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Biomedical subjects

J F Douglas

Publications and source records attributed to J F Douglas.

At least 19 recordsLinked to original sources
PubMed2006

Dielectric study of the antiplasticization of trehalose by glycerol.

Recent measurements have suggested that the antiplasticizing effect of glycerol on trehalose can significantly increase the preservation times of proteins stored in this type of preservative formulation. In order to better understand the physical origin of this phenomenon, we examine the nature of antiplasticization in trehalose-glycerol mixtures by dielectric spectroscopy. These measurements cover a broad frequency range between 40 Hz to 18 GHz (covering the secondary relaxation range of the fragile glass-former trehalose and the primary relaxation range of the strong glass-former glycerol) and a temperature (T) range bracketing room temperature (220 K to 350 K). The Havriliak-Negami function precisely fits our relaxation data and allows us to determine the temperature and composition dependence of the relaxation time tau describing a relative fast dielectric relaxation process appropriate to the characterization of antiplasticization. We observe that increasing the glycerol concentration at fixed T increases tau (i.e., the extent of antiplasticization) until a temperature dependent critical "plasticization concentration" xwp is reached. At a fixed concentration, we find a temperature at which antiplasticization first occurs upon cooling and we designate this as the "antiplasticization temperature," Tant. The ratio of the tau values for the mixture and pure trehalose is found to provide a useful measure of the extent of antiplasticization, and we explore other potential measures of antiplasticization relating to the dielectric strength.

Journal Article↗
PubMed2006

Quasiparticlelike peaks, kinks, and electron-phonon coupling at the (pi,0) regions in the CMR oxide La2-2x Sr1+2x Mn2 O7.

Using angle-resolved photoemission, we have observed sharp quasiparticlelike peaks in the prototypical layered manganite La(2-2x)Sr(1+2x)Mn(2)O(7) (x=0.36,0.38). We focus on the (pi,0) regions of k space and study their electronic scattering rates and dispersion kinks, uncovering bilayer-split bands, the critical energy scales, momentum scales, and strengths of the interactions that renormalize the electrons. To identify these bosons, we measured phonon dispersions in the energy range of the kink by inelastic neutron scattering, finding a good match in both energy and momentum to the oxygen bond-stretching phonons.

Journal Article↗
PubMed2006

Laser based angle-resolved photoemission, the sudden approximation, and quasiparticle-like spectral peaks in Bi2Sr2CaCu2O(8+delta).

A new low photon energy regime of angle-resolved photoemission spectroscopy is accessed with lasers and used to study the high T(C) superconductor Bi2Sr2CaCu2O(8+delta). The low energy increases bulk sensitivity, reduces background, and improves resolution. With this we observe spectral peaks which are sharp on the scale of their binding energy--the clearest evidence yet for quasiparticles in the normal state. Crucial aspects of the data such as the dispersion, superconducting gaps, and the bosonic coupling kink are found to be robust to a possible breakdown of the sudden approximation.

Journal Article↗
PubMed2005

Wetting-dewetting transition line in thin polymer films.

Thin polymeric films are increasingly being utilized in diverse technological applications, and it is crucial to have a reliable method to characterize the stability of these films against dewetting. The parameter space that influences the dewetting of thin polymer films is wide (molecular mass, temperature, film thickness, substrate interaction) and a combinatorial method of investigation is suitable. We thus construct a combinatorial library of observations for polystyrene (PS) films cast on substrates having orthogonal temperature and surface energy gradients and perform a series of measurements for a range of molecular masses (1800 g/mol < M < 35 000 g/mol) and film thicknesses h (30 nm < h < 40 nm) to explore these primary parameter axes. We were able to obtain a near-universal scaling curve describing a wetting-dewetting transition line for polystyrene films of fixed thickness by introducing reduced temperature and surface energy variables dependent on M. Our observations also indicate that the apparent polymer surface tension gamma(p) becomes appreciably modified in thin polymer films from its bulk counterpart for films thinner than about 100-200 nm, so that bulk gamma(p) measurements cannot be used to estimate the stability of ultrathin films. Both of these observations are potentially fundamental for the control of thin film stability in applications where film dewetting can compromise film function.

Journal Article↗
PubMed2003

Early-stage compositional segregation in polymer-blend films.

The existence of a transient period during the surface enrichment of a binary polymer blend by one of its components has been suggested by previous theoretical and experimental studies as well as computer simulations. Taking advantage of the high depth resolution of neutron reflectivity and the slow dynamics of polymers near their glass transition, we investigate this early-stage surface compositional enrichment in a phase separating polymer blend for the first time. Two stages of surface enrichment layer growth are observed. A rapid local surface enrichment at the chain segmental level occurs first, followed by a slower growth of a diffuse layer having a scale on the order of the bulk correlation length and the radius of gyration of the surface enriching polymer chains.

Journal Article↗
PubMed2002

Incoherent neutron scattering and the dynamics of confined polycarbonate films.

Incoherent elastic neutron scattering measurements are performed on thin (75 to 1015 A) polycarbonate films supported on Si wafers. We find that the mean-square atomic displacement is diminished by thin film confinement. For film thicknesses comparable to the unperturbed dimensions of the macromolecule, we observe two characteristic crossover temperatures in as a function of temperature T, one above and the other below the bulk T(g). Furthermore, the harmonic force constant kappa, defined by the low temperature dependence of (i.e., kappa approximately k(B)T/ ), increases as the film thickness decreases. These observations suggest that the atoms are more strongly localized in the thin supported films.

Journal Article↗
PubMed2001

Intrinsic viscosity and the electrical polarizability of arbitrarily shaped objects.

The problem of calculating the electric polarizability tensor alpha(e) of objects of arbitrary shape has been reformulated in terms of path integration and implemented computationally. The method simultaneously yields the electrostatic capacity C and the equilibrium charge density. These functionals of particle shape are important in many materials science applications, including the conductivity and viscosity of filled materials and suspensions. The method has been validated through comparison with exact results (for the sphere, the circular disk, touching spheres, and tori), it has been found that 10(6) trajectories yield an accuracy of about four and three significant figures for C and alpha(e), respectively. The method is fast: For simple objects, 10(6) trajectories require about 1 min on a PC. It is also versatile: Switching from one object to another is easy. Predictions have also been made for regular polygons, polyhedra, and right circular cylinders, since these shapes are important in applications and since numerical calculations of high stated accuracy are available. Finally, the path-integration method has been applied to estimate transport properties of both linear flexible polymers (random walk chains of spheres) and lattice model dendrimer molecules. This requires probing of an ensemble of objects. For linear chains, the distribution function of C and of the trace (alpha(e)), are found to be universal in a size coordinate reduced by the chain radius of gyration. For dendrimers, these distribution functions become increasingly sharp with generation number. It has been found that C and alpha(e) provide important information about the distribution of molecular size and shape and that they are important for estimating the Stokes friction and intrinsic viscosity of macromolecules.

Journal Article↗
PubMed2001

Combinatorial study of surface pattern formation in thin block copolymer films.

Surface pattern formation in diblock copolymer films is investigated as a function of film thickness h and molecular mass M. Smooth films are observed for certain h ranges centered about multiples of the lamellar thickness L0, and we attribute this effect to an increase in the surface chain density with h in the outer brushlike copolymer layer. We also observe apparently stable labyrinthine surface patterns for other h ranges, and the average size of these patterns is found to scale as lambda approximately L0(-2.5). Hole and island patterns occur for h ranges between those of the labyrinthine patterns and the smooth regions, and their size similarly decreases with L0 and M.

Journal Article↗
PubMed2001

Critical properties and phase separation in lattice Boltzmann fluid mixtures.

Basic equilibrium properties of lattice Boltzmann (LB) fluid mixtures (coexistence curve, surface tension, interfacial profile, correlation length) are calculated to characterize the critical phenomena occurring in these model liquids and to establish a reduced variable description allowing a comparison with real fluid mixtures. We observe mean-field critical exponents and amplitudes so that the LB model may be useful for modeling high molecular weight polymer blends and other fluid mixtures approximated over a wide temperature range by mean-field theory. We also briefly consider phase separation under quiescent and shearing conditions and point out the strong influence of interacting boundaries on the qualitative form of the late-stage phase-separation morphology.

Journal Article↗
PubMed2000

One thousand renal transplants at Belfast City Hospital: post-graft neoplasia 1968-1999, comparing azathioprine only with cyclosporin-based regimes in a single centre.

From 1968-1999, 868 recipients of 1,000 renal transplants were followed up for neoplasia. Altogether, 102 tumours were diagnosed in 94 patients (11.8% incidence). Eighty-seven occurred among 750 single and 15 occurred among 118 multiple graft recipients. Three of 11 patients with pre-existing tumour developed posttransplant neoplasia, either new or recurrent. The most frequently seen posttransplant neoplasms were squamous carcinoma of skin, basal cell carcinoma (BCC), posttransplant lymphoproliferative disease (PTLD) and gastro-intestinal (GI) cancer. Forty-one tumour-related deaths occurred (44% mortality). Patients on CSA (C) regimes had a greater cumulative incidence of tumour after transplantation than those on azathioprine and low-dose prednisolone alone (A regime) had--12.7% (34 of 268) vs. 4.5% (15 of 335) of those at risk up to 5 years (relative increased rate of incidence 2.4) with more early cases of PTLD. C-regime patients who developed neoplasia had been prescribed significantly higher CSA doses than tumour-free controls (4.5 vs. 3.4 mg/kg/day; p = 0.014). Patients who made a late conversion from the A to the C regime subsequently developed more neoplasms than nonconverted controls (25.7% vs. 12%), mainly due to early and often aggressive squamous carcinoma. Transplant survival figures were similar for both A- and C-regime groups. These findings suggest that current CSA doses are higher than are necessary for optimal graft survival and thus increase the risk of early neoplasia without any compensatory advantage. A dose reduction of CSA to less than 3.5 mg/kg/day in long-surviving, stable graft recipients should reduce tumour risk without imperilling function. Late conversion from the A to the C regime should be avoided where possible and CSA doses in this situation kept to a minimum.

Azathioprine↗
PubMed1999

Dynamic entropy as a measure of caging and persistent particle motion in supercooled liquids.

The length-scale dependence of the dynamic entropy is studied in a molecular dynamics simulation of a binary Lennard-Jones liquid above the mode-coupling critical temperature T(c). A number of methods exist for estimating the entropy of dynamical systems, and we utilize an approximation based on calculating the mean first-passage time (MFPT) for particle displacement because of its tractability and its accessibility in real and simulation measurements. The MFPT dynamic entropy S(epsilon) is defined as equal to the inverse of the average first-passage time for a particle to exit a sphere of radius epsilon. This measure of the degree of chaotic motion allows us to identify characteristic time and space scales and to quantify the increasingly correlated particle motion and intermittency occurring in supercooled liquids. In particular, we identify a "cage" size defining the scale at which the particles are transiently localized, and we observe persistent particle motion at intermediate length scales beyond the scale where caging occurs. Furthermore, we find that the dynamic entropy at the scale of one interparticle spacing extrapolates to zero as the mode-coupling temperature T(c) is approached.

Journal Article↗
PubMed1999

Filler-induced composition waves in phase-separating polymer blends.

The influence of immobile filler particles (spheres, fibers, platelets) on polymer-blend phase separation is investigated computationally using a generalization of the Cahn-Hilliard-Cook (CHC) model. Simulation shows that the selective affinity of one of the polymers for the filler surface leads to the development of concentration waves about the filler particles at an early stage of phase separation in near critical composition blends. These "target" patterns are overtaken in late-stage phase separation by a growing "background" spinodal pattern characteristic of blends without filler particles. The linearized CHC model is used to estimate the number of composition oscillations emanating from isolated filler particles. In far-off-critical composition blends, an "encapsulation layer" grows at the surface of the filler rather than a target pattern. The results of these simulations compare favorably with experiments on filled phase-separating ultrathin blend films in which the filler particles are immobilized on a solid substrate.

Journal Article↗
PubMed1998

Prevalence of central autonomic neuropathy in elderly dialysis patients.

BACKGROUND: Autonomic neuropathy is frequently present in dialysis patients. In addition, deterioration of autonomic function occurs with ageing. This study examines the true prevalence of autonomic neuropathy in elderly dialysis patients and questions whether the combination of age and uraemia further increases the chance of dysautonomia being present. METHODS: We compared the results of five different tests (30:15 ratio; Valsalva ratio; heart rate response to deep breathing and the blood pressure responses to sustained hand grip and standing) of parasympathetic and combined parasympathetic and sympathetic dysfunction in older haemodialysis patients (mean age 70.2 years), younger haemodialysis patients (mean age 48.1 years) and two groups of subjects with normal renal function (mean age 73.0 years and 42.5 years respectively). RESULTS: Parasympathetic dysfunction was most prevalent in older patients on dialysis (65.9% (95% confidence intervals 51.4-80.4%), compared with 33.3% (95% confidence intervals 19.0-47.5% in younger dialysis patients), and 11.8 and 0% in the old and young control groups respectively). Combined parasympathetic and sympathetic dysfunction was seen in 41.5% (95% confidence intervals 26.5-56.5%) and 11.9% (95% confidence intervals 2.1-56.5%) of the old and young dialysis patients respectively but not in any of the control subjects. No interaction was seen between age and subject type. CONCLUSIONS: We conclude that although older dialysis patients have severe impairment of cardiovascular autonomic innervation, the prevalence of dysfunction is not higher than would be expected in an ageing population with uraemia.

Age Factors↗
PubMed1997

Pharmacokinetics and disposition of methyl t-butyl ether in Fischer-344 rats.

Methyl t-butyl ether (MTBE) is a commonly used octane booster in gasoline. This study examines the pharmacokinetics and disposition of MTBE in Fischer-344 rats after i.v., oral, dermal and inhalation routes of administration. Groups of male and female rats were given single i.v. (40 mg kg-1), oral (40 and 400 mg kg-1) and dermal (40 and 400 mg kg-1 in occluded chambers) doses of [14C]MTBE. For inhalation studies, rats were exposed nose-only for 6 h to low (400 ppm), high (8000 ppm) and repeated daily 6-h low (400 ppm x 15 days) chamber concentrations of [14C]MTBE. Blood, expired air, and excreta (urine and feces) were collected at selected times up to 7 days post-dose and quantified for 14C content. Plasma concentrations of MTBE and t-butyl alcohol (TBA) were quantified and mean values used for pharmacokinetic analysis. The mean total recoveries of 14C ranged from 91 to 105%. Methyl t-butyl ether was rapidly and completely absorbed after oral and inhalation exposures; dermal absorption was low. After all routes, MTBE was rapidly eliminated from blood (ti = 0.5 h) by exhalation and metabolism to TBA. At the high doses, metabolism was saturated and the proportion of renal 14C excretion decreased relative to the pulmonary route. At 48 h post-exposure, virtually all of the 14C was eliminated. The major metabolites recovered in urine were 2-methyl-1,2-propanediol and alpha-hydroxyisobutyric acid. There were no significant gender or route-dependent differences in the pharmacokinetics and disposition of MTBE.

Absorption↗
PubMed1997

Assessment of the in vivo mutagenic potential of methyl tertiary-butyl ether.

Methyl tertiary-butyl ether (MTBE) is one of the highest production volume chemicals in the USA. Previous results from in vitro genetic toxicity studies suggested that it was not mutagenic. However, chronic exposure at high levels resulted in liver tumors in female mice and kidney tumors in male rats. The current program assessed in vivo genotoxicity and also explored the possibility that a mutagenic mechanism was involved in the carcinogenic process. The specific tests used included the Drosophila sex-linked-recessive-lethal test, the rat bone marrow cytogenetics test, the mouse bone marrow micronucleus test and the in vivo-in vitro hepatocyte unscheduled DNA synthesis test in the mouse. All tests produced negative results, indicating that the potential for in vivo mutagenic activity was low. These data also suggest that the tumorigenic activity was probably the result of a non-genotoxic process.

Air Pollutants↗
PubMed1997

Developmental toxicity evaluation of methyl tertiary-butyl ether (MTBE) by inhalation in mice and rabbits.

Pregnant CD-1 mice (30 per group) and female New Zealand White rabbits (15 per group) were exposed by inhalation to 0, 1000, 4000 and 8000 ppm methyl tertiary-butyl ether (MTBE) vapor for 6 h a day during gestational days (GD) 6-15 and 6-18, respectively. Maternal body weights, clinical observations and food consumption were recorded throughout gestation for both species. At scheduled euthanization (GD 18 for mice and GD 29 for rabbits), fetuses were weighed, sexed and examined for external, visceral (including craniofacial) and skeletal alterations. For both species, the pregnancy rate was high and equivalent across all groups; no pregnant animals died or aborted. There were no does that delivered early, but there were three mouse dams in the control group and two dams in the 4000 ppm group that delivered early and were removed from the study. In mice, maternal body weights, body weight gain, corrected maternal gestational weight change and food consumption were significantly reduced in mice at 8000 ppm. Hypoactivity and ataxia were observed in dams exposed to 4000 and 8000 ppm. Gestational parameters affected at 8000 ppm included post-implantation loss (due to increased late resorptions and dead fetuses) and altered sex ratio (decreased males); fetal body weights per litter were reduced at 4000 and 8000 ppm. There was a significantly increased incidence of cleft palate at 8000 ppm; this resulted in increased incidences of pooled external and visceral malformations and of total malformations at this exposure concentration. There were also treatment-related increases in the incidence of individual skeletal variations at 4000 and 8000 ppm. In rabbits, maternal weight gain and food consumption were significantly reduced at 4000 and 8000 ppm. Relative liver weights were also reduced at 8000 ppm. All gestational parameters were equivalent across all groups, including pre- and post-implantation loss, fetal sex ratios, litter size and fetal weights/litter. There was no evidence of treatment-related teratogenicity observed at any dose tested in rabbits. The no-observed-effect levels (NOELs) for maternal and developmental toxicity were both 1000 ppm in mice and 1000 ppm and at least 8000 ppm, respectively, in rabbits.

Abnormalities, Multiple↗
PubMed1997

Oncogenicity studies of inhaled methyl tertiary-butyl ether (MTBE) in CD-1 mice and F-344 rats.

Oncogenicity studies of methyl tertiary-butyl ether (MTBE) vapor were conducted in CD-1 mice and Fischer 344 rats. Fifty animals of each sex per species per group were exposed for 6 h a day, 5 days per week to 0 (control), 400, 3000 and 8000 ppm MTBE vapor in air for 18 months (mice) and 24 months (rats). Both species showed reversible central nervous system depression at 8000 ppm for the first week of exposure, which continued for mice for the study duration. For the 8000 ppm mice, reduced body weight gain and early mortality prior to terminal euthanasia were exposure related. In the males, these deaths appear to be due to exacerbation of uropathy or dysuria, which occurs spontaneously in this strain. Increases in absolute and relative liver (both sexes) and kidney weight (males only) were seen at 3000 and 8000 ppm and decreases in brain and spleen weights were also noted (the latter decreases were without microscopic lesions and occurred at 8000 ppm only). An increase in hepatocellular hypertrophy occurred in both sexes at the two highest concentrations. The only neoplastic lesion found in this study in mice was an increased incidence of hepatocellular adenomas in females at the 8000 ppm exposure. In a follow-up study, a statistically significant elevation of cell proliferation in female mouse liver has been shown to occur following 5 days, but not 28 days, of exposure to 8000 ppm MTBE, suggesting that MTBE induces mitogenesis. For male rats, early euthanasia was required at week 82 and week 97 for the 8000 and 3000 ppm groups, respectively, due to excessive mortality from a severe progressive nephrosis. The end stage of this process appeared earlier in the male rats of all MTBE exposure groups; the incidence of this lesion and mortality for exposed females was comparable to control females. No exposure-related changes in hematological parameters were observed for any group at any time point, but a decrease in corticosterone levels was seen for male rats from the 8000 ppm group. Absolute and relative kidney and liver weight increases occurred in 3000 and 8000 ppm exposure groups, but the liver weight change was not accompanied by histopathological change. At study termination, increases in the incidence and severity of a chronic nephropathy in males from all exposure groups and in females exposed to 3000 and 8000 ppm was associated with secondary lesions of hyperplasia of the parathyroid and mineralization of tissues. Renal tubular cell tumors were increased in male rats exposed to 3000 and 8000 ppm. This may be associated with an accumulation of protein (stainable by Mallory's Heidenhain) in kidney tubular epithelial cells after 4 weeks of exposure. An increased incidence of interstitial cell adenomas of the testes was seen in males exposed to 3000 and 8000 ppm but was believed to be an artefact of an unusually low control incidence and not considered to be exposure related. Based on the above effects, the no-observed-effect level (NOEL) for chronic toxicity is 400 ppm, and the NOEL for carcinogenic effects is 3000 ppm (mice) and 400 ppm (rats).

Administration, Inhalation↗