Biomedical subjects

Jacob Klein

Publications and source records attributed to Jacob Klein.

15 recordsLinked to original sources

PubMed2025

MUC5B promoter variant and survival in rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVE: The objective of this study was to investigate the association between the MUC5B rs35705950 promoter variant and survival in RA-associated interstitial lung disease (RA-ILD). METHODS: We studied participants in the Veteran Affairs Rheumatoid Arthritis (VARA) registry with validated ILD diagnoses. Participants were followed until death or till the end of the study period. The MUC5B rs35705950 promoter variant was measured using an Infinium genotyping array, assuming autosomal dominant inheritance. Survival and cause of death were determined from VA death records and the National Death Index. Associations of the MUC5B promoter variant with survival were tested in Cox regression models, adjusting for potential confounders. RESULTS: Among 263 participants with RA-ILD (mean age 69 years, 95% male, 73% White, 85% smoking history), the MUC5B promoter variant was present in 33.5%. The mortality rate was similar between those with [12.2/100 PY (95% CI: 9.4, 15.8)] and without [11.1/100 PY (95% CI: 9.1, 13.5)] the variant. MUC5B status was not significantly associated with survival overall [aHR 0.97 (95% CI: 0.68, 1.37)] or when stratified by ILD pattern [clinical usual interstitial pneumonia (UIP) aHR 0.86 (95% CI: 0.55, 1.35); clinical non-UIP aHR 1.15 (95% CI: 0.63, 2.09)]. Further, MUC5B status was not significantly associated with respiratory-related [aHR 0.83 (95% CI: 0.42, 1.66)] or non-respiratory causes of death [aHR 1.08 (95% CI: 0.72, 1.62)]. CONCLUSION: While associated with RA-ILD risk, the MUC5B promoter variant was not predictive of survival among RA-ILD patients in this multicentre cohort. Further studies are needed to identify other genetic and non-genetic prognostic factors in RA-ILD to inform disease management.

Humans↗

PubMed2006

Boundary lubrication under water.

Boundary lubrication, in which the rubbing surfaces are coated with molecular monolayers, has been studied extensively for over half a century. Such monolayers generally consist of amphiphilic surfactants anchored by their polar headgroups; sliding occurs at the interface between the layers, greatly reducing friction and especially wear of the underlying substrates. This process, widespread in engineering applications, is also predicted to occur in biological lubrication via phospholipid films, though few systematic studies on friction between surfactant layers in aqueous environments have been carried out. Here we show that the frictional stress between two sliding surfaces bearing surfactant monolayers may decrease, when immersed in water, to as little as one per cent or less of its value in air (or oil). We attribute this to the shift of the slip plane from between the surfactant layers, to the surfactant/substrate interface. The low friction would then be due to the fluid hydration layers surrounding the polar head groups attached to the substrate. These results may have implications for future technological and biomedical applications.

Adhesiveness↗

PubMed2006

Applying grazing incidence X-ray reflectometry (XRR) to characterising nanofilms on mica.

Molecularly smooth mica has hitherto not been widely used as a substrate for the X-ray reflectometry (XRR) technique. That is largely due to the difficulty of achieving flatness over a sufficiently large area of mica. Here we show that this difficulty can be overcome by slightly bending the mica substrate over an underlying cylinder; the enhanced rigidity of the bent mica sheet along the axis of the cylinder provides sufficient flatness along this axis for XRR measurements. To test this method, we have employed it to characterise three types of nanofilms on mica in air: (A) Cr-Au thin films; (B) a surface-grown zwitterionic polymer brush; and (C) a Langmuir-Blodgett (LB) phospholipid monolayer, using a table-top X-ray reflectometer. Fitting the obtained reflectivity curves with the standard Parratt algorithm allows us to extract the structural information of the nanofilms (both thickness and apparent roughness). Our simple method points to how XRR may be exploited as a useful characterisation tool for nanofilms on mica.

Journal Article↗

PubMed2006

Forces between mica surfaces, prepared in different ways, across aqueous and nonaqueous liquids confined to molecularly thin films.

We have measured normal and lateral interactions across a range of different liquids between mica surfaces using a surface force balance (SFB). The mica surfaces were prepared either by melt cutting using Pt wire and standard procedures in our laboratories or by tearing sheets (that had not been exposed to Pt) off from a freshly cleaved sheet of mica. AFM micrographs revealed the substantial absence of Pt nanoparticles on the melt cut and torn-off mica surfaces. Normal-force versus surface-separation (D) profiles and shear force versus D measurements for purified water (no added salt), for concentrated aqueous NaCl solutions, and for cyclohexane revealed that in all cases the behavior of the highly confined liquids between melt-cut and between torn-off mica sheets was identical within experimental scatter. These results demonstrate directly that interactions measured between melt-cut mica surfaces as routinely prepared using established procedures in our laboratories and in other laboratories are free of the effect of any Pt contamination.

Journal Article↗

PubMed2006

Long-range attraction between charge-mosaic surfaces across water.

We have measured directly the forces across water between hydrophilic surfaces covered with a random mosaic of positive and negative charged domains. We find a strong, long-ranged attraction between them at a surface separation comparable with the charge domain size (many tens of nanometers). This attraction persists at higher salt concentration, but its range then becomes comparable to the Debye screening length. We attribute the attraction to correlation between negative and positive regions on opposing surfaces, facilitated by the lateral mobility of the charge patches on the surfaces.

Electrochemistry↗

PubMed2006

[Therapeutic aspects in coronary cardiac patients who suffer from sexual dysfunction in a cardiac rehabilitation program].

Sexual dysfunction is one of the severe consequences of acute coronary events. Rehabilitation programs should address this aspect of functioning that has important implications for the patient's quality of life. In order to improve patients' sexual functioning and improve their quality of life we developed a comprehensive model of sexual therapy designed specifically for cardiac patients undergoing rehabilitation program. This model integrates educational, supportive and cognitive-behavioral therapy with appropriate medication (such as viagra). The model is implemented in co-therapy by two sexologists, a social worker and a physician. An empirical study has shown the positive outcomes of this model. This article describes the model and reports case vignettes that exemplify its effects on cardiac patients in rehabilitation and their spouses.

Behavior Therapy↗

PubMed2005

Stability of self-assembled hydrophobic surfactant layers in water.

Using contact angle measurements, surface force balance experiments, and AFM imaging, we have investigated the process of self-assembly of surfactants onto mica and the subsequent stability of those layers in pure water. In the case of cetyltrimethylammonium bromide (CTAB), the stability of a monolayer when immersed in pure water is found to be dependent on initial immersion time in surfactant, which is likely to be caused by an increase in the proportion of ion-exchange to ion-pair adsorption when incubated in surfactant for longer periods of time. Infinite dilution of the surfactant solution before withdrawal of the sample is found to have little effect on the stability of the resulting layer in pure water. The nature of the counterion is found to affect dramatically the stability of a self-assembled surfactant monolayer: cetyltrimethylammonium fluoride (CTAF) forms a layer that is much more stable in water than CTAB, which is likely to be due to faster and more complete ion-exchange with the mica surface for CTAF. Surface force balance experiments show that when the hydrophobic monolayer is immersed in pure water it does not simply dissolve into the water; instead it rearranges, possibly to patches of bilayer or hemimicelles. The time scale of this rearrangement agrees well with the time scale of the change from a hydrophobic to more hydrophilic surface observed using contact angle measurements. AFM imaging has also in some cases shown an evolution from an even monolayer to patches of bilayer.

Microscopy, Atomic Force↗

PubMed2005

Role of ion ligands in the attachment of poly(ethylene oxide) to a charged surface.

Using a surface force balance we demonstrate unambiguously that high-molecular-weight poly(ethylene oxide) (PEO) does not adsorb onto mica from purified water with no added salt, a surprising observation in view of its strong adsorption on mica from aqueous 0.1 M KNO3 solution. Analysis of the force profiles, together with the known complexation of PEO with metal ions, suggests that the polymer attachment to the negatively charged surface is mediated by the hydrated potassium ion acting as a ligand.

Adsorption↗

PubMed2005

Polymer bridging probed by magnetic colloids.

Superparamagnetic particles offer a new way to probe the kinetics of adhesive processes. Two different scenarios of physical adhesion are studied. The thermal activation of van der Waals adhesion is well described by an Arrhenius model. In contrast, it is necessary to go beyond the Arrhenius description to understand the thermal activation of bridging between colloidal particles by a polymer at equilibrium adsorbance. We show that polymer bridging requires some removal of adsorbed polymer and is strongly influenced by the proximity of a glass transition within the adsorbed polymer.

Adhesiveness↗

PubMed2004

Fluidity of water confined down to subnanometer films.

A surface force balance with extremely high sensitivity and resolution for measuring shear forces across thin films has been used to investigate directly the dynamic properties of salt-free water (so-called conductivity water) in a gap between two atomically smooth solid surfaces. Our results reveal that no shear stress can be sustained by water (within our resolution and shear rates) down to films of thickness D = D0 = 0.0 +/- 0.3 nm. At short range (D < 3.5 +/- 1 nm), an attractive van der Waals (vdW) force between the surfaces causes a jump into a flat adhesive contact at D0, at which the surfaces rigidly couple. Analysis of the jump behavior reveals that the viscosity of water remains within a factor of 3 or so of its bulk value down to D0. This contrasts sharply with the case of confined nonassociating liquids, whose effective viscosity increases by many orders of magnitude at film thicknesses lower than about five to eight monolayers. We attribute this to the fundamentally different mechanisms of solidification of organic liquids and of water. In the former case, the density increase induced in the films by the confinement promotes solidification, while, in the case of water, such densification (due to vdW attraction between the liquid molecules and the confining walls), in agreement with bulk behavior, suppresses the tendency of the water to solidify.

Nanostructures↗

PubMed2004

Persistent droplet motion in liquid-liquid dewetting.

When a nonvolatile liquid film dewets from a partly compatible liquid substrate, the advancing dewetting front leaves behind droplets formed through a Rayleigh instability mechanism at its rim. We have found that these droplets continue to move in the direction of the dewetting front for extended periods (of order one day) with an initial droplet velocity varying linearly with the droplet size, and a displacement varying logarithmically with time. We attribute this persistent motion to a transient surface tension gradient on the substrate liquid surface trailing the dewetting front.

Journal Article↗

PubMed2003

Lubrication by charged polymers.

Long-ranged forces between surfaces in a liquid control effects from colloid stability to biolubrication, and can be modified either by steric factors due to flexible polymers, or by surface charge effects. In particular, neutral polymer 'brushes' may lead to a massive reduction in sliding friction between the surfaces to which they are attached, whereas hydrated ions can act as extremely efficient lubricants between sliding charged surfaces. Here we show that brushes of charged polymers (polyelectrolytes) attached to surfaces rubbing across an aqueous medium result in superior lubrication compared to other polymeric surfactants. Effective friction coefficients with polyelectrolyte brushes in water are lower than about 0.0006-0.001 even at low sliding velocities and at pressures of up to several atmospheres (typical of those in living systems). We attribute this to the exceptional resistance to mutual interpenetration displayed by the compressed, counterion-swollen brushes, together with the fluidity of the hydration layers surrounding the charged, rubbing polymer segments. Our findings may have implications for biolubrication effects, which are important in the design of lubricated surfaces in artificial implants, and in understanding frictional processes in biological systems.

Journal Article↗

PubMed2003

Sliding friction with polymer brushes.

Using high-resolution shear force measurements, we examine in detail the frictional drag between rubbing surfaces bearing end-tethered polymeric surfactants (brushes). The drag attains a maximum on initial motion, attributed to elastic stretching of the chains, which falls by a cascade of relaxations to a value characteristic of kinetic friction. This has a very weak velocity dependence, attributed to chain moieties dragging within a self-regulating, mutual interpenetration zone. When sliding stops, the shear stress across the polymer layers decays logarithmically with time, consistent with the relaxation of a network of dangling ends.

Journal Article↗

PubMed2002

Fluidity of bound hydration layers.

We have measured the shear forces between solid surfaces sliding past each other across aqueous salt solutions, at pressures and concentrations typical of naturally occurring systems. In such systems the surface-attached hydration layers keep the compressed surfaces apart as a result of strongly repulsive hydration forces. We find, however, that the bound water molecules retain a shear fluidity characteristic of the bulk liquid, even when compressed down to films 1.0 +/- 0.3 nanometer thick. We attribute this to the ready exchange (as opposed to loss) of water molecules within the hydration layers as they rub past each other under strong compression.

Journal Article↗

PubMed2002

Additional attraction between surfactant-coated surfaces.

A simple model that shows an additional attraction between solvated surfactant-coated systems is developed. The model simply calculates the van der Waals attraction between the solvated surfactant layers. This attraction was previously neglected as it was expected to have a small energetic contribution. This is indeed the case; however, despite the small energetic contribution the force is large. In other words, although the expression that we get is small in energy, it is large in force. This is particularly important for surface force balance measurements, where using the developed expression, some apparent discrepancies between measured and theoretical values may now have a possible explanation, and especially those associated with surfactant-coated surfaces. We apply the new expression to a given system, and compare with the experimental results.

Journal Article↗