size on the spatial resolution of portal images, a concentric ring structure in the activity distribution of a Cobalt-60 teletherapy source has been observed. The activity distribution was measured using a strip integral technique and confirmed independently by a contact radiograph of an identical but inactive source replica. These two techniques suggested that this concentric ring structure is due to the packing configuration of the small 60Co pellets that constitute the source. The source modulation transfer function (MTF) showed that this ring structure has a negligible influence on the spatial resolution of therapy images when compared to the effect of the large size of the 60Co source.

Cobalt Radioisotopes↗

A quantitative autoradiographic study of the heterogeneous activity distribution of different indium-111-labeled radiopharmaceuticals in rat tissues.

In light of the increased interest in small scale dosimetry, this paper presents a quantitative autoradiographic method for evaluation of heterogeneous activity distribution in tissues. This was studied in rat tissues after administration of 111In-chloride, -oxine, -tropolone, 111In-labeled homologous blood cells and 111In-anti-CEA-F(ab')2, using quantitative whole-body autoradiography. Quantification was performed utilizing an image analyzing system designed for whole-body autoradiographs. Very heterogeneous activity distribution was found in several tissues including the liver, spleen, kidneys, bone marrow, lymph nodes and testes. Notable was the high 111In uptake in organs characterized as rapidly proliferating, and known to have numerous transferrin receptors. In the gastrointestinal tract, all activity was associated with the intestinal walls. The heterogeneous tissue distribution shown in this investigation accentuates the necessity for performing detailed studies of the tissue distribution of radiopharmaceuticals. This is especially important for the radiation dosimetry of radionuclides emitting beta-particles or low energy electrons. We suggest whole-body autoradiography as an excellent implement to determine local activity concentrations in organs and tissues necessary for accurate absorbed dose calculations.

Animals↗

The effect of three dimensional activity distribution on the dose planning of radioimmunotherapy for patients with advanced intraperitoneal pseudomyxoma.

BACKGROUND: Six patients with histologically proven peritoneal carcinomatous pseudomyxomas were treated with radioimmunotherapy. METHODS: All the patients received a tracer dose of iodine-131 (131I) labeled B72.3 anti-TAG-72 monoclonal antibody (MoAb) to test the in vivo affinity. After informed consent was obtained the therapeutic dose (>3.7 gigabecquerels [GBq], 100 mCi) of the 131I labeled B72.3 anti-TAG-72 MoAb was infused within 60 minutes intraperitoneally using 2 catheters on both sides of the abdomen. The patients were imaged with single photon emission computed tomography (SPECT) at 3, 10, and 24 days after the therapeutic infusion. Treatment-planning software has been developed in which functional information obtained from SPECT is integrated with anatomic information obtained from computed tomography (CT). The activity distribution from SPECT images is converted to absorbed dose distributions using a point source kernel convolution dose calculation. The absorbed dose calculation requires a radionuclide specific dose kernel. The activity map is divided into equally sized source voxels from which the distribution is calculated for the target voxels that cover the patient volume. The resulting three dimensional (3D) absorbed dose distribution is viewed as isodose contours superimposed on the CT images or as 3D isodose surfaces. RESULTS: The measured activity distribution shows that the cumulated activity and biologic half-life vary in the patient's body. The developed planning system provides a method for calculating patient specific absorbed dose distributions. CONCLUSIONS: The variation of biologic clearance indicates that a 3D dose calculation method incorporating measured activity distributions is needed to quantify absorbed dose distribution.

Humans↗

Mitochondrial activity, distribution and segregation in bovine oocytes and in embryos produced in vitro.

Contents Bovine oocytes and embryos produced in vitro were studied to determine the mitochondrial pattern of distribution, segregation and activity using DIOC 6 and Jc-1 fluorescence. The highest fluorescence level observed in mature oocytes was taken as 100% activity and six activity levels were estimated as follows: (1) 0%, (2) 1-15%, (3) 16-30%, (4) 31-50%, (5) 51-75% and (6) 76-100%. Three patterns of mitochondrial distribution were found: (1) diffused throughout the cytoplasm in oocytes and embryos, (2) pericytoplasmic in oocytes and embryos, and (3) perinuclear only in embryos. The segregation of mitochondria in blastomeres showed two distinct patterns: (1) symmetrical with an even mitochondrial population, and (2) asymmetrical with different numbers of mitochondria in each blastomere. In immature oocytes, mitochondrial activity was very low and the distribution was diffuse or negligible, while in mature oocytes the activity was high and the distribution was diffuse or pericytoplasmic. Competent embryos up to the 16-cell stage showed intermediate levels of activity (16-50%) but activity decreased thereafter up to the blastocyst stage. Non-competent embryos showed low levels of activity (1-15%) at all stages. These results suggest that mitochondria might play an important role during early development and that a minimum threshold of activity regulates the potential competence for reaching the blastocyst stage.

Animals↗

Examining the activity-distribution model of visual attention with exogenous cues and targets.

LaBerge and his co-workers (e.g., LaBerge & Brown, 1986, 1989; LaBerge, Carlson, Williams, & Bunney, 1997) used an experimental method consisting of three rapid successive displays, each requiring a difficult letter discrimination, to show that visual attention is best accounted for with an activity-distribution model rather than a moving-spotlight model. The present study sought to further this line of investigation by inserting exogenous cues and targets, often used in studies that have found support for the moving-spotlight model, into the basic method used by LeBerge and colleagues. The results from three experiments were consistent with the activity-distribution model and not with the moving-spotlight model.

Adult↗

Shifting attention in visual space: tests of moving-spotlight models versus an activity-distribution model.

Participants were induced to concentrate preparatory attention at a central location, to identify a letter there, to identify a 2nd letter to the extreme left or right of a central horizontal range of 5 locations, and then to identify a 3rd letter at 1 of the central 5 locations. Analog and discrete versions of the moving-spotlight model predict that response times to the 3rd letter will be most rapid at the location of the 2nd letter, whereas an activity-distribution model predicts that the most rapid responses to the 3rd letter will be at the central location, where preparatory attention is strongest. The data from 3 experiments, taken together, are inconsistent with the moving-spotlight models and are consistent with the activity-distribution model.

Adult↗

The distribution, activity, and function of the cilia in the frog brain.

1. The distribution, activity, and function of the cilia in the brain was studied using in vitro preparations of the frog choroid plexuses and ependyma.2. Scanning electron microscopy revealed that twenty to forty cilia, about 20 mum long, project from the cells of the choroidal epithelium and ependyma into the ventricular system of the brain.3. These cilia beat at a constant frequency which ranged from 5 to 20 c/s. Ciliary activity was enhanced by ATP, cyclic AMP, theophylline, and acetylcholine, and was depressed by DNP, IAA, Ni(2+), La(3+), and Co(2+).4. Ciliary motion produced a flow of c.s.f. over the surface of the cells lining the ventricles, and in the choroid plexus this flow reduced the effective thickness of the unstirred layer adjacent to the epithelium by about 100 mum.5. These results are discussed in relation to the factors that control the frequency of ciliary beating, and the role of the cilia in the circulation of the c.s.f.

Acetylcholine↗

Distribution, activation and tryptase/chymase phenotype of mast cells in the rheumatoid lesion.

OBJECTIVE: To determine the distribution, activation, and tryptase/chymase phenotype of mast cells (MCs) in the rheumatoid lesion. METHODS: MC tryptase and chymase were studied by immunohistochemistry using monoclonal antibodies and examination by brightfield, interference, and fluorescent microscopy. Thirty four specimens of cartilage-pannus junction and 26 specimens of rheumatoid synovium, all derived from knee surgery, were examined. RESULTS: MCs were identified in all specimens examined, but their distribution and local concentrations varied, both within and between specimens. As a proportion of total synovial cells, there were more MCs in fibrous synovial tissues than in those with active inflammatory cell infiltrations; MCs usually showed a peripheral distribution around lymphocytic/mononuclear cell infiltrations. Most cartilage-pannus specimens demonstrated local concentrations of MCs at, or close to, sites of cartilage erosion, a significant proportion of which showed extracellular tryptase indicative of MC degranulation. MC degranulation was often associated with localised oedema and disruption of the stromal matrix. Two MC phenotypes were identified: one population contained tryptase alone (MCT) whilst another contained both tryptase and chymase (MCTC). The ratio MCT:MCTC approximated 8:1. CONCLUSIONS: This histological study demonstrated that local concentrations of MCs and their activation/degranulation are commonly observed in the rheumatoid lesion, and especially at sites of cartilage erosion. Such observations add weight to the concept that MCs contribute to the processes of inflammation, matrix degradation and tissue remodelling.

Aged↗

In vitro mass: activity distribution of lecithin--cholesterol acyltransferase among human plasma lipoproteins.

In order to compare the mass-activity distribution of lecithin-cholesterol acyltransferase (LCAT) among plasma lipoproteins separated by various ultracentrifugal or chromatographic procedures, we have quantified the enzyme by an electroimmunoassay technique using a specific antibody raised in the rabbit. This antibody, when added to whole serum, inhibited all of the enzyme activity present in it. The percent mass distribution of the enzyme among the lipoproteins isolated by rate-zonal ultracentrifugation (d 1.00-1.36 g/ml, SW 40 rotor, 37 000 rpm, 16 h) was as follows: very low density lipoproteins (VLDL), 0; low density lipoproteins (LDL), 6.2; HDL2, 6.5; HDL3, 12 and d greater than 1.21 g/ml fraction, 75. Measurement of LCAT activity of each lipoprotein fraction against mixed single bilayer lecithin-cholesterol vesicles (molar ratio, 4:1) containing apo A-I, indicated that VLDL, LDL and HDL2 were inactive or minimally active under the experimental conditions used, whereas HDL3 and the d greater than 1.21 g/ml fraction contained 17.5 and 79.9% of the total enzyme activity. Prolonged ultracentrifugation of the LCAT-containing lipoproteins resulted in the recovery of activity in the lipoprotein-free infranatant. In studies with lipoproteins linked to Sepharose 4B, LCAT was found to bind LDL, HDL2, and HDL3. It is concluded that LCAT is present in all the major lipoproteins except for VLDL. The activity appears to be dependent, at least in part, on the type of lipoproteins to which the enzyme is associated with.

Centrifugation, Isopycnic↗

[Quantitative topographic characterization of the myoelectric activity distribution of the masseter muscle: mapping of spectral EMG parameters].

A new method for quantitative characterization of myoelectrical masseter activity distribution by mapping of spectral EMG-parameters is described. The surface electromyograms of M. masseter were monopolarly recorded (16 channels). On the basis of registered EMG intervals (512 ms) the spectral EMG power of several frequency bands was calculated (Fast Fourier Transformation). The spectral EMG parameters between the 16 electrode positions were estimated by linear interpolation (4-nearest neighbours algorithm). Afterwards the spectral EMG parameters were fitted in a grey-tone or colour scale with 10 intervals. The so obtained EMG activity maps ("EMG-Maps") permit a quantitative-topographic characterization of myoelectrical masseter activity during different functional load procedures. The frequency range which is to consider in masseter surface-EMG investigations encloses frequencies between 15 and 500 Hz. The topography of EMG activation pattern of M. masseter is only described in a comprehensive manner when the electrode array consists of 16 electrodes and more. During defined motor tasks like clenching with controlled forces the reproducibility of EMG-Maps which respect to the topography of EMG activity pattern is very high. The absolute values of spectral EMG power as well as power changes of selected band ranges during clenching correlate to the extent of chewing forces.

Adult↗