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Biomedical subjects

R J Roy

Publications and source records attributed to R J Roy.

10 recordsLinked to original sources
PubMed1992

Binding of a nuclear protein to the rat growth hormone silencer element.

The rat growth hormone (rGH) gene is uniquely expressed in a subset of cells from the anterior pituitary. This strongly cell type specific expression is controlled by both cis-acting positive sequences that bind the pituitary specific transcription factor Pit-1 and cis-acting negative regulatory elements that lie upstream of the Pit-1 sites. The negative elements act to prevent expression of the gene in inappropriate cell types. Here we report that the most proximal rGH silencer element is specifically bound by a protein found in a number of rGH non-expressing cell types and which exerts a negative regulatory effect through the recognition of this rGH element in transient transfection assays. The sequence recognized by this protein is similar to sequences of several other negative regulatory elements as well as to the consensus binding site for the transcription factor NF1. However, the 45 KDa molecular weight identified for this protein does not correspond to any of the sizes previously reported for NF1 suggesting that it is likely to represent a new member amongst this family of transcription factors.

Animals↗
PubMed1992

Multiple-model adaptive predictive control of mean arterial pressure and cardiac output.

A multiple-model adaptive predictive controller has been designed to simultaneously regulate mean arterial pressure and cardiac output in congestive heart failure subjects by adjusting the infusion rates of nitroprusside and dopamine. The algorithm is based on the multiple-model adaptive controller and utilizes model predictive controllers to provide reliable control in each model subspace. A total of 36 linear small-signal models were needed to span the entire space of anticipated responses. To reduce computation time, only the six models with the highest probabilities were used in the control calculations. The controller was evaluated on laboratory animals that were either surgically or pharmacologically altered to exhibit symptoms of congestive heart failure. During trials, the controller performance was robust with respect to excessive switching between models and nonconvergence to a single dominant model. A comparison is also made with a previous multiple-drug controller design.

Animals↗
PubMed1992

Adaptive control of multiplexed closed-circuit anesthesia.

This paper describes the design of an adaptive closed-circuit anesthesia controller based on a multiplexed mass spectrometer system. The controller deals with measurement deterioration caused by measurement delay and rise time through a long catheter as well as long sampling times due to the multiplexed measurements. Measurement data are extrapolated between sampling periods to increase the estimation convergence rate. A multiple-step-ahead predictive control algorithm is used to calculate intermediate control inputs between sampling intervals. Simulations are used to validate the designed controller.

Algorithms↗
PubMed1991

Modeling the hemodynamic response to dopamine in acute heart failure.

A descriptive incremental nonlinear single-input-multiple-output (SIMO) model of the hemodynamic response [cardiac output (CO) and mean aortic pressure (MAP)] to the inotropic drug dopamine in acute ischemic heart failure was constructed to facilitate the design of closed-loop control systems. The structure of the CO component of the model is a first-order system with a sigmoidal relationship. The MAP component is a first-order system with a threshold. Parameter identification was performed on data collected during positive step (drug on) and negative step (drug off) testing using multiple levels (2-6 mcg/kg/min) of infusion of dopamine in a canine model of acute ischemic heart failure. Parameter estimation utilized a least squares objective function and a linearized form of the step response of the model in the time domain. The model provides good approximations to the mean empirical responses.

Animals↗
PubMed1991

Adaptive control of closed-circuit anesthesia.

Closed-circuit anesthesia (CCA) is more economical and ecologically safer than open circuit anesthesia. However, gas concentrations are more difficult to control. Computer control of CCA has been proposed to facilitate its use. Past efforts have either been limited to the control of anesthetic gas concentrations or apply only to a small group of patients. This paper describes a comprehensive control system applicable to a large class of patients. This system controls the end-tidal oxygen and anesthetic gas concentrations, and the circuit volume. The CCA process was modeled by writing mass balance equations. Simplifying assumptions yielded a bilinear single-input-single-output model for the anesthetic gas concentration and a bilinear multiple-input-multiple-output model for the circuit volume and oxygen concentration. One-step-ahead controllers were used to control these two subsystems. Simulations showed that the control performance was most sensitive to the gas uptakes. Three independent, least-mean-squares estimation schemes were implemented to estimate the uptakes of oxygen, nitrous oxide, and anesthetic gas. These estimates were used in the control law and resulted in explicit adaptive control. The performance of the adaptive controller was compared to that of a fixed controller (with precalculated gas uptakes) in five animal experiments. The adaptive controller performed better than the fixed controller in all cases. The most significant difference was in the anesthetic gas response time 3.6 +/- 0.70 min for adaptive control and 7.04 +/- 5.62 min for fixed control. The adaptive controller was also robust with respect to variations in the system parameters such as the functional residual capacity, leak, deadspace and gas uptakes.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Closed-Circuit↗
PubMed1991

A short protocol for micro-purification of nuclear proteins from whole animal tissue.

Although a number of small-scale procedures have been described for the preparation of crude nuclear extracts from established cell lines, none were provided for the preparation of similar extracts from small amounts of animal tissue. In addition, no small-scale procedures contain enrichment steps that render the detection of low-abundant DNA-binding proteins easier. Here we describe a simple, efficient procedure for the rapid preparation of high-quality nuclear extracts from either whole animal tissue or established cell lines. It is based on a rapid isolation of the nuclei followed by a KCl extraction and a further micro-enrichment of the DNA binding proteins on heparin Sepharose CL-6B. Extracts prepared in such a way are suitable for the analysis of specific DNA/protein interactions by the use of gel shift assays or by DNaseI and dimethylsulfate footprinting techniques. Most importantly, the entire process can be fulfilled at minimal cost within a day on as little as one gram of fresh tissue, which renders this procedure extremely attractive for the analysis of DNA binding proteins involved in the control of gene expression.

Animals↗
PubMed1990

A circulatory model for combined nitroprusside-dopamine therapy in acute heart failure.

A computer model was developed to approximate the hemodynamic responses of dopamine and nitroprusside in acute left ventricular pump failure. The model is intended to aid the design of a multiple drug infusion system. A non-linear electrical analog model with baroreflex feedback was used to simulate the circulatory system. Heart failure was represented by a reduction in left ventricular inotropy. Pharmacodynamic relationships between the drugs studied and several elements of the system were incorporated into the model to simulate the overall drug responses which include secondary interactions between vascular components. Despite several shortcomings, the model showed good agreement with experimental and clinical data.

Acute Disease↗
PubMed1985

A feedback controller for ventilatory therapy.

A computerized system that uses feedback of end-tidal CO2 fraction (FETCO2) to adjust minute volume of a ventilator has been developed and tested. The effectiveness and robustness of the controller were evaluated in five anesthetized dogs. The controller responded to step-changes in the set-point for FETCO2 by adjusting minute volume so that the FETCO2 settled to the new set-point in less than 60 sec with less than 20% overshoot. The system exhibited suitable dynamic response to step-changes in set-point with loop gains as large as two times and as small as one-half the optimal value. The breath-to-breath variation in FETCO2 values during prolonged periods of closed-loop controlled ventilation was smaller than the variation during periods of constant minute volume ventilation in three of five experiments. The controller generally maintained FETCO2 within +/- 0.1 vol% of the set-point. A disturbance to the controlled system was produced by releasing an occlusion of a branch of the pulmonary artery. The controller always responded to this disturbance in a stable manner, returning the FETCO2 to its desired value within 30 sec. Accurate control of arterial partial pressure of CO2(PaCO2) will require modifications enabling the system to determine the relationship between FETCO2 and PaCO2.

Animals↗