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Biomedical subjects

R J Feldmann

Publications and source records attributed to R J Feldmann.

11 recordsLinked to original sources
PubMed1979

Evaporation of diethyltoluamide from human skin in vivo and in vitro.

Relative evaporation and penetration of the insect repellent, N,N-diethyl-m-toluamide, has been measured by 3 methods, 2 in vivo and 1 in vitro. The evaporation rate 30 min after application was found to be similar by all 3 methods. At an applied dose of 0.25 microgram/cm2, 9.6% in vivo and 9.7% in vitro evaporated from the skin in the first hour after application. Although the techniques used produced similar results in vivo and in vitro for diethyltoluamide, studies are being conducted to further elucidate kinetics of loss by evaporation.

Benzamides↗
PubMed1978

Interactive computer surface graphics approach to study of the active site of bovine trypsin.

A descriptive medium for the presentation of protein structure has been developed and used to evaluate the structure of the active site of bovine trypsin (EC 3.4.21.4). This technique, involving advanced computer graphics technology, permits the facile display of a representation of the molecular surface of proteins of known structure and employs color to code the structural or chemical features of this surface. Benzamidine derivatives were inserted into the benzamidine-binding site of trypsin and the binary inhibitor-trypsin complex was evaluated by using the computer-generated structure. On the basis of qualitative assessments of the contribution of electrostatic and hydrophobic forces to the binding energy associated with complex formation, we made predictions concerning the effects of interaction of benzamidine substituents and amino acid side chains upon the binding energy associated with inhibitor-protein binding. The computer display of the molecular surfaces of the binary complex of substituted benzamidines and trypsin permitted unique insight into the identity and chemical properties of the atoms that participate at the interface of the molecular surfaces of the inhibitor and the protein. The computer-generated molecular surface display can potentially be combined with quantitative definition of the physical forces involved in the interaction of molecular surfaces. This technology should facilitate the study of the structure-activity relationship of substrates, inhibitors, and drugs that bind to proteins of known three-dimensional structure.

Animals↗
PubMed1978

Animal models of percutaneous penetration: comparison between Mexican hairless dogs and man.

In an attempt to find better animal models for percutaneous penetration studies relevant to man, urinary excretion of 14C-labeled compounds was studied in the Mexican hairless dog and in man. With benzoic acid, progesterone and testosterone, the total absorption and maximum absorption rate were greater in man than in the hairless dog. As urinary excretion lasted days longer in the dog than in man, it is possible that the thin dog skin held the chemicals longer than man. Surface-counting experiments with a Geiger counter with a thin mica window protected by a special screen of fine stainless steel wires showed that benzoic acid and progesterone did persist on the dog skin far longer than on human skin. We conclude that the Mexican hairless dog has permeability characteristics significantly different from those of human skin.

Administration, Topical↗
PubMed1976

1H and 31P Fourier transform magnetic resonance studies of the conformation of enzyme-bound propionyl coenzyme A on the transcarboxylase.

The relaxation rates of the carbon-bound protons and of the three assigned phosphorus resonances of propionyl-CoA were measured in solutions of free propionyl-CoA and of the transcarboxylase-propionyl-CoA complex. In free propionyl-CoA, analysis of the 1/T1 values of 15 protons at 100 and 220 MHz and of 1/T1 and 1/T2 of the three phosphorus atoms at 40.5 MHz indicated free rotation of the propionyl region (taur approximately 3 x 10(-11) sec) but hindered motion of the remainder of the molecule with correlation times of 1-3. 5 x 10(-10) sec, approaching the tumbling time of the entire molecule (taur - 6 x 10(-10) sec. The correlation times of the three phosphorus atoms were indistinguishable from those of their nearest neighbor protons. The effects of three homogeneous enzyme preparations with varying contents of Zn(II), Co(II), and Cu(II) on 1/T1 of 12 protons and 3 phosphorus atoms of prionyl-CoA were analyzed with the help of simultaneous equations to yield the individual contributions at the three metal sites. Only diamagnetic effects were detected on the relaxation rates of the three phosphorus atoms. From the diamagnetic effects it was calculated that the motions of the prionyl side chain and of the terminal pantetheine methylene protons were hindered on the enzyme by an order of magnitude (taur approximately 6 x 10(-10) sec) and that the phosphorus atoms were hindered by two orders of magnitude (taur approximately 1 x 10(-8) sec) over the taur values found in free propionyl-CoA, but that these taur values remained well below that of the entire protein molecule (taur =6 x 10(-7) sec)...

Binding Sites↗
PubMed1975

Pattern recognitiion and structure-activity relationship studies. Computer-assisted prediction of antitumor activity in structurally diverse drugs in an experimental mouse brain tumor system.

This paper reports the application of pattern recognition and substructural analysis to the problem of predicting the antineoplastic activity of 24 test compounds in an experimental mouse brain tumor system based on 138 structurally diverse compounds tested in this tumor system. The molecules were represented by three types of substructural fragments, the augmented atom, the heteropath, and the ring fragments. Of the two pattern recognition methods used to predict the activity of the test compounds the nearest neighbor method predicted 83% correctly while the learning machine method predicted 92% correctly. The test structures and the important substructural fragments used in this study are given and the implications of these results are discussed.

Animals↗