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Biomedical subjects

H Eyring

Publications and source records attributed to H Eyring.

At least 19 recordsLinked to original sources
PubMed1982

Biochemical and biophysical approaches to improving the anticancer effectiveness of Ara-adenine.

Ara-C at very low dosage has been reported to decrease the host toxicity of ara-AMP or ara-A in combination with 2'-deoxycoformycin, a potent adenosine deaminase inhibitor, while increasing the toxicity to intracerebral L1210 leukemia. The possibility of increasing the selectivity of ara-A by prior administration of ara-C is explored. The importance of deoxynucleoside kinases, some of which may be cancer-induced, in obtaining selective anticancer effects is discussed. The possibility of a conformational basis for the differing degrees of selectivity and activity of various novel arabinosyl nucleosides is evaluated. The levels of cyclic nucleotides, which have opposing effects on leukemia, may possibly be manipulated to interfere with the growth of cancer cells. Approaches to minimizing major metabolic distortions, such as the progressive accumulation of dATP associated with the use of potent adenosine deaminase inhibitors and which limit the therapeutic effects of ara-A, are proposed.

Adenosine Deaminase Inhibitors↗
PubMed1981

Optical activity and electronic absorption spectra of some simple nucleosides related to cytidine and uridine: all-valence-shell molecular orbital calculations.

The circular dichroism and electronic absorption of three simple model systems for cytidine and uridine have been measured to 190 nm. The molecular spectral properties (excitation wavelengths, oscillator strengths, rotational strengths, and polarization directions) and electronic transitional patterns were investigated by using wave functions of the entire nucleoside with the goal of establishing the reliability of the theoretical method. The computed electronic absorption quantities were shown to be in satisfactory agreement with experimental data. It was found that the computed optical rotatory strengths of the B2u and E1u electronic transitions and lowest observed n-pi transition are in good agreement with experimental values. Electronic transitions were characterized by their electronic transitional patterns derived from population analysis of the transition density matrix. The theoretical rotational strengths associated with the B2u and E1u transitions stabilize after the use of just a few singly excited configurations in the configuration interaction basis and, hypothetically, are more reliable as indicators of conformation in pyrimidine nucleosides related to cytidine.

3-Deazauridine↗
PubMed1981

Anesthetics and high-pressure interaction upon elastic properties of a polymer membrane.

Anesthetics expand cell membranes, and high pressures (about 10-15 MPa) antagonize the anesthetic action. It is also known that inhalation anesthetics expand elastomer membranes. The mechanism of pressure antagonism of anesthetic action on membrane expansion was investigated in the present study with Silastic membranes. Halothane increased the length of Silastic membrane (0.14% per kPa), with an accompanying decrease of Young's modulus (3.7.10(5) Newton/m2 per kPa). High pressure decreased the length of the membrane and increased Young's modulus. The magnitudes of the pressure effect on the length and Young's modulus of the Silastic membrane in the presence of the anesthetic were not identical with those observed in the absence of the anesthetic. In the presence of halothane at pressures common to clinical applications, the bulk modulus of the membrane decreased about 4.6-4.0%. These results suggest that the effects of pressure and anesthetic upon the elastomer may not be completely independent of each other.

Adsorption↗
PubMed1981

Reaction kinetics in living systems.

In this report we treat reaction rates, equilibrium theory, and irreversible thermodynamics as different aspects of a single discipline. In biological reactions the rate is ultimately controlled by enzymes and other proteins of complex structure and high molecular weight. The needed formalism can be placed in one-to-one correspondence with appropriate electrical and mechanical networks. An enzyme molecule has zwitter ions anchored in the polypeptide chain, which enable it to distort the substrate by electrostatic polarization. Water weakens the induced or existing polar bonds and so speeds reaction. Several biological processes, such as luminescence, catalysis, nerve excitation, and anesthesia, in which enzymatic reactions play a major part are discussed from this point of view. We also have discussed the energy consumption and coupling effect in living systems. It is likely that a small fraction of bonds can become energy rich through the process of quenching and that unsymmetrical barriers in biological systems act like transistors in making the driving forces more efficient by a valve effect.

Anesthetics↗
PubMed1980

Pressure-anesthetic antagonism on the phase separation of non-ionic surfactant micelles.

An aqueous solution of non-ionic surfactants becomes suddenly turbid when heated to a critical temperature, known as the cloud point, and concomitantly expands the volume. The volume expansion is caused by release of structured water molecules from the hydrophilic polyoxyethyelene moieties. Inhalation anesthetics decreased the cloud-point temperature of hexaoxyethylene dodecyl ether micelles. The concentrations of methoxyflurane, halothane and enflurane causing a 1 degree C depression of the cloud-point temperature were 0.51, 0.71 and 0.78 mmolal, respectively. Hydrostatic pressure increased the cloud-point temperature in the absence and presence of the anesthetics. The change of the apparent molal volume at the cloud point was estimated to be 2.2 cm3/mol in the absence of anesthetics. This value decreased in the presence of the anesthetics, dose dependently. The results indicate that the anesthetics favor dehydration of the hydrophilic surface of the non-ionic surfactant micelles.

Anesthetics↗
PubMed1980

Surface activities of tertiary amine local anesthetics at air/water interface in the presence and absence of phospholipid monolayers.

Adsorption of procaine and tetracaine to the dipalmitoyl phosphatidylcholine monolayers at the air/water interface is analyzed in terms of two types of interaction: (1) between the phospholipid molecules and the ligand molecules, and (2) among the ligand molecules themselves. The presence of the phospholipid monolayer increases the surface concentration of the anesthetics. The interaction energy, omega AB, between the phospholipid molecules and the anesthetic molecules at the interface accounts for this excess adsorption. The values were --2.95 kT for procaine and --2.99 kT for tetracaine where k is the Boltzmann constant and T = 298 K. The adsorption of the local anesthetics to the interface was cooperative. The interaction energy, omega AA, between the anesthetics molecules on the surface determines the cooperativity. The values were --0.056 kT for procaine and --0.397 kT for tetracaine, where T = 298 K. This parameter determines the slope of the curve plotted relating the surface concentration (gamma) and the logarithm of the bulk concentration (log C). When (omega AA/kT) greater than or equal to 1, the adsorption follows the phase-transition. A parameter KA, which is related to the difference of the free energy of anesthetics between the surface and the bulk molecules, locates the take-off point of the adsorption curve at the log C axis. The values were 2.15 x 10(3) for procaine and 7.00 x 10(3) for tetracaine. In spite of the general assumption that the difference in the clinical potency among local anesthetics are attributable to their lipid solubility, the present results showed that the phospholipid-anesthetic interaction energies for procaine and tetracaine were similar. The larger surface concentration of tetracaine than procaine at the same bulk concentration was due to the combined effect of KA and omega AA. KA represents the tendency of the anesthetic molecules to escape from the hydrogen-bonded water phase, and omega AA determines the cooperativity factor causing these molecules to aggregate at the interface. It was also observed that the charged forms of the anesthetics have non-zero surface activities.

Adsorption↗
PubMed1980

Wavelength regulation in rhodopsin: effects of dipoles and amino acid side chains.

The effects of dipoles and aromatic amino acid side-chain models on the absorption and optical activity of the rhodopsin chromophore were calculated by using perturbation theory, and the results were compared with those of a Pariser-Parr-Pople calculation for the unperturbed system. The interaction was assumed to result from purely electrostatic interactions. It was concluded that the side chains of phenylalanine and tryptophan should have no important effects. However, the charge separation in tyrosine is sufficient to cause substantial electrostatic perturbation; in fact, the effect of tyrosine is large enough to approximately many of the spectral properties of rhodopsin quantitatively. This is encouraging because the use of aromatic amino acid side-chain analogs probably provides a better physical model than the use of isolated full charges, except in the case of the counterion to the protonated Schiff base.

Chemical Phenomena↗
PubMed1979

Antagonism between high pressure and anesthetics in the thermal phase-transition of dipalmitoyl phosphatidylcholine bilayer.

The antagonizing action of hydrostatic pressure against anesthesia is well known. The present study was undertaken to quantitate the effects of hydrostatic pressure and anesthetics upon the phase-transition temperature of dipalmitoyl phosphatidylcholine vesicles. The drugs used to anesthetize the phospholipid vesicles included an inhalation anesthetic, halothane, a dissociable local anesthetic, lidocaine and an undissociable local anesthetic, benzyl alcohol. All anesthetics decreased the phase-transition temperature dose-dependently. In the case of lidocaine, the depression was pH dependent and only uncharged molecules were effective. The application of hydrostatic pressure increased the phase-transition temperature both in the presence and the absence of anesthetics. The temperature-pressure relationship was linear over the entire pressure range studied up to 340 bars. Through the use of Clapeyron-Clausius equation, the volume change accompanying the phase-transition of the membrane was calculated to be 27.0 cm3/mol. Although the anesthetics decreased the phase-transition temperature, the molar volume change accompanying the phase-transition was not altered. The anesthetics displaced the temperature-pressure lines parallel to each other. The mole fraction of the anesthetics in the liquid crystalline membrane, calculated from the van't Hoff equation, was independent of pressure. This implies that pressure does not displace the anesthetics from the liquid membrane, and the partition of these agents remains constant. The volume change of the anesthetized phospholipid membranes is entirely dependent upon the phase-transition and not on the space occupied by the anesthetics.

Anesthetics↗
PubMed1979

Hydrophilic region of lecithin membranes studied by bromothymol blue and effects of an inhalation anesthetic, enflurane.

A pH-indicator dye, bromothymol blue, was used to probe the hydrophilic surface of dimyristoyl-, dipalmitoyl-, and distearoylphosphatidylcholine bilayer vesicles. The apparent pK of the surface-adsorbed dye was larger than the bulk pK value. The contribution of the choline positive charge on the dissociation constant of the dye adsorbed on the vesicle surface was estimated by screening the charge interaction with 2 M KCl. The effective surface potentials interacting with the dye were thus estimated to be 33.2, 45.6, and 46.8 mV, respectively, for the dimyristoyl-, dipalmitoyl-, and distearoylphosphatidylcholine vesicles. From the differences between the obtained effective potentials and the calculated surface potentials of the charge-determining plane of the choline head, the distances between the prototropic part of the dye and the choline charge-determining plane were estimated to be 10.5, 8.0, and 7.8 A, respectively. These values were obtained at 25 degrees C; the dimyristoylphosphatidylcholine membrane was in the liquid-crystalline phase and the other two were in the solid gel phase. Addition of an inhalation anesthetic, enflurane, decreased the distance in the dimyristoylphosphatidylcholine vesicles and increased the distance in the dipalmitoyl- and distearoylphosphatidylcholine vesicles. The increase of precessional motion of choline head by the inhalation anesthetic is apparently responsible for the changes.

Bromthymol Blue↗
PubMed1979

Conformation of nucleosides: circular dichroism study on the syn-anti conformational equilibrium of 2-substituted benzimidazole nucleosides.

The solution conformations of 2-substituted derivatives of 1-(beta-D-ribofuranosyl)benzimidazole have been determined by circular dichroism spectroscopy in aqueous solutions. It is shown that analogs with methyl, amino, or methylamino substituents at position 2 of the benzimidazole ring (position 8 of the purine ring) have predominantly anti conformations, whereas analogs with chloro, aza, methoxy, or methylmercapto substituents have predominantly syn conformations. The preferred solution conformations of the benzimidazole nucleosides and analogous purine nucleosides are compared. The results demonstrate that the replacement of nitrogen by carbon at position 3 of the purine ring of purine (beta) nucleosides leads to important conformational consequences, which are strengthened or neutralized by substituents at position 8 of the purine ring.

Benzimidazoles↗
PubMed1979

Interferon induction: a conformational hypothesis.

The ability of polynucleotides or polynucleotide duplexes such as poly(I).poly(C) to induce interferon production is proposed to depend on the existence of certain stable glycosidic orientations. It appears that a slight increase in instability of 1--3 kcal/mole (1 cal = 4.184 J) in the conformational regions near 20 degrees, 80 degrees, and 160 degrees leads to a loss of potency with respect to interferon induction. Thus, it is proposed that, for a polynucleotide to exist in the overall conformation necessary for interferon induction, stability of glycosidic orientations near 20 degrees, 80 degrees, and 160 degrees may be necessary to confer flexibility and activity on polynucleotide structures. This proposed conformational triad of stable conformational regions essential to interferon induction is based on the results of conformational energy calculations of the glycoside rotational profiles of adenosine, 7-deazaadenosine, inosine, and 7-deazainosine, as well as the conformational properties of other purine nucleoside analogs, and on inferences derived from calculations about the conformational effect in polynucleotides of removing the 2'-OH group.

Adenosine↗
PubMed1978

A conformational basis for the antiviral inactivity of tetrazole ribonucleosides.

The antiviral activity of ribavirin has been associated with its inhibition of the enzyme, IMP dehydrogenase. The ability of ribavirin to inhibit this enzyme has previously been shown to be related to its stability in the high anti glycosidic conformation. The antiviral effectiveness of several analogs of ribavirin have been investigated recently. The evidence indicates their antiviral effectiveness is related to their stability in the high anti conformation. Recently the disposition of purine analogs that pass through the inosine monophosphate branch point has been investigated. The results of these studies are consistent with the concept that the conversion of IMP to XMP requires the high anti conformation and that the conversion of IMP to adenylosuccinate requires some other conformation, possibly the anti conformation.

Azoles↗
PubMed1978

Ion flow through a membrane: concentration and current responses to a step potential change.

Solutions of the simplified time-dependent Nernst-Planck electrodiffusion equations for various membrane models under the influence of a step voltage change are presented. Comparison of the results for a membrane with continuous sites to those for membranes with two, three or five intermediate sites shows little difference either qualitatively or quantitatively in the concentration of the diffusible ion inside the membrane, although some quantitative differences are evident in the calculated currents.

Electric Conductivity↗
PubMed1978

Ion flow through a membrane: effect of chemical reaction on time dependence.

The membrane model previously described [Hays, T.R., Buckwalter, C.Q., Lin S.H. & Eyring, H. (1978) Proc. Natl. Acad. Sci. USA 75, 1612-1615] for ion flow through a membrane is expanded to include the effect of binding of the mobile ion at the occupiable sites in the membrane. Two different effects were investigated: alteration of the association-dissociation rates at constant equilibrium constant and alteration of the equilibrium constant at constant dissociation constant. Increasing the rates of association and dissociation initially causes an increased slowing of the relaxation to the final steady state, though ultimately the curves for the faster rates cross those for the slower states. Increasing the equilibrium constant causes a greater delay in the relaxation curve, with the curves for different equilibrium constants not crossing. Overall, the effect of binding is not very great unless the equilibrium constant for binding is quite large.

Binding Sites↗
PubMed1977

Reversible and irreversible inhibition by anesthetics of the calcium-induced luminescence of aequorin.

The actions of various kinds of so-called membrane-stabilizing drugs on Ca2+-induced flash intensity of purified aequorin, a photoprotein obtained from Aequorea aequorea, were examined. All drugs used in this experiment, including inhalational anesthetics, tetracaine, chlorpromazine, and morphine, depressed flash intensity, and the inhibition increased with time. The inhibition followed a mixture of reversible and irreversible kinetics. A method of analyzing irreversible kinetics is presented. The dissociation constants for reversible inhibition and the rate constants for irreversible inhibition are presented for each agent.

Aequorin↗
PubMed1977

Circular dichroism of adenosine dinucleotides.

The circular dichroism and absorption spectra of (3'-5')ApA, (5'-5')AppA, and (5'-5')ApcpA [diadenosine(5'5') pyrophosphonate] under various ionic coditions and at various temperatures are reported. Temperature studies reveal that under the same ionic strength and solvation conditions the probability of base-base interaction is ApA greater than AppA greater than ApcpA. It is found that increasing the molar refractivity of the solvent decreases the base-base interaction for both ApA and AppA and that both compounds proceed to a monomeric state in solvents of high molar refractivity. Solvent effect studies also indicate that a major percentage of the driving force for the base-base interaction can be accounted for by London dispersion forces. Low ionic strength appears to favor the base-base interacted conformation. All compounds tend toward the same noninteracted form at high temperatures. Plots of [theta]lambda against X (where X is an experimental parameter) were constructed in order to obtain information concerning which transitions might be undergoing oscillator coupling. To a first approximation, transitions coupled to each other should have very similar deta[theta]lambda/detaX for the experimental range of X. Applying this technique to the experimental data yielded information concerning possible transition coupling.

Adenine Nucleotides↗