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PubMed1980

Dynamic theory of leucocyte adhesion.

Leucocyte chemotaxis in in vitro chambers is analysed by applying the theory of transient diffusion to the chemotactic agent. This illustrates that use of physical principles can help in the interpretation of such experiments. A fluid-dynamical background is sketched for analysis of the dynamics of leucocyte adhesion in flow through blood vessels: this background includes the flow field induced around a particle in a velocity gradient. Discussion of the dynamics of leucocyte adhesion centres on estimation of the wall collisional rate of leucocytes from the bloodstream and leads to questions concerning measurement of collision efficiency. Specific experiments to elucidate factors remaining in question are suggested.

Blood Flow Velocity↗
PubMed2004

Disseminating effective cancer screening interventions.

A large gap exists between the results of research concerning efficacious cancer screening programs and the programs delivered in practice. In this article, the authors discuss issues in, barriers to, and lessons learned regarding the dissemination of interventions. They summarize previous reviews, exemplary studies, and theories regarding the diffusion and dissemination of cancer screening interventions. Six lessons learned address the involvement of key stakeholders, factors influencing diffusion, the need for different types of efficacy and effectiveness studies with greater attention to external validity, replication, the use of theoretical and evaluation models, and the importance of policy infrastructure. In this article, the authors make recommendations for future research and practice, including improving the understanding of the intervention process and changing the types of grants funded and review criteria used. Also needed are an enhanced infrastructure, including policies to support dissemination, and the involvement of researchers, health care administrators, clinicians, and funding organizations in dissemination if the gap between research and practice in cancer screening is to be reduced.

Delivery of Health Care↗
PubMedDate not supplied

Macromolecular crowding in biological systems: hydrodynamics and NMR methods.

Most biologically relevant environments involve highly concentrated macromolecular solutions and most biological processes involve macromolecules that diffuse and interact with other macromolecules. Macromolecular crowding is a general phenomenon that strongly affects the transport properties of macromolecules (rotational and translational diffusion) as well as the position of their equilibria. NMR methods can provide information on molecular interactions, as well as on translational and rotational diffusion. In fact, rotational diffusion, through its determinant role in NMR relaxation, places a practical limit on the systems that can be studied by NMR. While in dilute solutions of non-aggregating macromolecules this limit is set by macromolecular size, in crowded solutions excluded volume effects can have a strong effect on the observed diffusion rates. Hydrodynamic theory offers some insight into the magnitude of crowding effects on NMR observable parameters.

DNA↗
PubMed1983

Determination of the dissociation constant of a weak acid using a dissolution rate method.

Based on theories of diffusion-controlled mass transport for dissolution processes of weak acids in aqueous alkaline media, a method for the determination of the dissociation constant of a weak monoprotic acid is described. The method includes measurements of the initial dissolution rate as a function of pH, using the rotating-disk technique, and determination of the intrinsic solubility. The method was applied to determine the apparent dissociation constant (mu = 0.1) of 5,5-dimethyl-3-(alpha,alpha,alpha,4-tetrafluoro-m-tolyl)hydantoin, a new schistosomicide. For comparison, a spectrophotometric method for the pKa determination was developed. Due to rapid hydrolysis of the compound in the pH range required for the determination of the pKa, the development of the latter method turned out to be complicated and tedious. The results of both methods were in good agreement. For compounds with unfavorable properties for titrimetric or spectrophotometric determination of the pKa value, the dissolution rate method can be a useful alternative.

Hydrogen-Ion Concentration↗
PubMed1976

Renal tubular necrosis due to shock: light and electron-microscope observations.

The renal biopsy findings in a 76 yr-old woman suffering grom anuria due to acute tubular necrosis are described. The glomeruli were normal on light- and electron microscopy. Immunofluorescent studies failed to reveal any fibrin or immunoglobulins in the glomerular capillaries. Extensive focal areas of necrosis were seen in the tubular epithelium often exposing the lumen of the tubule directly to the tubular basement-membrane. In some areas necrotic cells lay adjacent to normal or near normal cells. The proximity of the necrotic tubular epithelium to the oedematous interstitial tissue and the peritubular capillaries, together with the finding of normal glomeruli is compatible with the theory of back diffusion as a mechanism for the oliguria.

Acute Kidney Injury↗
PubMed2000

STAND: a peer educator training curriculum for sexual risk reduction in the rural South. Students Together Against Negative Decisions.

BACKGROUND: The incidence of AIDS in rural areas continues to increase rapidly, with teenagers continuing to report high rates of sexual risk behaviors. Unfortunately, there is a dearth of effective HIV prevention programs targeting youth in rural settings where there are often formidable barriers to sex education programs. This paper describes a theoretically based intervention designed to meet the needs of rural youth. METHODS: Students Together Against Negative Decisions (STAND) is a 28-session teen peer educator training program implemented in a rural county in a southeastern state, promoting both abstinence and sexual risk reduction. The theoretical foundation of the curriculum includes both Diffusion of Innovations Theory and the Transtheoretical Model, focusing on both individual and community norm change. STAND is teen-centered and skills-based; activities focus on active learning. Educator trainees are selected on the basis of their opinion leadership within their peer group, resulting in a training group of both virgin and sexually active teens, balanced for gender and matched to the racial proportions of the school. RESULTS: Acceptance and participation in STAND suggest that adolescents in rural communities can be accessed through community-based interventions, that they are willing to participate in such intensive programs, and that they perceive the intervention as valuable and enjoyable. Moreover, the STAND program has thrived in a relatively conservative rural environment, and has had a positive impact on adolescents' sexual risk taking. Results from a pilot study showed significantly greater increases in condom use self-efficacy (16% vs a 1% decrease among controls) and in consistent condom use (+28% vs +15%). Adolescent trainees also reported a sevenfold larger increase in condom use (+213% vs +31%) and a 30% decrease in unprotected intercourse compared to a 29% increase among controls. CONCLUSIONS: STAND represents a new genre of HIV prevention program, one that utilizes complementary theoretical models to develop a program that targets both individual- and community-level change for rural adolescents.

Adolescent↗
PubMed1977

Divalent cation binding to phospholipids: an EPR study.

Divalent cation association to sonicated phospholipid liposomes has been examined with electron paramagnetic spectroscopy. Spectra were obtained suggesting that, in some cases, divalent cations associated with acidic phospholipid head groups are highly mobile. Using the amplitude of its characteristic sextet signal as a measure of free Mn(H2O)+6+, the apparent affinities of cardiolipin and phosphatidylserine for Mn2+ were measured as a function of monovalent electrolyte. Monovalent cations having smaller nonhydrated radii were more effective in displacing Mn from the phospholipids. Under conditions of low divalent cation concentrations, it is shown that the Gouy-Chapman diffuse double layer theory predicts a Mn-affinity (KA) inversely proportional to the square of monovalent salt concentration. Although this relationship was closely obeyed for Mn binding to cardiolipin, the fall-off in KA with added sodium chloride was slower in the cases of Mn binding to phosphatidylserin or phosphatidic acid. When phosphatidylcholine or cholesterol was incorporated into mixed vesicles along with a fixed amount of charged phospholipid, the Mn-binding strength was roughly proportional to the weight fraction of the latter. This result is consistent with: (1) a random dispersal of lipids in the bilayer, and (2) a 1:2 divalent cation-phospholipid interaction.

Binding Sites↗
PubMed1981

Comparison of the action of La3+ and Ca2+ on contraction threshold and other membrane parameters of frog skeletal muscle.

The influence of La3+ on contraction threshold, on membrane input resistance, and on action potential parameters was investigated in fibers of the sartorius muscle of the frog, and it was compared to that of Ca2+. The dependence of the contraction threshold on [La3+]0 in the presence of 0.5mM Ca3+ gave a sigmoid relationship between 0.1 and 5 mM La3+ with a shift of 23 to 34 mV to less negative potentials following a 10-fold increase of [La3+]0. The membrane input resistance was increased to various degrees in La-containing solutions, the increase being irreversible. The threshold of action potential generation was shifted to less negative potentials by 28 mV, and the duration at half-maximal amplitude was tripled by 0.5 mM La3+. In comparison a 10-fold increase of [Ca2+]0 in the range of 0.5 to 50 mM shifted the contraction threshold by 15 mV to less negative potentials. 17 mM Ca3+, a concentration having the same effect on contraction threshold as 0.5 mM La3+, increased membrane input resistance reversibly, shifted the action potential threshold by 16 mV to less negative potentials, and had only minor effects on action potential duration. Conduction was never blocked by Ca3+ as it was with 1 mM La3+. In the theoretical treatment, it is shown that the influence of Ca3+ on contraction threshold, but not that of La3+, may be accounted for by its screening and binding to negative surface charges according to the Gouy-Chapman theory of the diffuse double layer. To describe the action of La3+ on the contraction threshold an additional interaction of La3+ with neutral but amphoteric sites was considered.

Action Potentials↗
PubMed1985

Calcium at the surface of cardiac plasma membrane vesicles: cation binding, surface charge screening, and Na-Ca exchange.

Calcium binding and Na-Ca exchange activity were measured in isolated cardiac plasma membrane vesicles under various ionic conditions. A model was developed to describe the Ca binding characteristics of cardiac sarcolemmal vesicles using the Gouy-Chapman theory of the diffuse double layer with specific cation binding to phospholipid carboxyl and phosphate groups. The surface association constants used for Ca, Na, K and H binding to both of these groups were 7,0.63, 0.3 and 3800 M-1, respectively. This model allows the estimation of surface [Ca] under any specific ionic conditions. The effects of the divalent screening cation, dimethonium, on Ca binding and Na-Ca exchange were compared. Dimethonium had no significant effect on Ca binding at high ionic strength (150 mM KCl), but strongly depressed Ca binding at low ionic strength. Dimethonium had no significant effect on Na-Ca exchange (Na-inside dependent Ca influx) at either high or low ionic strength. These results suggest that the Ca sites of the Na-Ca exchanger are in a physical environment where they are either not exposed to or not sensitive to surface [Ca].

Animals↗
PubMed1990

Coupling of K(+)-gating and permeation with Ca2+ block in the Ca2(+)-activated K+ channel in Chara australis.

The patch-clamp technique is used here to investigate the kinetics of Ca2+ block in single high-conductance Ca2(+)-activated K+ channels. These channels are detected in the membrane surrounding cytoplasmic drops from Chara australis, a membrane which originates from the tonoplast of the parent cell. The amplitudes and durations of single channel events are measured over a wide range of membrane potential (-300 to 200 mV). Ca2+ on either side of the channel reduces its K+ conductance and alters its ion-gating characteristics in a voltage-dependent manner. This Ca2(+)-induced attenuation of conductance is analyzed using the theory of diffusion-limited ion flow through pores. Interaction of external Ca2+ with the channel's ion-gating mechanism is examined in terms of a kinetic model for ion-gating that includes two voltage-dependent gating mechanisms. The kinetics of channel block by external Ca2+ indicates that (i) external Ca2+ binds at two sites, a superficial site and a deep site, located at 8 and 40% along the trans-pore potential difference, (ii) the external vestibule cannot be occupied by more than one Ca2+ or K+, and (iii) the kinetics of Ca2+ binding at the deep site is coupled with that of a voltage-dependent gate on the external side of the channel. Kinetics of channel block by internal Ca2+ indicates that more than one Ca2+ is involved.

Calcium↗
PubMed1983

Transport in QSAR VIII. The influence of viscosity on transport rate constants in two-phase systems organic solvent-water.

In the system cyclohexane-water transport rate constants and partition coefficients of nine sulfonamides are determined at six temperatures. Kinematic viscosities of the organic and aqueous layer are determined at the same temperatures. Experimentally bilinear relationships between transport rate constants and partition coefficients are obtained in good agreement with theory. According to this theory convection and diffusion are important features in the overall transport process. Using the experimental data, the influence of viscosity on transport rate constants is established and expressed in terms of the relationships between maximum transport rate constants and viscosities. These relationships correspond with laminar flow at both sides of the interface.

Biological Transport↗
PubMed1986

Pathogenesis of osteoarthritis.

This article reviews the etiology and pathogenesis of osteoarthritis, particularly one of several current concepts concerning the possible central mechanisms regulating degradation of cartilage. According to this theory, degradation involves diffuse or focal exposure of the extracellular matrix to active neutral metalloproteinases, which then results in injury as well as initiation of repair processes. Diffuse matrix exposure is probably not a physiologic aberrancy but rather a pathologic result of either physical injury to local chondrocytes or inflammatory mediators.

Animals↗
PubMed1978

Membrane surface potential and the reactivity of the system II primary electron acceptor to charged electron carriers in the medium.

A hypothesis is proposed to explain the changes in the apparent rate constant for the reaction between the primary electron acceptor of System II situated in the thylakoid membrane and the artificial electron acceptors added in the medium. Dark oxidation rate of the primary acceptor by artificial electron acceptors was monitored by measuring the induction of chlorophyll fluorescence in the presence of an electron transport inhibitor, 3-(3',4'-dichlorophenyl)-1,1-dimethylurea, in spinach chloroplasts. The apparent rate constant for the oxidation changed widely when the medium pH or salt concentrations were varied, or ionic detergents were added. The change was quantitatively ascribed (1) to the change in the local concentration of electron acceptors at the thylakoid surface due to the electrical potential difference between the surface and the bulk aqueous phase (Gouy-Chapman diffuse double layer theory) and (2) to the situation whereby the apparent rate constant is determined with respect to concentration in the bulk phase. Values for the surface potential in the vicinity of System II were estimated from the change in the apparent rate constant under various conditions. The results closely agreed with those obtained previously from the rate constant of the dark step of the System II-dependent Hill reaction with ferricyanide (Itoh, S. (1978) Plant Cell Physiol. 19, 149--166). Application of the hypothesis to various reactions between the added ionic reagents and the endogenous components in the membrane or between the endogenous components situated in different parts of the membrane is discussed.

Chloroplasts↗
PubMed1979

Surface potential and reaction of the membrane-bound electron transfer components. II. Integrity of the chloroplast membrane and reaction of P-700.

Electrostatic characteristics of the membrane in the vicinity of P-700 were estimated by analyzing the salt and detergent effects on its reaction rate with ionic reagents using the Gouy-Chapman diffuse double layer theory in various preparations of chloroplasts. Upon disruption of thylakoid membranes by sonic treatment or by treatment with digitonin, the reaction rate markedly increased, while the estimated surface charge density became smaller. It was concluded that the membrane surface which determines the reaction rate between P-700 and the ionic reagents changed as the disruption of thylakoid structure. The outer thylakoid surface had more negative charges than the inner one. Changes in the electrical potential profile across the thylakoid membrane during the illumination were also discussed from these results.

Ascorbic Acid↗
PubMed1980

Electrostatic control of chloroplast coupling factor binding to thylakoid membranes as indicated by cation effects of electron transport and reconstitution of photophosphorylation.

1. Increase in electron transport rate and the decay rate of the 518 nm absorption change, induced by EDTA treatment, is prevented by cations. The order of effectiveness is C3+ > C2+ > C+. 2. In this respect methyl viologen is an effective divalent cation in addition to its action as an electron acceptor. 3. Complete cation irreversible EDTA-induced uncoupling occurs in the dark in 2 min. Light greatly stimulates the rate of uncoupling by EDTA. It is concluded that the uncoupling is due to release of coupling factor I from the thylakoid membrane. 4. Binding of purified coupling factor I to coupling factor I-depleted thylakoids can be achieved with any cation. The order of effectiveness is C3+ > C2+ > C+, reconstituted thylakoids are active in photophosphorylation regardless of the cation used for coupling factor I binding. 5. The marked difference in the concentration requirements for cation effects on 9-aminoacridine fluorescence yield and for prevention of uncoupling by EDTA indicate that coupling factor I and its binding site have a lower surface charge density than the net surface charge density of the thylakoid membrane. 6. It is concluded that coupling factor I binding only occurs when negative charges on coupling factor I and its binding site are electrostatically screened by cations. 7. Previously reported examples of uncoupling by low ionic conditions are discussed in relation to the basic concepts of diffuse electrical layer theory.

Cations↗
PubMed1980

Effects of surface potential and membrane potential on the midpoint potential of cytochrome c-555 bound to the chromatophore membrane of Chromatium vinosum.

The values of midpoint potential (Em) of cytochrome c-555 bound to the chromatophore membranes of a photosynthetic bacterium Chromatium vinosum was determined under various pH and salt conditions. After a long incubation at high ionic concentrations in the presence of carbonylcyanide m-chlorophenylhydrazone, which was added to abolish electrical potential difference between the inner and outer bulk phases of chromatophore, the Em value was almost constant at pH values between 4.0 and 8.4. With the decrease of salt concentration, the pH dependence of the Em value became more marked. Under low ionic conditions, Em became more positive with the decrease of pH. Addition of salt made the value more positive or negative at pH values higher or lower than 4.5, respectively. Divalent cation salts were more effective than monovalent cation salts in producing the positive shift of Em at pH 7.8. The Em value became more positive when the electrical potential of the inner side of the chromatophore was made more positive by the diffusion potential induced by the K+ concentration gradient in the presence of valinomycin. These results were explained by a change of redox potential at the inner surface of the chromatophore membrane, at which the cytochrome is assumed to be situated, due to the electrical potential difference with respect to the outer solution induced by the surface potential or membrane potential change. The values for the surface potential and the net surface charge density of the inner surface of the chromatophore membrane were estimated using the Gouy-Chapman diffuse double layer theory.

Bacterial Chromatophores↗
PubMed1977

Surface potential effects on metal ion binding to phosphatidylcholine membranes 31P NMR study of lanthanide and calcium ion binding to egg-yolk lecithin vesicles.

31P NMR of phosphatidylcholine (lecithin) from egg-yolk in sonicated vesicles has been measured in the presence of various ions. Addition of Ln3+ or Ca2+ shifted the 31P resonance of the phosphate groups of the outer surface of the vesicles. These shifts were measured at varied lanthanide or Ca2+ concentration at different ionic strengths obtained by addition of NaCl. The shifts induced by Tb3+ and Ca2+ have been analyzed using the theory of the diffuse double layer. Corrections were introduced for the effect of the ionic strength on the activities of the ions. The binding efficiency is shown to be controlled by the electrostatic potential produced by the bound cations at the membrane surface. This potential is slightly modified due to weak chloride binding. Binding constants have been derived.

Binding Sites↗
PubMed1979

The interaction of various lanthanide ions and some anions with phosphatidylcholine vesicle membranes. A 31P NMR study of the surface potential effects.

The interaction of various lanthanide ions with vesicles of phosphatidylcholine from egg yolk has been followed by 31P NMR at 30 degrees C. From known magnetic properties of these ions, separation of the paramagnetic shift into a pure contact and a pseudo-contact part was carried out. Binding curves for the contact contribution (F curves) were obtained from vesicles in solutions of sodium salts with monovalent anions over a wide concentration range. These curves should be insensitive to any conformational effects due to ion binding. Indication of a conformational change in the lipid head group at low ion binding was obtained by studying the ratio between the contact and the pseudo-contact contributions. Besides the adsorption of lanthanide ions, specific anion binding to the surface was introduced to account for the enhanced chemical shifts (Cl- < Br- < NO3-). The results were analyzed in terms of the theory for the diffuse double layer (Gouy-Chapman-Grahame) with equilibrium conditions for the adsorbing cations and anions. Simulations of the titration curves furnished parameters for the ion-lipid interactions. The synergism between the cations and anions follows from the potential effects. Comparison of results with lanthanide ions and Ca2+ indicates that the anion adsorption probably depends on the nature of the adsorbed cation. Lanthanide ion binding to L-glycerophosphorylcholine is not influenced by sodium salts. The binding constant for this complex is weaker than with phosphatidylcholine. The chemical shifts for the lanthanide ion complexes with these two phosphorus compounds seem to be about the same.

Anions↗