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Biomedical subjects

L E Widman

Publications and source records attributed to L E Widman.

23 records · Page 2Linked to original sources
PubMed1989

Expert system reasoning about dynamic systems by semi-quantitative simulation.

Current symbolic knowledge representation techniques are inadequate for describing complex dynamic systems, which are time-varying and contain feedback loops. These systems are particularly difficult to represent when quantitative knowledge about the relationships within the system is incomplete. This paper describes a symbolic extension of the system dynamics method which can answer 'what if' questions about system dynamics models semi-quantitatively. The method consists of (1) definition of generic model 'building blocks' which map directly onto difference equations; (2) development of a symbolic causal model of a system in terms of the generic functional 'building blocks', any available quantitative or semi-quantitative parameters, and a set of generic default values; (3) automatic translation of the model into a system of first-order difference equations; and (4) numerical integration of the equations by standard methods. A complex model with semi-quantitative parameters, representing the human cardiovascular system, is used to illustrate the method. This method couples the descriptive abilities of mathematics with the symbolic power of causal inference methods by providing the same knowledge base for both computational levels. It also eases truth maintenance, knowledge acquisition, and explanation. It may prove useful for expert system development in a variety of application domains whose processes are time-varying and homeostatic.

Computer Simulation↗
PubMed1988

Electrocardiographic body surface potential maps of the QRS and T of normal young men. Qualitative description and selected quantifications.

A qualitative and quantitative analysis of the Body Surface Potential Maps (BSPM) of 40 young men, ages 19-41, is presented utilizing a 180 electrode system, with 135 anterior leads and 45 posterior leads. Evidence for epicardial right ventricular breakthrough was demonstrated in 36/40 at 27.9 +/- 6.8 ms, whereas our previous studies on normal children (average age 12.5 years) have demonstrated evidence for epicardial right ventricular breakthrough at 25.0 +/- 8.9 ms. The peak-to-peak magnitude at maximal potential (at 42.3 +/- 4.8 ms) was not significantly different from that of the children (4,430 +/- 1,165 microV), and the peak-to-peak magnitude of ST-T was virtually the same as that of the children (1,182 +/- 376.2 microV). The terminal activation pattern of late QRS on the body surface map appeared in the true posterior, anterior superior, posterior right superior and/or right anterior superior positions, in order of frequency. There were other regions appearing less frequently. In contrast, this pattern in children was seen only in the anterior superior, right anterior superior, posterior right superior, and true posterior in order of frequency. In 18/40, the body surface manifestation of repolarization was seen an average of 9.4 +/- 4.8 ms before the end of the QRS. A new pseudocolor display with 31 color levels representing body surface potentials allowed excellent resolution of isopotential detail.

Adult↗
PubMed1982

Multihormonal induction of alpha 2u-globulin in an established rat hepatoma cell line.

A subclone of the FU5-5 rat hepatoma cell line has been isolated which is inducible more than several hundred fold for the 20,000 dalton form of the major rat urinary protein alpha 2u-globulin. The basal relative synthetic rate (RSR) in growth medium containing 10% fetal calf serum was less than 2 X 10(-6) of total protein synthesis. Both dexamethasone and insulin were necessary for induction, and yielded a maximum induced RSR of 4-8 X 10(-3). Triiodothyronine (T3), dihydrotestosterone (DHT), rat growth hormone (GH), and estrogen, all of which have been shown to influence the induction of alpha 2u-globulin in the intact rat, were without effect on the cell line. A factor present in fetal calf serum was also necessary for maximum induction, since dexamethasone plus insulin in serum-free medium raised the RSR to only 3 X 10(-5); exogenous T3, GH, and DHT could not substitute for this serum factor. The kinetics of induction by dexamethasone were slow, with a lag of approximately 48 hr followed by a period of increasing RSR for 6-20 days. Removal of dexamethasone from induced cells led to an exponential decline in the RSR (t 1/2 15 hr). The concentrations of dexamethasone and insulin that could yield half maximum induction were 5 X 10(-8)M and 3 X 10(-11)M, respectively. Higher concentrations of insulin, although still in physiological range (10(-9)M), inhibited induction. At yet higher insulin levels, beyond the physiological range, alpha 2u-globulin synthesis returned to maximum values. The lack of DHT, T3, and GH requirement for alpha 2u-globulin induction in this cell line may mean that a regulatory aberrancy has occurred in this transformed cell line, or, alternatively, that these hormones act indirectly in the intact animal. This cell line should prove useful for the study of the molecular events associated with alpha 2u-globulin induction and for genetic approaches to the problem of multihormonal regulation of gene expression.

Alpha-Globulins↗
PubMed1979

Immortalization of normal liver functions in cell culture: rat hepatocyte-hepatoma cell hybrids expressing ornithine carbamoyltransferase activity.

Normal rat hepatocytes have been fused with highly differentiated rat hepatoma cells. Some of the hybrids express a physiologically significant level of activity of the urea cycle enzyme ornithine carbamoyltransferase (OCT), a liver-specific function not found in the hepatoma cells. These hybrids have 10% of the adult rat liver OCT specific activity, incorporate 3H-ornithine into protein arginine, and can be selectively grown in arginine-free medium supplemented with ornithine. Somatic cell hybridization of normal differentiated cells with highly differentiated neoplastic cells of the same tissue type may be useful as a general method for obtaining permanent cell lines with new tissue-specific phenotypes.

Animals↗