Biomedical subjects

Matthew J Walker

Publications and source records attributed to Matthew J Walker.

3 recordsLinked to original sources

PubMed2006

Cardiac imaging using multislice computed tomography scanners: technical considerations.

Conventional coronary angiography is currently the gold standard in the detection and diagnosis of coronary artery disease. This modality, however, is invasive in nature. Hence, there is a need for noninvasive imaging techniques to provide comprehensive assessment of coronary artery disease, especially in stable patients at low to moderate risk of disease. In recent years, a number of noninvasive modalities have found wide applications in cardiac imaging. Most recent investigations have used magnetic resonance imaging, multislice computed tomography and electron-beam computed tomography scanners. This review discusses the clinical challenges existing in the field of cardiac imaging and focuses on the technical advancements of multislice computed tomography scanners that have made them a very attractive noninvasive option for the detection and diagnosis of coronary artery disease.

Atherosclerosis↗

PubMed2003

A model for predicting likely sites of CYP3A4-mediated metabolism on drug-like molecules.

We have developed a rapid semiquantitative model for evaluating the relative susceptibilities of different sites on drug molecules to metabolism by cytochrome P450 3A4. The model is based on the energy necessary to remove a hydrogen radical from each site, plus the surface area exposure of the hydrogen atom. The energy of hydrogen radical abstraction is conventionally measured by AM1 semiempirical molecular orbital calculations. AM1 calculations show the following order of radical stabilities for the hydrogen atom abstractions: sp2 centers > heteroatom sp3 centers > carbon sp3 centers. Since AM1 calculations are too time intensive for routine work, we developed a statistical trend vector model, which is used to estimate the AM1 abstraction energy of a hydrogen atom from its local atomic environment. We carried out AM1 and trend vector calculations on 50 CYP3A4 substrates whose major sites of metabolism are known in the literature. A plot of the lowest hydrogen radical formation energy versus its sterically accessible surface area exposure for these 50 substrates shows that only those hydrogen atoms with solvent accessible surface area exposure > or = 8.0 A(2) are susceptible to CYP3A4-mediated metabolism. This approach forms the basis for our general model, which predicts sites on drugs that are susceptible to cytochrome P450 3A4-mediated hydrogen radical abstraction followed by a hydroxylation reaction. This model, in conjunction with specific enzyme site binding requirements, can aid in identifying possible sites of metabolism catalyzed by other cytochrome P450 enzymes.

Binding Sites↗

PubMedDate not supplied

CKB - the compound knowledge base: a text based chemical search system.

The Compound Knowledge Base (CKB) was developed as a means of locating structures and additional relevant information from a given known structural identifier. Any of Chemical Abstracts Service Registry Number, company code (code number the producing company refers to the chemical entity internally), generic name (trivial or class name), or trade name (name under which the compound is marketed) can be provided as a query. CKB will provide the remaining available information as well as the corresponding structure for any matching compound in the database. The interface to the Compound Knowledge Base is Internet/World Wide Web-based, using Netscape Navigator and the ChemDraw Pro Plugin, which allows Merck scientists quick and easy access to the database from their desktop. The design and implementation of the database and the search interface are herein detailed.

Journal Article↗