A four-dimensional computed tomography comparison of healthy and asthmatic human lungs

The purpose of this study was to explore new insights in non-linearity, hysteresis and ventilation heterogeneity of asthmatic human lungs using four-dimensional computed tomography (4D-CT) image data acquired during tidal breathing. Volumetric image data were acquired for 5 non-severe and one severe asthmatic volunteers. Besides 4D-CT image data, function residual capacity and total lung capacity image data during breath-hold were acquired for comparison with dynamic scans. Quantitative results were compared with the previously reported analysis of five healthy human lungs. Using an image registration technique, local variables such as regional ventilation and anisotropic deformation index (ADI) were estimated. Regional ventilation characteristics of non-severe asthmatic subjects were similar to those of healthy subjects, but different from the severe asthmatic subject. Lobar airflow fractions were also well correlated between static and dynamic scans (R² > 0.84). However, local ventilation heterogeneity significantly increased during tidal breathing in both healthy and asthmatic subjects relative to that of breath-hold perhaps because of airway resistance present only in dynamic breathing. ADI was used to quantify non-linearity and hysteresis of lung motion during tidal breathing. Non-linearity was greater on inhalation than exhalation among all subjects. However, exhalation non-linearity among asthmatic subjects was greater than healthy subjects and the difference diminished during inhalation. An increase of non-linearity during exhalation in asthmatic subjects accounted for lower hysteresis relative to that of healthy ones. Thus, assessment of non-linearity differences between healthy and asthmatic lungs during exhalation may provide quantitative metrics for subject identification and outcome assessment of new interventions.     

In vitro dynamics of chromatin organization and migration

The organization of eukaryotic chromatin is not static but changes as a function of cell status during processes such as proliferation, differentiation, and migration. DNA quantification has not been used extensively to investigate chromatin dynamics in combination with cellular migration. In this context, an optimized DNA-specific, nonperturbant method has been developed for studying chromatin organization, using the fluorescent vital bisbenzimidazole probe Hoechst 33342: this property has been described by Hamori et al. (1980). Computer-assisted image analysis was used to follow migratory activity and chromatin organization of L929 fibroblasts during in vitro wound healing. Cell movements were analyzed using an optical flow technique, which consists in the calculation of the velocity field of cells and nuclear movements in the frame. This system allows the correlation of cell migration and position in the cell cycle. It makes it possible to study chromatin dynamics using a quantitative analysis of nuclear differentiation reorganization (nuclear texture) and to correlate this with migration characteristics. The present system would be of interest for studying cell-extracellular matrix interactions using differing substrates, and also the migratory response to chemotactic factors. Such a model is a prerequisite for gaining better understanding of drug action.     

Turnover of Brain Monoamine Oxidase Measured In Vivo by Positron Emission Tomography Using l-[11C]Deprenyl

The distribution of carbon-11-labeled L-deprenyl, an irreversible inhibitor of monoamine oxidase type B (MAO-B), was determined in the baboon brain by positron emission tomography. The irreversible blood-to-brain transfer constant (influx constant, K_i) was measured using a complete metabolite-corrected arterial plasma concentration curve. This influx constant was used as a measure of functional enzyme activity for sequential determinations of MAO-B recovery following a single high dose of unlabeled l -deprenyl. The half-life for turnover of MAO-B was thus determined to be 30 days. Using appropriate irreversible inhibitors, this procedure should be generally useful for determining enzyme turnover rates in any organ in vivo and can be applied to some human studies as well.     

Stereoselective formation of a 2′(3′)-aminoacyl ester of a nucleotide

Summary Reaction ofDl-serine and adenosine-5-phosphorimidazolide in the presence of adenosine-5-(O-methylphosphate) and imidazole resulted in the stereoselective synthesis of the aminoacyl nucleotide ester 2(3)-O-seryl-adenosine-5-(O-methylphosphate). The enantiomeric excess ofd-serine incorporated into 2(3)-O-seryl-adenosine-5-(O-methylphosphate) was about 9%. Adenylyl-(5N)-serine and an unknown product also incorporated an excess ofd-serine; however, serylserine showed an excess ofl-serine. The relationship of these results to the origin of the biological pairing ofl-amino acids and nucleotides containingd-ribose is discussed.     

Measurement of light within thin plant tissues with fiber optic microprobes

Vogelmann, T. C., Knapp, A. K., McClean, T. M. and Smith, W. K. 1988. Measurement of light within thin plant tissues with fiber optic microprobes. - Physiol. Plant. 72: 623–630.
The measurement of light with fiber optic microprobes has been extended to thin (200–300 μm) plant tissue samples. To test the method, light measurements were made in thin aqueous films and paradermal sections from 10-day-old etiolated Cucurbita pepo L. cv. Fordhook cotyledons. The measurements obtained were highly reproducible. Paradermal sections of spongy mesophyll that were irradiated with collimated light scattered light more effectively than the palisade layer of intact cotyledons. These results demonstrate that different plant tissues have different light scattering characteristics. The successful extension of the fiber optic microprobe technique to thin systems makes it possible to examine the optical properties of different cell layers within leaves and other plant organs.     

4',6-Dichloroflavan (BW683C): Enantiomeric separation by hplc/dad and antirhinovirus activity

Racemic 4',6-dichloroflavan (BW683C), a highly effective inhibitor of rhinovirus serotype 1B in vitro, was resolved by high-performance liquid chromatography on a chiral stationary phase. The enantiomers were separately collected and circular dichroism curves were obtained, in order to determine the absolute configuration of the two enantiomers. The activity of the isomers was studied on human rhinovirus serotype 1B multiplication in HeLa cell cultures, by means of the plaque reduction assay. Both enantiomers were potent inhibitors of virus replication; by comparing the IC₅₀ values, the S form was 3.5 times more effective than the R form.     

Computed tomography and automated image analysis of prehistoric femora

Non-invasive characterization of limb bone cross-sectional geometry would be useful for biomechanical analyses of skeletal collections. Computed tomography (CT) is potentially the method of choice. Additionally, CT images are suitable for automated analysis. CT is here shown to be both accurate and precise in the analysis of cross-sectional geometry of prehistoric femora. Beam hardening artifacts can be reduced by using a water bath. As the availability of CT for research increases, both bone density and geometry could be determined simultaneously with this method.     

Molecular motion underlying activation and inactivation of sodium channels in squid giant axons

Summary Measurements of the changes in birefringence associated with changes in membrane potential were made with internally perfused squid giant axons in low sodium solutions at 0–8°C. The time course of the birefringence changes share many properties of the gating (polarization) currents previously studied in this nerve. Both can be demonstrated as an asymmetry in the response to voltage pulses symmetrical about the resting potential which is not present about a hyperpolarized holding potential. Both have a rapid relaxation, which precedes the sodium permeability change. Both exhibit an initial delay or rising phase. Both are reversibly blocked by perfusion with 30mm colchicine; neither are altered by changes on sodium concentrations or 300nm tetrodotoxin. The birefringence response has a decrease in the amplitude of the rapid relaxation associated with the appearance of a slow relaxation. This is similar to the immobilization of fast gating charges which parallels sodium current inactivation.The amplitude of the birefringence and the gating current responses is consistent with a change in the alignment of several hundred peptide bonds per sodium channel.     

Stereoisomeric flavour compounds XXXV: Chiral aroma compounds of sherry I. Optically pure stereoisomers of solerone and solerole

The enantioseparation of the sherry aroma components 5-oxo-4-hydroxyhexanoic acid γ-lactone (solerone) and 4,5-dihydroxyhexanoic acid γ-lactone (solerole) is achieved, using Chiraspher (Merck) as the chiral HPLC phase and the optical purity ascertained directly by HRGC with heptakis(3-O-acetyl-2,6-di-O-pentyl)-β-cyclodextrin (Lipodex D) as the chiral stationary phase. The absolute configurations of 4,5-dihydroxyhexanoic acid γ-lactones are assigned by ¹H-NMR spectral data of diastereomeric α-methoxy-α-trifluoromethylphenylacetic acid (MTPA) esters, according to Mosher's model. Sensory qualities of the isomers are given.     

Chiral stationary phase high-performance liquid chromatographic resolution and absolute configuration of enantiomeric benzo[a]pyrene diol-epoxides and tetrols

Enantiomers of diastereomeric benzo[a]pyrene (BP) diol-epoxides, r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydro-BP (BP 7,8-diol-anti-9,10-epoxide), r-7,t-8-dihydroxy-c-9,10-epoxy-7,8,9,10-tetrahydro-BP (BP 7,8-diol-syn-9,10-epoxide), r-9,t-10-dihydroxy-t-7,8-epoxy-7,8,9,10-tetrahydro-BP (BP 9,10-diol-anti-7,8-epoxide), and several 7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrenes (BP tetrols) were resolved by high-performance liquid chromatography (HPLC) using columns packed with either (R)-N-(3,5-dinitrobenzoyl)phenylglycine[(R)-DNBPG] or (S)-N-(3,5-dinitrobenzoyl)leucine [(S)-DNBL], which is either ionically or covalently bonded to gamma-aminopropylsilanized silica. Resolution of enantiomers was confirmed by ultraviolet-visible absorption and circular dichroism spectral analyses. Resolved enantiomers of BP diol-epoxides were each hydrolyzed in acidic solution to a pair of diastereomeric tetrols which were separated by reversed-phase HPLC. Absolute stereochemistries of enantiomeric diol-epoxides were deduced by the absolute configuration of their hydrolysis products.