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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

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

[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

The perinatal development of glucose-6-phosphatase activity distribution pattern in rat liver. A microdensitometrical study.

The ontogenetic development of the intralobular distribution pattern of glucose-6-phosphatase activity in the rat liver is described in terms of histochemical changes determined with microdensitometry. A newly developed cerium-lead technique was employed and compared with the common lead technique optimized by Teutsch (1978a). The cerium technique has advantages, meets the prerequisites for quantitative determinations and yields results comparable to biochemically obtained data from microdissected tissue. The first signs of a heterogeneous distribution pattern of glucose-6-phosphatase activity are observed on the 3rd d after birth, and differences between periportal and centrolobular areas are largest around 10th and 15th d. At 30th d after birth, the adult pattern is complete with a centrolobular glucose-6-phosphatase activity of 67% of the periportal value.

Aging

Activity distribution of seven digestive enzymes along small intestine in calves during development and weaning.

Ten groups of calves were used to study the changes in activity levels and distribution of seven hydrolases in the intestinal mucosa during development and weaning. The calves in the first group were sacrificed at birth while those in the remaining nine groups were either milk-fed until slaughter on days 2, 7, 28, 56, 70, and 119; or weaned between days 28 and 56 and then slaughtered on days 56, 70, and 119, respectively. The small intestine was immediately cut off and divided into five segments, ie, duodenum, proximal jejunum, median jejunum, distal jejunum, and ileum. In the milk-fed animals, the activity levels of aminopeptidases A and N, alkaline phosphatase, lactase, and isomaltase were maximum at 2 days of age, and then declined sharply between days 2 and 7 but did not change significantly thereafter. By contrast, the maltase activity increased between days 7 and 119, while no sucrase activity was detected. Weaning resulted in a decrease in the activity of lactase and an increase in that of aminopeptidase N, maltase, and isomaltase. The distribution of all these enzymes along the small intestine was slightly influenced by age but not at all by weaning.

Animals

Kinetics and activity distribution of urease coencapsulated with hemoglobin within polyamide membranes.

A 91.5% mass yield of urease and hemoglobin (Hb), co-encapsulated within polyamide membranes, was determined spectrophotometrically. The specific activity yield of microencapsulation was 84%, twofold higher than values previously reported, as a result of optimization of encapsulation conditions. The kinetic parameters and pH activity profiles of intracapsular urease were determined to be similar to those corresponding to the free enzyme. Similar activities were also observed for intact and microcapsule homogenate, indicating minimal mass transfer and diffusional limitation. The active configuration of the enzyme appears to remain intact upon microencapsulation. The application of a kinetic model for encapsulated urease further indicated that the kinetics were reaction-controlled with minimal mass transfer restrictions.

Capsules

[Activity distribution of SDH in liver of mice. A histophotometrical study (author's transl)].

The paper presents histophotometrical measurements of the histochemical SDH reaction with INT as redoxindicator in comparison with biochemical techniques of the determination of SDH activity (with K3[Fe(CN)6] and INT as indicators) and a histochemical method of elution (with INT as indicator). The measurements were performed on liver of mice. For each method absolute values of activity (10(-9) mol substrat/min-mg liver) are calculated as relative values of activity [%]. The standard deviation of the biochemical methods is approximate +/- 4%, of the histochemical methods +/- 8%. The smallest value of detection is 2.5-10(-14) mol formazan of histophotometrical measurement. The correspondence between the measurements of the relative values of activity by the described methods was secured by statistical tests. A statistically significant proportion of activities between periportal zone and central zone like 100:82 was determinated by histophotometrical measurement.

Animals

Activity distribution of cytochrome oxidase in the rat retina. A quantitative histochemical study.

Cytochrome oxidase (CYO) is a key enzyme in the respiratory chain. Therefore, CYO has an important role in the cell metabolism. In the present study CYO activity in the rat retina was identified by histochemical staining. The density of the staining, corresponding to the activity of the CYO, was evaluated quantitatively by densitometry. A high CYO activity was found in the retinal pigment epithelium, in the inner segment of the photoreceptors, in the outer plexiform layer and in the inner plexiform layer. In the outer segment of the photoreceptors, in the outer nuclear layer, and in the inner nuclear layer the CYO activity was relatively low. An analysis of variance demonstrated that the precision in an estimation of a mean depends on the number of animals and the number of retinal sections per animal.

Animals

Angiotensin-converting enzyme in the rat kidney. Activity, distribution, and response to angiotensin-converting enzyme inhibitors.

While it is known that angiotensin-converting enzyme (ACE) in the kidney is concentrated at the brush borders of the proximal tubule, the role of tubular ACE in renal physiology is not well understood. The active site of tubular ACE is exposed on the luminal surface of the brush borders and may hydrolyze peptides in the glomerular filtrate. However, a positive correlation between blood pressure and renal ACE activity was observed in spontaneously hypertensive rats, as well as in cases of ACE inhibition. Determination of ACE activity in different renal zones and immunohistochemistry demonstrated that ACE predominates in the inner cortex and that the proximal tubule in the outer cortex contains less ACE. Perhaps the inner cortex is the area responsible for alteration of renal ACE activity, since only ACE activity in the inner cortex increased following administration of the ACE inhibitor captopril. This would suggest that the induction of ACE occurs in the inner cortex. Renal ACE activity is also affected by oxidation. Thus, the activity increased when diamide, an oxidizing agent, was added to the crude extract of renal cortex and when oxygen was introduced into the extract. Therefore, tissue oxidation may be one factor affecting renal ACE activity.

Animals

Macroscopic dosimetry for radioimmunotherapy: nonuniform activity distributions in solid tumors.

In the context of radioimmunotherapy of cancer, there is a need for continued improvement of dosimetry of radionuclides localized in tumors. Current methods assume uniform distribution of radionuclides in the tumor despite experimental evidence indicating nonuniormity. We have developed a model in which nonuniform distribution of radioactivity in the tumor is taken into account. Spherically symmetric radionuclide distributions, depending linearly and exponentially on the radial position, are considered. Dose rate profiles in the tumor are calculated for potentially useful beta-emitting radionuclides, including 32P, 67Cu, 90Y, 111Ag, 131I, and 188Re, and for 193mPt, an emitter of conversion electrons and low-energy Auger electrons. For the radionuclide distributions investigated, high-energy beta emitters, such as 90Y, are most effective in treating large tumors (diameter, d greater than approximately 1 cm), whereas for small tumors (d approximately 1 mm), medium energy beta emitters such as 67Cu are better suited. Very small tumors (d less than 1 mm), and micrometastases are best handled with low-energy electron emitters such as 193mPt.

Antibodies, Monoclonal

T-cell control of IgA production. I. Distribution, activation conditions and culture of isotype-specific regulatory helper cells.

The capacity of T cells from different sites to augment IgA production by LPS-stimulated B cells has been investigated. Peyer's patch T lymphocytes activated with Con A induced up to a 20-fold increase in IgA production. The effect was isotype-specific, in that no consistent effect on IgG and a diminution of IgM synthesis were observed. Less activity was recorded in spleen and mesenteric lymph node T cells. Optimal activation of the Thy 1+ Lyt 1+2- helper cells required the addition of splenic adherent cells and the elimination of Thy 1+ Lyt 2+ suppressor cells prior to activation. T lymphocytes maintained regulatory activity for several months after expansion in medium supplemented with IL-2 and are now being cloned. We conclude that IgA production is under control of T cells sited preferentially, but not exclusively, in gut-associated lymphoid tissue, and that these T cells can augment IgA production by B lymphocytes from sites with low commitment to production of this isotype.

Animals

Contributions of topography and parallel processing to odor coding in the vertebrate olfactory pathway.

Odor information appears to be encoded by activity distributed across many neurons at each level in the olfactory pathway. Thus olfactory circuits function as parallel distributed processors. New methods for observing distributed activity in such systems permit computer simulations to be constructed that are constrained by patterns of activity observed in the real system. Analysis of the system using a combination of physiological measurements and computational approaches might elucidate the principles by which odors are discriminated.

Animals

Total cellular activity and distribution of a subpopulation of galactosyl receptors in isolated rat hepatocytes are differentially affected by microtubule drugs, monensin, low temperature, and chloroquine.

We studied the effects of low temperature (20-37 degrees C), monensin, chloroquine, and microtubule drugs on the cellular distribution and activity of galactosyl (Gal) receptors in isolated rat hepatocytes. After equilibration at 37 degrees C, hepatocytes were incubated at 37 degrees C, 31 degrees C, 25 degrees C, or 20 degrees C or treated with or without inhibitors at 37 degrees C in the absence of ligand. The cells were then assayed at 4 degrees C for 125I-asialo-orosomucoid binding, to measure receptor activity, or 125I-anti-Gal receptor IgG binding, to measure receptor protein. Surface or total (surface and intracellular) Gal receptor activity and protein were measured on intact or digitonin-permeabilized cells, respectively. These inhibitors fell into two categories. Type I inhibitors (sub-37 degrees C temperatures or colchicine) induced receptor redistribution but not inactivation. Treated cells lost up to 40% of surface Gal receptor activity and protein. Lost surface receptors were recovered intracellularly with no loss of receptor activity. Type II inhibitors (monensin or chloroquine) induced receptor inactivation but not redistribution. Treated cells lost 50-65% of their surface Gal receptor activity but only less than or equal to 15% of their surface receptor protein. These cells lost up to 60% of total cellular Gal receptor activity with no loss of total receptor protein. Of the total inactive Gal receptors, up to 50% and 75%, respectively, were present intracellularly in monensin- and chloroquine-treated cells. Loss of ligand binding to permeable treated cells was not due to changes in receptor affinity. A third category, Type III inhibitors (metabolic energy poisons that deplete ATP) induce both Gal receptor redistribution and inactivation (Biochemistry 27:2061, 1988). We conclude that only one of the two previously characterized subpopulations of Gal receptors on hepatocytes, termed State 2 receptors (J Biol Chem 265:629, 1990), recycles constitutively. The activity and distribution of State 2 but not State 1 Gal receptors are differentially affected by these specific drugs or treatments.

Animals

Human hexosaminidase isozymes. III. Distribution and activity of isozymes in peripheral blood leukocytes and platelets.

The specific activity and distribution of the isozymes of hex have been studied in platelets, granulocytes, monocytes, and lymphocytes isolated from venous blood. Since there are considerable differences in the content of the various hexosaminidase isozymes in these cell types, the relative activity of the A isozyme, expressed as a percent of total hexosaminidase in a mixed leukocyte preparation, is dependent on the proportion of the individual cell types present in a sample of peripheral blood. Because of variation in the proportion of cell types, the results may not accurately reflect the genotype of the blood donor. In contrast, chromatographic separation and assay of platelet extracts for activity of hexosaminidase isozymes provides a most convenient and satisfactory method of discriminating carriers and noncarriers of the Tay-Sachs mutant gene. Moreover, the ease of isolating platelets and the smaller volume of blood required compared with methods for obtaining purified leukocyte preparations offer additional advantages for identification or verification of the Tay-Sachs heterozygote state.

Blood Platelets