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Biomedical subjects

W J Dunn

Publications and source records attributed to W J Dunn.

At least 37 records · Page 2Linked to original sources
PubMed1987

The role of solvent-accessible surface area in determining partition coefficients.

The logarithm of the partition coefficient (log P) of low-molecular-weight organic compounds is a physicochemical parameter used extensively in structure-biological activity studies to model interactions of the compounds with nonpolar phases in vitro and in vivo. The partition coefficient can be determined between water and a number of nonpolar solvents. The most common nonpolar solvent is 1-octanol, but solvents such as benzene, carbon tetrachloride, and chloroform are frequently used as models for the nonpolar phases. The functional relationship between chemical structure and partitioning is not well-understood. In this paper, partition coefficient data for 50 solutes in six nonpolar solvent systems are analyzed by using principal components analysis. The objective of the work is to explore the relationship between solute structure and partitioning behavior for simple organic compounds. Two structural factors are found to be important, with the isotropic surface area being the most important. The isotropic surface area can be used to estimate log P in some solvents and as an independent variable in quantitative structure-activity relationships (QSAR). This is illustrated by estimating the rate of epidermal diffusion of steroids.

Diffusion↗
PubMed1986

Botulinum toxin for the treatment of dysthyroid ocular myopathy.

Eight consecutive patients with acquired deviations due to dysthyroid ocular myopathy were injected with botulinum A toxin for relief of their diplopia. Seven patients were acute in the onset of symptoms and one was chronic. All showed improvement in motility and experienced a reduction if not total relief of their symptoms. Six patients required reinjection. Complications were limited to transient ptosis, transient involvement of adjacent muscles and transient but prolonged paralysis that eventually resolved. No systemic complications were noted. We conclude that chemodenervation with botulinum A toxin may have a role in the management of dysthyroid ocular myopathy not amenable to prism treatment and may act as an adjunct to or eliminate the need for surgical correction in some patients.

Adult↗
PubMed1985

Toxicity modeling and prediction with pattern recognition.

Empirical models can be constructed relating the change in toxicity to the change in chemical structure for series of similar compounds or mixtures. The first step is to translate the variation in structure to quantitative numbers. This gives a data table, a data matrix denoted by X, which then is analyzed. The same type of the models can be used to relate the variation of in vivo data to the variation of a battery of in vitro tests. A single data analytical model cannot be applied to a set of compounds of diverse chemical structure. For such data sets, separate models must be developed for each subgroup of compounds. The data analytical problem then partly is one of classification, pattern recognition (PARC). The assumption of structural and biological similarity within each subset of modeled compounds is then essential for empirical models to apply. PARC is often used to classify compounds as active (toxic) or inactive. The data structure is then often asymmetric which puts special demands on the data analysis, making the traditional PARC methods inapplicable. Depending on the desired information from the data analysis and on the type of available data, four levels of PARC can be distinguished: (I) the data X are used to develop rules for classifying future compounds into one of the classes represented in X; (II) same as I, but the possibility of future compounds belonging to "unknown" classes not represented in X is taken into account; (III) same as II, plus the quantitative prediction of one activity variable (here toxicity) in some classes; (IV) same as III, but several quantitative activity (toxicity) variables are predicted.

Mathematics↗
PubMed1983

Substituted 1,4-naphthoquinones vs. the ascitic sarcoma 180 of mice.

Twelve 1,4-naphthoquinones have been tested against the ascitic form of sarcoma 180 in Swiss mice. Statistical analysis shows that the most important molecular parameter determining their effectiveness in prolonging the life of mice bearing this tumor is their redox potentials. Although the toxicities of the compounds are also related to the redox potentials in the same way, the therapeutic indexes can be increased by adding substituents of greater lipophilicity. The naphthoquinones differ greatly in antitumor activities and may inhibit the growth of malignant cells by different mechanisms.

Animals↗
PubMed1983

Computer methods for the assessment of toxicity.

The prediction of the biological activity of chemical compounds by means of mathematical models is discussed. Biological activity of chemicals, including their toxicity on man and other biological organisms and systems, involves too complex phenomena to presently be predictable by fundamental models such as ab initio quantum mechanical models or statistical mechanical models. Hence one takes recourse to semi-empirical and empirical models which relate the variation in chemical structure of chemical compounds to the variation in their measured biological activity, e.g. toxicity in one or several test systems. These models are "calibrated" on series of similar compounds with "known" toxicity, the training set. Thereafter the models can--in fortunate cases--be used to predict the toxicity of compounds which are structurally similar to the training set compounds. The formulation and applicability of semi-empirical and empirical models relating chemical structure to biological activity is discussed. Causes and remedies for commonly encountered fallacies are presented.

Animals↗
PubMed1983

Protein levels and monensin for growing and finishing steers.

One hundred sixty-eight Angus X Hereford crossbred beef steers were utilized to evaluate the influence of two levels of monensin (0 or 33 ppm) on three levels of dietary protein (9, 11 or 13% on a dry matter basis). The study was divided into a growing phase when steers received ad libitum corn silage and the needed protein supplement to supply the appropriate protein level. The finishing diet consisted of 85% dry corn and 15% corn silage plus a protein supplement to yield an 11% protein diet fed to all steers. Estimates of carcass composition were made at the beginning, at the end of the growing phase and at completion of the study. During the growing phase, growth rate (GR), dry matter intake (DMI) and efficiency of gain (F/G) were all improved (P less than .01) with increasing protein level, while monensin reduced (P less than .01) DMI and improved (P less than .01) F/G, with the greatest improvement coming on the 9% protein diet. The rate of protein deposition was increased (P less than .05) with increasing protein level and was increased (P less than .01) on the 9% protein diet while being reduced on the 13% protein diet when monensin was included in the diet. Previous protein level influenced steer performance during the finishing phase, with the steers previously receiving the 13% protein diet having the poorest GR and F/G while those having received the 11% protein diet having the highest GR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗