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Biomedical subjects

J C Hanson

Publications and source records attributed to J C Hanson.

At least 19 recordsLinked to original sources

In situ time-resolved characterization of Au-CeO2 and AuOx-CeO2 catalysts during the water-gas shift reaction: presence of Au and O vacancies in the active phase.

Synchrotron-based in situ time-resolved x-ray diffraction and x-ray absorption spectroscopies were used to study the behavior of nanostructured {Au+AuO(x)}-CeO(2) catalysts under the water-gas shift (WGS) reaction. At temperatures above 250 degrees C, a complete AuO(x)-->Au transformation was observed with high catalytic activity. Photoemission results for the oxidation and reduction of Au nanoparticles supported on rough ceria films or a CeO(2)(111) single crystal corroborate that cationic Au(delta+) species cannot be the key sites responsible for the WGS activity at high temperatures. The rate determining steps for the WGS seem to occur at the gold-ceria interface, with the active sites involving small gold clusters (<2 nm) and O vacancies.

Journal Article↗

Anti-Fas induces hepatic chemokines and promotes inflammation by an NF-kappa B-independent, caspase-3-dependent pathway.

Agonistic antibodies against the Fas receptor, when administered to mice in vivo, cause significant apoptosis in the liver. In this study we show that anti-Fas antibody not only causes apoptosis of liver cells but also provokes hepatic inflammation. Two hours after injection of anti-Fas, when mice displayed evidence of caspase-3 activation and apoptosis, we found significant hepatic induction of the CXC chemokines macrophage inflammatory protein-2 and KC. Coincident with the chemokine induction was infiltration of the hepatic parenchyma by neutrophils. Neutralization experiments identified that chemokines were the cause of Fas-induced hepatic inflammation, with KC having the predominant effect. Chemokine induction in the livers of anti-Fas-treated mice was not associated with activation of NF-kappa B. Instead, it coincided with nuclear translocation of activator protein-1 (AP-1). AP-1 activation in liver was detected 1-2 h after anti-Fas treatment, suggesting a connection to the onset of apoptosis. When apoptosis was prevented by pretreating mice with a caspase-3 inhibitor, AP-1 activation and hepatic chemokine production were both significantly reduced. Hepatic inflammation was also reduced by 70%. Taken together, these findings indicate that Fas ligation can induce inflammation in the liver in vivo. Inflammation does not arise from Fas-mediated signaling through NF-kappa B; rather, it represents an indirect effect, requiring activation of caspase-3 and nuclear translocation of AP-1.

Animals↗

Kinetics and mechanism of the beta- to alpha-CuAlCl(4) phase transition: a time-resolved (63)Cu MAS NMR and powder X-ray diffraction study.

The beta and alpha phases of CuAlCl(4) have been characterized by solid-state (27)Al and (63)Cu magic angle spinning nuclear magnetic resonance. The very short spin--lattice relaxation times of the copper spins, and the sensitivity of the I = 3/2 (63)Cu nucleus to the small differences in the local structure of Cu in the two phases, allowed (63)Cu spectra to be acquired in very short time periods (1 min), in which the beta and alpha phases were clearly resolved. This time resolution was exploited to follow the phase transition from the pseudohexagonal close-packed beta-CuAlCl(4) into the pseudocubic close-packed alpha-CuAlCl(4), which occurs above 100 degrees C. In situ time-resolved (63)Cu MAS NMR and synchrotron X-ray diffraction experiments were used to measure the kinetics of this phase transition as a function of temperature. The transformation was shown to be a first-order phase transition involving no intermediate phases with an activation energy of 138 kJ/mol. The kinetic data obey a first-order Avrami--Erofe'ev rate law. A one-dimensional growth mechanism is proposed that involves a combination of Cu(+) ion self-diffusion and a translational reorganization of the close-packed anion layers imposed by the periodic rotations of [AlCl(4)](-) tetrahedra. This beta to alpha phase transformation can be induced at ambient temperatures by low partial pressures of ethylene.

Journal Article↗

Statistical aspects of quantitative image analysis of beta-amyloid in the APP(V717F) transgenic mouse model of Alzheimer's disease.

Cerebral beta-amyloidosis is a central part of the neuropathology of Alzheimer's disease (AD). Quantitation of beta-amyloid plaques in the human AD brain, and in animal models of AD, is an important study endpoint in AD research. Methodologic approaches to the measurement of beta-amyloid in the brain vary between investigators, and these differences affect outcome measures. Here, one quantitative approach to the measurement of beta-amyloid plaques in brain sections was analyzed for sources of variability due to sampling. Brain tissue was from homozygous APP(V717F) transgenic male mice. Sampling variables were at the mouse and microscopic slide and field levels. Results indicated that phenotypic variability in the mouse sample population was the largest contributor to the standard error of the analyses. Within each mouse, variability between slides or between fields within slides had smaller effects on the error of the analyses. Therefore, when designing studies of adequate power, in this and in other similar models of cerebral beta-amyloidosis, sufficient numbers of mice per group must be included in order for change in mean plaque burden attributable to an experimental variable to outweigh phenotypic variability.

Alzheimer Disease↗

In situ X-ray diffraction and solid-state NMR study of the fluorination of gamma-Al(2)O(3) with HCF(2)Cl.

In situ X-ray diffraction (XRD) and NMR methods were used to follow the structural changes that occur during the dismutation reaction of hydrochlorofluorocarbon-22 (CHClF(2)) over gamma-alumina. Use of a flow cell allowed diffraction patterns to be recorded, while the reaction products were simultaneously monitored downstream of the catalyst bed, by gas chromatography. No visible structural changes of gamma-Al(2)O(3) were observed at 300 degrees C, the temperature at which this material becomes active for catalysis. A new phase began to form at 360 degrees C, which by 500 degrees C completely dominated the XRD powder pattern. (19)F/(27)Al cross-polarization (CP) experiments of gamma-Al(2)O(3) activated at 300 degrees C showed that AlF(3) had already begun to form at this temperature. By 400 degrees C, resonances from a phase that resembles alpha-AlF(3) dominate both the (19)F and (27)Al NMR spectra of the used catalyst. In situ XRD experiments of the catalytically inactive alpha-AlF(3) phase were performed to investigate the structural changes of this material, associated with the extent of tilting of the AlF(6) octahedra in this ReO(3)-related structure, as a function of temperature. Structural refinements of this sample, and the catalytically active phase that grows over gamma-Al(2)O(3), demonstrate that the catalyst is structurally similar to the rhombohedral form of alpha-AlF(3). Differences between the two phases are ascribed to defects in the catalyst, which limit the flexibility of the structure; these may also be responsible for the differences in the catalytic behavior of the two materials.

Journal Article↗

Transition state structure of purine nucleoside phosphorylase and principles of atomic motion in enzymatic catalysis.

Immucillin-H [ImmH; (1S)-1-(9-deazahypoxanthin-9-yl)-1,4-dideoxy-1,4-imino-D-ribitol] is a 23 pM inhibitor of bovine purine nucleoside phosphorylase (PNP) specifically designed as a transition state mimic [Miles, R. W., Tyler, P. C., Furneaux, R. H., Bagdassarian, C. K., and Schramm, V. L. (1998) Biochemistry 37, 8615-8621]. Cocrystals of PNP and the inhibitor are used to provide structural information for each step through the reaction coordinate of PNP. The X-ray crystal structure of free ImmH was solved at 0.9 A resolution, and a complex of PNP.ImmH.PO(4) was solved at 1.5 A resolution. These structures are compared to previously reported complexes of PNP with substrate and product analogues in the catalytic sites and with the experimentally determined transition state structure. Upon binding, ImmH is distorted to a conformation favoring ribosyl oxocarbenium ion formation. Ribosyl destabilization and transition state stabilization of the ribosyl oxocarbenium ion occur from neighboring group interactions with the phosphate anion and the 5'-hydroxyl of the ribosyl group. Leaving group activation of hypoxanthine involves hydrogen bonds to O6, N1, and N7 of the purine ring. Ordered water molecules provide a proton transfer bridge to O6 and N7 and permit reversible formation of these hydrogen bonds. Contacts between PNP and catalytic site ligands are shorter in the transition state analogue complex of PNP.ImmH.PO(4) than in the Michaelis complexes of PNP.inosine.SO(4) or PNP.hypoxanthine.ribose 1-PO(4). Reaction coordinate motion is dominated by translation of the carbon 1' of ribose between relatively fixed phosphate and purine groups. Purine and pyrimidine phosphoribosyltransferases and nucleoside N-ribosyl hydrolases appear to operate by a similar mechanism.

Animals↗

In Situ Single-Crystal X-ray Diffraction Study of Crystallization Kinetics in Clathrasil Dodecasil-3C.

The formation of single crystals of the clathrasil dodecasil-3C from a solvothermal synthesis has been followed by in situ diffraction techniques using synchrotron radiation and an image-plate area detector. The high intensity of the X-ray beam, coupled with the ability to record time-resolved two-dimensional data using the image plates, allowed the crystallization kinetics to be studied and rate expressions to be fitted to the crystallization curves.

Journal Article↗

The linear energy transfer dependence of excited singlet-state lifetimes of hydrocarbon liquids exposed to X rays.

The absorption of X rays in liquids provides low-energy electrons in the energy range 2 to 20 keV when synchrotron radiation is used as the X ray source. Such low-energy electrons have short ranges and produce a dense track of ionization where dE/dx = 10(7) to 10(8) eV/cm. Fluorescent molecules provide a sensitive probe of the early-time structure of such tracks. From the extent of quenching of excited states and the consequent decrease in fluorescence lifetimes, the concentration of free radicals in the track can be inferred. Experiments done with the hydrocarbons cis-decalin and dodecane demonstrate this effect. In both hydrocarbons, the lifetimes (tau) are significantly smaller with excitation by X rays than with UV radiation, and tau-1 increases linearly with dE/dx.

Alkanes↗

Structure of a copper-isoniazid complex.

It is well-known that complex formation with copper ions increases the in vitro mycobactericidal action of the antituberculosis agent isoniazid. We report here the preparation and structure of a copper(II)-isoniazid complex. Unit cell parameters are a = 9.575, b = 14.855, and c = 7.056 A and space group P2(1)2(1)2(1). Copper bonding geometry is square planar with the isoniazid carbonyl oxygen and hydrazide amino nitrogen atoms and two chlorines occupying coordination positions. Complexing with copper(II) does not significantly alter the isoniazid molecular conformation.

Chemical Phenomena↗

Location of amino acid residues in human deoxy hemoglobin.

A table has been compiled of the spatial disposition of the amino acid residues in the human deoxy hemoglobin tetramer. The table also indicates regions of possible contact between residues in each subunit and possible contacts between subunits.

Amino Acids↗

Preparation, hydrolysis, and oral absorption of lactonyl esters of penicillins.

Lactonyl esters of ampicillin and other penicillins have been synthesized as prodrugs designed to improve the oral absorption of the parent penicillins. In general, the esters hydrolyzed rapidly in the presence of tissues including blood and certain of the esters were better absorbed than the parent penicillin. The phthalidyl ester of ampicillin [talampicillin (British Pharmacopoeia approved name), BRL 8988] was selected for extended studies. The compound was found to be well absorbed in various animal species and gave ampicillin serum concentrations in fasting human volunteers 2.5-3 times those obtained for ampicillin itself.

Administration, Oral↗