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Biomedical subjects

C W Frank

Publications and source records attributed to C W Frank.

At least 19 recordsLinked to original sources

Capillary aging of the contacts between glass spheres and a quartz resonator surface.

The strength of the contacts between small glass spheres and the surface of a quartz crystal resonator has been probed based on the increase of resonance frequency induced upon sphere contact. The acoustic interaction between the sphere and the plate is modeled as a low-frequency coupled resonance; the dependence of the resonant parameters on overtone order lends support to this model. After exposing the sample to humid air and drying it again, the contact strength increases at least tenfold due to capillary forces--we observe a hysteretic form of the sand-castle effect. Repeated wet-dry cycles reveal logarithmic capillary aging with time. The experiments suggest that the drying of the liquid bridges leads to a contraction of small voids in the contact zone, subsequently increasing cohesion.

Journal Article↗

Polymer-supported lipid bilayers on benzophenone-modified substrates.

Solid-supported lipid membranes are important for their roles in fundamental biophysical research as well as in applications such as biosensors. In our study, lipopolymers containing alkyl side chains were synthesized and a mixture of the lipopolymer and free lipids was preorganized at the air-water interface and then transferred to a solid substrate using the Langmuir-Blodgett technique. A photochemical reaction between a substrate-functionalized benzophenone and C-H bonds on the lipopolymer was used to attach the lipopolymers to the substrate. The final assembly of the membrane was completed by vesicle fusion. Langmuir film experiments at the air-water interface indicate tighter molecular packing for the lipopolymers with 28 mol % alkyl side chains than for the ones with 22 mol %. Atomic force microscopy images point to phase separation of lipopolymers on the substrates due to their dewetting from hydrophobic surfaces. However, a mixture of lipopolymers and free lipids formed a smooth film on the same substrate. After the addition of the second lipid layer on the lipopolymer/free lipid layer, the fluorescence images of the polymer-supported bilayer suggested that the distal lipid layer is homogeneous on the micrometer scale. The relaxation of the fluorescent probe lipids was analyzed after application of an electric field to determine their diffusion coefficient; the distal lipid layer was mobile with an average diffusion coefficient of approximately 0.1 microm(2)/s. Moreover, the immobile fraction of the lipids in the distal layer was estimated to be around 15%.

Benzophenones↗

Hindered diffusion in polymer-tethered membranes: a monolayer study at the air-water interface.

Polymer-tethered phospholipid bilayers, which are based on a phospholipid-lipopolymer mixture, represent a very promising approach to stabilize complex biomimicking composite membranes. Furthermore, they are interesting model systems to study problems of hindered diffusion in two-dimensional liquids. Here, we present fluorescence recovery after photobleaching experiments (FRAP) on mixed phospholipid-lipopolymer monolayers of DMPC and DSPE-EO(45) at the air-water interface. In contrast to recent polymer-tethered bilayer experiments where the hydrophobic lipopolymer anchors behaved as immobile obstacles within the fluid phospholipid matrix,(1) this paper investigates the influence of mobile lipopolymer obstacles on the lateral diffusion of phospholipids. We found that the lateral diffusion of phospholipids with D = 7.1 +/- 0.5 microm(2)/s is independent of the lipopolymer obstacle concentration if adjacent polymer chains do not interact with each other. However, the diffusion coefficient of nontethered phospholipids gradually decreases from D = 7.1 +/- 0.5 microm(2)/s to D = 3.4 +/- 0.1 microm(2)/s in the case of increasing polymer-polymer interactions based on frictional coupling. This can be understood by a slowing down of the obstacle mobility. While phospholipids still show a significant lateral diffusion as long as the polymer moieties interact with each other only via frictional coupling, they become rather immobile (D = 0.9 +/- 0.1 microm(2)/s) if lipopolymers form a two-dimensional physical network.

Air↗

Functional tethered lipid bilayers.

Our strategy to provide the structural basis for the build-up of functional tethered membranes focuses on three approaches: the first one is based on the pre-organization of a monomolecular layer of a lipopolymer at the water/air interface which is then transferred to a solid support. Prior to deposition, the substrate is coated with a layer of benzophenone-derivatized silane molecules that allow for a stable covalent attachment by photo-cross-linking of some of the monomer units of the lipopolymer to the support. An alternative concept realizes a layer-by-layer deposition of the various structural elements: (1) the attachment layer with the reactive sites for the chemical stabilization; (2) a polymer 'cushion' prepared by adsorption and simultaneous or subsequent partial covalent binding to the reactive sites; and (3) a lipid monolayer transferred from the water/air interface, that contains a certain amount of lipids with reactive headgroups which, upon binding to the polymer tether, act as anchor lipids stabilizing the whole monolayer/cushion-composite. And finally, we build peptide-supported monolayers by first (self-) assembling amino acid sequences of various lengths via a SH-group near their N-terminus onto Au substances and use then their COO(-)-terminus to chemically attach phosphatidyl-ethanolamine lipids to form a stable monolayer of lipid-peptide conjugates. All the individual preparation steps and the various resulting (multi-) layers are characterized by surface plasmon spectroscopy, X-ray and neutron-reflectometry, contact angle measurements, IR spectroscopy, fluorescence microscopy, scanning probe microscopies, as well as, electrochemical techniques. For all tethering systems, the final membranes' architecture is obtained by fusing lipid vesicles onto the lipid monolayer. Proteins can be incorporated by either fusing vesicles that are loaded with the respective receptors, pores, or ion pumps via a reconstitution procedure, or via a transfer directly from a micellar solution to the pre-formed lipid bilayer at the solid support by a dialysis step. Two structural/dynamical features of tethered membranes which are considered to be of particular functional relevance, i.e. the degree of water uptake and, hence, the degree of swelling of the polymer support, as well as the lateral mobility of the lipid molecules in the membrane, are tested by surface plasmon optics and by measurements of the fluorescence recovery after photobleaching (FRAP), respectively. The results confirm that the presented preparation protocols yield fluid bilayers that mimic certain relevant properties of biological membranes. The functional characterization of tethered membranes, which is briefly summarized, is based on various electrochemical techniques, in particular, impedance spectroscopy, cyclic voltammetry, and chronoamperometric studies. The results obtained for reconstituted H(+)-ATPase from chloroplasts and E. coli and for cytochrome oxidase (with and without cytochrome c) confirm the incorporation of the proteins in an active form, thus, opening opportunities for novel sensor formats or offering a completely new model membrane system.

Biopolymers↗

Adaptation of bulk constitutive equations to insoluble monolayer collapse at the air-water interface.

A constitutive equation based on stress-strain models of bulk solids was adapted to relate the surface pressure, compression rate, and temperature of an insoluble monolayer of monodendrons during collapse at the air-water interface. A power law relation between compression rate and surface pressure and an Arrhenius temperature dependence of the steady-state creep rate were observed in data from compression rate and creep experiments in the collapse region. These relations were combined into a single constitutive equation to calculate the temperature dependence of the collapse pressure with a maximum error of 5 percent for temperatures ranging from 10 degrees to 25 degrees C.

Air↗

Discrimination of DNA hybridization using chemical force microscopy.

Atomic force microscopy (AFM) can be used to probe the mechanics of molecular recognition between surfaces. In the application known as "chemical force" microscopy (CFM), a chemically modified AFM tip probes a surface through chemical recognition. When modified with a biological ligand or receptor, the AFM tip can discriminate between its biological binding partner and other molecules on a heterogeneous substrate. The strength of the interaction between the modified tip and the substrate is governed by the molecular affinity. We have used CFM to probe the interactions between short segments of single-strand DNA (oligonucleotides). First, a latex microparticle was modified with the sequence 3'-CAGTTCTACGATGGCAAGTC and epoxied to a standard AFM cantilever. This DNA-modified probe was then used to scan substrates containing the complementary sequence 5'-GTCAAGATGCTACCGTTCAG. These substrates consisted of micron-scale, patterned arrays of one or more distinct oligonucleotides. A strong friction interaction was measured between the modified tip and both elements of surface-bound DNA. Complementary oligonucleotides exhibited a stronger friction than the noncomplementary sequences within the patterned array. The friction force correlated with the measured strength of adhesion (rupture force) for the tip- and array-bound oligonucleotides. This result is consistent with the formation of a greater number of hydrogen bonds for the complementary sequence, suggesting that the friction arises from a sequence-specific interaction (hybridization) of the tip and surface DNA.

Base Sequence↗

The effect of dental amalgam restorations on blood mercury levels.

Mercury levels in blood and in mouth air before and after chewing were measured in 47 persons with and 14 persons without dental amalgam restorations. Questionnaires relating to exogenous sources of mercury exposure were administered to both groups. Differences in the mouth air mercury levels before and after chewing were statistically significant in the group with amalgams, but not in the group without amalgams. Analysis of the data from the questionnaires indicated that little or no exogenous exposure to mercury occurred among the two groups. Blood mercury concentrations were positively correlated with the number and surface area of amalgam restorations and were significantly lower in the group without dental amalgams.

Adult↗

Mortality after first myocardial infarction. Search for a secular trend.

Two earlier studies of prognosis of coronary heart disease among men enrolled in the Health Insurance Plan in the 1960s and 1970s permitted us to examine whether prognosis had improved over this ten-year period. The new comparison involved 1,133 men aged 35 to 64 years who had survived a first acute myocardial infarction and were followed up for mortality after a baseline examination. Mortality estimates were controlled for clinical and demographic differences between the two cohorts by multivariate methods and by comparing subgroups. The analyses showed no difference in long-term prognosis between patients in the two decades. The observations in this population suggest that any contribution of improved medical care to the nationally observed secular decline in mortality from coronary heart disease in the time period studied was probably restricted to the acute stage of myocardial infarction.

Acute Disease↗

Repeated 1 hour electrocardiographic monitoring of survivors of myocardial infarction at 6 month intervals: arrhythmia detection and relation to prognosis.

In a study of the relation between ventricular premature beats and sudden death among 1,739 male of myocardial infarction enrolled in the Health Insurance Plan of Greater New York (HIP), patients underwent 1 hour of electrocardiographic monitoring at a baseline examination. During follow-up periods of up to 5 1/2 years, survivors underwent repeated monitoring at 6 month intervals for a maximum of four monitorings. At each monitoring a constant proportion of the men--25 percent--showed complex ventricular premature beats (runs of two or more, R on T phenomenon, bigeminal or multiform beats) during the hour. In comparison with men free of such arrhythmia, those demonstrating these complex forms in a given hour were three times as likely to show such beats in a subsequent monitoring hour. The mortality risk over 3 1/2 years after each of the four monitoring observations was in all cases elevated among men with complex ventricular premature beats. The risk of sudden death over this period was 6 percent for men without and 13 to 17 percent for men with such complexes. A study of the 1,445 men who underwent monitoring both at baseline examination and 6 months later identified the presence of runs of ventricular premature betas in either observation as a particularly important harbinger of sudden death.

Acute Disease↗

Ventricular premature complexes and sudden death after myocardial infarction.

Among 1739 male survivors of myocardial infarction, mortality over 5 years was examined in relation to presence of complex ventricular premature complexes (R on T, runs of two or more, multiform or bigeminal complexes) identified during 1 hour of monitoring. Such arrhythmia was associated with excess risk of death over the entire period. Men with R on T or runs during the hour show a 5-year sudden coronary death rate of 25%, compared with 6% of men free of premature complexes. Men with complex ventricular premature complexes are also at relatively higher risk for nonsudden cardiac death than the other men (5-year mortality 15% and 7%, respectively), but no additional disadvantage was associated with the presence of R on T or runs. Multivariate survival analyses, controlling simultaneously for other important clinical factors, identify complex ventricular premature complexes as the strongest influence on risk of sudden coronary death and congestive heart failure as the strongest influence on risk of other cardiac death.

Actuarial Analysis↗

The effect of dental amalgams on mercury levels in expired air.

The expired air of a group of 48 persons, 40 with and eight without dental amalgam restorations, was analyzed for its mercury content before and after chewing. Expired air samples were collected in polyethylene bags, and a known quantity of each was pumped into the mercury detector for measurement. The results showed that examined subjects with dental amalgams had higher pre-chewing mercury levels in their expired air than those without amalgams. After chewing, these levels were increased an average of 15.6-fold in the former and remained unchanged in the latter group. It was concluded that in situ dental amalgams can increase the level of mercury in expired air.

Dental Amalgam↗

Ventricular premature complexes in prognosis of angina.

We studied the prognostic role of ventricular premature complexes occurring during 1 hour of electrocardiographic monitoring of 416 men with effort angina who had never had myocardial infarction, and compared mortality over 5 years with that of 1739 men with infarction before first observation. Multivariate analyses of survival identified the presence of ventricular premature complexes in 1 hour of monitoring, the presence of ST-segment depression on the standard ECG, and age as the variables making the most important independent contributions to risk of death (all causes and sudden coronary deaths) among the men with angina. The relatively lower age-adjusted 5-year mortality among men with angina compared with those who had a prior myocardial infarction reflects the lower prevalence in the former group of indicators of myocardial dysfunction, such as ventricular ectopic activity and ST-segment depression.

Adult↗

Relation of education to sudden death after myocardial infarction.

We studied the influence of social and personal characteristics on prognosis among 1739 male survivors of myocardial infarction who had been monitored for one hour at a standard examination and subsequently followed for mortality. Over a three-year period men with little education (eight years of schooling or less) who had complex ventricular premature beats in the monitoring hour had over three times the risk of sudden coronary death found among better educated men with the same arrhythmia (cumulative mortality of 33 per cent and 9 per cent, respectively). No such differential appeared in the absence of complex ventricular premature beats. Neither risk factors for incidence of coronary heart disease nor clinical characteristics affecting prognosis accounted for the differences observed. There was no relation between education level and risk of recurrent infarction.

Acute Disease↗