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Biomedical subjects

A H Lowrey

Publications and source records attributed to A H Lowrey.

10 recordsLinked to original sources
PubMed2001

Scaled quantum mechanical force field for alanyl-alanine peptide in solution.

We have obtained ab initio scale factors and assigned frequencies for the alanine-alanine peptide in water. Calculations were performed on the isolated acidic and basic Ala-Ala structures, two one-water basic Ala-Ala supermolecules, and one two-water acidic and one two-water basic Ala-Ala supermolecules. Force constants were scaled using the experimentally determined Raman and Fourier transform infrared vibrational frequencies of four isotopic species of Ala-Ala in water at pH 13 and pH 1. Most of the 4-31G scale factors were transferable from smaller molecules. All but one scale factor were directly transferable between the pH 1 and pH 13 species for coordinates unchanged by protonation in both the isolated and two-water supermolecule structures. Scale factors for nonpolar coordinates were transferable between all Ala-Ala species with only a few small changes. Good agreement was obtained between the calculated and experimental frequencies for all isotopic species and structures.

Dipeptides↗
PubMed1997

Modeling drug-melanin interaction with theoretical linear solvation energy relationships.

The affinity of drugs and other xenobiotic agents for melanin is a well-known phenomenon, often occurring with serious physiological consequences. For example, the interaction of anti-psychotic drugs with neuromelanin may play a pivotal role in the induction of extrapyramidal movement disorders associated with the chronic administration of phenothiazine and other neuroleptic agents. Little, however, is known about the complete nature of melanin-drug binding and the impact of these interactions on the physico-chemical properties of melanin. Data, such as binding affinities, can be analyzed using recently developed computational methods that combine mathematical models of chemical structure with statistical analysis. In particular, theoretical linear solvation energy relationships provide a convenient model for understanding and predicting biological, chemical, and physical properties. By using this modeling technique, drug-melanin binding of a set of 16 compounds has been analyzed with correlation analysis and a set of theoretical molecular parameters in order to better understand and characterize drug-melanin interactions. The resulting correlation equation supports a charge transfer model for drug-melanin complex formation and can also be used to estimate binding constants for related compounds.

Antipsychotic Agents↗
PubMed1994

Usefulness of one electron properties in the study of the nitromethane-to-methyl nitrite rearrangement.

Large-scale multiple reference configuration interaction calculations for a unimolecular rearrangement reaction of nitromethane to methyl nitrite are presented. The complicated structure of potential energy curves is explained in terms of interactions between ground and excited states. An explanation for an extremely long C--N and C--O bond distances in the transition state is also given. The study of corresponding dipole moments and electrostatic molecular potentials enhances the overall understanding of the reaction.

Computer Graphics↗
PubMed1993

An enforceable indoor air quality standard for environmental tobacco smoke in the workplace.

Environmental tobacco smoke (ETS) has recently been determined by U.S. environmental and occupational health authorities to be a human carcinogen. We develop a model which permits using atmospheric nicotine measurements to estimate nonsmokers' ETS lung cancer risks in individual workplaces for the first time. We estimate that during the 1980s, the U.S. nonsmoking adult population's median nicotine lung exposure (homes and workplaces combined) was 143 micrograms (micrograms) of nicotine daily, and that most-exposed adult nonsmokers inhaled 1430 micrograms/day. These exposure estimates are validated by pharmacokinetic modeling which yields the corresponding steady-state dose of the nicotine metabolite, cotinine. For U.S. adult nonsmokers of working age, we estimate median cotinine values of about 1.0 nanogram per milliliter (ng/ml) in plasma, and 6.2 ng/ml in urine; for most-exposed nonsmokers, we estimate cotinine concentrations of about 10 ng/ml in plasma and 62 ng/ml in urine. These values are consistent to within 15% of the cotinine values observed in contemporaneous clinical epidemiological studies. Corresponding median risk from ETS exposure in U.S. nonsmokers during the 1980s is estimated at about two lung cancer deaths (LCDs) per 1000 at risk, and for most-exposed nonsmokers, about two LCDs per 100. Risks abroad appear similar. Modeling of the lung cancer mortality risk from passive smoking suggests that de minimis [i.e., "acceptable" (10(-6))], risk occurs at an 8-hr time-weighted-average exposure concentration of 7.5 nanograms of ETS nicotine per cubic meter of workplace air for a working lifetime of 40 years. This model is based upon a linear exposure-response relationship validated by physical, clinical, and epidemiological data. From available data, it appears that workplaces without effective smoking policies considerably exceed this de minimis risk standard. For a substantial fraction of the 59 million nonsmoking workers in the U.S., current workplace exposure to ETS also appears to pose risks exceeding the de manifestis risk level above which carcinogens are strictly regulated by the federal government.

Adult↗
PubMed1990

Relation between calculated amide frequencies and solution structure in Ala-X peptides.

Computational techniques have been used to aid interpretation of observed systematic shifts in the amide III frequencies of Ala-X peptides. Optimized structures and frequencies have been calculated for Ala-X peptides using GAUSSIAN86/88 with the 4-31G basis, MOPAC, and normal mode methods based on empirical force fields. We observe the following: (1) Frequencies calculated using scaled GAUSSIAN86 force constants correlate well with the experimental results. (2) Structures of the Ala-X peptides optimized by GAUSSIAN show a clear trend toward lower values of the dihedral angle phi as the X side chain becomes larger, while structures optimized here using semiempirical and empirical force fields do not show trends. (3) Computational changes in peptide conformations from beta-sheet to alpha-helix produce large changes in both amide I and amide III frequencies that are inconsistent with the experimental results. (4) Computational changes in the dihedral angle phi of Ala-Ala produce a change in the amide III frequency consistent with the experimental results. (5) The experimental frequency shifts cannot be attributed directly to the effects of changing mass.

Alanine↗
PubMed1990

Risk assessment methodologies for passive smoking-induced lung cancer.

Risk assessment methodologies have been successfully applied to control societal risk from outdoor air pollutants. They are now being applied to indoor air pollutants such as environmental tobacco smoke (ETS) and radon. Nonsmokers' exposures to ETS have been assessed based on dosimetry of nicotine, its metabolite, continine, and on exposure to the particulate phase of ETS. Lung cancer responses have been based on both the epidemiology of active and of passive smoking. Nine risk assessments of nonsmokers' lung cancer risk from exposure to ETS have been performed. Some have estimated risks for lifelong nonsmokers only; others have included ex-smokers; still others have estimated total deaths from all causes. To facilitate interstudy comparison, in some cases lung cancers had to be interpolated from a total, or the authors' original estimate had to be adjusted to include ex-smokers. Further, all estimates were adjusted to 1988. Excluding one study whose estimate differs from the mean of the others by two orders of magnitude, the remaining risk assessments are in remarkable agreement. The mean estimate is approximately 5000 +/- 2400 nonsmokers' lung cancer deaths (LCDSs) per year. This is a 25% greater risk to nonsmokers than is indoor radon, and is about 57 times greater than the combined estimated cancer risk from all the hazardous outdoor air pollutants currently regulated by the Environmental Protection Agency: airborne radionuclides, asbestos, arsenic, benzene, coke oven emissions, and vinyl chloride.

Epidemiologic Factors↗
PubMed1980

Indoor air pollution, tobacco smoke, and public health.

An experimental and theoretical investigation is made into the range and nature of the exposure of the nonsmoking public to respirable suspended particulates from cigarette smoke. A model incorporating both physical and sociological parameters is shown to be useful in understanding particulate levels from cigarette smoke in indoor environments. Observed levels of particulates correlate with the predictions of the model. It is shown that nonsmokers are exposed to significant air pollution burdens from indoor smoking. An assessment of the public health policy implications of these burdens is presented.

Air Pollution↗