Biomedical subjects

Carson C Chow

Publications and source records attributed to Carson C Chow.

12 recordsLinked to original sources

PubMed2006

Patterns in food intake correlate with body mass index.

Quantifying eating behavior may give clues to both the physiological and behavioral mechanisms behind weight regulation. We analyzed year-long dietary records of 29 stable-weight subjects. The records showed wide daily variations of food intake. We computed the temporal autocorrelation and skewness of food intake mass, energy, carbohydrate, fat, and protein. We also computed the cross-correlation coefficient between intake mass and intake energy. The mass of the food intake exhibited long-term trends that were positively skewed, with wide variability among individuals. The average duration of the trends (P = 0.003) and the skewness (P = 0.006) of the food intake mass were significantly correlated with mean body mass index (BMI). We also found that the lower the correlation coefficient between the energy content and the mass of food intake, the higher the BMI. Our results imply that humans in neutral energy balance eating ad libitum exhibit a long-term positive bias in the food intake that operates partially through the mass of food eaten to defend against eating too little more vigorously than eating too much.

Body Mass Index↗

PubMed2006

A reduced mathematical model of the acute inflammatory response II. Capturing scenarios of repeated endotoxin administration.

Bacterial lipopolysaccharide (LPS; endotoxin) is a potent immunostimulant that can induce an acute inflammatory response comparable to a bacterial infection. Experimental observations demonstrate that this biological response can be either blunted (tolerance) or augmented (potentiation) with repeated administration of endotoxin. Both phenomena are of clinical relevance. We show that a four-dimensional differential equation model of this response reproduces many scenarios involving repeated endotoxin administration. In particular, the model can display both tolerance and potentiation from a single parameter set, under different administration scenarios. The key determinants of the outcome of our simulations are the relative time-scales of model components. These findings support the hypothesis that endotoxin tolerance and other related phenomena can be considered as dynamic manifestations of a unified acute inflammatory response, and offer specific predictions related to the dynamics of this response to endotoxin.

Acute Disease↗

PubMed2006

In silico models of acute inflammation in animals.

Trauma and hemorrhagic shock elicit an acute inflammatory response, predisposing patients to sepsis, organ dysfunction, and death. Few approved therapies exist for these acute inflammatory states, mainly due to the complex interplay of interacting inflammatory and physiological elements working at multiple levels. Various animal models have been used to simulate these phenomena, but these models often do not replicate the clinical setting of multiple overlapping insults. Mathematical modeling of complex systems is an approach for understanding the interplay among biological interactions. We constructed a mathematical model using ordinary differential equations that encompass the dynamics of cells and cytokines of the acute inflammatory response, as well as global tissue dysfunction. The model was calibrated in C57Bl/6 mice subjected to (1) various doses of lipopolysaccharide (LPS) alone, (2) surgical trauma, and (3) surgery + hemorrhagic shock. We tested the model's predictive ability in scenarios on which it had not been trained, namely, (1) surgery +/- hemorrhagic shock + LPS given at times after the beginning of surgical instrumentation, and (2) surgery + hemorrhagic shock + bilateral femoral fracture. Software was created that facilitated fitting of the mathematical model to experimental data, as well as for simulation of experiments with various inflammatory challenges and associated variations (gene knockouts, inhibition of specific cytokines, etc.). Using this software, the C57Bl/6-specific model was recalibrated for inflammatory analyte data in CD14-/- mice and was used to elucidate altered features of inflammation in these animals. In other experiments, rats were subjected to surgical trauma +/- LPS or to bacterial infection via fibrin clots impregnated with various inocula of Escherichia coli. Mathematical modeling may provide insights into the complex dynamics of acute inflammation in a manner that can be tested in vivo using many fewer animals than has been possible previously.

Animals↗

PubMed2005

Competitive dynamics in cortical responses to visual stimuli.

Neurons in the visual cortex of the macaque monkey exhibit a variety of competitive behaviors, including normalization and oscillation, when presented with multiple visual stimuli. Here we argue that a biophysically plausible cortical circuit with opponent inhibition, spike-frequency adaptation, and synaptic depression can account for the full range of behaviors. The governing parameter is the strength of inhibition between competing neuronal pools. As the strength of inhibition is increased, the pattern of network behavior shifts from normalization mode to oscillatory mode, with oscillations occurring at progressively lower frequency until, at the extreme, winner-take-all behavior appears.

Action Potentials↗

PubMed2005

The acute inflammatory response in diverse shock states.

A poorly controlled acute inflammatory response can lead to organ dysfunction and death. Severe systemic inflammation can be induced and perpetuated by diverse insults such as the administration of toxic bacterial products (e.g., endotoxin), traumatic injury, and hemorrhage. Here, we probe whether these varied shock states can be explained by a universal inflammatory system that is initiated through different means and, once initiated, follows a course specified by the cellular and molecular mechanisms of the immune and endocrine systems. To examine this question, we developed a mathematical model incorporating major elements of the acute inflammatory response in C57Bl/6 mice, using input from experimental data. We found that a single model with different initiators including the autonomic system could describe the response to various insults. This model was able to predict a dose range of endotoxin at which mice would die despite having been calibrated only in nonlethal inflammatory paradigms. These results show that the complex biology of inflammation can be modeled and supports the hypothesis that shock states induced by a range of physiologic challenges could arise from a universal response that is differently initiated and modulated.

Acute Disease↗

PubMed2004

Calcium time course as a signal for spike-timing-dependent plasticity.

Calcium has been proposed as a postsynaptic signal underlying synaptic spike-timing-dependent plasticity (STDP). We examine this hypothesis with computational modeling based on experimental results from hippocampal cultures, some of which are presented here, in which pairs and triplets of pre- and postsynaptic spikes induce potentiation and depression in a temporally asymmetric way. Specifically, we present a set of model biochemical detectors, based on plausible molecular pathways, which make direct use of the time course of the calcium signal to reproduce these experimental STDP results. Our model features a modular structure, in which long-term potentiation (LTP) and depression (LTD) components compete to determine final plasticity outcomes; one aspect of this competition is a veto through which appropriate calcium time courses suppress LTD. Simulations of our model are also shown to be consistent with classical LTP and LTD induced by several presynaptic stimulation paradigms. Overall, our results provide computational evidence that, while the postsynaptic calcium time course contains sufficient information to distinguish various experimental long-term plasticity paradigms, small changes in the properties of back-propagation of action potentials or in synaptic dynamics can alter the calcium time course in ways that will significantly affect STDP induction by any detector based exclusively on postsynaptic calcium. This may account for the variability of STDP outcomes seen within hippocampal cultures, under repeated application of a single experimental protocol, as well as for that seen in multiple spike experiments across different systems.

Action Potentials↗

PubMed2004

The dynamics of acute inflammation.

When the body is infected, it mounts an acute inflammatory response to rid itself of the pathogens and restore health. Uncontrolled acute inflammation due to infection is defined clinically as sepsis and can culminate in organ failure and death. We consider a three-dimensional ordinary differential equation model of inflammation consisting of a pathogen, and two inflammatory mediators. The model reproduces the healthy outcome and diverse negative outcomes, depending on initial conditions and parameters. We analyze the various bifurcations between the different outcomes when key parameters are changed and suggest various therapeutic strategies. We suggest that the clinical condition of sepsis can arise from several distinct physiological states, each of which requires a different treatment approach.

Acute Disease↗

PubMed2004

Inflammatory modulation of hepatocyte apoptosis by nitric oxide: in vivo, in vitro, and in silico studies.

Nitric oxide (NO*) and its reaction products are key players in the physiology and pathophysiology of inflammatory settings such as sepsis and shock. The consequences of the expression of inducible NO* synthase (iNOS, NOS-2) can be either protective or damaging to the liver. We have delineated two distinct hepatoprotective actions of NO*: the stimulation of cyclic guanosine monophosphate and the inhibition of caspases by S-nitrosation. In contrast, iNOS/NO* promotes hepatocyte death under conditions of severe redox stress, such as hemorrhagic shock or ischemia/reperfusion. Redox stress activates an unknown molecular switch that transforms NO*, which is hepatoprotective under resting conditions, into an agent that induces hepatocyte death. We hypothesize that the magnitude of the redox stress is a major determinant for the effects of NO* on cell survival by controlling the chemical fate of NO*. To address this hypothesis, we have carried out studies in relevant in vivo and in vitro settings. Moreover, we have constructed an initial mathematical model of caspase activation and coupled it to a model describing some of the reactions of NO* in hepatocytes. Our studies suggest that modulation of iron, oxygen, and superoxide may dictate whether NO* is hepatoprotective or hepatotoxic.

Animals↗

PubMed2002

Frequency-dependent synchrony in locus ceruleus: role of electrotonic coupling.

Electrotonic coupling synchronizes the spontaneous firing of locus ceruleus (LC) neurons in the neonatal rat brain, whereas in adults, synchronous activity is rare. This report examines the role of action potential frequency on synchronous activity in the adult LC. Decreasing the firing frequency in slices from adult animals facilitated the appearance of subthreshold oscillations and increased the correlation of the membrane potential between pairs of neurons. Conversely, increasing the firing frequency decreased the amplitude and synchrony of the oscillations among pairs. The frequency-dependent synchrony was not observed in slices from neonatal rats, where synchrony was observed at all frequencies, suggesting a developmental change in the properties of the LC network. A mathematical model confirmed that a reduction of the coupling strength among a pair of coupled neurons could generate frequency-dependent synchrony. In slices from adult animals, the combination of electrotonic coupling and firing frequency are the key elements that regulate synchronous firing in this nucleus.

Action Potentials↗

PubMed2002

Modeling neural oscillations.

A brief review of oscillatory activity in neurons and networks is given. Conditions required for neural oscillations are provided. Three mathematical methods for studying the coupling between neural oscillators are described: (i) weak coupling, (ii) firing time maps, and (iii) leaky integrate-and-fire methods. Several applications from macroscopic motor behavior to slice phenomena are provided.

Algorithms↗

PubMed2002

Is the world full of circles?

The statistical arrangement of oriented segments in natural scenes was recently proposed to be indicative of a cocircularity rule. In particular, the probability density function of the relative position of two oriented segments was found to be maximal along fixed angles on the plane, consistent with the two segments being tangent to two points of a circle. Does this observation point to a prevalence of circles in natural scenes? Here we demonstrate that similar statistics can be obtained even when circles are not very common in visual scenes. The reason is that circles or near circular objects can heavily skew the distribution in favor of the cocircularity rule.

Discrimination, Psychological↗

PubMedDate not supplied

A spiking neuron model for binocular rivalry.

We present a biologically plausible model of binocular rivalry consisting of a network of Hodgkin-Huxley type neurons. Our model accounts for the experimentally and psychophysically observed phenomena: (1) it reproduces the distribution of dominance durations seen in both humans and primates, (2) it exhibits a lack of correlation between lengths of successive dominance durations, (3) variation of stimulus strength to one eye influences only the mean dominance duration of the contralateral eye, not the mean dominance duration of the ipsilateral eye, (4) increasing both stimuli strengths in parallel decreases the mean dominance durations. We have also derived a reduced population rate model from our spiking model from which explicit expressions for the dependence of the dominance durations on input strengths are analytically calculated. We also use this reduced model to derive an expression for the distribution of dominance durations seen within an individual.

Action Potentials↗