PubMed Health⌕ Search

Biomedical subjects

D W Bennett

Publications and source records attributed to D W Bennett.

13 recordsLinked to original sources
PubMed2002

Molecular wires, switches, and memories.

Design and measurements of molecular wires, switches, and memories offer an increased device capability with reduced elements. We report: Measurements on through-bond electronic transport properties of nanoscale metal-1,4-phenylene diisocyanide-metal junctions are reported, where nonohmic thermionic emission is the dominant process, with isocyanide-Pd showing the lowest thermionic barrier of 0.22 eV; robust and large reversible switching behavior in an electronic device that utilizes molecules containing redox centers as the active component, exhibiting negative differential resistance (NDR) and large on-off peak-to-valley ratio (PVR) are realized; erasable storage of higher conductivity states in these redox-center-containing molecular devices are observed; and a two-terminal electronically programmable and erasable molecular memory cell with long bit retention time is demonstrated.

Cyanides↗
PubMed1999

Studies of molecular pharmacophore/receptor models for GABAA/benzodiazepine receptor subtypes: binding affinities of substituted beta-carbolines at recombinant alpha x beta 3 gamma 2 subtypes and quantitative structure-activity relationship studies via a comparative molecular field analysis.

Binding affinities of a series of 44 beta-carbolines with various substituents at the 3-, 4-, 6- and 7-positions are reported at 5 distinct recombinant GABAA/benzodiazepine receptor (BzR) subtypes [alpha x beta 3 gamma 2 (x = 1-3, 5, 6)]. Many of these ligands displayed better selectivity for the alpha 1 containing GABAA isoform. The most selective BCCT 2 and SPH 195 (17) displayed potent affinity (Ki = 0.72 and 7.2 nM for the alpha 1 beta 3 gamma 2 receptor subtype, respectively) and an overall selectivity of 20 and 23 fold, respectively, for the alpha 1 beta 3 gamma 2 receptor subtype. These are the most selective ligands in vitro for the alpha 1 containing GABAA/Bz receptor isoform reported to date to our knowledge. QSAR studies of these ligands for each receptor subtype have been carried out via a Comparative Molecular Field Analysis (CoMFA) and an included volume analysis. Geometries and charge distributions of these ligands have been optimized using ab initio methods (J. Med. Chem., 1992, 35, 4001-4010). Active conformations of flexible 3-alkoxylated beta-carbolines have been examined via a CoMFA approach. QSAR studies via CoMFA support the previous hypothesis that beta-carbolines with different intrinsic activities may follow an alternative alignment rule when they bind into the pharmacophore/receptor site of the BzR. Examination of binding affinities of beta-carbolines by this modeling strategy has established some of the differences, in particular, topologic differences between the lipophilic pockets in the alpha 1 beta 3 gamma 2, alpha 2 beta 3 gamma 2, alpha 3 beta 3 gamma 2, alpha 5 beta 3 gamma 2 and alpha 6 beta 3 gamma 2 subtypes as well as some of the similarities among the pharmacophore/receptor models of these five distinct GABAA/Bz receptor subtypes.

Binding Sites↗
PubMed1998

Predictive models for GABAA/benzodiazepine receptor subtypes: studies of quantitative structure-activity relationships for imidazobenzodiazepines at five recombinant GABAA/benzodiazepine receptor subtypes [alphaxbeta3gamma2 (x = 1-3, 5, and 6)] via comparative molecular field analysis.

Affinities of a series of substituted imidazobenzodiazepines at recombinant alpha1beta3gamma2, alpha2beta3gamma2, alpha3beta3gamma2, alpha5beta3gamma2, and alpha6beta3gamma2 GABAA/benzodiazepine receptor subtypes are reported. Many of these ligands displayed high affinities (low-nanomolar to subnanomolar scale) at all five receptor subtypes. Furthermore, a number of imidazobenzodiazepines exhibited relatively good selectivity at the alpha5-containing receptor isoform. For example, ligand 27 (RY-023) demonstrated a 55-fold higher selectivity at alpha5beta3gamma2 isoforms in comparison to other receptor subtypes. The affinity ratio of alpha1 (the most prevalent subtype in the brain) to alpha5 of this series of ligands ranged from 60- to 75-fold for the most selective ligands. Studies of quantitative structure-activity relationships (QSAR) by means of comparative molecular field analysis (CoMFA) were carried out. As a result, examination of CoMFA models for all five receptor subtypes demonstrated their predictability for affinities of imidazobenzodiazepines at the five receptor subtypes. Regions of molecular fields which would favor or disfavor the binding affinity of a ligand at a specific receptor subtype were examined via CoMFA for alpha1, alpha2, alpha3, alpha5, and alpha6 subtypes. A CoMFA regression analysis was applied to predict the ratio of Ki alpha1/Ki alpha5, an index for the selectivity of a ligand at the alpha5 subtype. All of the CoMFA models offered good cross-validated correlations for the ligands in the test set as well as the ratios of Ki alpha1/Ki alpha5, which demonstrated their potential for prediction.

Animals↗
PubMed1998

Cystoid macular edema associated with the use of latanoprost.

BACKGROUND: Cystoid macular edema is a common clinical finding following intraocular surgery. Certain medications have been associated with an increased incidence of cystoid macular edema. This article describes the clinical findings in two eyes of two patients in whom cystoid macular edema developed directly following treatment with the anti-glaucoma medication latanoprost, and assesses the possible causal relationship. CASE REPORTS: Clinical correlative and angiographic studies of two patients in a referral practice are presented. The main outcome measurement was visual acuity and fundus examination on discontinuation of latanoprost. RESULTS: Cystoid macular edema developed in two pseudophakic patients after the use of latanoprost. CONCLUSION: Latanoprost should be used with caution in pseudophakic and aphakic patients--especially those with retinal vascular fragility, any inflammatory uveal disease, or other factors that may predispose to the breakdown of the blood-retinal barrier.

Administration, Topical↗
PubMed1994

Identification of the site of phosphorylation on the osmosensor, EnvZ, of Escherichia coli.

EnvZ is a membrane-bound histidine kinase that functions as an osmotic sensor capable of phosphorylating the regulator protein OmpR in Escherichia coli. To characterize the site of phosphorylation biochemically, we overexpressed a 36-kDa truncated EnvZ protein (Glu-106 to Gly-450) that formed inclusion bodies in the cell. After solubilization, the inclusion body form of EnvZ was cleaved into two major fragments with molecular weights of 25,000 and 10,000. The 25-kDa fragment, EnvZc, was purified and found to exist as a dimer. N-terminal sequence analysis established that cleavage had occurred at Arg-214, indicating that EnvZc contained most of the cytoplasmic domain of EnvZ. After labeling EnvZc with [gamma-32P]ATP, the protein was proteolytically digested, and the resulting peptides were separated by reverse phase chromatography using high performance liquid chromatography. One major radioactive peptide containing greater than 90% of the recovered peptide-associated radioactivity was isolated. Amino acid analysis of this purified peptide indicated that the composition was consistent with a peptide that contained His-243. The amino acid sequence of this peptide was determined to be MAGVSHDLRTP (residues 238-248). These results indicate that His-243 is the major site of phosphorylation on EnvZ and represents the first biochemical characterization of the site of phosphorylation of a membrane histidine kinase of the two-component regulatory family of molecules in bacteria.

Amino Acid Sequence↗
PubMed1994

Theoretical study of arsenical-antidote adducts.

Structures, stabilities, and physical parameters for arsenical-antidote adducts in the gas phase were determined using semiempirical self consistent field (CNDO) calculations. In this work, methyldichloroarsine was used as the arsenical and racemic-dimercaptosuccinate, the diamide of racemic-dimercaptosuccinic acid, meso-dimercaptosuccinic acid, meso-dimercaptosuccinate, and the diamide of meso-dimercaptosuccinic acid were studied as the antidotes. For the case of the meso compounds, the influence of intramolecular hydrogen bonding was also investigated.

Antidotes↗
PubMed1992

Development of a proton nuclear magnetic resonance spectroscopic method for determining plasma lipoprotein concentrations and subspecies distributions from a single, rapid measurement.

We are developing a method for quantifying plasma lipoproteins by proton nuclear magnetic resonance (NMR) spectroscopy that offers advantages over existing clinical methods. We showed that the major lipoproteins have distinct NMR properties sufficient to permit their concentrations to be extracted from a computer lineshape analysis of the plasma lipid methyl resonance envelope (Clin Chem 1991; 37:377-86). We have now discovered that the spectra of the subspecies within each lipoprotein class are different enough to influence the composite spectrum of that class and hence the spectrum of whole plasma. By including spectra representative of these subspecies as additional components in the lineshape-fitting analysis, a complete concentration profile of very-low-density, low-density (LDL), and high-density (HDL) lipoproteins plus the subspecies distributions within these classes can be simultaneously generated. A pilot study of 30 plasma samples of widely varied composition demonstrated good agreement between NMR-derived values and lipoprotein lipid concentrations and LDL and HDL subspecies distributions determined by gradient-gel electrophoresis.

Feasibility Studies↗
PubMed1991

Quantification of plasma lipoproteins by proton nuclear magnetic resonance spectroscopy.

A new analytical procedure for quantifying plasma lipoproteins by proton nuclear magnetic resonance (NMR) spectroscopy has been developed that potentially offers significant advantages over existing clinical methods used for assessing risk of coronary heart disease. Analysis of a single spectrum of a nonfasting plasma sample, acquired simply and rapidly at moderate magnetic field strength (250 MHz), yields a complete profile of lipoprotein concentrations: chylomicrons and very-low-, low-, and high-density lipoproteins. The method is based on curve-fitting (spectral deconvolution) of the plasma methyl lipid resonance envelope, the amplitude and shape of which depend directly on the amplitudes of the superimposed methyl resonances of the lipoprotein components. A linear least-squares curve-fitting algorithm was developed to efficiently extract the signal amplitudes (concentrations) of the lipoproteins from the plasma spectrum. These signal amplitudes correlate well with lipoprotein concentrations determined by triglyceride and cholesterol measurements.

Cholesterol↗
PubMed1977

Radiation-induced bladder tumors.

A recent 25-year experience with patients treated for carcinoma of the uterine cervix who subsequently had bladder tumors is presented. Of the 3,091 patients treated 2,674 had received radiotherapy and 8 suffered vesical malignancies of varied histopathological type 6 months to 20 years after irradiation. This incidence rate is 299.9 per 100,000, which is 57.6 times that of the general female population. Benign radiation reactions of the bladder and the possible etiology of radiation-induced bladder cancers are discussed.

Adult↗
PubMed1975

Squamous cell carcinoma of the ureterovesical junction after renal transplantation.

A case of squamous cell carcinoma of the bladder occurring at the ureterovesical junction in a renal transplant recipient is presented. References are made to ureteral obstruction in transplanted kidneys, the broader field of squamous cell carcinoma of the bladder in non-transplanted patients and the relationship of malignancy to transplantation. We anticipate that an ever increasing number of these unusual cases will be forthcoming in the urological literature as renal transplantation develops.

Carcinoma, Squamous Cell↗
PubMed1975

Waxed windshields are hazardous in the rain.

Seven automobiles were washed and waxed at four car washes. Photographic determinations were made of the glare produced by the wet or dry waxed windshield in a headlight beam. When wet, the waxed windshields scattered three times more light than in the normal human eye. The wet wax scattering was 24.8 times higher than when dry. No wax residues should be permitted on windshields and the National Highway Traffic Safety Administration should issue a mandatory windshield cleaning requirement after waxing.

Automobile Driving↗
PubMedDate not supplied

A computational study of the effectiveness of the frontier molecular orbital formalism in predicting conformational isomerism in (p-RC6H4NC)2W(dppe)2.

Ab initio electronic structure calculations on a series of ligands, p-RC6H4NC:, indicate, that the energy of the LUMO correlates with the electron-withdrawing/donating capabilities of the substituent group, which determines the relative pi-acidity of the ligand. Depending on the nature of the para substituent group on the aryl isocyanide ligand, bis(aryl isocyanide) complexes of tungsten-containing bulky bidentate arylphosphine ligands adopt either cis or trans conformations. The frontier molecular orbital formalism predicts that strong pi-acids, which contain electron-withdrawing groups, tend to polarize sufficient charge density away from the metal center to effect the formation of the sterically less favorable but electronically stabilized cis conformer. Density functional theory calculations on similar complexes containing phosphines which do not impose severe steric contraints indicate that the balance between steric and electronic stabilization can be effectively predicted by comparing the relative energies of the ligand LUMOs.

Journal Article↗