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Field potential evidence for long-term potentiation of feed-forward inhibition in the rat dentate gyrus.

Trains of high-frequency stimulation to the perforant path cause (i) long-term potentiation (LTP) of the population excitatory post-synaptic potential (EPSP), (ii) a lasting increase in the population spike, and (iii) a lasting alteration of the relationship between the EPSP and population spike (E-S relationship), consisting of a decreased x-intercept and decreased slope of the linear regression. To compare the thresholds of these changes, we applied a series of trains, increasing in duration from below LTP threshold. The EPSP potentiated with about the same low threshold as the reduction in E-S slope, whereas the reduction in E-S x-intercept required longer trains. In the second experiment, LTP of the EPSP was reduced by concurrent high-frequency stimulation of the commissural input and a lasting reduction of the population spike height was observed. In a third experiment, picrotoxin, an antagonist of gamma-aminobutyric acid (GABA)-mediated inhibition, blocked the decrease in slope of the E-S relationship which normally accompanies LTP. These results imply that perforant path/granule cell LTP is normally accompanied by long-term potentiation of a feed-forward inhibitory pathway which may involve interneurones.

Animals↗

An analysis of frequency response of motor units during voluntary isometric contractions at various speeds.

To ascertain the differences in discharge properties of a hand muscle between ramp and ballistic contractions, firing frequencies of 48 motor units of adductor pollicis muscle were analyzed during 3-kg isometric voluntary contractions at various force speeds. The force exertions were classified into 3 degrees: slow ramp, fast ramp, and ballistic contractions. The instantaneous frequencies (IFs) of motor units increased gradually when the force exertions were progressed to the target in slow and fast ramp contractions. The slopes of the linear regression equations between IFs and force levels were almost all constant during slow ramp contractions and were scattered slightly during fast ramp contractions. However, the slopes during ballistic contractions scattered widely. The y-intercepts of the same regression lines increased slightly with respect to the increment of force speed when slow and fast ramp contractions were performed. However, a remarkably wide variation of the y-intercepts was observed during ballistic contractions. Motor units could be fired at high frequencies at the beginning of discharge when ballistic contractions were performed as compared with slow and fast ramp contractions.

Adult↗

Evaluation of the Kodak EKTACHEM clinical chemistry slide for the measurement of bilirubin in newborns.

Measurement of neonatal bilirubin using the Jendrassik-Grof method (x) and the EKTACHEM NBIL assay (y) was compared over a 6-month period in a total of 1191 specimens from 483 patients less than 30 days of age. Linear regression analysis of the data yields a slope of 0.937, an intercept of 0.387, and Sy,x of 0.55 and a correlation coefficient of 0.983 for a total of 1032 specimens from patients less than or equal to 14 days of age and a slope of 1.090, an intercept of 0.002, an Sy,x of 1.03 and a correlation coefficient of 0.950 for a total of 159 specimens from patients greater than 14 days of age. The best correlation between EKTACHEM NBIL assay and the reference Jendrassik-Grof method was observed in samples from patients less than or equal to 14 days of age. Data from patients older than 14 days showed a higher proportional bias and a lower correlation coefficient between the methods. High performance liquid chromatographic analysis demonstrated that patients greater than 14 days of age had a higher incidence of elevated delta-bilirubin. Linearity extends to 200 mg/l. The NBIL assay provides a rapid, precise micromethod that is less sensitive than the Jendrassik-Grof method to the in vitro photo degradation of bilirubin and is not subject to the interference from hemoglobin and lipids. Because delta-bilirubin is not measured by this method, it is only recommended for newborns less than or equal to 14 days of age.

Bilirubin↗

Contraceptive efficacy of tamoxifen in female hamsters.

Systemic administration of tamoxifen (trans-1-(4-B-dimethylaminoethoxyphenyl)-1,2-diphenyl-but-1-ene), an antiestrogen, at a dose level of 2 mg/kg body weight on days 1, 2 and 3 post-coitum (p.c.) intercepts pregnancy during the peri-implantation period in 70-80% of hamsters. Significant alterations in the circulating levels of estradiol and progesterone were accompanied by the abolition of peak activities of various uterine lysosomal enzymes in the treated animals. The present study, therefore, suggests that estrogen plays a crucial role during the process of ovum-implantation in hamsters, and tamoxifen displays an interceptive role in this species.

Animals↗

A review of parameter values used to assess the transport of plutonium, uranium, and thorium in terrestrial food chains.

A general methodology of predicting the food chain transport of atmospherically deposited radionuclides is reviewed with an emphasis on variation in parameter values important for realistic behavioral characterization of environmental releases of plutonium, uranium, and thorium. Parameters important to generic simulations of food chain transport, given a known constant deposition onto vegetation, include: fractional interception of particulates by vegetation, vegetation density, effective half-life of contamination on vegetation, soil-to-plant transfer factors, consumption rates by cattle and man, and transfer of nuclides from forage to meat and from forage to milk. Variation in these parameters, which has been encountered in field studies, is summarized. A partial reduction in the variation of predicted concentrations of actinides in foods can be accomplished by more accurately determining critical parameter values like fractional interception of deposition by vegetation, vegetation biomass, and the effective half-life of contamination on vegetation. Field research describing the site dependency and time dependency of probability density functions for model parameter values is needed to make probabilistic predictions concerning Pu, U, and Th transport in food chains and to reduce the uncertainty associated with model predictions and generic assessments of environmental impact.

Biological Transport↗

Application of linear integration in the morphometric study of mild and severe pulmonary alveolar injury.

In this study we applied linear integration morphometry to characterize the pulmonary alveolar reaction to toxic injury and to study possible relationships between the major tissue and cell compartments of alveolar tissue, normal and injured. Acute alveolar injury of mild and severe intensity was induced in Swiss-Webster mice by the ip administration of the chemicals diquat (4 mg/kg) and butylated hydroxytoluene (BHT; 400 mg/kg). Animals were sacrificed at Days 1 and 2 after diquat treatment and at Days 1, 3, and 5 after BHT treatment. Sampling and analysis of alveolar tissue were conducted at both levels of light and electron microscopy. Thickness distributions of arithmetic and reciprocal intercepts, as well as the arithmetic (tau) and harmonic (tau h) mean thicknesses, were established for the following alveolar compartments: septum, alveolo-capillary barrier (ACB), type I and total epithelia, capillary endothelium, and interstitium. A relative measure of the pulmonary diffusion capacity and the capillary load of alveolar septa were also determined. The parameters calculated from these thickness distributions, such as their slopes, percentages of thin intercepts, and tau/tau h ratios, proved very sensitive and useful in the detection and characterization of morphological alterations in the type I epithelial and capillary endothelial cells following either mild or severe alveolar injury. The epithelial, endothelial, and interstitial layers of pulmonary septa were all characterized by their own pattern of structural changes, so that it proved impossible to relate them in a simple way to the tissue reaction, which can be easily studied at the light microscopic level. Linear integration morphometry thus proved very useful as a morphometric approach to the study of pulmonary alveolar injury and repair.

Animals↗

Alteration in dentate neuronal activities associated with perforant path kindling. II. Decrease in granule cell excitability.

Changes in the excitability of the dentate granule cells after perforant path kindling were examined by the analysis of perforant path-dentate gyrus field potentials recorded in freely moving rats. Using a range of test pulse intensities, the population spike heights (cellular output) were plotted against the magnitudes of the associated population EPSPs (synaptic input), and a linear regression (input/output) was estimated from the relative linear portion of the plot. The x-intercept of this regression defines the population spike threshold. With kindling, the overall amplitude of the population spikes decreased, in spite of an increase in the population EPSPs resulting in a flatter input/output regression. The x-intercept of the regression was unaffected by the first kindling stimulation, but consistently and significantly increased with subsequent kindling. These changes gradually reverted to near the prekindling control values during a postkindling rest period of 1 month, and were reinstated by rekindling after the period of rest. Similarly, the onset and peak latencies of the population spike were significantly retarded during the period of kindling. These results suggest that seizure activity causes a significant but temporary reduction in the excitability of dentate granule cells. This effect would tend to counteract the process of kindling and provide an explanation for some of the phenomena of postictal depression.

Animals↗

Low density lipoprotein is saturable by pro-oxidant copper.

The oxidative resistance of low density lipoprotein (LDL) can be experimentally described by the length of time during which no significant lipid peroxidation is observed in a pro-oxidant environment. This period of inhibited oxidation, termed the 'lag phase', is partially due to the radical scavenging reactions of the anti-oxidants contained in the LDL particle. We have shown that the LDL lag time decreases with increasing copper concentration, leveling out at a relatively high copper-to-LDL ratio. This behaviour demonstrates the existence of a finite number of saturable pro-oxidant copper binding sites within the LDL particle. The relationship is described by the equation, lag time = [Cu]-1.K.tmin+tmin where the constant, K, is the negative reciprocal of the x-axis intercept of the graphed function, and tmin is given by the y-axis intercept. By this definition of the constant, K is the amount of copper that will produce a lag time of twice tmin, while tmin is the minimum time a particular LDL will resist oxidation at a maximum copper concentration.

Adult↗

Direct calculation of the surface-to-volume ratio for human cancellous bone.

There are many diseases which cause detrimental changes in the trabecular structure of cancellous bone, leading to mechanical failure of the tissue. One approach to understanding the mechanisms of these diseases is to create idealized models that recreate the morphology of the tissue. This paper presents a partial development of such a model. Further histological methods must be developed before a complete definition of morphologically valid models is possible. In a histological section of cancellous bone, the orientation and length of the trabecular surfaces determine how a line drawn across the bone section will intersect the bone-marrow interface. The distribution of the average length between intersections for a set of parallel lines is defined as the mean intercept length distribution. In this paper, the average surface morphology and volume of the average structure of cancellous bone is determined from an examination of the mean intercept length. The average structure of cancellous bone contains a repeated structural element (SE). As a result, the basic bone structure is analogous to a brick wall made from many similar bricks. For a group of 107 specimens, a strong relationship between structural element volume (SE.V) and bone volume fraction (BV/TV) is demonstrated, SE.V = 0.017 kappa (BV/TV)-2.05 mm3, R2 = 0.93, with kappa a model-dependent constant. For the same specimens, the structural element surface (SE.S) showed the relationship, SE.S = 0.144 kappa (BV/TV)-1.35, R2 = 0.92. As a result of the inverse square dependence of structural element volume on bone volume fraction, it is predicted that cancellous bone strength is inversely proportional to structural element volume.

Adult↗

A comparison of reflection and transmission ultrasonic techniques for measurement of cancellous bone elasticity.

A reflection ultrasonic technique, which offers several advantages over transmission ultrasonic techniques, has been described for elastic property measurement of bone. Ultrasonic velocities from specimens of cancellous bone were compared using a reflection ultrasound technique and the more traditional transmission ultrasonic technique. The two techniques were found to yield velocities which were reasonably well correlated (r2 = 0.74). However, a statistical difference was found between the line of identity and the regression between transmission and reflection velocities (due to an offset in the intercept). In spite of differences in intercept between velocities measured by the two techniques, significant correlation was found between the two methods, suggesting that the reflection technique can measure wave velocities meaningful to bone elasticity.

Animals↗

Finite element modeling of damage accumulation in trabecular bone under cyclic loading.

A two-dimensional finite element model of an idealized trabecular bone specimen was developed to study trabecular bone damage accumulation during cyclic compressive loading. The specimen was modeled as a two-dimensional honeycomb-like structure made up of an array of hexagonal cells. Each trabecula was modeled as a linearly elastic beam element with the same material properties as cortical bone. Initial microcracks were assumed to exist within the oblique trabeculae and to grow according to the Paris law. Forces and moments were computed in each trabecula and the microcracks were allowed to propagate until fracture occurred. Between cycles, fractured trabeculae were removed from the finite element mesh, and force and moment distributions were calculated for the next cycle. This iterative process was continued until the simulated trabecular bone specimen showed a 10% reduction in modulus. Creep failure was also studied using a single cell analysis, in which a closed-form solution was obtained after prescribing the creep properties of the trabeculae. The results of the crack propagation analysis showed that fractures of only a small number of individual trabeculae can cause a substantial reduction in the modulus of the trabecular bone specimen model. Statistical tests were performed to compare the slopes and intercepts of the S-N curves of our model predictions to those of experimentally derived S-N curves for bovine trabecular bone. There was no significant difference (p > 0.2 for both slope and intercept) between our model predictions and the experimentally derived S-N curves for the low-stress, high-cycle range. For the high-stress, low-cycle range, the crack propagation model overestimated the fatigue life for a given stress level (for slope, p < 0.001), while the creep analysis agreed well with the experimental data (for slope, p > 0.2). These findings suggest that the primary failure mechanism for low-stress, high-cycle fatigue of trabecular bone is crack growth and propagation, while the primary failure mechanism for high-stress, low-cycle fatigue is creep deformation and fracture. Furthermore, our results suggest that the modulus of trabecular bone at the specimen level may be highly sensitive to fractures of individual trabeculae.

Algorithms↗

Solute and mobile phase contributions to retention in hydrophobic interaction chromatography of proteins.

Hydrophobic interaction chromatography utilizes high salt concentrations mobile phases to induce an interaction between a weakly hydrophobic matrix and exposed hydrophobic amino acids of a native protein. Proteins with a hydrophilic exterior have shorter retention times on a hydrophobic interaction column than do proteins with more hydrophobic exteriors. To examine the effect of amino acid substitutions on protein retention, lysozyme isolated from related bird species was chromatographed on a hydrophobic interaction column at increasing ammonium sulfate concentrations. Chromatographic retention deviated only when amino acid substitutions occurred on the surface of lysozyme opposite the catalytic cleft. This area may constitute a contact surface area and extends from Residue 41 to 102 and from 75 to the alpha-helical region starting with Residue 89. Retention was analyzed by plotting log k' versus the molal concentration of ammonium sulfate. The slope did not deviate significantly for each of the bird lysozymes, indicating a similar contact surface area. However, there was significant deviation in the intercept of each of the lysozyme lines, which probably reflects the strength of the hydrophobic interaction. The intercept increased as the lysozyme became more hydrophobic. Hydrophilic amino acid substitutions affected retention as much as hydrophobic ones. The ionization state of histidine residues within the contact area between lysozyme and the column surface also influenced retention. An uncharged histidine residue increased retention, while a decrease in retention was seen with a charged histidine residue. The amino acid substitutions did not appear to affect the size of the hydrophobic contact surface area, but rather the strength of the hydrophobic interaction. The effect of salt composition on protein retention indicated that factors other than surface tension could influence retention. These factors appear to include protein hydration and specific interactions between the protein and the salt ions. Of these, the latter may or may not result in an alteration in protein structure. The magnitude of the effect of salt composition was found to be dependent upon the protein.

Amino Acid Sequence↗

Chromatographic separation and molecular modelling of triazines with respect to their inhibition of the growth of L1210/R71 cells.

The potential anti-cancer activity of triazines was characterized by the inhibition of the growth of L1210/R71 cells. The retention times for fifteen triazine derivatives were measured by high-performance liquid chromatography on octyl silica and silica gel columns. The slope and intercept values of the plot of the logarithmic capacity factor versus acetonitrile concentration were calculated from the reversed-phase retention measurements. The adsorption properties of the compounds were characterized by the retention data obtained on silica gel columns using high and low concentrations of ammonium salts in the hydro-organic mobile phase. The non-polar, non-polar unsaturated and polar surface areas, the surface energies, the dipole moments and the Van der Waals radii of the molecules were calculated from their chemical structures after energy minimization on the basis of molecular mechanics. Correlation analysis of these parameters showed that the inhibitory effect is dependent on the polar and non-polar surface areas of the molecules. The reversed-phase slope showed a significant correlation with the difference between the accessible and the total non-polar surface areas of the compounds, whereas the intercept values correlated with the non-polar accessible surface area. The adsorption properties of the triazines on silica gel cannot be described by the molecular parameters investigated here.

Animals↗

The effect of lung edema on pulmonary vasoactivity of furosemide.

Previous data suggest that furosemide improves gas exchange in pulmonary edema by preferential perfusion of nonedematous lung units. To test whether this is a direct effect of furosemide on the pulmonary vasculature as opposed to a secondary phenomenon resulting from the known peripheral effects of this drug, the effect of furosemide on the pressure-flow characteristics of the pulmonary vasculature was studied in six isolated perfused canine lungs with different degrees of gravimetrically determined edema. Furosemide shifted the pressure-flow curve by decreasing the mean intercept or average closing pressure of the pulmonary vascular bed from 13.8 +/- 5.3 to 9.5 +/- 5.4 cm H2O and the zero-flow critical closing pressure from 9.3 +/- 4.3 to 4.7 +/- 3.5 cm H2O (P less than 0.05). The slopes of these curves did not change between control and furosemide treatment. The decrease in intercept and the decrease in zero-flow critical closing pressures were closely correlated with the increase in edema (r = 0.895 for average closing pressure and r = -0.928 for critical closing pressure) (P less than 0.05). Furosemide doubled the pulmonary blood flow in the isolated lobe for the same driving pressure and the greater the amount of lobar edema the less pronounced was this furosemide-associated increase in blood flow. This direct effect of furosemide on the pulmonary vasculature could explain the improved gas exchange seen before a decrease in pulmonary edema, since this pulmonary vasoactivity would result in preferential perfusion of nonflooded alveolar units.

Animals↗

Molecular dosimetry of DNA damage caused by alkylation. I. Single-strand breaks induced by ethylating agents in cultured mammalian cells in relation to survival.

Cultured Chinese hamster ovary cells were treated with ethylating agents. DNA lesions giving rise to single-strand breaks (ssb) or alkali-labile sites were measured by centrifugation in alkaline sucrose gradients after lysis in alkali. 4 agents with different tendencies to ethylate preferentially either at N or O atoms were compared, namely N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG), N-ethyl-N-nitrosourea (ENU), ethyl methanesulphonate (EMS) and diethyl sulphonate (DES). The compounds differed greatly in their potency to induce the lesions measured when compared on a molar basis, but comparison at equicytotoxic doses showed relatively small differences. Upon prolonged incubation of the DNA in alkali, the number of ssb increased considerably. DNA from untreated cells showed biphasic kinetics: slow ssb formation for about 10 h, then the rate increased and remained constant for up to 40 h. Treated cells showed an accelerated, dose-dependent linear generation of ssb for 10 h, followed by a short plateau; then ssb were formed again at a constant rate, somewhat higher than that in controls. Ssb formed in the initial phase are ascribed to phosphotriester hydrolysis, those after the plateau to unidentified causes. Zero intercepts appeared to be a measure of apurinic sites generated intracellularly. A 24-h repair period preceding lysis reduced the ENNG intercept, but not that of DES. Rapid degradation of DES during the 1-h treatment occurred, so most "apurinic-site lesions" were induced in the beginning of exposure and possibly were already repaired at the end. The types of lesion distinguished (reparable and non-reparable apurinic sites, phosphotriesters) appeared of little consequence for cell survival.

Alkylating Agents↗

Interpretation of UV-survival curves of Aspergillus conidiospores.

Semi-logarithmic dose-response curves for survival of UV-irradiated conidiospores of A. nidulans have an initial shoulder (at low doses) followed by a decline which becomes linear. To explain the initial shoulder and the resulting extrapolation number (log S intercept of the linear extrapolation line) a general model is presented, which includes multi-target (n) and multi-hit (h) effects and allows for the effect of initial repair and of a compound parameter k, which stands for inherent sensitivity of the spores and for dose received inside the spores. From experiments on (a) the modification of k (spore wall colour and shelter effects), (b) a repair-deficient strain (shoulderless) and (c) preincubation during which DNA-replication takes place, it is concluded that the shoulder is generated by initial repair rather than by a multi-hit nature of the cell-killing process. In experiments where k takes different values (sub a and c), notably the position of the point of intersection of the linear lines gives conclusive information. In general, the log S intercept of the linear extrapolation line cannot be used to estimate the target number.

Aspergillus nidulans↗

Cyclic-ratio schedule analysis of a serotonin agonist and depletor on consummatory behaviour.

Four male Wistar rats, 180 days old at the start of the experiment, at 85% of their free-feeding body weight were trained to respond on a geometric cyclic-ratio schedule comprised of the following ratio values: 2, 4, 8, 16, 32 and 64, for 0.1 ml of 5% sucrose reinforcement. The response functions (response rates plotted against reinforcement rates) were linear and of negative slope over the range of ratio values from 2 to 16. IP administration of 1.0 mg/kg 5-MeODMT reduced the x- and y-intercepts of the linear portion of the response function without altering the slope relative to 2.0 ml/kg 0.85% saline IP. This was interpreted as a perceived palatability effect. IP administration of 100 mg/kg pCPA elevated the reinforcement rate intercept but also decreased the slope of the response function. This finding was interpreted as an increase in the perceived palatability of the reinforcer, coupled with a decrease in motivation at higher schedule conditions, possibly due to peripheral effects of pCPA.

Animals↗

Relationships between performance and skin resistance evolution involving various motor skills.

The aim of this article was to question the classical inverted-U curve relationship between activation and performance. It was hypothesized that changes in performance were related to both activation and the degree of skill difficulty, suggesting a more complex relation. Fifty-one subjects took part in one of three experiments requiring sensory and motor anticipation abilities. They were divided into three different groups, each performing one particular anticipation task. Skin resistance was continuously recorded during task performance. This autonomic variable is well known to be a reliable index in predicting activation variations. The first task, carried out in a seated position, was to intercept a moving spot on a computer screen by pressing the space bar on the keyboard. The second task, performed standing, required subjects to intercept a moving table tennis ball with palm of the hand, by extending the forearm and the arm. The third task, executed in movement was performed on a volley-ball ground. The aim was to hit a ball to reach a moving human target, using the forearm-blow technique. Results showed that 90.9% of subjects'performance in Experiment 1 was related to skin resistance tonic level variations, thus establishing a strong relationship between performance and arousal. Subjects' performance (43.8%) in Experiment 2 was related to skin resistance tonic level variations, whereas only 12.5% of performance was related to this variable in Experiment 3. In conclusion, tonic level variations can only account for success or failure in the first experiment. Conversely, success or failure were dependent upon information processing, decision making, and motor execution in the third experiment. The second experiment, requiring intermediate abilities, was found to show intermediate results. The role of skin resistance tonic level fluctuations and their use in the study of sporting performance are discussed, suggesting that arousal/performance relationships do not correspond to a simple inverted-U curve in complex motor skills requiring a steady level of arousal.

Adolescent↗