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Biomedical subjects

J A Forrest

Publications and source records attributed to J A Forrest.

At least 19 recordsLinked to original sources
PubMed2006

Anomalous thermal denaturing of proteins adsorbed to nanoparticles.

We have used localized surface plasmon resonance (LSPR) to monitor the structural changes that accompany thermal denaturing of bovine serum albumin (BSA) adsorbed onto gold nanospheres of size 5nm-60nm. The effect of the protein on the LSPR was monitored by visible extinction spectroscopy. The position of the resonance is affected by the conformation of the adsorbed protein layer, and as such can be used as a very sensitive probe of thermal denaturing that is specific to the adsorbed protein. The results are compared to detailed calculations and show that full calculations can lead to significant increases in knowledge where gold nanospheres are used as biosensors. Thermal denaturing on spheres with diameter > 20 nm show strong similarity to bulk calorimetric studies of BSA in solution. BSA adsorbed on nanospheres with d [Symbol: see text] 15nm shows a qualitative difference in behavior, suggesting a sensitivity of denaturing characteristics on local surface curvature. This may have important implications for other protein-nanoparticle interactions.

Adsorption↗
PubMed2006

Spinodal wrinkling in thin-film poly(ethylene oxide)/polystyrene bilayers.

Optical microscopy and atomic force microscopy were used to study a novel roughness-induced wrinkling instability in thin-film bilayers of poly(ethylene oxide) (PEO) and polystyrene (PS). The observed wrinkling morphology is manifested as a periodic undulation at the surface of the samples and occurs when the bilayers are heated above the melting temperature of the semi crystalline PEO (T(m) = 63 Celsius) layer. During the wrinkling of the glassy PS capping layers the system selects a characteristic wavelength that has the largest amplitude growth rate. This initial wavelength is shown to increase monotonically with increasing thickness of the PEO layer. We also show that for a given PEO film thickness, the wavelength can be varied independently by changing the thickness of the PS capping layers. A model based upon a simple linear stability analysis was developed to analyse the data collected for the PS and PEO film thickness dependences of the fastest growing wavelength in the system. The predictions of this theory are that the strain induced in the PS layer caused by changes in the area of the PEO/PS interface during the melting of the PEO are sufficient to drive the wrinkling instability. A consideration of the mechanical response of the PEO and PS layers to the deformations caused by wrinkling then allows us to use this simple theory to predict the fastest growing wavelength in the system.

Computer Simulation↗
PubMed2005

Qualitative discrepancy between different measures of dynamics in thin polymer films.

We have used ellipsometry to measure the initial stages of interface healing in bilayer polystyrene films. We also used ellipsometry to measure the glass transition temperature T(g) of the same or identically prepared samples. The results indicate that as the film thickness is decreased, the time constant for the interface healing process increases, while at the same time the measured glass transition temperature in the same samples decreases as the film thickness is decreased. This qualitative difference in the behavior indicates that it is not always possible to make inferences about one probe of polymer dynamics from measurements of another. We propose a reason for this discrepancy based on a previously discussed origin for reduction in the T(g) value of thin films.

Computer Simulation↗
PubMed2004

The properties of free polymer surfaces and their influence on the glass transition temperature of thin polystyrene films.

We present a detailed study of free polymer surfaces and their effects on the measured glass transition temperature (T(g)) of thin polystyrene (PS) films. Direct measurements of the near-surface properties of PS films are made by monitoring the embedding of 10 and 20 nm diameter gold spheres into the surface of spin-cast PS films. At a temperature T = 378 K( > T(g)), the embedding of the spheres is driven by geometrical considerations arising from the wetting of the gold spheres by the PS. At temperatures below T(g) (363 K < T < 370 K), both sets of spheres embed 3-4 nm into the PS films and stop. These studies suggest that a liquid-like surface layer exists in glassy PS films and also provide an estimate for the lower bound of the thickness of this layer of 3-4 nm. This qualitative idea is supported by a series of calculations based upon a previously developed theoretical model for the indentation of nanoscale spheres into linear viscoelastic materials. Comparing data with simulations shows that this surface layer has properties similar to those of a bulk sample of PS having a temperature of 374 K. Ellipsometric measurements of the T(g) are also performed on thin spin-cast PS films with thicknesses in the range 8 nm < h < 290 nm. Measurements are performed on thin PS films that have been capped by thermally evaporating 5 nm thick metal (Au and Al) capping layers on top of the polymer. The measured T(g) values (as well as polymer metal interface structure) in such samples depend on the metal used as the capping layer, and cast doubt on the general validity of using evaporative deposition to cover the free surface. We also prepared films that were capped by a new non-evaporative procedure. These films were shown to have a T(g) that is the same as that of bulk PS (370+/-1 K) for all film thicknesses measured (> 7 nm). The subsequent removal of the metal layer from these films was shown to restore a thickness-dependent T(g) in these samples that was essentially the same as that observed for uncapped PS films. An estimate of the thickness of the liquid-like surface layer was also extracted from the ellipsometry measurements and was found to be 5+/-1 nm. The combined ellipsometry and embedding studies provide strong evidence for the existence of a liquid-like surface layer in thin glassy PS films. They show that the presence of the free surface is an important parameter in determining the existence of T(g) reductions in thin PS films.

Journal Article↗
PubMed2003

Free surfaces cause reductions in the glass transition temperature of thin polystyrene films.

The effect of free surfaces on the glass transition temperature (T(g)) of thin polystyrene films was studied. Measurements were performed on films (8 nm<h<290 nm) with one free surface and on films capped with a 5 nm thick metal layer (no free surfaces). Potential problems with evaporative deposition were eliminated by studying samples made of two supported films placed with their free surfaces in contact and annealed. Uncapped films displayed reduced T(g) values for h less, similar 40 nm while all "properly" capped films exhibited a T(g) value the same as that of the bulk polymer (370+/-1 K). When the free surface was restored, the measured T(g) values the same as those of uncapped films of the same thickness. These results show that free surfaces are crucial for observing T(g) reductions in thin polymer films and address the role of the sample preparation history.

Journal Article↗
PubMed2003

First inelastic neutron scattering studies on thin free standing polymer films.

Glass transition studies in free standing polymer films have revealed values of the transition temperature, T(g), which were substantially reduced below the bulk for sufficiently thin films. Here we report on the preparation of two stacks of free standing polystyrene films: 70 films with a thickness of h approximately 107 nm and 140 films with h approximately 55 nm with equivalent total sample thicknesses of approximately 7.5 microm. We have performed the first measurements on such samples using inelastic neutron scattering, and demonstrate that inelastic neutron scattering experiments, performed on the time-of-flight spectrometer IN6 and the backscattering spectrometer IN16 at the Institut Laue-Langevin, are feasible.

Journal Article↗
PubMed2003

Thickness dependence of the dynamics in thin films of isotactic poly (methylmethacrylate).

The film thickness dependence of both the glass transition temperature (T(g)) and the 1 kHz alpha relaxation were studied for thin films of isotactic Poly (methylmethacrylate) (i-PMMA) supported on aluminium substrates. Films in the thickness range 7-200 nm were studied. The ellipsometrically determined T(g) was found to show reductions for films thinner than 60 nm, with the largest observed reduction being 12 K for a 7 nm thick film. Measurements of the T(g) were also performed on i-PMMA films supported on silicon substrates. Dielectric studies of the temperature dependent 1 kHz alpha relaxation peak, showed that the position (T(alpha)) and shape of the peak have no film thickness dependence. This was shown to hold for films with one free surface and films with a 30 nm thermally evaporated capping layer. Capping the films was shown to have no effect on the thickness dependence of either T(g) or T(alpha). The implications of these results are discussed further and the different film thickness dependencies of T(g) and T(alpha) are discussed. This is done within the framework of the Vogel-Fulcher-Tamann (VFT) theory of glass forming materials and also in the context of the existence of a dynamic correlation length xi.

Journal Article↗
PubMed2003

Direct imaging of nanoparticle embedding to probe viscoelasticity of polymer surfaces.

Atomic force microscopy was used to study the embedding of gold nanoparticles into the surface of polystyrene films. The rate of embedding was determined at temperatures near the bulk glass transition temperature T(g) by measuring the apparent nanosphere height as a function of annealing time. In particular, relative height measurements of the adhered particles were made at temperatures below the bulk T(g) value. In the absence of enhanced surface dynamics or yield processes no embedding is expected to occur for T<T(g). Measurements on 10 and 20 nm particles both indicated that the particles did embed 3-4 nm into the polymer for T<T(g). Both the extent and time frame for engulfment appear to be independent of the particle diameter. The results suggest a more mobile surface region on the order of 3-4 nm thick, with a lower glass transition temperature than the bulk.

Journal Article↗
PubMed2003

Dielectric and ellipsometric studies of the dynamics in thin films of isotactic poly(methylmethacrylate) with one free surface.

We have performed dielectric loss measurements at 1 kHz on thin films of isotactic poly(methyl methacrylate). A key distinction of our studies is that the samples measured were supported films with one free surface rather than films that have metallic electrodes covering both surfaces. This unique sample geometry allows us to eliminate any effects due to evaporation of metal onto the top film surface and provides a unique opportunity to make direct comparisons between dielectric loss and glass transition measurements. Film thicknesses in the range from 6 microm to 7 nm were prepared on Al coated substrates. The dielectric loss peak and ellipsometric glass transition temperature of all films were measured. The dielectric loss was found to exhibit no discernible film thickness dependence in either the temperature of the maximum loss value or the shape of the loss curve. In contrast, the measured T(g) values were found to decrease with decreasing film thickness with a maximum shift of 10 K for a 7-nm film. Dielectric measurements were also made on Al coated films and these samples also showed no shift in the temperature of the loss peak. Finally, the T(g) measurements were also made on Si substrates. These values exhibited an increasing T(g) value with film thickness with a maximum increase of approximately 15 K being measured for a 7-nm film.

Journal Article↗
PubMed2003

Crystallization kinetics and crystal morphology in thin poly(ethylene oxide) films.

We present a detailed study of the kinetics of crystallization for thin films of poly(ethylene oxide) (PEO). Measurements of the growth rate have been carried out using optical-microscopy techniques on films of monodisperse PEO. Films with thicknesses from 13 nm to approximately 2 microm were crystallized isothermally at temperatures approximately 20 degrees C below the melting point. A remarkable non-monotonic slowing-down of the crystal growth is observed for films with thickness less than approximately 400 nm. The changes in the growth rate from bulk-like values is significant and corresponds to a factor of 40 decrease for the thinnest films studied. The morphologies of isothermally crystallized samples are studied using atomic-force microscopy. We find that a morphology, similar to diffusion-controlled growth (dendritic growth and densely branched growth), is observed for films with h<150 nm. In addition, changes in the morphology occur for thicknesses consistent with changes in the growth rate as a function of film thickness.

Journal Article↗
PubMed2002

Surface denaturation and amyloid fibril formation of insulin at model lipid-water interfaces.

We consider the effects that different lipid surfaces have upon the denaturation and subsequent formation of amyloid fibrils of bovine insulin. The adsorption and unfolding kinetics of insulin being adsorbed onto the different lipid surfaces under denaturing conditions are studied using FTIR ATR spectroscopy and are compared to the bulk solution behavior of the protein. Atomic force microscopy studies are also performed to compare the fibrils growing on the different surfaces. This study shows that both the adsorption and unfolding kinetics of insulin can be described by a sum of exponential processes and that different surfaces behave differently, with respect both to one another and to the bulk protein solution. The proteins adsorbed onto the surfaces are observed to have faster unfolding kinetics than those in the bulk, and the fibril-like structures formed at the surfaces are shown to be different in a number of ways from those found in bulk solution. The beta-sheet content and growth kinetics of the adsorbed proteins also differ from those of the bulk system. An attempt is made to describe the observed behavior in terms of simple physical arguments involving adsorption, unfolding, and aggregation of the proteins.

Adsorption↗
PubMed2002

Using adhesion to probe viscoelasticity of polymer film surfaces: a quartz crystal microbalance study.

We have used a quartz crystal microbalance to monitor the adhesion of small particles to the surface of polystyrene films. This technique is shown to provide a signature of viscoelastic relaxation processes at the polymer surface. For M(n) values less than 10(4) and greater than 10(5), this signature occurs at a temperature approximately 12.5 K above the measured bulk glass transition temperature, T(g). For intermediate values of M(n) however, the relaxation signature occurs at temperatures as low as 7 K above the bulk T(g). This observation suggests a slight decrease in the T(g) value near the polymer surface. A model incorporating the effects of enrichment of polymer chain ends at the free surface was considered and found to provide a quantitative description of the data.

Journal Article↗
PubMed2001

Molecular weight dependence of reductions in the glass transition temperature of thin, freely standing polymer films.

We have used transmission ellipsometry to perform a comprehensive study of the glass transition temperature T(g) of freely standing polystyrene films. Six molecular weights M(w), ranging from 575 x 10(3) to 9100 x 10(3), were used in the study. For each M(w) value, large reductions in T(g) (as much as 80 degrees C below the bulk value) were observed as the film thickness h was decreased. We have studied in detail the dependence of the T(g) reductions on M(w) in a regime dominated by chain confinement effects. The empirical analysis presented is highly suggestive of the existence of a mechanism of mobility in thin freely standing films that is inhibited in the bulk and distinct from the usual cooperative motion associated with the glass transition.

Journal Article↗
PubMed2001

Surreptitious abuse of magnesium laxatives as a cause of chronic diarrhoea.

Surreptitious laxative abuse is increasingly considered as a possible cause of unexplained chronic diarrhoea. Laboratory services for detection of colonic stimulant laxatives are widely available; however, laboratory facilities for identifying patients with magnesium-induced diarrhoea are not commonly provided, making diagnosis difficult. We describe three patients who surreptitiously abused magnesium laxatives, and whose diagnoses were delayed, leading in each case to extensive investigations and lengthy in-patient stays. In all three cases, the diagnosis was eventually made by the simple measurement of magnesium in a random faecal sample. We would like to increase the awareness of surreptitious magnesium laxative abuse as a cause of chronic diarrhoea so that costly and unnecessary investigations may be minimized.

Adult↗
PubMed1998

Randomised controlled double-blind trial of the calcium channel antagonist amlodipine in the treatment of acute alcoholic hepatitis.

BACKGROUND/AIMS: Calcium channel blockers have a hepatoprotective action in animal models of alcohol-induced liver injury but their effect in alcoholic liver disease in humans has not been previously investigated. We have conducted a randomised, placebo-controlled trial to investigate the possible benefit of the calcium channel blocker amlodipine in terms of 4-week survival in hospitalised patients with severe acute alcoholic hepatitis. METHODS: Sixty-two patients with acute alcoholic hepatitis were randomised to receive 5-10 mg amlodipine each day for 1 year or an identical capsule containing placebo. In 36 (58%), acute alcoholic hepatitis was confirmed on biopsy and in the remainder on clinical and laboratory criteria. There were no statistically significant differences in clinical characteristics and disease severity in the treated and placebo groups. RESULTS: Of the 32 patients receiving amlodipine, there were six deaths (19%) in the first 4 weeks compared with seven (23%) of the placebo patients (p=0.329). Causes of death were similar in the amlodipine and control groups, with liver failure predominant. Analysis by the Cox proportional hazards model after adjustment for other prognostic factors showed survival was not significantly influenced by active treatment (p=0.07). One patient in each group was withdrawn because of the development of hypotension, but this did not recur on reintroduction of the capsules. CONCLUSIONS: This study shows that calcium channel blockers are well tolerated with few side effects in advanced alcoholic liver disease, but there is no conclusive evidence from this study that calcium channel blockers are helpful in the treatment of alcoholic hepatitis.

Acute Disease↗
PubMed1995

AIDS-related cholangitis: diagnostic features and course in four patients.

Radiological features of sclerosing cholangitis are an uncommon but well recognised complication of HIV infection in homosexual males. In this report we document the clinical features and course of the disease in four patients. Four homosexual males with established AIDS were referred in 1990-92. Three of the four had intractable upper abdominal pain which was poorly responsive to opiates. Three of the patients had diarrhoea and all had weight loss. The diagnosis of AIDS related cholangitis was confirmed by endoscopic retrograde cholangiography in three cases, but in only one patient was there no evidence of biliary disease on ultrasound scanning. In the two cases with cholangiographic features of papillary stenosis, endoscopic sphincterotomy was carried out and there was subsequently a dramatic improvement in the abdominal pain. Three of the patients had evidence of gastrointestinal infection with Microsporidia (1) or Cryptosporidia (2). All the patients died within 2-9 months of the diagnosis of cholangitis, but none of the deaths resulted from hepatobiliary disease.

AIDS-Related Opportunistic Infections↗
PubMed1991

Ranitidine suppresses aluminium absorption in man.

1. Intragastric pH monitoring was performed before and after the single-blind administration of ranitidine or placebo (saline) in eight healthy subjects and four patients with end-stage renal disease who were on regular haemodialysis. 2. The subjects were studied on two occasions and were given aluminum hydroxide (1185 mg) orally 90 min after the administration of ranitidine or saline. 3. Plasma aluminum concentrations and, in normal men, urinary excretion of aluminum were monitored before and after the oral aluminum load. 4. Intragastric pH increased significantly with ranitidine but not with placebo (P less than 0.001). Urinary aluminum excretion increased significantly after the administration of aluminum hydroxide during the placebo phase (P less than 0.001) but not during the ranitidine phase. Plasma aluminium concentrations were higher in the patients with renal failure than in the normal subjects (P less than 0.05), but were unchanged in both groups after the oral aluminium load. 5. This study shows that gastric pH is an important factor in the modulation of aluminum absorption in man, and indicates that reducing gastric acid secretion with ranitidine may reduce the toxicity of orally administered aluminium compounds.

Adult↗