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Biomedical subjects

William Jones

Publications and source records attributed to William Jones.

18 recordsLinked to original sources
PubMed2006

In vitro cytotoxicity of Manville Code 100 glass fibers: effect of fiber length on human alveolar macrophages.

BACKGROUND: Synthetic vitreous fibers (SVFs) are inorganic noncrystalline materials widely used in residential and industrial settings for insulation, filtration, and reinforcement purposes. SVFs conventionally include three major categories: fibrous glass, rock/slag/stone (mineral) wool, and ceramic fibers. Previous in vitro studies from our laboratory demonstrated length-dependent cytotoxic effects of glass fibers on rat alveolar macrophages which were possibly associated with incomplete phagocytosis of fibers >or= 17 microm in length. The purpose of this study was to examine the influence of fiber length on primary human alveolar macrophages, which are larger in diameter than rat macrophages, using length-classified Manville Code 100 glass fibers (8, 10, 16, and 20 microm). It was hypothesized that complete engulfment of fibers by human alveolar macrophages could decrease fiber cytotoxicity; i.e. shorter fibers that can be completely engulfed might not be as cytotoxic as longer fibers. Human alveolar macrophages, obtained by segmental bronchoalveolar lavage of healthy, non-smoking volunteers, were treated with three different concentrations (determined by fiber number) of the sized fibers in vitro. Cytotoxicity was assessed by monitoring cytosolic lactate dehydrogenase release and loss of function as indicated by a decrease in zymosan-stimulated chemiluminescence. RESULTS: Microscopic analysis indicated that human alveolar macrophages completely engulfed glass fibers of the 20 microm length. All fiber length fractions tested exhibited equal cytotoxicity on a per fiber basis, i.e. increasing lactate dehydrogenase and decreasing chemiluminescence in the same concentration-dependent fashion. CONCLUSION: The data suggest that due to the larger diameter of human alveolar macrophages, compared to rat alveolar macrophages, complete phagocytosis of longer fibers can occur with the human cells. Neither incomplete phagocytosis nor length-dependent toxicity was observed in fiber-exposed human macrophage cultures. In contrast, rat macrophages exhibited both incomplete phagocytosis of long fibers and length-dependent toxicity. The results of the human and rat cell studies suggest that incomplete engulfment may enhance cytotoxicity of fiber glass. However, the possibility should not be ruled out that differences between human versus rat macrophages other than cell diameter could account for differences in fiber effects.

Journal Article↗
PubMed2005

Screening for crystalline salts via mechanochemistry.

Neat grinding and solvent-drop grinding methods are found to be effective screening tools for indicating the potential for crystalline salt formation involving a given acid-base pair, as demonstrated with two model pharmaceuticals.

Journal Article↗
PubMed2005

Selective polymorph transformation via solvent-drop grinding.

A method of inducing specific polymorph transformations is exemplified with two single-component systems, whereby a given crystal form undergoes conversion when subjected to solid state grinding in the presence of a minor quantity of a certain solvent.

Combinatorial Chemistry Techniques↗
PubMed2005

Occurrence of pharmaceutically acceptable anions and cations in the Cambridge Structural Database.

The occurrence of a number of pharmaceutically acceptable counterions in the Cambridge Structural Database (CSD) has been investigated. The results have been compared to the occurrence of the same counterions in a list of known pharmaceutical salts. Chloride salts are by far the highest occurring in both groups. The occurrence of hydrates in the structures of salts of pharmaceutically acceptable counterions in the CSD has also been investigated. It was found that salts of these counterions show an increased tendency to hydrate when compared to the database average. The CSD was also searched for co-crystals of the list of pharmaceutically acceptable acids and bases corresponding to the list of counterions used for the salt investigation.

Acids↗
PubMed2005

Characterization of respiratory exposures at a microwave popcorn plant with cases of bronchiolitis obliterans.

Eight former workers from a microwave popcorn packaging plant were reported to have severe obstructive lung disease consistent with bronchiolitis obliterans. Investigations into respiratory exposures at this plant were done during August through November of 2000. Samples were collected to assess airborne particulate concentrations, particle size distributions, endotoxins, oxides of nitrogen, organic gases and vapors, and other analytes. Bulk corn and flavoring components were also analyzed for endotoxins and culturable bacteria and fungi. Workers in the microwave production areas of the plant were exposed to particulates and a range of organic vapors from flavorings. The particles were comprised largely of salt and oil/grease particles. Respirable dust concentrations (area plus personal) in the microwave mixer job category, the highest job exposure category in the plant, ranged from 0.13 milligrams per cubic meter of air (mg/m3) to a high of 0.77 mg/m3. Endotoxin concentrations were below 60 endotoxin units per cubic meter of air (EU/m3). Qualitative sampling for volatile organic compounds (VOCs) in the air detected over 100 different VOCs in the microwave area. The predominant compounds identified in the microwave mixing room included the ketones diacetyl, methyl ethyl ketone, acetoin, and 2-nonanone, and acetic acid. Diacetyl, the predominant ketone in the plant, was present in concentrations ranging from below detectable limits to 98 parts per million parts air by volume (ppm), with a mean of 8.1 ppm (standard deviation 18.5 ppm). The average ketone concentrations were highest in the microwave mixing room where the 10 area samples had a mean diacetyl concentration of 37.8 ppm (SD 27.6 ppm) and a mean acetoin concentration of 3.9 ppm (SD 4.3 ppm). These data show that workers involved in microwave popcorn packaging can be exposed to a complex mixture of VOCs from flavoring ingredients; animal studies show that diacetyl can cause airway epithelial injury, although the contributions of other specific compound(s) associated with obstructive respiratory disease in these workers is still unresolved.

Air Pollutants, Occupational↗
PubMed2005

The phytotoxin coronatine and methyl jasmonate impact multiple phytohormone pathways in tomato.

Coronatine (COR) is a phytotoxin produced by several pathovars of Pseudomonas syringae and consists of coronafacic acid (CFA), an analog of methyl jasmonic acid (MeJA), and coronamic acid (CMA), which resembles 1-aminocyclopropane-1-carboxylic acid (ACC), a precursor to ethylene. An understanding of how COR functions, is perceived by different plant tissues, and the extent to which it mimics MeJA remain unclear. In this study, COR and related compounds were examined with respect to structure and function. The results indicate that conjugation of CFA to an amino acid is required for optimal activity in tomato, including chlorosis, changes in chloroplast structure, cell wall thickening, accumulation of proteinase inhibitors, induction of anthocyanins, and root growth inhibition. cDNA microarrays were utilized to understand the molecular processes that are regulated by MeJA, COR, CFA and CMA in tomato leaves. A comparison of COR- and MeJA-regulated transcriptomes revealed that COR regulated 35% of the MeJA-induced genes. There was significant overlap in the number of COR and CFA-regulated genes with CFA impacting the expression of 39.4% of the COR-regulated genes. Taken together, the results of biological assays, ultrastructural studies, and gene expression profiling demonstrate that: (1) the intact COR molecule impacts signaling in tomato via the jasmonic acid, ethylene, and auxin pathways; (2) CMA does not function as a structural analog of ACC; (3) COR has a broader range of functions than either CFA or CMA; and (4) COR and MeJA share similar, but not identical activities and impact multiple phytohormone pathways in tomato.

Acetates↗
PubMed2004

A molecular dynamics simulation of the melting points and glass transition temperatures of myo- and neo-inositol.

The heat of sublimation, density, melting point, and glass transition temperature are calculated for myo- and neo-inositol, using the condensed-phase optimized molecular potentials for atomistic simulation studies (COMPASS) force field and molecular dynamics techniques. Our results show that the calculated heats of sublimation and density are very close to the experimental values for both compounds. Furthermore, our simulated melting temperatures for myo- and neo-inositol also compare very well to the experimentally obtained data. The glass transition temperatures for myo- and neo-inositol have been calculated to be ca. 494 K and ca. 518 K, respectively, and the shape of the volume versus temperature plots produced are typical for a glass transition. As a result, it is our view that the COMPASS force field suitably describes these two compounds in molecular simulations and that molecular dynamics techniques, combined with this force field, can be used to simulate the melt and glass transitions for such molecules.

Journal Article↗
PubMed2004

Infrared multiphoton dissociation spectroscopy of gas-phase mass-selected hydrocarbon-Fe+ complexes.

Infrared spectra in the mid-infrared region (800-1600 cm(-1)) of highly unsaturated Fe(+)-hydrocarbon complexes isolated in the gas phase are presented. These organometallic complexes were selectively prepared by ion-molecule reactions in a Fourier transform ion cycloton mass spectrometer (FTICR-MS). The infrared multiphoton dissociation (IRMPD) technique has been employed using the free electron laser facility CLIO (Orsay, France) to record the infrared spectra of the mass selected complexes. The experimental IRMPD spectra present the main features of the corresponding IR absorption spectra calculated ab initio. As predicted by these calculations, the experimental spectra of three selectively prepared isomers of Fe+(butene) present differences in the 800-1100 cm(-1) range. On the basis of the comparison with calculated IR spectra, the IRMPD spectrum of Fe(butadiene)(+) suggests that the ligand presents the s-trans isomeric form. This study further confirms the potentialities of IRMPD spectroscopy for the structural characterization of organometallic ionic highly reactive intermediates in the gas phase. In conjunction with soft ionization techniques such as electrospray, this opens the door to the gas-phase characterization of reactive intermediates associated with condensed phase catalysts.

Journal Article↗
PubMed2004

Tolerance for error and computational estimation ability.

Previous investigators have suggested that the personality variable tolerance for error is related to success in computational estimation. However, this suggestion has not been tested directly. This study examined the relationship between performance on a computational estimation test and scores on the NEO-Five Factor Inventory, a measure of the Big Five personality traits, including Openness, an index of tolerance for ambiguity. Other variables included SAT-I Verbal and Mathematics scores and self-rated mathematics ability. Participants were 65 college students. There was no significant relationship between the tolerance variable and computational estimation performance. There was a modest negative relationship between Agreeableness and estimation performance. The skepticism associated with the negative pole of the Agreeableness dimension may be important to pursue in further understanding of estimation ability.

Adaptation, Psychological↗
PubMed2002

Comparative pulmonary toxicity of blasting sand and five substitute abrasive blasting agents.

Blasting sand is used for abrasive blasting, but its inhalation is associated with pulmonary inflammation and fibrosis. Consequently, safer substitute materials for blasting sand are needed. In a previous study from this laboratory, the comparative pulmonary toxicity of five abrasive blasting substitutes and blasting sand was reported. In this study, the pulmonary toxicity of blasting sand was compared to five additional abrasive blasting substitutes: steel grit, copper slag, nickel slag, crushed glass, and olivine. Exposed rats received by intratracheal instillation 10 mg of respirable-size particles of blasting sand or an abrasive blasting substitute, while controls were instilled with vehicle. Pulmonary inflammation, damage, and fibrosis were examined 28 d postexposure. Pulmonary inflammation was monitored by determining bronchoalveolar lavage polymorphonuclear cell counts and alveolar macrophage activation by chemiluminescence. Pulmonary damage was assessed by acellular bronchoalveolar (BAL) fluid serum albumin concentrations and lactate dehydrogenase activities. Histological examination of lung tissue samples was made to assess the severity and distribution of pulmonary fibrosis, alveolitis, and alveolar epithelial cell hypertrophy and hyperplasia. In comparison to blasting sand, olivine exposed rats had higher levels of pulmonary inflammation and damage with a similar level of fibrosis. Steel grit-exposed rats had lower levels of pulmonary inflammation and damage, and did not develop fibrosis. However, steel grit-exposed rats had a level of epithelial cell hypertrophy and hyperplasia similar to blasting sand. The other abrasive blasting substitutes gave a mixed profile of toxicity. The data demonstrate that steel grit produced less acute pulmonary toxicity than blasting sand or any of the other abrasive blasting substitutes. Notwithstanding, the data also suggest that chronic exposure to steel grit may pose a health risk due to its effects on epithelial cell proliferation in the lung.

Administration, Inhalation↗
PubMed2002

Structure prediction as a tool for solution of the crystal structures of metallo-organic complexes using powder X-ray diffraction data.

A simulated-annealing direct-space approach has been applied to predict the crystal structures of a series of metallo-organic complexes containing Zn, Cu and Ni. The prediction methodology generates a set of energetically reasonable crystal structures among which the actual structure is present, but it is not always possible to specify unambiguously the known crystal structure solely on the basis of energy. In each case, however, the ambiguity may be resolved by recourse to laboratory powder X-ray diffraction (PXRD) data. In this manner, structure prediction is shown to be a powerful tool for structure solution using PXRD data, with the additional advantage that indexing of the PXRD profile is not required at the outset.

Journal Article↗
PubMedDate not supplied

The use of the suicide CYP450 inhibitor ABT for distinguishing absorption and metabolism processes in in-vivo pharmacokinetic screens.

Since drug candidates with low oral systemic exposure may be due to either or both absorption and metabolism factors, determining what factors limit the oral systemic exposure is not always obvious in a single in-vivo pharmacokinetic (PK) assay. A rapid rat in-vivo PK screen where the oxidative drug metabolism has been attenuated using the suicide CYP450 inhibitor aminobenzotriazole (ABT) is described. We have shown that the roles of absorption and metabolism for drug candidates with low oral systemic exposure can be determined by comparing the PK parameters of drug candidates orally administered to non-treated and ABT-treated rats. Propranolol, metoprolol and climetidine are used as model drugs. Propranolol and metoprolol have low oral systemic exposures in rats primarily due to metabolism factors while the oral systemic exposure of climetidine is high in rats. For propranolol and metoprolol, large increases in the systemic exposure of these drugs were observed between non-treated and ABT-treated rats. ABT appeared not to increase or decrease significantly the rate and extent of absorption or metabolism of cimetidine since that oral systemic exposure of non-treated and ABT-treated rats did not significantly change. These experiments suggest that for drug candidates with low systemic exposures in rats an observation of no change in the oral systemic exposure in ABT-treated rats when compared to the non-treated rats imply that absorption (or formulation) factors limit the systemic exposure of the drug while an increase in the systemic exposure in ABT-treated rats imply that metabolism factors limit the systemic exposure. Due to the ease of preparing and interpreting PK data from ABT-treated rats, is suggested that this assay could be used as an alternative to in vivo cannulation assays.

Absorption↗