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PubMedDate not supplied

Experimental regional cerebral ischemia in the middle cerebral artery territory in primates. Part 1: Angio-anatomy and description of an experimental model with selective embolization of the internal carotid artery bifurcation.

Selective embolization of the internal carotid artery bifurcation (ICA bifurcation) was performed in monkeys (Macaca mulatta) to study acute regional cerebral ischemia in the middle cerebral artery (MCA) territory with minimum surgical intervention in the neck under sedated conditions. The anthropomorphic similarity in angio-anatomy of the carotid system of monkeys and the use of silastic spheres, as artificial emboli, of the critical diameter of 1.2 to 1.4 mm resulted in the overall success rate of 87% in localizing the site of embolization to the ICA bifurcation, producing ischemia in the whole middle cerebral artery territory. All the animals with ICA-bifurcation embolization had contralateral deep motor weakness and conjugate eye deviation with nystagmus toward the site of embolization. Simultaneous EEG recording showed flattening of the basic background activities over the affected MCA area and cerebral arteriograms showed definite retrograde filling of the proximally occluded MCA. Clinical recovery was observed in a few animals within two to five hours of embolization. Gross ischemic swelling in the affected MCA territory, particularly in the gray matter, became obvious in six of eight animals which were exposed to four to five hours of ischemia. The angio-anatomical study of the carotid system of this experimental animal as a background for this MCA stroke model confirmed the previous observations of other investigators that the extremely abundant leptomeningeal anastomoses would be one of the major factors leading to the variability in the clinicopathological pictures seen in the models of proximal MCA occlusion. In addition, the pre-parenchymal anastomoses in the base of brain between the medial striate arteries from the proximal anterior cerebral (ACA) and lateral lenticulostriate arteries from the MCA were observed and described as a possible functional collateral to the basal ganglia in case of proximal MCA occlusion.

Animals↗
PubMed1994

Transglomerular transport of DEAE dextran in the isolated perfused kidney.

OBJECTIVE: The renal fractional clearance of [3H]DEAE dextran has been widely used to substantiate the charge selective model for renal permselectively, although there has only been one reported study on this type of clearance. This study sets out to examine the fractional clearance and glomerular processing of DEAE dextran. METHODS: Fractional clearance studies were performed using isolated perfused rat kidneys. The glomerular processing of DEAE dextran was assessed by examining the kinetics of DEAE dextran uptake in glomeruli isolated post perfusion. RESULTS: The fractional clearance of DEAE dextran used in the concentration range of 15-150 micrograms/ml in the perfusate of the isolated perfused kidney did not produce the classical in vivo facilitated transport of DEAE dextran as compared to dextran as observed by Bohrer et al. The fractional clearance curve displays retarded clearance of low molecular weight (small radii) DEAE dextran, giving the appearance of a 'flat curve'. Similar results were obtained when an oxygen free radical scavenger cocktail was included in the perfusate. These results may be due to the fact that DEAE dextran binds to the glomeruli (at an order of magnitude greater than dextran sulfate). Perfused kidneys with [3H]DEAE dextran for 1 h followed by a five minute perfusion with unlabelled DEAE dextran revealed no significant change in the glomerular levels of [3H]DEAE dextran (unlike dextran sulfate). Perfusion of rat kidneys with 15 micrograms/ml DEAE dextran produced no changes in the electron microscopical morphology of the glomerulus and no changes in the fractional clearance of dextran. CONCLUSIONS: These results do not support the glomerular charge selectivity model that involves a non-binding electrostatic interaction of the charged dextran with the fixed anion charges of the glomerular capillary wall.

Animals↗
PubMed2003

Locating disease genes using Bayesian variable selection with the Haseman-Elston method.

BACKGROUND: We applied stochastic search variable selection (SSVS), a Bayesian model selection method, to the simulated data of Genetic Analysis Workshop 13. We used SSVS with the revisited Haseman-Elston method to find the markers linked to the loci determining change in cholesterol over time. To study gene-gene interaction (epistasis) and gene-environment interaction, we adopted prior structures, which incorporate the relationship among the predictors. This allows SSVS to search in the model space more efficiently and avoid the less likely models. RESULTS: In applying SSVS, instead of looking at the posterior distribution of each of the candidate models, which is sensitive to the setting of the prior, we ranked the candidate variables (markers) according to their marginal posterior probability, which was shown to be more robust to the prior. Compared with traditional methods that consider one marker at a time, our method considers all markers simultaneously and obtains more favorable results. CONCLUSIONS: We showed that SSVS is a powerful method for identifying linked markers using the Haseman-Elston method, even for weak effects. SSVS is very effective because it does a smart search over the entire model space.

Bayes Theorem↗
PubMed1989

Statistical analysis of complex health and social data.

The selection of appropriate statistical models is a vital aspect of the analysis of complex health and social data. This paper examines issues related to model selection. It is concluded that the range of methods now available makes old controversies less relevant. Researchers may now look for strategies that combine the advantages of non-parametric and parametric approaches without automatically accepting the limitations of either. Examples of new directions are provided.

Analysis of Variance↗
PubMed1991

Variable threshold as a model for selective attention, (de)sensitization, and anesthesia in associative neural networks.

We study the influence of a variable neuronal threshold on fixed points and convergence rates of an associative neural network in the presence of noise. We allow a random distribution in the activity levels of the patterns stored, and a modification to the standard Hebbian learning rule is proposed for this purpose. There is a threshold at which the retrieval ability, including the average final overlap and the convergence rate, is optimized for patterns with a particular activity level at a given noise level. This type of selective attention to one class of patterns with a certain activity level may be obtained at the cost of reducing the retrieval ability of the network for patterns with different activity levels. The effects of a constant threshold independent of noise, time, and pattern are discussed. For high-(low-) activity patterns, the average final overlap is shown to be increased at high noise levels and decreased at low noise levels by a negative (positive) constant threshold, whereas a positive (negative) threshold always reduces the final average overlap. When the magnitude of the constant threshold exceeds a critical value, there is no retrieval. Rates of convergence towards the stored pattern with negative (positive) thresholds are greater than those with positive (negative) thresholds. These results are related to (de)sensitization and anesthesia. For certain threshold values and patterns with certain activity levels, hysteresis appears in the plot of the average final overlap versus the noise level, even for first order interactions. We make the analogy between the pattern-dependent neuronal threshold proposed in the present paper and the "task-related" modulation in neuronal excitability determined by cognitive factors, such as the attentional state of a higher animal. A constant threshold is associated with overall changes in neuronal excitability caused, e.g., by various drugs and physical injuries. Neurophysiological evidence of a dynamically variable neuronal threshold, such as accommodation and potentiation, is presented.

Anesthesia↗
PubMed1991

Spontaneous generation of selectable variation in the brain.

Selection models of behavior presuppose "selectable variation", diversity in the brain that is stable over time. Diversity can arise spontaneously through the mutual interactions of cell assemblies, which are postulated to align or disalign their neighbors into processing modes conforming to or opposite from their own. These processes are similar to magnetization and crystallization. If aligning and disaligning influences are distributed at random, a state resembling a spin glass can arise, where processing modes are highly varied in space but stable in time. If disalignment occurs regularly at the points of a two-dimensional lattice, and elsewhere the interactions are aligning, a pattern emerges with properties remarkably similar to visual orientation columns. These patterns are maintained dynamically, and emerge statistically without detailed genetic specification.

Animals↗
PubMed2006

Chick embryos exposed to trichloroethylene in an ex ovo culture model show selective defects in early endocardial cushion tissue formation.

BACKGROUND: Formation of the primitive heart is a critical step for establishing a competent circulatory system necessary for continued morphogenesis, and as such has significant potential as a target for environmental insult. The goal of this study was to identify the initial cellular events that precede more superficially observable abnormalities resulting from exposing early chick embryos to trichloroethylene (TCE). METHODS: A whole embryo culture method was used to assess the susceptibility of endocardial epithelial-mesenchymal transformation in the early chick heart to TCE. This method has the benefits of maintaining the anatomical relationships of developing tissues and organs, instantaneously exposing precisely staged embryos to quantifiable levels of TCE in a protein-free medium, and the ability to directly monitor developmental morphology. RESULTS: A minority of embryos (Hamburger and Hamilton [HH] stage 13-14) exposed to TCE (10-80 ppm) were not viable after 24 hr in culture and exhibited a variety of gross malformations in a dose-dependent fashion. However, the majority of treated embryos remained viable and developed into HH stage 17 embryos that were superficially indistinguishable from vehicle-treated controls. Further analysis of the hearts of these superficially normal embryos by whole-mount confocal microscopy revealed selective reduction in the number of atrioventricular canal mesenchymal cells. Additionally, those mesenchymal cells that did develop migrated abnormally as long thin cords of adherent cells. CONCLUSIONS: The regional selectivity of these effects in the chick heart suggests a critical window of susceptibility to TCE in the epithelial-mesenchymal transformation of atrioventricular canal endocardium.

Animals↗
PubMedDate not supplied

A comparison of alternative models of prescription drug utilization.

The two-part estimation technique has been advocated for estimating models using individual level health care utilization data characterised by a large proportion of non-consumption and small proportions of heavy users. This paper compares the two-part model to several other estimators, including the Poisson, negative binomial and 'zero altered' negative binomial models on the basis of within-sample forecasting accuracy and non-nested model selection tests. The empirical model estimates the differential effect of the removal of copayments for prescription medicines on the prescription drug utilization by older adults with differing levels of health status. The two-part estimator of this model is found to dominate the competitors. Results from this model indicate that utilization increases appear to be higher among individuals with lower levels of health status.

Aged↗
PubMed1986

Determination of rat beta 2-microglobulin in urine and in serum. II. Application of its urinary measurement to selected nephrotoxicity models.

beta 2-microglobulin (beta 2-m) was measured in the urine of rats by a specific immunoassay based on latex particles agglutination. The excretion of this protein was compared to the excretion of the enzyme beta-N-acetyl-D-glucosaminidase (NAG), albumin and amino acids in rats treated with either a single dose of sodium chromate (5 and 10 mg kg-1), repeated doses of gentamicin (5 and 20 mg kg-1), or cadmium (1 mg kg-1), and in aging rats (from 2 to 20 months). All treatments resulted in an early increased excretion of beta 2-m indicative of functional alterations of the proximal tubular cells. An increased NAG excretion was observed only at the highest dose of chromate and in the cadmium model but the relative increases of beta 2-m were much larger (up to 200 times the control values against four times the control values for NAG). From 2 to 20 months of age, urinary beta 2-m increases by a factor of four. Aminoacids excretion showed little sensitivity in the various models. Albumin showed little variations in purely tubular or in the tubular phase of renal injury but the chronic progressive nephrosis of aging rats caused a 40-fold increase in its excretion between 2 and 20 months of age. Therefore urinary beta 2-m, albumin and albumin/beta 2-m ratio provide useful tools in the assessment of nephrotoxicity and of its mechanisms in various experimental models.

Acetylglucosaminidase↗
PubMed2004

A new mathematical approach to the diffusion approximation theory for selective photothermolysis modeling and its implication in laser treatment of port-wine stains.

BACKGROUND AND OBJECTIVES: Monte Carlo (MC) simulations of light-tissue interactions and analytical solutions for the diffusion approximation theory have been used to determine the optimal laser wavelength and radiant exposure to treat port-wine stains (PWS). Both approaches suggest that optimal parameters are a wavelength of 585 or 595-nm with pulse times of 0.45-20 milliseconds. However, which parameters are optimal is still unclear. As differences in vessel size and in temperature distribution within vessels appeared to be the main reasons for the varied responses to the same laser treatments, we sought to develop a solution to the diffusion approximation in order to calculate temperature distribution and the resulting coagulation pattern within specific blood vessels. STUDY DESIGN/MATERIALS AND METHODS: The light and heat diffusion equations were simultaneously solved with the finite element method (FEM). The latent heat of evaporation was included in the thermal analysis. The temperature and coagulation patterns across specific blood vessels, within a heterogeneous medium, were calculated for laser wavelengths of 585 and 595-nm with clinical parameters. RESULTS: At 1.2 mm deep, the calculations predicted that vessels ranging from 50 to 100 microm in diameter would be coagulated from top to bottom, small vessels (10 microm) would be spared, and vessels larger than 150 microm would be partially coagulated. Coagulation across vessels was more uniform for the 595-nm than for the 585-nm wavelength. Maximal temperatures did not exceed 100 degrees C because of the inclusion of latent heat in the thermal calculations. CONCLUSIONS: To study laser treatments of PWS with the diffusion approximation, FEM is an effective method to calculate the coagulation patterns within specific blood vessels. To improve coagulation efficacy at 585 and 595-nm wavelengths, the radiant exposure should be increased without increasing the irradiance.

Body Temperature↗
PubMed1990

Pharmacological characterization of ear-scratch response in mice as a behavioral model for selective 5-HT2-receptor agonists and evidence for 5-HT1B- and 5-HT2-receptor interactions.

(+/-) 1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane [(+/-)-DOI], a phenylisopropylamine hallucinogen, is a 5-HT2-receptor agonist. The drug induced a dose-dependent increase in ear-scratch response (ESR) in mice, and the R(-)-isomer was more than 6 times as potent as its S(+)-enantiomer. The induced behavior was potently inhibited by selective 5-HT2-receptor antagonists such as ketanserin and spiperone. The (+/-)-DOI-induced ESR is also inhibited by stimulation of 5-HT1-receptors and the inhibition seems to be through a 5-HT1B-receptor mechanism. Thus, taken together, the present investigation indicates that ESR is due to selective stimulation of 5-HT2-receptors and that simultaneous costimulation of 5-HT1B-receptors inhibits the induced behavior. The study further suggests that the inability of the indolealkylamine hallucinogens to induce ESR is due to simultaneous excitation of 5-HT1B-receptors which are inhibitory to induction of ESR. Moreover, the data suggest possible inhibitory control mechanisms through 5-HT1-receptor subtypes to provide a damping mechanism to reduce excessive 5-HT2-receptor excitation due to exogenous drug stimulation or pathological conditions.

Amines↗
PubMed2005

The human placental derived BeWo cell line: a useful model for selecting Plasmodium falciparum CSA-binding parasites.

Chondroitin sulfate A (CSA) present in the placental intervillous blood spaces has been described as the main receptor involved in the massive sequestration of Plasmodium falciparum parasitized erythrocytes to the placenta. Placental parasite isolates are functionally distinct from isolates that sequester in other organs, because they do not cytoadhere to CD36 but instead bind to CSA. To investigate for the parasites molecules associated with the CSA adhesion phenotype, different methodologies have been developed to select for CSA-binding lines in vitro mainly using non-placental sources of CSA that differ in their sulfation pattern. In this study, we show that the human trophoblastic BeWo cell line is a very efficient alternative to select for the CSA-binding phenotype in parasitized erythrocytes.

Animals↗
PubMed2005

Identifying crash propensity using specific traffic speed conditions.

INTRODUCTION: In spite of recent advances in traffic surveillance technology and ever-growing concern over traffic safety, there have been very few research efforts establishing links between real-time traffic flow parameters and crash occurrence. This study aims at identifying patterns in the freeway loop detector data that potentially precede traffic crashes. METHOD: The proposed solution essentially involves classification of traffic speed patterns emerging from the loop detector data. Historical crash and loop detector data from the Interstate-4 corridor in the Orlando metropolitan area were used for this study. Traffic speed data from sensors embedded in the pavement (i.e., loop detector stations) to measure characteristics of the traffic flow were collected for both crash and non-crash conditions. Bayesian classifier based methodology, probabilistic neural network (PNN), was then used to classify these data as belonging to either crashes or non-crashes. PNN is a neural network implementation of well-known Bayesian-Parzen classifier. With its superb mathematical credentials, the PNN trains much faster than multilayer feed forward networks. The inputs to final classification model, selected from various candidate models, were logarithms of the coefficient of variation in speed obtained from three stations, namely, station of the crash (i.e., station nearest to the crash location) and two stations immediately preceding it in the upstream direction (measured in 5 minute time slices of 10-15 minutes prior to the crash time). RESULTS: The results showed that at least 70% of the crashes on the evaluation dataset could be identified using the classifiers developed in this paper.

Accidents, Traffic↗