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Biomedical subjects

J Polanski

Publications and source records attributed to J Polanski.

9 recordsLinked to original sources
PubMed2000

The comparative molecular surface analysis (COMSA): a novel tool for molecular design.

A new method allowing for 3-D QSAR analysis and the prediction of biological activity is presented. Unlike comparative molecular field analysis (CoMFA)-like techniques, it is based not on a comparison of the properties characterizing a discrete set of points but on the mean electrostatic potential (MEP) calculated and labeling specific areas defined on the molecular surface. A Kohonen self-organizing neural network and partial least square (PLS) analysis have been used for performing such an operation. The series of steroids complexing the corticosteroid (CBG) and testosterone (TBG) globulins, which forms a benchmark measuring the performance of the methods in molecular design, and a series of benzoic acids described by the Hammett sigma constants is used for testing the method. It is demonstrated that a method can be used efficiently to evaluate the responses determined both by the combination of electrostatic and steric effects or by electrostatic effects alone, therefore, two different schemes were developed. The first one, which involves PLS analysis of the full comparative networks, covers both steric and electrostatic effects. This scheme works well for both the CBG and TBG data. The second scheme takes into account only the properties (MEP) of these regions within molecules that can be superimposed with the template molecule. This scheme provides the best predictive power for the benzoic acids series. Comparison of the results from a CoMFA analysis proves that method is at least as effective for the responses limited by electrostatic effects, although it significantly outperforms CoMFA for CBG affinity which is dominated by steric effects.

Benzoates↗
PubMed2000

Self-organizing neural networks for screening and development of novel artificial sweetener candidates.

The use of Kohonen feature maps for the visualization of various aspects of molecular similarity is briefly reviewed and illustrated. It is shown that a specific feature of self-organizing maps (SOM) makes them of special interest for the screening of compounds. In particular, these methods were used to design candidates for new sweeteners, which were then synthesized.

Databases, Factual↗
PubMed1996

The comparison of geometric and electronic properties of molecular surfaces by neural networks: application to the analysis of corticosteroid-binding globulin activity of steroids.

It is shown how a self-organizing neural network such as the one introduced by Kohonen can be used to analyze features of molecular surfaces, such as shape and the molecular electrostatic potential. On the one hand, two-dimensional maps of molecular surface properties can be generated and used for the comparison of a set of molecules. On the other hand, the surface geometry of one molecule can be stored in a network and this network can be used as a template for the analysis of the shape of various other molecules. The application of these techniques to a series of steroids exhibiting a range of binding activities to the corticosteroid-binding globulin receptor allows one to pinpoint the essential features necessary for biological activity.

Drug Design↗
PubMed1984

Prolonged left ventricular dysfunction induced by sequential multifocal ischemic infarcts in dogs.

A method of creating multifocal ischemia in animals leading to left ventricular (LV) functional impairment is described. In a series of 10 mongrel dogs, electrodes were implanted in multiple branches of the coronary arteries. Subsequently, in seven animals, an 800-microA anodal current was applied for 3 h repeatedly over a span of 4-9 weeks. After current application, serum creatine kinase cardiac isoenzyme increased by 12.2 +/- 4.6 U/L (p less than 0.01) and ischemic electrocardiographic changes were consistently present. After an average of 10.7 current applications, all animals were tachypneic on mild exertion. Repeated measurement of LV function demonstrated a substantial reduction in cardiac reserve. No significant changes in three control animals were observed. The animals were sacrificed 80 days (range 49-108 days) after the initial current application. Presacrifice cineangiography and postmortem examination disclosed coronary artery occlusions, stenoses, recanalizations, and collateralization in the distributions expected on the basis of the time elapsed since electrode activation. In all cases, the myocardium exhibited diffuse fibrosis. This method reliably brings about multifocal myocardial ischemic changes in dogs and may provide a chronic LV failure model particularly suitable for the evaluation of LV assist systems.

Animals↗
PubMed1983

A method for generating obstructive thrombi in the coronary arteries of the conscious dog.

A technique for staging the generation of obstructive thrombi in the coronary arteries of conscious dogs is described. At thoracotomy, electrodes are placed in the lumina of coronary artery branches. When thrombus generation in proximity to the intraluminal electrode tip is desired, anodal current is applied to the exteriorised end of the electrode. In each of nine anaesthetised adult mongrel dogs two to seven intracoronary electrodes were implanted for a total of 35. One to 75 days later, 50 to 800 microA anodal current was applied to 16 electrodes for 30 min to 48 h. Upon autopsy, thrombi in various stages of organisation were found in proximity to the intracoronary portion of 15 electrodes. Six electrodes were found to be damaged or broken. In contrast, only four of the 13 control electrodes were sites of thrombus formation. In seven dogs tissue sections indicated either myocardial ischaemia or infarct in regions whose perfusion was blocked by thrombi. This method may provide for discretionary generation of intracoronary thrombi in the desired quantity, at the preferred site(s), at selected times of onset. Consequently, it offers the possibility of adjusting the onset, severity, and time course of myocardial ischaemia.

Animals↗