Biomedical subjects

Richard J Thomas

Publications and source records attributed to Richard J Thomas.

6 recordsLinked to original sources

PubMed2004

Oligosaccharide receptor mimics inhibit Legionella pneumophila attachment to human respiratory epithelial cells.

Legionnaire's disease is caused by the intracellular pathogen Legionella pneumophila, presenting as an acute pneumonia. Attachment is the key step during infection, often relying on an interaction between host cell oligosaccharides and bacterial adhesins. Inhibition of this interaction by receptor mimics offers possible novel therapeutic treatments. L. pneumophila attachment to the A549 cell line was significantly reduced by treatment with tunicamycin (73.6%) and sodium metaperiodate (63.7%). This indicates the importance of cell surface oligosaccharide chains in adhesion. A number of putative anti-adhesion compounds inhibited attachment to the A549 and U937 cell lines. The most inhibitory compounds were polymeric saccharides, GalNAcbeta1-4Gal, Galbeta1-4GlcNAc and para-nitrophenol. These compounds inhibited adhesion to a range of human respiratory cell lines, including nasal epithelial, bronchial epithelial and alveolar epithelial cell lines and the human monocytic cell line, U937. Some eukaryotic receptors for L. pneumophila were determined to be the glycolipids, asialo-GM1 and asialo-GM2 that contain the inhibitory saccharide moiety, GalNAcbeta1-4Gal. The identified compounds have the potential to be used as novel treatments for Legionnaire's disease.

Adhesins, Bacterial↗

PubMed2003

Through-bond 13C-13C correlation at the natural abundance level: refining dynamic regions in the crystal structure of vitamin-D3 with solid-state NMR.

Recently, we presented a novel nuclear magnetic resonance experiment for establishing through-bond connectivity in disordered solids using scalar coupling-driven correlation. This method, a variant of the popular double-quantum-filtered correlation spectroscopy experiment in liquids, is robust under fast magic-angle-spinning conditions and in the presence of dynamics. Here, we show that this new experiment, the UC2QF COSY, can be extended to 13C natural abundance correlation in moderately sized molecules, allowing the assignment of the 54 peaks of the solid-state NMR spectrum of microcrystalline vitamin-D3. In this case, comparison between the assigned peaks and ab initio calculations of the chemical shifts based on the crystal coordinates permits a refinement of the average structure in dynamic regions reported as disordered in the crystal structure.

Carbon Isotopes↗

PubMed2002

Synthesis and NMR studies of (13)C-labeled vitamin D metabolites.

Isotope-labeled drug molecules may be useful for probing by NMR spectroscopy the conformation of ligand associated with biological hosts such as membranes and proteins. Triple-labeled [7,9,19-(13)C(3)]-vitamin D(3) (56), its 25-hydroxylated and 1 alpha,25-dihydroxylated metabolites (58 and 68, respectively), and other labeled materials have been synthesized via coupling of [9-(13)C]-Grundmann's ketone 39 or its protected 25-hydroxy derivative 43 with labeled A ring enyne fragments 25 or 26. The labeled CD-ring fragment 39 was prepared by a sequence involving Grignard addition of [(13)C]-methylmagnesium iodide to Grundmann's enone 28, oxidative cleavage, functional group modifications leading to seco-iodide 38, and finally a kinetic enolate S(N)2 cycloalkylation. The C-7,19 double labeling of the A-ring enyne was achieved by the Corey-Fuchs/Wittig processes on keto aldehyde 11. By employing these labeled fragments in the Wilson-Mazur route, the C-7,9,19 triple-(13)C-labeled metabolites 56, 58, and 68 as well as other (13)C-labeled metabolites have been prepared. In an initial NMR investigation of one of the labeled metabolites prepared in this study, namely [7,9,19-(13)C(3)]-25-hydroxyvitamin D(3) (58), the three (13)C-labeled carbons of the otherwise water insoluble steroid could be clearly detected by (13)C NMR analysis at 0.1 mM in a mixture of CD(3)OD/D(2)O (60/40) or in aqueous dimethylcyclodextrin solution and at 2 mM in 20 mM sodium dodecyl sulfate (SDS) aqueous micellar solution. In the SDS micellar solution, a double half-filter NOESY experiment revealed that the distance between the H(19Z) and H(7) protons is significantly shorter than that of the corresponding distance calculated from the solid state (X-ray) structure of the free ligand. The NMR data in micelles reveals that 58 exists essentially completely in the alpha-conformer with the 3 beta-hydroxyl equatorially oriented, just as in the solid state. The shortened distance (H(19Z))-H(7)) in micellar solutions as compared to that in the solid state is most easily rationalized on the basis that the 5(10)-torsion angle in 58 is decreased in micellar solutions as compared to that in the solid state.

Carbon Isotopes↗

PubMed2002

Acute pulmonary effects from o-chlorobenzylidenemalonitrile "tear gas": a unique exposure outcome unmasked by strenuous exercise after a military training event.

o-Chlorobenzylidenemalonitrile, more commonly called CS, is grouped with several other irritant agents referred to as "tear gas." It is a riot-control agent used frequently in military settings to test the ability and speed of personnel in donning their military gas masks. When personnel are exposed to CS without proper personal protective equipment, it has potent irritant effects. We report a unique cluster of hospitalizations of nine U.S. Marines who developed a transient pulmonary syndrome. All nine patients had symptoms of cough and shortness of breath. Five of the nine presented with hemoptysis, and four presented with hypoxia. Symptoms were associated with strenuous physical exercise from 36 to 84 hours after heavy exposure of CS in a field training setting. Four of the nine Marines required intensive care observation as a result of profound hypoxia. All signs and symptoms resolved within 72 hours of hospital admission. One week after CS exposure, all nine Marines demonstrated normal lung function during spirometry before and after exercise challenge using cycle ergometry.

Adolescent↗

PubMed2002

Moving toward the eradication of syphilis.

This study analyzed syphilis incidence among active duty U.S. Sailors and Marines and explored opportunities and strategies for the Department of the Navy to contribute to the achievement of the National Syphilis Elimination Plan. From 1987 through 1999, there were 1,886 cases of syphilis among active duty members reported to the Navy Environmental Health Center. Most were male (90%), younger than 30 years (81%), and black (64%). Most were diagnosed within the continental United States (79%). Incidence rates of primary and secondary syphilis per 100,000 among the active duty force declined steadily, from 37 in 1990 to 3 in 1999. Strategies suggested to further reduce syphilis among active duty members include the following: (1) Navy Medicine adoption and tracking of the national target of < 0.4 cases per 100,000 by 2005; (2) expand training of medical professionals in client-centered prevention counseling; (3) include affected populations in the design of interventions; (4) conduct outcome evaluations of educational interventions; (5) examine condom access policies; and (6) evaluate the current syphilis surveillance system.

Adolescent↗

PubMedDate not supplied

Traditional sampling with laboratory analysis and solid phase microextraction sampling with field gas chromatography/mass spectrometry by military industrial hygienists.

The opinions or assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the United States Department of Defense or the Uniformed Services University of the Health Sciences. Rapid on-site detection and identification of environmental contaminants to which personnel may be exposed is often needed during military deployment situations. The availability of military industrial hygienists with capabilities for "complete" on-site exposure assessment of chemical species should allow detection and identification of a number of important stressors almost immediately following sample collection. Portable gas chromatography/mass spectrometry (GC/MS) provides a rapid and efficient separation of volatile and semivolatile organic analytes, accompanied by sensitive electron impact ionization-mass spectrometry (EI-MS) detection. The use of GC/MS in the field is limited, however, by equipment cost, complexity of the equipment, and the analytical process. Additionally, a skilled operator is needed to obtain useful separations and to interpret mass spectral data. To demonstrate benefits and limitations of "complete" exposure assessment capabilities, a previously unidentified complex mixture, produced by thermal dispersion of riot control agents, was examined. Established active sampling methods were used with laboratory analyses. Solid phase microextraction, a passive sampling method that simplifies preparation for GC/MS analysis, also was used with a field-portable GC/MS system. Both sampling/analysis methods were used to detect CS riot control agent-derived air contaminants dispersed from riot control type canisters through oxidizer-supported combustion of a chemical fuel.

Chemistry Techniques, Analytical↗