Biomedical subjects

M R Johnson

Publications and source records attributed to M R Johnson.

At least 19 recordsLinked to original sources

PubMed2006

Crystallization on heating and complex phase behavior of alpha-cyclodextrin solutions.

Solutions composed of alpha-cyclodextrin (alpha-CD), water, and various methylpyridines, in particular, 4-methylpyridine (4MP), undergo reversible liquid-solid transitions upon heating, the crystalline solid phases undergoing further phase transformations at higher temperatures. This unusual behavior has been characterized by an ensemble of measurements, including solubility, differential scanning calorimetry, quasielastic neutron scattering, as well as x-ray powder diffraction. For the alpha-CD/4MP system five crystalline phases have been identified. The unit cell parameters and corresponding changes with temperature indicate a scenario for the crystallization process. A simple model is proposed that mimics the observed disorder-order transition.

Journal Article↗

PubMed2006

ABCB1 genotype and PGP expression, function and therapeutic drug response: a critical review and recommendations for future research.

The product of the ABCB1 gene, P-glycoprotein (PGP), is a transmembrane active efflux pump for a variety of drugs. It is a putative mechanism of multidrug resistance in a range of diseases. It is postulated that ABCB1 polymorphisms contribute to variability in PGP function, and that therefore multidrug resistance is, at least in part, genetically determined. However, studies of ABCB1 genotype or haplotype and PGP expression, activity or drug response have produced inconsistent results. This critical review of ABCB1 genotype and PGP function, including mRNA expression, PGP-substrate drug pharmacokinetics and drug response, highlights methodological limitations of existing studies, including inadequate power, potential confounding by co-morbidity and co-medication, multiple testing, poor definition of disease phenotype and outcomes, and analysis of multiple drugs that might not be PGP substrates. We have produced recommendations for future research that will aid clarification of the association between ABCB1 genotypes and factors related to PGP activity.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2006

Myometrial prostaglandin E2 synthetic enzyme mRNA expression: spatial and temporal variations with pregnancy and labour.

We have investigated the hypothesis that the expression of the enzymes involved in PGE(2) synthesis in the human uterus is co-ordinated. We have studied (i) the mRNA expression of the enzymes involved in PGE(2) synthesis [phospholipases (cPLA(2) and sPLA(2)), prostaglandin H synthase (PGHS)-2 and PG E synthases (PGES-1 and -2)] and their relationship to the expression of inflammatory cytokines in samples of myometrium obtained from pregnant women undergoing caesarean section (LSCS) either before or after the onset of labour at or before term; and (ii) the effect of IL-1beta, IL-6, TNF-alpha, PGE(2) and stretch on PGE(2) enzyme mRNA expression. We found that cPLA(2), sPLA(2) and PGHS-2 mRNA expression were greater in labour samples; cPLA(2), sPLA(2), PGHS-2, PGES-1 and -2 mRNA expression were greater in lower- than upper-segment samples; and there was no effect of gestational age. PGHS-2 mRNA levels correlated with those of PGES-1, cPLA(2), IL-1beta and IL-8; PGES-1 mRNA levels correlated with those of IL-1beta, IL-8 and cPLA(2). In primary cultures of uterine myocytes, cPLA(2) mRNA expression was increased by IL-1beta and IL-6; PGHS-2 mRNA expression was increased by IL-1beta, PGE(2) and stretch; and PGES-1 mRNA expression was increased by IL-1beta only. These data show that labour is associated with increased expression of the enzymes involved in PGE(2) synthesis and their expression is greater in the lower uterine segment. The presence of associations between the levels of PGE(2) enzyme mRNA expression and the effects of IL-1beta suggest that their expression is co-ordinated and that IL-1beta is the responsible factor.

Cells, Cultured↗

PubMed2006

Phonon driven proton transfer in crystals with short strong hydrogen bonds.

Recent work on understanding why protons migrate with increasing temperature in short, strong hydrogen bonds is extended here to three more organic, crystalline systems. Inelastic neutron scattering and density functional theory based simulations are used to investigate structure, vibrations, and dynamics of these systems as functions of temperature. The mechanism determined in a previous work on urea phosphoric acid of low frequency vibrations stabilizing average crystal structures, in which the potential energy well of the hydrogen bond has its minimum shifted towards the center of the bond, is found to be valid here. The new feature of the N-H...O hydrogen bonds studied in this work is that the proton is transferred from the donor atom to the acceptor atom. Molecular dynamics simulations show that in an intermediate temperature regime, in which the proton is not completely transferred, the proton is bistable, jumping from one side of the hydrogen bond to the other. In the case of 3,5-pyridine dicarboxylic acid, which has been studied in most detail, specific phonons are identified, which influence the potential energy surface of the proton in the short, strong hydrogen bond.

Journal Article↗

PubMed2006

Intermolecular interactions in solid benzene.

The lattice dynamics and molecular vibrations of benzene and deuterated benzene crystals are calculated from force constants derived from density-functional theory (DFT) calculations and compared with measured inelastic neutron-scattering spectra. A very small change (0.5%) in lattice parameter is required to obtain real lattice-mode frequencies across the Brillouin zone. There is a strong coupling between wagging and breathing modes away from the zone center. This coupling and sensitivity to cell size arises from two basic interactions. Firstly, comparatively strong interactions that hold the benzene molecules together in layers. These include an intermolecular interaction in which H atoms of one molecule link to the center of the aromatic ring of a neighboring molecule. The layers are held to each other by weaker interactions, which also have components that hold molecules together within a layer. Small changes in the lattice parameters change this second type of interaction and account for the changes to the lattice dynamics. The calculations also reveal a small auxetic effect in that elongation of the crystal along the b axis leads to an increase in internal pressure in the ac plane, that is, elongation in the b direction induces expansion in the a and c directions.

Journal Article↗

PubMed2006

Prostanoid receptors in human uterine myocytes: the effect of reproductive state and stretch.

In the human, prostanoids are known to be important mediators of uterine relaxation and contraction during pregnancy and parturition. We have previously shown that stretch of uterine smooth muscle cells increased prostaglandin H synthase 2 (PGHS-2) mRNA expression, PGHS-2 peptide synthesis and activity, however, the net effect on uterine contractility of this increase in prostaglandin synthesis would be determined by the expression of the different prostanoid receptors. Therefore, the aims of this study were to establish the expression of prostanoid receptor mRNA in uterine myocytes obtained from women in different reproductive states and to test the hypothesis that stretch of uterine myocytes alters prostanoid receptor mRNA expression to promote uterine contractility. Myocytes were isolated from women undergoing hysterectomy (NP) and pregnant women undergoing LSCS either before (NL) or after the onset of labour (L) and were subjected to 11% stretch for 1 h (n = 6 in all cases). Copy numbers of the individual receptors varied widely with reproductive state but followed the pattern: FP > IP = DP = EP-4 > TP = EP-3 = EP-2 > EP-1. FP mRNA expression was significantly lower in the NL group compared to the NP group and EP-3, EP-4 and TP mRNA expression was significantly lower in both NL and L groups compared to NP group levels. The level of mRNA expression of EP-1, EP-2, DP and IP did not differ between NP, NL and L groups. Stretch of cells derived from the NP group resulted in a significant decrease in EP-4 mRNA expression alone and of the NL group a significant decrease in EP-2 mRNA expression alone. Stretch had no effect on cells derived from the L group. These data show that pregnancy is associated with a significant reduction in 3 of 4 pro-contraction associated prostanoid receptor mRNA expression and 1 of 4 pro-relaxant. Stretch elicited no consistent change in prostanoid receptor mRNA expression.

DNA Primers↗

PubMed2006

The Thermotoga maritima phenotype is impacted by syntrophic interaction with Methanococcus jannaschii in hyperthermophilic coculture.

Significant growth phase-dependent differences were noted in the transcriptome of the hyperthermophilic bacterium Thermotoga maritima when it was cocultured with the hyperthermophilic archaeon Methanococcus jannaschii. For the mid-log-to-early-stationary-phase transition of a T. maritima monoculture, 24 genes (1.3% of the genome) were differentially expressed twofold or more. In contrast, methanogenic coculture gave rise to 292 genes differentially expressed in T. maritima at this level (15.5% of the genome) for the same growth phase transition. Interspecies H2 transfer resulted in three- to fivefold-higher T. maritima cell densities than in the monoculture, with concomitant formation of exopolysaccharide (EPS)-based cell aggregates. Differential expression of specific sigma factors and genes related to the ppGpp-dependent stringent response suggests involvement in the transition into stationary phase and aggregate formation. Cell aggregation was growth phase dependent, such that it was most prominent during mid-log phase and decayed as cells entered stationary phase. The reduction in cell aggregation was coincidental with down-regulation of genes encoding EPS-forming glycosyltranferases and up-regulation of genes encoding beta-specific glycosyl hydrolases; the latter were presumably involved in hydrolysis of beta-linked EPS to release cells from aggregates. Detachment of aggregates may facilitate colonization of new locations in natural environments where T. maritima coexists with other organisms. Taken together, these results demonstrate that syntrophic interactions can impact the transcriptome of heterotrophs in methanogenic coculture, and this factor should be considered in examining the microbial ecology in anaerobic environments.

Bacterial Proteins↗

PubMed2005

Anharmonic motions of Kr in the clathrate hydrate.

The anomalous glass-like thermal conductivity of crystalline clathrates has been suggested to be the result of the scattering of thermal phonons of the framework by 'rattling' motions of the guests in the clathrate cages. Using the site-specific (83)Kr nuclear resonant inelastic scattering spectroscopy in combination with conventional incoherent inelastic neutron scattering and molecular-dynamics simulations, we provide unambiguous evidence and characterization of the effects on these guest-host interactions in a structure-II Kr clathrate hydrate. The resonant scattering of phonons led to unprecedented large anharmonic motions of the guest atoms. The anharmonic interaction underlies the anomalous thermal transport in this system. Clathrates are prototypical models for a class of crystalline framework materials with glass-like thermal conductivity. The explanation of the unusual molecular dynamics has a wide implication for the understanding of the thermal properties of disordered solids and structural glasses.

Computer Simulation↗

PubMed2005

One-dimensional and two-dimensional quantum systems on carbon nanotube bundles.

We report the first measurement of the structure of 4He atoms adsorbed on bundles of single-walled carbon nanotubes. Neutron diffraction techniques and nanotube samples closed at the end were used. At low coverage, 4He forms a 1D, single line lattice along the grooves between two nanotubes on the surface of the nanotube bundles. As coverage is increased, additional lines of 1D lattices form along the grooves. This is followed by an incommensurate, 2D monolayer covering the whole nanotube bundle surface. The lattice constants of these 1D and 2D systems are largely independent of filling once a single 1D line is formed. No occupation of the interstitial channels between nanotubes is observed in the present sample.

Journal Article↗

PubMed2005

Numerical simulation of a laboratory-scale turbulent V-flame.

We present a three-dimensional, time-dependent simulation of a laboratory-scale rod-stabilized premixed turbulent V-flame. The experimental parameters correspond to a turbulent Reynolds number, Re(t) = 40, and to a Damköhler number, D(a) = 6. The simulations are performed using an adaptive time-dependent low-Mach-number model with detailed chemical kinetics and a mixture model for differential species diffusion. The algorithm is based on a second-order projection formulation and does not require an explicit subgrid model for turbulence or turbulence/chemistry interaction. Adaptive mesh refinement is used to dynamically resolve the flame and turbulent structures. Here, we briefly discuss the numerical procedure and present detailed comparisons with experimental measurements showing that the computation is able to accurately capture the basic flame morphology and associated mean velocity field. Finally, we discuss key issues that arise in performing these types of simulations and the implications of these issues for using computation to form a bridge between turbulent flame experiments and basic combustion chemistry.

Journal Article↗

PubMed2005

Polymorphism of crystalline alpha-quaterthiophene and alpha-sexithiophene: ab initio analysis and comparison with inelastic neutron scattering response.

Phonons in the alpha-quaterthiophene (4T) and alpha-sexithiophene (6T) polymorph phases are investigated using the direct method combined with density functional theory (DFT)-based total energy calculations. The simulation of inelastic neutron scattering spectra (INS) on the LT and HT polymorph phases of 4T and 6T enable the corresponding spectral signatures of these materials to be identified. In particular, there are two fingerprints: (i) the low-frequency vibrational modes (frequencies lower than 200 cm(-1)) and (ii) the vibrational modes in the 600-900 cm(-1) frequency range. The good agreement with the INS experimental data allows us to assign unambiguously the origin of all features (first-order and high-order processes) of these spectra and to predict that the LT phase is the phase measured experimentally both on the 4T and 6T materials. Moreover, the broad background in the 600-1400 cm(-1) frequency range and the well-defined features which appear around 940 cm(-1) in the calculated INS spectra of 4T/HT and 6T/HT are assigned to multiphonon contributions. This multiphonon contribution at 940 cm(-1), which is absent in the 4T/LT and 6T/LT INS spectra, also constitutes a fingerprint of the HT phases. Finally, the calculated dispersion curves of the two polymorph phases of 4T and 6T are given.

Journal Article↗

PubMed2005

Neutron vibrational spectroscopy gives new insights into the structure of poly(p-phenylene terephthalamide).

The vibrational spectra of benzanilide and poly(p-phenylene terephthalamide) have been measured using inelastic neutron scattering. These compounds have similar hydrogen-bond networks, which, for poly(p-phenylene terephthalamide), lead to two-dimensional hydrogen-bonded sheets in the crystal. Experimental spectra are compared with solid-state, quantum chemical calculations based on density functional theory (DFT). Such "parameter-free" calculations allow the structure-dynamics relation in this type of compound to be quantified, which is demonstrated here for benzanilide. In the case of poly(p-phenylene terephthalamide), vibrational spectroscopy and DFT calculations help resolve long-standing questions about the packing of hydrogen-bonded sheets in the solid state.

Journal Article↗

PubMed2005

The mitogen-activated protein kinase dependent expression of prostaglandin H synthase-2 and interleukin-8 messenger ribonucleic acid by myometrial cells: the differential effect of stretch and interleukin-1{beta}.

Infection and uterine stretch are the common causes of preterm labor. IL-1beta plays a key role in infection-induced preterm labor and increases prostaglandin H synthase 2 (PGHS-2) and IL-8 expression. We have shown that mechanical stretch of uterine myocytes in vitro up-regulates the expression of PGHS-2 and IL-8. In this study, we tested the hypotheses that both IL-1beta and mechanical stretch increase the myometrial expression of PGHS-2 and IL-8 via MAPK activation and that their effects are synergistic. MAPK activation was assessed in myocytes obtained from pregnant women undergoing cesarean section before the onset of labor after exposure to IL-1beta and stretch either alone or in combination. Specific inhibitors of ERK, p38, and c-Jun N-terminal kinase were used to define the role of each in the increased expression of PGHS-2 and IL-8 mRNA. We found that both IL-1beta and stretch activated all three MAPK subtypes but that they had no synergistic effect. The inhibitor studies showed that stretch-induced increases in both PGHS-2 and IL-8 mRNA expression were ERK1/2 and p38 dependent and that IL-1beta-induced increases of PGHS-2 mRNA expression were also ERK1/2 and p38 dependent, but those of IL-8 were dependent only on ERK1/2 activation. These data show that exposure of human uterine myocytes to both stretch and IL-1beta activates the MAPK system, which is responsible for the increase in PGHS-2 and IL-8 mRNA expression. We found no evidence of a synergistic effect of IL-1beta and stretch on myometrial expression of PGHS-2 and IL-8 mRNA.

Base Sequence↗

PubMed2005

Far- and mid-infrared of crystalline 2,2'-bithiophene: ab initio analysis and comparison with infrared response.

Infrared intramolecular vibrations and lattice modes in the crystalline phase of 2,2'-bithiophene (2T) are investigated using the direct method combined with density functional theory (DFT)-based total energy calculations. For the first time, the far- and mid-infrared responses have been calculated from the Gamma-point modes and the Born effective charge tensors of the 2T crystalline phase. The relative good agreement between the calculated and experimental infrared spectra allows us to assign the origin of the main features of the experimental spectra, which is of particular interest in the far-infrared domain. These assignments are useful for understanding all the properties of the 2T crystalline phase in which phonon-phonon and electron-phonon interactions play an important role.

Journal Article↗

PubMed2004

Mechanical stretch of human uterine smooth muscle cells increases IL-8 mRNA expression and peptide synthesis.

Labour is associated with increased synthesis of interleukin-8 (IL-8) by the fetal membranes and myometrium, which leads to an inflammatory infiltrate. Stretch has been shown to increase the expression of contraction-associated proteins in animal models of labour and in human myocytes in vitro. In this study, we tested the hypothesis that mechanical stretch of human myometrial cells increases IL-8 messenger ribonucleic acid (mRNA) expression. We isolated myocytes from non-pregnant women undergoing hysterectomy and pregnant women undergoing Caesarean section before and after the onset of labour. Myocytes in culture were subjected to stretch of varying intensity (6-16%) and duration (1 or 6 h) using the Flexercell system. IL-8 mRNA expression was lowest in myocytes from pregnant women not in labour, intermediate in those from non-pregnant women and greatest in those from pregnant women in labour. Stretch increased IL-8 mRNA expression independent of reproductive state. The stretch-induced increase in IL-8 mRNA expression was associated with higher IL-8 levels in the culture supernatant and enhanced promoter activity. These data suggest that stretch contributes to the increase in myometrial IL-8 synthesis associated with the onset of labour in humans.

Female↗

PubMed2004

Freezing on heating of liquid solutions.

We report a reversible liquid-solid transition upon heating of a simple solution composed of a-cyclodextrine (alpha CD), water, and 4-methylpyridine. These solutions are homogeneous and transparent at ambient temperature and solidify when heated to temperatures between 45 degrees and 75 degrees. Quasielastic and elastic neutron scattering show that molecular motions are slowed down in the solid and that crystalline order is established. The solution "freezes on heating." This process is fully reversible, on cooling the solid melts. A rearrangement of hydrogen bonds is postulated to be responsible for the observed phenomenon.

Crystallization↗

PubMed2004

Isotope effects associated with tunneling and double proton transfer in the hydrogen bonds of benzoic acid.

The isotope effects associated with double proton transfer in the hydrogen bonds of benzoic acid (BA) dimers have been measured using field-cycling (1)H NMR relaxometry and quasielastic neutron scattering. By studying mixed isotope (hydrogen and deuterium) samples, the dynamics of three isotopologues, BA-HH, BA-HD, and BA-DD, have been investigated. Low temperature measurements provide accurate measurements of the incoherent tunneling rate, k(0). This parameter scales accurately with the mass number, m, according to the formula k(0)=(E/m)e(-Fm) providing conclusive evidence that the proton transfer process is a strongly correlated motion of two hydrons. Furthermore, we conclude that the tunneling pathway is the same for the three isotopologue species. Measurements at higher temperatures illuminate the through barrier processes that are mediated via intermediate or excited vibrational states. In parallel with the investigation of proton transfer dynamics, the theoretical and experimental aspects of studying spin-lattice relaxation in single crystals of mixed isotope samples are investigated in depth. Heteronuclear dipolar interactions between (1)H and (2)H isotopes contribute significantly to the overall proton spin-lattice relaxation and it is shown that these must be modeled correctly to obtain accurate values for the proton transfer rates. Since the sample used in the NMR measurements was a single crystal, full account of the orientation dependence of the spin-lattice relaxation with respect to the applied B field was incorporated into the data analysis.

Journal Article↗

PubMed2004

The structure of methane hydrate under geological conditions a combined Rietveld and maximum entropy analysis.

We present a study of the structure of a fully deuterated methane hydrate under the geological conditions found in the world's oceans. In situ high-resolution neutron diffraction experiments have been performed at temperatures of 220, 275, and 280 K and a pressure of 100 bar, corresponding to the conditions at 1000 m water depth. The data were analyzed with a combination of Rietveld refinement and maximum entropy methods. From the Rietveld refinement, precise atomic parameters of the host lattice could be determined, indicating increasing distortions of the structure of the cages at elevated temperatures and pressures. Debye-Waller factors of the encaged CD(4) molecules have been found to exceed the values of the Debye-Waller factors of the D(2)O molecules considerably. In the large cage of structure type I the thermal center-of-mass displacements of the guests are 5-10 times larger than those of the water molecules. From the maximum entropy analysis maps of the scattering length density have been obtained, showing details of the vibrational amplitudes of the atoms in methane hydrate. The Debye-Waller factors of all molecules have been found to deviate considerably from a simple spherical geometry.

Journal Article↗