Admittance change of squid axon during action potentials. Change in capacitive component due to sodium currents. Since the discovery of Cole and Curtis (1938. Nature (Lond.). 142:209 and 1939. J. Gen. Physiol. 22:649) that the imaginary components, i.e., capacitive and inductive components, of the admittance of squid axon membrane remained unchanged during the action potential, there have been numerous studies on impedance and admittance characteristics of nerves. First of all, it is now known that the dielectric capacitance of the membrane is frequency dependent. Second, the recent observation of gating currents indicates that dipolar molecules may be involved in the onset of ionic currents. Under these circumstances, the author felt it necessary to reinvestigate the membrane admittance characteristics of nerve axons. The measurements by Cole and Curtis were performed mainly at 20 kHz, indicating that their observation was limited only to the passive membrane capacitance. To detect the change in the capacitive component during the action potential, we performed transient admittance measurements at lower frequencies. However, the frequency range of the measurements was restricted because of the short duration of the normal action potential. In addition, a change in the inductive component obscured the low frequency behavior of the capacitance. To use wider frequency range and simplify the system by eliminating the inductive component, the potassium current was blocked by tetraethyl ammonium, and the increase in the capacitive component was reinvestigated during the long action potential. The admittance change under this condition was found to be mostly capacitive, and conductance change was very small. The increase in the capacitive component was from 1.0 to 1.23 muF/cm2.


On phasing the small-angle x-ray diffraction pattern from nerve myelin. Using a method they developed, Stamatoff and Krimm (1976) have phased swelling data from nerve myelin. Although most phases agree with those I determined previously, there are a few differences. In this letter the two different phasings, theirs and my own, are used to compute the corresponding electron-density profiles, which are then closely compared. For both phasings, small differences are seen in the membrane profile at different degrees of swelling. The explanation that these differences are due simply to errors in measuring intensity is shown to be quite improbable; thus the differences indicate a real change in the profile. It follows that the assumption of a constant membrane profile appears to be invalid in the case of myelin swelling. The differences therefore are assumed to indicate a real change in the profile. It is shown that this change can be attributed consistently to interdigitation of protein molecules at the surfaces of neighboring membranes, while the membrane structure itself remains unchanged. In this case, valid phases still can be determined by swelling, but the phases determined by Stamatoff and Krimm are not valid.


Time dependence of triplet-singlet excitation transfer from compact poly rA to bound dye at 77 K. The nonexponential phosphorescence decay of a highly folded form of poly-riboadenylic acid (poly rA) with noncovalently bound dye is explained by a novel application of a well-known theory of electronic excitation transfer based on the Förster mechanism. This theory, originally used to describe singlet-singlet energy transfer from donor molecules to an acceptor in a solution, is here applied to the transfer of triplet excitation from the adenine (in poly rA) to the singlet manifold of either of the bound dyes, ethidium bromide or proflavine. New experimental data are presented that allow straight-forward theoretical interpretation. These data fit the form predicted by the theory, U(t) exp(-Bt1/2), where U(t) is the decay of the poly rA phosphorescence in the absence of dye, for a range of relative concentrations of either dye. The self-consistency of these theoretical fits is demonstrated by the proportionality of B to the square root of the Förster triplet-singlet overlap integrals for transfer from poly rA to each of the dyes, as demanded by the theory. From these self-consistent values of B, the theory enables one to deduce the mean packing density of nucleotides in this folded poly rA, which we estimate to be approximately 1 nm-3. We conclude that some variations of the method described here may be useful for deducing packing densities of nucleotides in other compact nucleic acid structures.


A systems-theory approach to the analysis of multiexponential fluorescence decay. A mathematical model of the fluorescence decay experiment based on linear systems theory is presented. The model suggests an experimental technique that increases the probability of correctly determining the decay constants of a multicomponent system. The use of moment methods for data analysis improves accuracy by combining information obtained from several discrete experiments. Examples are presented to show that the analysis of a three component system composed of known standards is improved as the number of experimental determinations is increased from one to four. The discrete measurements are made by changing the excitation and emission wavelengths.


Light scattering of normal human lens I. Application of random density and orientation fluctuation theory. Light-scattering intensities in the I parallel and I+ mode were obtained on thin sections of three human lenses. Random density and orientation fluctuation theory, without cross correlation, was employed to evaluate light-scattering parameters. Both the density correlation distances, as well as the orientation correlation distances, were related to structural elements in the lens fiber cell that have been observed by other investigators with different techniques. The magnitude of these fluctuations were evaluated, and it was demonstrated that the density fluctuations are the main contributors to light scattering in normal human lenses. Changes in the light-scattering parameters were evaluated as a function of position within the lens. The changes observed agree with the biochemical data in the literature that reflects that an aging process occurs when one proceeds from the periphery of the lens toward the center.


The orientational freedom of molecular probes. The orientation factor in intramolecular energy transfer. The measurement of the efficiency of Förster long-range resonance energy transfer between donor (D) and acceptor (A) luminophores attached to the same macromolecular substrate can be used to estimate the D-A separation, R. If the D and A transition dipoles sample all orientations with respect to the substrate (the isotropic condition) in a time short compared with the transfer time (the dynamic averaging condition), the average orientation factor less than K2 greater than is 2/3. If the isotropic condition is not satisfied but the dynamic averaging condition is, upper and lower bounds for less than K2 greater than, and thus R, may be obtained from observed D and A depolarizations, and these limits may be further narrowed if the transfer depolarization is also known. This paper offers experimental protocols for obtaining this reorientational information and presents contour plots of less than K2 greater than min and less than K2 greater than max as functions of generally observable depolarizations. This permits an uncertainty to be assigned to the determined value of R. The details of the D and A reoreintational process need not be known, but the orientational distributions are assumed to have at least approximate axial symmetry with respect to a stationary substrate. Average depolarization factors are derived for various orientational distribution functions that demonstrate the effects of various mechanisms for reorientation of the luminophores. It is shown that in general the static averaging regime does not lend itself to determinations of R.


Energy transfer in lipid bilayers.

Energy transfer in lipid bilayers. The quenching of fluorescence due to energy transfer between a dilute, random array of donor and acceptor chromophores in lipid bilayer was measured and compared to theoretical expressions developed to predict the decrease in emission intensity under these circumstances. The observed intensity was found to be the same function of quencher concentration in both planar, multilamellar dispersions and small, spherical vesicles. The degree of quenching was accurately predicted by a simple relation derived in this paper, as well as a more complex equation previously developed by Tweet, et al. The results suggest that significant quenching may be observed even when the average donor-acceptor separation exceeds the Förster critical distance by severalfold. Application of these results to problems of current interest in membrane research are discussed.


Experimental confirmation of calculated phases and electron density profile for wet native collagen. An experimental procedure is developed to phase the reflections obtained in x-ray diffraction investigations of collagen in native wet tendons. Phosphotungstic acid was used for isomorphous addition in phase determination and was located by electron microscopy. Structure factors (with phases) were obtained from the electron microscopy data for the heavy metal. Structure-factor magnitudes for collagen with and without the heavy metal were obtained from the x-ray diffraction data. The first 10 orders were investigated. Standard Argand diagrams provided two solutions for each of these, except the weak sixth order. In each case, one of the two possible solutions agrees well with the phases proposed on theoretical grounds by Hulmes et al. The present results suggest that their other proposed phases are probably correct. An electron density profile along the unit cell of the fibril is presented that shows a distinct step, as expected on the basis of the hole-overlap model. The overlap region is 48% of the length of the unit cell.


Cytochrome f function in photosynthetic electron transport. The questions of whether the stoichiometry of the turnover of cytochrome f, and the time-course of its reduction subsequent to a light flash, are consistent with efficient function in noncyclic electron transport have been investigated. Measurements were made of the absorbance change at the 553-nm alpha-band maximum relative to a reference wavelength. In the dark cytochrome f is initially fully reduced, oxidized by a 0.3-s flash, and reduced again in the dark period after the flash. In the presence of gramicidin at 18 degrees C, the dark reduction was characterized by a half-time of 25-30 ms, stoichiometries of cytochrome f:chlorophyll and P700:chlorophyll of 1:670 and 1:640, respectively, and a short time delay. The time delay in the dark reduction of cytochrome f, which is expected for a component in an intermediate position in the chain, becomes more apparent in the presence of valinomycin and K+. Under these conditions the half-time for cytochrome f dark reduction is 130-150 ms, and the delay is approximately equal to 20 ms. The measured value for the activation energy of the dark reduction of cytochrome f (11 +/- 1 kcal/mol) is the same as that for noncyclic electron transport in steady-state light. A sigmoidal time-course for the reduction of cytochrome f has been calculated for a simple linear electron transport chain. The kinetics for reduction of cytochrome f predicted by the calculation, in the presence of valinomycin and K+, are in reasonably good agreement with the experimental data. There is an appreciable amount of data in the literature to document complex properties of cytochrome f after illumination with short flashes, and evidence for complexity in a light-minus-dark transition. The data presented here, obtained after a long flash that should establish steady-state conditions, either fulfill or are consistent with the basic criteria for efficient function of cytochrome f in noncyclic electron transport.


Quantitative simulation of endplate currents at neuromuscular junctions based on the reaction of acetylcholine with acetylcholine receptor and acetylcholinesterase. Two kinetic models are introduced which predict amplitudes and time-courses of endplate currents and miniature endplate currents at neuromuscular junctions, at both normal and acetylcholinesterase-inhibited endplates. Appropriate differential rate equations reflecting interactions of acetylcholine with acetylcholine receptor and with esterase, diffusion of acetylcholine both within and from the synaptic cleft, and cooperativity between receptor site occupancy and ion channel opening are solved. Acetylcholine release into the cleft is assumed to be instantaneous. The simpler homogeneous reaction space model accurately predicts decay phase time constants are inaccurate. The two-reaction space model predicts amplitudes and time constants within a factor of two of those observed experimentally. The simulations indicate that the amplitudes and time-courses are primarily determined by the chemical reaction rates that characterize acetylcholine interactions with receptor and esterase and that these interactions occur under nonequilibrium conditions. Approximately 50% of the total ion channels in the initial reaction space are predicted to be opened at the peak endplate current. The cooperative opening of ion channels by acetylcholine requires that acetylcholine be introduced into the cleft in discrete, concentrated elements. Virtually all the open channels are confined to the initial reaction space, although acetylcholine-bound receptor sites can be much more widely distributed.


Impedance analysis of a tight epithelium using a distributed resistance model. This paper develops techniques for equivalent circuit analysis of tight epithelia by alternating-current impedance measurements, and tests these techniques on rabbit urinary bladder. Our approach consists of measuring transepithelial impedance, also measuring the DC voltage-divider ratio with a microelectrode, and extracting values of circuit parameters by computer fit of the data to an equivalent circuit model. We show that the commonly used equivalent circuit models of epithelia give significant misfits to the impedance data, because these models (so-called "lumped models") improperly represent the distributed resistors associated with long and narrow spaces such as lateral intercellular spaces (LIS). We develop a new "distributed model" of an epithelium to take account of these structures and thereby obtain much better fits to the data. The extracted parameters include the resistance and capacitance of the apical and basolateral cell membranes, the series resistance, and the ratio of the cross-sectional area to the length of the LIS. The capacitance values yield estimates of real area of the apical and basolateral membranes. Thus, impedance analysis can yield morphological information (configuration of the LIS, and real membrane areas) about a living tissue, independently of electron microscopy. The effects of transport-modifying agents such as amiloride and nystatin can be related to their effects on particular circuit elements by extracting parameter values from impedance runs before and during application of the agent. Calculated parameter values have been validated by independent electrophysiological and morphological measurements.


An approach for time-resolved x-ray scattering. Recent biological optical spectroscopic studies have correlated discrete spectroscopic states with biological function in several systems. One of the challenges of molecular biophysics is to correlate structural changes with these spectroscopic states. From small-angle x-ray scattering one can obtain a key structural parameter, the radius of gyration of solubilized proteins. The method described in this paper would permit determination small changes in the radius using polychromatic synchrotron radiation. The high flux of the storage ring combined with an enhancement factor of approximately 10(4), obtained by removing the requirement for monochromatic radiation, will permit determining the radius on a millisecond time scale. Unlike energy-dispersive methods, this method would use all available energies over a wide range of angles.


Amide hydrogen exchange rates of peptides in H2O solution by 1H nuclear magnetic resonance transfer of solvent saturation method. Conformations of oxytocin and lysine vasopressin in aqueous solution. The NH exchange rates in aqueous media of oxytocin and 8-lysine vasopressin (LVP) have been measured by using transfer of solvent saturation method. The data are consistent with a "highly motile" dynamic equilibrium between folded and highly solvated conformations. The highly-motility limit applies to the exchange of NH hydrogens of oxytocin and LVP. Folded structures are more prevalent in oxytocin than in LVP. Partial shielding is indicated for peptide hydrogens of Asn5 and perhaps also Cys6 of oxytocin and for Cys6 of LVP. It is tentatively proposed that the folded conformation of oxytocin in aqueous media may contain a parallel beta-structure in the tocinamide ring consisting of two hydrogen bonds: one between the Tyr2 C = O and Asn5 peptide NH as originally proposed for the preferred conformation of oxytocin in dimethyl sulfoxide (D. W. Urry and R. Walter), and the second between he Cys1 C = O and the Cys6 NH. In LVP the hydrogen bond between the Tyr2 C = O and Asn5 peptide NH appears to be absent. The acylic tripeptide sequences (-Pro-X-Gly-NH2) of both hormones appear to be predominantly solvated. The second-order rate constants for acid catalyzed exchange of the primary amide hydrogens of Gln4, Asn5, and Gly9 of oxytocin are consistently greater for the trans NH than for the corresponding cis NH. This observation can be rationalized in terms of mechanisms involving protonation of either the amide oxygen, or the amide nitrogen, but with limited rotation about the C - N bond.


Prediction of beta-turns.

Prediction of beta-turns. An automated computer prediction of the chain reversal regions of globular proteins is described herein using bend frequencies and beta-turn conformational parameters (Pt) determined from 408 beta-turns in 29 proteins calculated from x-ray atomic coordinates. The probability of bend occurrence at residue i is pt = fi X fi+1 X fi+2 X fi+3 with the average bend probability less than Pt greater than = 0.55 X 10(-4). Tetrapeptides with pt greater than 0.75 X 10(-4) ( approximately to 1.5 X less than pt greater than) as well as less than Pt greater than 1.00 and less than Pa greater than less than less than Pt greater than greater than less than P beta greater than are selected by the computer as probable bends. Adjacent probable bends (i.e., 11-14, 12-15, 13-16) are compared pairwise by the computer, and the tetrapeptide with the higher pt value is predicted as a beta-turn. The percentage of bend and nonbend residues predicted correctly for 29 proteins by this computer algorithm is %t+nt = 70%, whereas 78% of the beta-turns were localized correctly within +/- 2 residues. The average beta-turn content in the 29 proteins is 32%, with helical proteins having fewer bends (17%) than beta-sheet proteins (41%). Three proteins having iron-sulfur clusters were found with the highest percentages of beta-turns: Chromatium high potential iron protein (65%), ferredoxin (57%), and rubredoxin (65%). Finally, the bend frequencies at all 12 positions from 457 beta-turns in 29 proteins (Chou and Fasman, 1977) were used to test the effectiveness of predicting bends using 2, 4, 8, and 12 residues as well as different cut-off pt values. The computer analysis showed that 1.25 less than pt greater than to be the best cut-off yielding 70% accuracy in %t+nt for 4 residues and %t+nt = 73% for 12 residues in predicting the bend and nonbend regions of proteins.


Conservation of chain reversal regions in proteins. Using the bend frequencies based on 29 proteins in the previous paper (Chou and Fasman, 1979), beta-turn probability profiles were calculated for the C-peptides of 10 mammalian proinsulins, for 7 proteinase inhibitors, and for 12 species of pancreatic ribonucleases. Beta-turn correlation coefficient matrix tables were also computed to obtain the statistical mean between 45 pairs of proinsulin C-peptides, less than Ct greater than = 0.57 +/- 0.31; 21 pairs of proteinase inhibitors, less than Ct greater than = 0.73 +/- 0.13; and 66 pairs of ribonucleases, less than Ct greater than = 0.83 +/- 0.08. Despite relatively low sequence conservation in these three sets of proteins, beta-turns were predicted to be highly conserved: 33% sequence vs. 78% bend for the proinsulins, 20% sequence vs. 85% bend for the proteinase inhibitors, and 65% sequence vs. 92% bend for the ribonucleases. These results suggest that chain reversal regions play an essential role in keeping the active structural domains in hormones and enzymes intact for their specific biological function.


The undamped and damped series elastic components of a vascular smooth muscle. Small arterial resistance vessels (internal diameter about 175 micrometer) have been mounted on a myograph that enabled their wall tension, T, and internal circumference, L, to be measured and controlled with a time resolution of about 4 ms. Maximally activated vessels were subjected to isometric releases (step changes in L) and isotonic releases (step changes in T) of varying extents and at two different temperatures (27 degree C and 37 degree C). The recovery from an isometric release was monotonic and did not include the two phases seen in skeletal muscles. The isotonic release response did, however, contain a velocity transient lasting about 150 ms: the velocity immediately after the release was about six times the steady shortening velocity. The form of both the isometric and isotonic release responses and their dependence on the extent of release can be explained in terms of a modified Hill model in which the "series elastic component" (SEC) is replaced by the series combination of an undamped-SED (that is, an undamped elastic element) and a damped-SEC (a Voigt element). Although the initial response to both types of release was independent of temperature, all stages of subsequent responses were temperature dependent, with Q10's in the range 1.5 - 2.0. The results suggest that the responses to isotonic and isometric releases may in part be due to active processes.


The rotational diffusion of cytochrome b5 in lipid bilayer membranes. Influence of the lipid physical state. A derivative of the integral membranes protein, cytochrome b5, has been prepared in which the native heme group has been replaced by the structurally similar rhodium(III)-protoporphyrin IX. This metalloporphyrin has a finite triplet yield with a single exponential decay time of 22 microsecond in water. After insertion of the metalloporphyrin into the protein, its triplet-state decay becomes strongly nonexponential with at least three equal amplitude components with time constants varying over a range of 100. The derivatized protein has been incorporated into unilamellar liposomes prepared from dimyristoyllecithin, and the rotational diffusion of the protein in the lipid bilayer has been studied at temperatures above and below the lipid phase transition temperature via triplet absorbance anisotropy decay. The anisotropy decay curves are biphasic both above and below the lipid phase transition. The rotational diffusion constant is found to be 2.4 X 10(5) s-1 at 35 degrees C, and 1.1 X 10(4) s-1 at 10 degrees C, both being calculated from the fast decay component. The ratio of the limiting anisotropy to the initial anisotropy is 0.6 at both temperatures. This implies a cone of restricted motion of 34 degrees for the protein in the bilayer.


Interpretation of the absorption and circular dichroic spectra of oriented purple membrane films. The absorption and circular dichroic (CD) spectra of purple membrane films in which the plane of the membranes is oriented perpendicular to the incident beam are compared with the solution spectra. This enables one to relate structural features of the purple membrane to a coordinate system as defined by a normal to the membrane plane and two mutually perpendicular in-plane axes. The film and solution absorption spectra were similar except for a relative depression in the 200 - 225-nm region of the film spectrum. However, the CD spectra showed significant differences in the visible region, where the biphasic band in the solution spectrum was replaced by a single positive band at 555 nm in the film spectrum and in the far ultraviolet region, where the 208-nm band was deleted from the film spectra of the native and regenerated membranes. Moreover, a small shoulder occurred at 208 nm in the film spectrum of the bleached membrane. The near ultraviolet spectra also showed differences, whereas the 317-nm band remained essentially the same for both spectra. Based on excitonic interpretations of the visible and far ultraviolet spectra the following conclusions were reached: (a) a relatively strong in-plane monomeric interaction occurs between te retinyl chromophore and apoprotein; (b) the helical axes of the native and regenerated membrane proteins are oriented primarily normal to the membrane plane; and (c) the helical axes of the bleached membrane proteins are tilted more in-plane than the axes of the native or regenerated membrane. Additional conclusions were that an interaction occurs between an in-plane magnetic dipole moment of the retinyl chromophore and probably an in-plane electric dipole moment of a nearby aromatic amino acid(s), and that although the membrane is anisotropic with respect to coupling between electric and magnetic moments of the aromatic amino acids, the transition dipole moments of the aromatic amino acids are not preferentially oriented in either direction.


Modification of ion transport in lipid bilayer membranes in the presence of 2,4-dichlorophenoxyacetic acid. II. Suppression of tetraphenylborate conductance and changes of interfacial potentials. It has been shown that the blocking of negatively charged tetraphenylborate ion transport in phosphatidylcholine (PC)-cholesterol membranes by the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is dominated by suppression of TPhB- diffusion across the membrane interior, rather than by the decrease of adsorption of TPhB- ions at the membrane surface. The blocking effect can be associated with the decrease of electric potential inside the membrane with respect to that of the aqueous medium, this decreases being proportional to the concentration of 2,4-D in the aqueous solution. It has been estimated that 25 - 30% of the total 2,4-D-induced change of the potential difference is between the plane of absorption of TPhB- and the aqueous solution, and the remaining fraction is between the membrane interior and the absorption plane. The results of this study support the dipolar hypothesis of 2,4-D action in lipid membranes. These conclusions are further supported by measurements changes of electric potential difference across air/water and air/lipid monolayer/water interfaces. It has been found that the electric potential of the nonpolar side of the interface decreases in the presence of neutral molecules of 2,4-D and that this effect becomes more prominent in presence of electrolyte. We have confirmed that PC-cholesterol monolayer cannot be considered as a model for half of the bilayer membrane because of the disagreement between the changes of the interfacial potential difference of PC-cholesterol monolayers and those determined from studied of transport of positive and negative ions across bilayer membranes. In contract, we have found close agreement between the 2,4-D-induced changes of electric potential of the lipid hydrocarbon region in glycerolmonooleate (GMO) membranes and GMO monolayers. We suggest that the action of 2,4-D in lipid membranes is not associated with the changes of orientation of dipoles of lipids constituting the membranes, but rather with a layer of 2,4-D molecules absorbed at the nonpolar/polar membrane boundary.


Interference reflection microscopy. A quantitative theory for image interpretation and its application to cell-substratum separation measurement. We propose a quantitative theory of microscope interferometry where the specimen is illuminated by a cone of monochromatic light of solid angle 0 - 100 degree, corresponding to an illuminating numerical aperture of 0 to approximately 1.2. Computed results compare favorably with photometric measurements of fringe irradiance for a water wedge 0 - 2,000-nm thick. The interpretation of cell-substratum interference images is discussed in relation to the theory. We conclude that in assessing cell-glass separation, the cytoplasmic thickness does in general contribute significantly to the final image, but this contribution is minimized at high illuminating apertures. In these circumstances, however, normal incidence theory is inapplicable and the theory for finite illuminating aperture is essential. Neglect of this fact can lead to errors of up to 100% in estimated cell-glass separation.


Time-resolved resonance Raman characterization of the bL550 intermediate and the two dark-adapted bRDA/560 forms of bacteriorhodopsin. The resonance Raman spectrum of the second intermediate in the bacteriorhodopsin cycle, bL550, is obtained by a simple flow technique. The Schiff base linkage in this intermediate appears to be protonated, contrary to previous suggestion. The fingerprint region of the spectrum of bL550 does not closely match those of any presently available model Schiff bases of retinal isomers, though some comparisons can be made. The resonance Raman spectrum of dark-adapted bacteriorhodopsin is obtained and decomposed by computer subtraction of the spectrum of bR570. The remaining spectrum does not match the spectra of any model compounds presently in the literature. The spectra of bL550 and dark-adapted bRDA/560 from purple membrane in H2O are compared to those in D2O. It is found that changes in the spectrum occur in the 1,600 - 1,650 cm-1 region as well as in the 800 - 1,000 cm-1 region, but apparently not in the fingerprint region (1,100 - 1,400 cm-1). The possibilities of conformational changes of the retinal chromophore in the light adaptation process as well as the photosynthetic cycle are discussed.


Structural interpretation of the birefringence gradient in retinal rod outer segments. The birefringence of frog retinal rod outer segments is analyzed in terms of a three-dielectric layer model. The possibility that the birefringence gradient found in such cells is due to changes in the disk membrane-pair spacing is investigated using previously published glycerol imbibition data (Kaplan et al., 1978. Biophys. J. 23: 59-70). The higher net birefringence of the basal end compared to the midpoint of rod outer segments can be accounted for by a smaller negative form birefringence term due to either a smaller or larger intradiskal space, depending upon the assumed relative solids contents of the intradiskal and cytoplasmic spaces.


Motility evaluation of human spermatozoa by photon correlation spectroscopy. The application of photon correlation spectroscopy for the evaluation of motility parameters of undiluted human sperm is investigated. Measurements on semen samples, selected visually as good (i.e., fraction motile spermatozoa larger than 0.6 and a positive appreciation of the motion), gave estimates of the fraction motile spermatozoa, reproducible within 10%, and of the mean velocity of the motile cells, reproducible within 5%.


Electrochemical properties of Na+- and K+-selective glass microelectrodes. Electrochemical properties of Na+-selective glass microelectrodes were studied and compared with those of K+-selective glass microelectrodes. The selectivity of Na+-selective glass microelectrodes depended on the ion concentration of test solutions. With aging, resistance of Na+-selective microelectrodes increased and their selectivity for Na over K decreased. Na+-selective microelectrodes potential measured in NaCl solution remained constant with aging, while the potential measured in KCl solution decreased and became more positive. The changes in resistance and potential of Na+-selective microelectrodes may be due to the effects of the less mobile cation, i.e., H+ or K+ on the Na ion exchange in the Na-sensing region. The results indicate that Na+-selective microelectrodes must be used as soon after filling as possible. The selectivity of Na+-selective microelectrodes increased with increase of the sensitive exposed-tip length, whereas their response time became slow due to a large recessed volume, indicating requirement of an optimum exposed-tip length for intracellular applications. The changes in the properties of Na+-selective glass microelectrodes with aging contrasted with those of K+-selective glass microelectrodes in which resistance decreased and K+-selectivity increased. The K+-selective microelectrodes required aging before use for a high selectivity and low resistance. The K+-selective microelectrodes with low resistance after sufficient aging can be used without insulation to measure K+ and Na+ activities in aqueous solutions. The different properties between Na+- and K+-selective microelectrodes are understandable, because hydration of N+-selective glass is much less extensive than that of K+-selective glass.


Photoinitiated mediated transport of H3O+ and/or OH- across glycerol monooleate bilayers doped with magnesium octaethylporphyrin. Photogenerated magnesium octaethylporphyrin cation in glycerol monooleate bilayers is shown to mediate the transport of H3O+ and/or OH-. Data from voltage clamp and open-circuit experiments are consistent with the classic Markin or Laüger carrier model. Photoinitiated currents exhibit the expected transient and steady-state behavior.


A simple case of the Wilson-Cowan equations. The stability of equilibria, for Wilson-Cowan equations with piecewise-constant threshold functions, is investigated. It is shown that the characteristic equation has roots with positive real part, when the physiological parameters have reasonable magnitudes. The significance of this fact is discussed.


A mathematical model for the motion of mechanoreceptor hairs in fluid environments. A differential equation has been derived for the motion of the mechanosensory hairs of animals when they are stimulated by the motion of their fluid environment. Specific solutions of the equation are obtained for three states of fluid flow including steady-state sinusoidal oscillations. The model is specifically applied to crayfish sensilla in an aqueous medium, but the assumptions of the model are also shown to be valid in air for the sensory hairs of insects. The calculations are consistent with available experimental data.


Do cardiac aneurysms blow out?

Do cardiac aneurysms blow out? The possibility is suggested that cardiac aneurysms are formed when an infarcted region of the ventricular wall becomes elastically unstable and "blows out". The consequence of such a blowout could be a large saccular aneurysm or even cardiac rupture. We use a nonlinear stress-strain relation capable of describing both the passive and active myocardial wall to examine this possibility in terms of large-deformation membrane theory. Ventricular infarcts made of a material having physical properties like rubber would be expected to blow out, but those made of passive myocardium would not.


Voltage transients from photo-isomerizing azo dye in bilayer membranes. Voltage transients are induced by brief light flashed on bilayer membranes with absorbed 3,3'-bis(alpha-(trimethylammonium)methyl)azobenzene (Bis-Q). The voltages are positive for trans-to-cis photo-isomerization, and negative for cis-to-trans photo-isomerization. The risetimes in phosphatidylethanolamine-decane bilayer membranes indicate that absorbed trans-Bis-Q is photo-isomerized to cis within 2 microseconds, and that cis is photo-isomerized to trans within 15 microseconds.


Diffusion-controlled reactions on spherical surfaces. Application to bacteriophage tail fiber attachment. We have explored the kinetic implications of a model that may account for the acceleration of tail fiber (F) attachment to baseplates (B) by whiskers (W) on bacteriophage T4. The model assumes that a W-F complex is formed initially, and that the tethered fiber then undergoes rotational diffusion until a B-F encounter takes place. In the absence of whiskers, B-F complexes must form unassisted. Formation of a W-F intermediate will accelerate F attachment to B if (a) the bimolecular rate constant for W-F complex formation is larger than that for direct B-F interaction and (b) subsequent rotational diffusion of the tip of F to B is not much slower than the dissociation of W-F. Condition a was investigated by applying a recent theory of orientational effects on translational diffusion-controlled reactions. This theory suggests that substantial rate enhancement is expected if the reaction half-angle theta 0 is larger for W-F than for B-F complex formation. Condition b was investigated by calculating the mean and the variance of the time required for the diffusion of a molecule (the proximal tip of the fiber) on a spherical surface (whose radius is the distance from the tip to the whisker tethering point) into a circular sink (the baseplate site). The mean time is on the order of the inverse rotational diffusion coefficient, DR, of the fiber, but is sensitive to theta 0. Both conditions are satisfied for plausible choices of parameters. The solution to the diffusion equation we have obtained should have application to other physical situations, such as the rate of quenching of a fluorophore as it diffuses on the surface of a spherical membrane into proximity with a quencher.


Electrochemical healing similarities between animals and plants. A brief summary of the major results in enhanced wound healing by electrolysis in animals and humans is presented along with the results of enhanced growth by electrolysis in plants. Hypotheses of normal and enhanced wound healing in animal and plants are reviewed. A comparison of the experimental results indicates strong similarities in the optimum magnitude and polarity of the externally applied galvanic current in animals and plants. There are, however, differences in optimum current densities, There are strong similarities in animal and plant electropotential changes during normal healing.


Nuclear magnetic resonance study of acetic acid permeation of large unilamellar vesicle membranes. The permeation of acetic acid through large unilamellar phospholipid vesicle membranes has been investigated using the unique capability of nuclear magnetic resonance to characterize flow under pseudo-equilibrium conditions. Two types of experiments have been employed: total line shape analysis and selective population transfer. These techniques are sensitive to permeation on time scales ranging form 0.001 to 10.0 s. The permeation rate dependence on pH and acetic acid concentration indicates that the neutral acetic acid monomer is the dominant permeant species with a permeation coefficient of 5 +/- 2 x 10-4 cm/s. Mechanisms of permeation and the applicability of nuclear magnetic resonance methodology are discussed.


A theoretical model for lipid mixtures, phase transitions, and phase diagrams. We present a new model for the thermodynamic properties of lipid bilayers. The model consists of a system of hard cylinders of varying radii that correspond to the different molecular radii of lipids having different numbers of gauche rotations in their chains. Scaled particle theory is used to provide an accurate estimate of the entropy of packing of the cylinders. To apply the model to bilayers we introduce a semiempirical attractive potential energy. Once the form of this potential is chosen, we adjust one parameter, the interaction strength, so that the model fits the transition temperatures and entropies for various phospholipids. The model then agrees quite well with other published data for these systems. We also directly generalize our model to lipid mixtures, and we obtain phase diagrams that we compare to existing data for these systems. We use the model to describe lipid protein interactions in bilayers as well.


Diffusion of water in the endosperm tissue of wheat grains as studied by pulsed field gradient nuclear magnetic resonance. Pulsed field gradient nuclear magnetic resonance has been used to measure water self-diffusion coefficients in the endosperm tissue of wheat grains as a function of the tissue water content. A model that confines the water molecules to a randomly oriented array of capillaries with both transverse dimension less than 100 nm has been used to fit the data and give a unique diffusion coefficient at each water content. The diffusion rates vary from 1.8 x 10(-10) m2s-1 at the lowest to 1.2 x 10(-9) m2s-1 at the highest moisture content. This variation can be explained in terms of an increase in water film thickness from approximately 0.5 to approximately 2.5 nm over the moisture range investigated (200-360 mg g-1).


Diastolic pressure-volume relations and distribution of pressure and fiber extension across the wall of a model left ventricle. A model for left ventricular diastolic mechanics is formulated that takes into account noneligible wall thickness, incompressibility, finite deformation, nonlinear elastic effects, and the known fiber architecture of the ventricular wall. The model consists of a hollow cylindrical mass of muscle bound between two plates of negligible mass. The wall contains fiber elements that follow a helical course and carry only axial tension. The fiber angle (i.e., helical pitch) is constant along the length of each fiber but varies through the wall in accordance with the known distribution of fiber orientations in the canine left ventricle. To simplify the analysis and reduce the number of degrees of freedom, the anatomic distribution of fiber orientations is divided into a clockwise and counterclockwise system. The reference configuration for the model corresponds to a state in which, by hypothesis, the transmural pressure gradient is zero, the tension is zero for all fibers across the wall, and all fibers are assumed to have a sarcomere length of 1.9 micrometer. This choice of reference configuration is based on the empirical evidence that canine ventricles, fixed in a state of zero transmural pressure gradient and dissected, demonstrate sarcomere lengths between 1.9 and 2.0 micrometer in inner, middle, and outer wall layers, while isolated ventricular muscle bundles are observed to have zero resting tension when the sarcomere length ranges from 1.9 to 2.0 micrometer. An equation representing the global condition for equilibrium is derived and solved numerically. It is found that the model's pressure-volume relation is representative of diastolic filling in vivo over a wide range of filling pressures, and the calculated midwall sarcomere lengths in the model compare favorably with published experimental data. Subendocardial fibers are stretched beyond Lmax even at low filling pressures, i.e., 5 mm Hg, while fibers located between 60-80% of wall thickness extend minimally between 5 and 12 mm Hg. The hydrostatic pressure field within the wall is highly nonlinear. The pressure rises steeply in the subendocardial layers so that the net gain in pressure in the inner third of the wall is 85% of the filling pressure. It is demonstrated that these results are independent of heart size for a family of heart models that are scale models of each other. They are, however, critically dependent on the existence of longitudinally oriented fibers in the endocardial and epicardial regions of heart wall.


Displacements of backbone vibrational modes of A-DNA and B-DNA. We display the displacement vectors or eigenvectors of calculations of the A- and B-DNA backbones. These calculations are based on a refinement scheme that simultaneously fit several backbone modes of A-DNA, B-DNA, and A-RNA. We discuss the role of symmetry operations in mode calculations and the relevance of these displacement vectors to the interpretation of linear dichroism measurements performed on the A- and B-DNA helix.


Effect of low dose rate radiation on cell growth kinetics. Experimental determinations were made of cell number as a function of time for two strains of L5178Y mammalian cells maintained continuously in various environments of radiation. One strain possessed a shoulder in its dose response curve whereas the other did not. Neither strain showed any significant difference in growth rate for interdivision doses on the order of the median lethal dose or less delivered continuously at a low dose rate or pulsed every 4 h at a high instantaneous dose rate. It was also shown that large numbers of dead cells have little effect on growth rate and that these dead cells last as discrete entities for many days. A simple theory of growth rate in the presence of radiation is presented, and the agreement with the observations implies that there is no effect of any sublethal low dose rate radiation received in one generation on the growth rate or radiation sensitivity of the succeeding generation. Further analysis of the data also showed that for the no-shoulder cells at 37 degrees C, tritiated water had a relative biological effect close to unity for cell sterilization.


Regulation of IgE antibody production by serum molecules. VI: Preliminary biochemical and immunological characterization of serum molecules active in suppressing IgE antibody production. Molecules present in the serum and ascites fluids of low IgE responder mice previously inoculated with complete Freund's adjuvant have been analyzed in terms of certain biochemical and immunological characteristics. These studies demonstrate that the active molecules, termed "suppressive factors of allergy" (SFA), are (1) nondialyzable, (2) not associated with low-density or high-density lipoproteins, (3) heat stable, (4) precipitable by ammonium sulfate, and (5) approximately 150,000 daltons in molecular size. Studies with immunoadsorbents prepared from various antisera indicate that the suppressive molecules are (1) not immunoglobulin in nature, (2) not reactive with specific anti-H-2 alloantibodies, but (3) reactive with anti-beta 2m antibodies as well as (4) heterologous antisera raised against CFA-immune mouse serum.


The role of macrophages in stimulation of immune induction and myelopoiesis. I: Comparison of activity of macrophage-derived factors in granulopoiesis and immunostimulation. Hemopoietic growth and immunological inductive factors from human peripheral leukocyte conditioned medium and mouse macrophage culture supernatant fluids were compared. Factors derived from human peripheral leukocyte conditioned medium were found to substitute for those of mouse macrophage derivation in immunological assays, namely, induction of a cytotoxic T-lymphocyte response in macrophage-depleted mouse spleen cultures. Association of macrophage-derived factors with B2-microglobulin (B2m) antigen determinants was observed by inhibition with great antihuman B2m, affinity chromatography, and direct replacement of mouse macrophage-derived factors with human urinary B2m.


The role of macrophages in stimulation of immune induction and myelopoiesis: II: analysis of genetic restriction involved in the stimulation of granulocyte colony precursors or mature lymphocytes using factors prepared from different recombinant inbred strains of mice. The genetic restriction involved in the reconstitution of immune responses in macrophage-depleted mouse spleen cultures, or the induction of colony formation in bone marrow cultures, by different molecular-weight species of lymphostimulatory molecules derived from mouse peritoneal cell suspensions is reported. The data suggest little evidence for genetic restriction in the ability of any of the factors to stimulate bone marrow colony formation in vitro. However, when immunological stimulation was investigated, a restriction coded for by genes in the K/D end of the MHC (70-90K factor) or in the I region of the MHC (30-45K factor) was observed. A third species of lymphostimulatory molecule (15K) showed no such restriction. Further evidence is presented to suggest that the active moiety in the 70-90K molecule(s) is a 15K-like species (nonrestricted in its ability to reconstitute cells from different strains of mice.


The effect of immunopharmacological agents on mouse natural cell-mediated cytotoxicity and on its augmentation by poly I:C. Treatment of young mice with lethal X-irradiation (900 R), cyclophosphamide, or hydrocortisone significantly depressed their spontaneous NK activity. The same treatments, however, did not inhibit the augmentation of NK function by poly I:C, suggesting the existence of a treatment resistant pre-NK cell. Both the spontaneous activity and its augmentation were readily inhibited by macrophage-toxic agents such as silica and carrageenan in vivo. Since the NK cells themselves were not macrophages, as shown by the inability of silica or carrageenan to block in vitro cytolysis of target cells, we postulated that macrophages were required to maintain NK activity in vivo and that they were essential accessory cells in the augmentation. The induction of interferon by poly I:C was also inhibited by silica and carrageenan. The augmentation of NK activity induced by poly I:C was consistently accompanied by the rise in serum IF levels of the treated mice, and its inhibition by the macrophage-toxic agents was followed by decreased production of interferon. These observations support our hypothesis that macrophages, in response to poly I:C, produced interferon which in turn activated NK cells to become cytolytic.


Stimulation by a hydroxythiazolobenzimidazole of enhanced formation of antibodies to sheep erythrocytes in vitro and in vivo. A hydroxythiazolobenzimidazole, a low molecular weight compound, was found to have an immunoenhancing effect on both the in vivo and in vitro antibody response of mouse spleen cells to an optimum immunizing dose of sheep red blood cells. At noncytotoxic concentrations the optimum range of 25 to 50 micrograms per 5 x 19(6) spleen cells was most effective in vitro. Concentrations greater than 100 micrograms per culture were toxic in vitro and reduced cell viability as well as antibody responsiveness. The compound enhanced to an even greater degree the antibody response of spleen cell cultures immunized with suboptimum doses of SRBC. The background PFC response, in the absence of SRBC, also was stimulated by the benzimidazole. These immunoenhancing responses were not related to mitogenic effects, since increased thymidine uptake did not occur when normal mouse spleen cells were incubated with graded doses of the compound. Therefore, the immunostimulatory properties of the compound, both in vivo and in vitro, were not due to mitogenic stimulation of lymphoid cells.


In vitro induction of E-rosette formation in human bone marrow cells by the thymic proteins LSHr and LSHh. Two thymic factors, LSHh and LSHr, were found to be active in the induction of E-rosette formation. In vitro incubation of human bone marrow cells, isolated by Ficoll gradient centrifugation, with subnanogram quantities of either of these LSH proteins increased the number of E-rosette-forming cells in the bone marrow cultures by a factor of two. Kidney extract and bovine serum albumin did not show significant activity when tested as controls. Commercial thymopoietin II peptide was found to be active in the assay at comparable concentrations. The data allow a comparison of LHS proteins with other preparations tested in this manner.


Parents' subjective evaluation of a self-help education-exercise program for asthmatic children and their parents. A self-help education-exercise program for asthmatic children and their parents was evaluated in Denver, Colorado. The objective of the program was to instill better self-care practices in the child which are expected to reduce utilization and cost of medical services and reduce the amount of interference in the child's normal activities. The program was designed to educate the family about the nature of asthma and its treatment, the importance of self-responsibility for the child, and the psychosocial aspects which may affect both the child and the parents in a family with an asthmatic child. The program also included specific lessons pertaining to self-care practices including general health exercises on land and in water, relaxation training, and diaphragmatic breathing. The results of subjective evaluations of the parents indicated that the program was successful in achieving its goals to: Reduce the number of severe attacks, reduce medication usage, improve compliance, reduce days of school missed, increase exercise activity, and control wheezing by the steps taught in the course. While the results are suggestive, a further, controlled evaluation of the program is recommended.


Development of a distinctive feature discrimination test. Construction and standardization is described of a distinctive feature discrimination test (DFDT) incorporating a modified Miller-Nicely system of distinctive features. The test is a rhyme-type where error responses in a closed set were chosen to be one, two, and three distinctive features removed from the stimulus word. Performance-intensity (P.I) functions were established with 6 normal-hearing young women (12 ears) at SPLs or 20, 25, 30, 35, and 40 db under each of three filter bandpass conditions: .2-6, .2-1.2, and .2-.6 kc/s. P-I functions were presented for unweighted scores and for scores where error responses were weighted in terms of distinctive feature differences from stimulus items. The 4 DFDT lists generated, and their 3 randomizations each, appear to have a reasonable degree of inter-list reliability and it is felt that the 12 resultant list may be used interchangeably, This preliminary study indicated that the DFDT test may provide more diagnostic information than currently-used discrimination test.


Time-compressed spondaic words as a measure of speech reception threshold. Lists A and B of the C.I.D. W-1 spondees were time-compressed with a Lexicon Varispeech I unit. SRTs were collected from one ear of each of 60 normal-hearing young adults. No list differences were found. The R ears of 30 Ss were superior to the L ears of 30 Ss by 0.8 db. Mean SRTs collapsed across lists and ears were 9.3-10.7-13.2 db for the compressions in the order 0-40-60%. The differences were judged clinically insignificant, nevertheless when considered with earlier data it may be concluded that time-compressed spondees may come to have use as a clinical device.


The additive effects of two mutant genes on otolith formation in mice: an animal model to assess otolith function. This study examined the additive effects of two mutant genes, pallid (pa) and tilted head (th), on otolith formation in mice. Four strains of mice were bred: (1) a control strain, heterozygous for both pa and th. (2) a pallid strain, homozygous for pa, (3) a tilted head strain, homozygous for th, and (4) a double mutant strain, homozygous for both pa and th. The results were confirmed (1) behaviorally, by the animals' ability to swim, and (2) by histological examination of the inner ear. The findings suggest significant differences in mean otolith scores between all possible pairs of strains. As expected, the controls had normal otoliths and the pa/th strain the most severe otolith defects. Furthermore, there was a significant directional asymmetry in mean otolith scores between the utricle and saccule of the R and L ears for both pa and th strains. The results also showed a highly significant linear relationship between poor swimming ability and reduction of otoconia (r = 0.94, F = 92.14, p less than .001).


Level dependence of critical bandwidth: notched-noise masking paradigm. The effect of increased stimulus level on critical bandwidth was investigated. Noise-masked, pulsed-tone thresholds were obtained by a Bekesy tracking procedure from 4 practiced normal-hearing adults at .5, 1, 2, and 4 kc/s. Tones were placed symmetrically within a band-reject region. Critical bandwidth was taken as the frequency separation between noise bands at which masked tonal threshold began to change and was found to increase fairly regularly as the spectrum level of the noise increased from 30-60 db SPL. However, the data at 60 db SPL may have been influenced a 2 and 4 kc/s by the detection of aural distortion products. The suggestion was made that when signal frequency is outside the spectral limits of the masker, critical bandwidth widens as masker level is raised; however, when signal frequency is within the spectral limits of the masker (as with a continuous noise wit no notches), critical bandwidth remains unchanged up to 80 bd SPL.


Dynamic auditory localization: systematic replication of the auditory velocity function. Two experiments explored the capability of normal-hearing adults to judge the apparent velocity of an unseen moving sound source. In exper. I, 9 naive and, 1 experienced S judged the velocity of a moving source emitting a .5-kc/s tone at 50 db SPL. S's head was in the center of a circle of 1.88-m radius swept by a small loudspeaker. In exper. II the sound was a low-pass-filtered (0.1-1 kc/s) noise at 50 db sound spectrum level. In both experiments perceived velocity was directly proportional to the actual velocity of the source. These results support out initial observations (Waugh et al, J. Aud. Res., 1979, 19, 103-1 10) that auditory velocity discrimination can be described as a power function with an exponent of 1.0. In exper. II the Ss also varied the sound source velocity by means of a variable resistor to produce a perceived velocity of 100 degrees/sec. Performance on the adaptive velocity production task was successfully predicted from the data of the absolute velocity judgment task. The Weber fraction was .052 for relatively fast-moving sound sources (100 degrees/sec). The ability to discriminate sound source velocity appears to be a well-defined feature of the dynamic binaural spatial system.


Field and laboratory studies of moving and temporally variable noise sources (aircraft); perception of location, movement, and direction. The conditions were examined under which more valid and reliable estimates could be made of the effects of aircraft noise on people. In Exper. 1, 12 Ss in 2 different houses directly under the flight path of a major airport (JFK) indicated 1 of 12 possible flight paths (4 directly overhead and 8 to one side) for each of 3 jet aircraft flyovers: 3% of cases in House A and 56% in House B (which had open windows) were correctly identified. Despite judgment inaccuracy, Ss were more than moderately certain of the correctness of their judgments. In Exper. II. Ss either inside or outside of 2 houses in Wallops Station, Virginia, indicated on diagrams the direction of flyovers. Each of 4 aircraft (Boeing 737, C-54, UE-1 helicopter, Queenaire) made 8 flyovers directly over the houses and 8 to one side. Windows were either open or closed. All flyovers and conditions were counterbalanced. All sound sources under all conditions were usually judged to be overhead and moving, but for Ss indoors with windows closed the to-the-side flyovers were judged to be off to the side in 24% of cases. Outdoor Ss reported correct direction in 75% of cases while indoor Ss were correct in only 25% (windows open) or 18% (windows closed). Judgments "to the side" were significantly better (p = less than .02) with windows open vs closed, while with windows closed judgments were significantly better (p = less than .05) for flyovers overhead vs to the side. In Exper. III, Ss localized in azimuth and in the vertical plane recorded noises (10 1-oct noise bands of CF = 28.12 c/s - 14.4kc/s, spoken voice, and jet aircraft takeoffs and landings), presented through 1, 2, or 4 floor-level loudspeakers at each corner of a simulated living room (4.2 x 5.4m)built inside an IAC soundproof room. Aircraft noises presented by 4 loudspeakers were localized as "directly" overhead 80% of the time and "generally overhead" about 90% of the time; other sounds were so localized about 50% and 75% of the time respectively. Through only 2 loudspeakers, aircraft noises were localized 25-36 degrees above horizontal. Implications are that acoustic realism can be achieved in simulated aircraft overflights and that future laboratory noise-effects research should incorporate the required conditions.


[Significance of the depressed state in obese people: definition of a risk group]. This study concerns frequency and meaning of depressive conditions in obese patients. The examination was carried out with two groups of 39 obese subjects, 30 women and 9 men. The patients with depressive symptoms differed highly significantly from those without depressive symptoms in relation to the age of the beginning of their overweight. They became overweight preponderantly as adults, striking frequently in correlation with the situations of emotional stress. This would support the hypothesis of this study, that depressive states as an organism variable in this group of patients has essential influence as well for the onset as for the maintenance of the overweight.


[Word field disturbances and sentence field disturbances as differential diagnosis criteria between endogenous and exogenous paranoid-hallucination syndrome]. Through the 'classical' psychopathological symptoms only, one sometimes cannot clearly differentiate between an endogenous and an exogenous psychosis. But through the identification of word field disturbances and sentence field disturbances, which are characteristic schizophrenic symptoms, one can put the diagnosis of schizophrenia in such cases. This diagnosis can be stated through the course of the illness and its therapy.


[An interpretation deduced from word field disturbances and sentence disturbances in schizophrenia: a psychological study]. We investigated the occurrence of word field disturbances and sentence field disturbances in the text of schizophrenic patients. Through the connection of these disturbances with relevant biographical data of the patient and through a psychological interpretation we found that the occurrence of these disturbances is not accidental, but has a relevant psychological meaning for the patient.


Sulpiride and headache syndromes.

Sulpiride and headache syndromes. Numerous studies have indicated that sulpiride exerts a positive effect upon several psychosomatic symptoms. This effect is generally believed to depend on the thymoanaleptic activity of the molecule. Since headache can often represent the warning symptom of a masked depression, in the present study sulpiride has been administered to patients suffering from nonorganic headache syndromes. The results obtained confirm the efficacy of sulpiride in relieving headache and other psychosomatic discomforts.


Variations in self-assessment of personality characteristics in depressed patients, with special reference to aspects of aggression. 30 in-patients, 14 male and 16 female, aged 24-69 years (mean age 47.1 +/- 2.7) suffering from a moderately severe or severe depressive syndrome completed a new personality inventory, the KSP, on two separate occasions. The first-when they were depressed and had just been admitted to the hospital, the second when they were at home and in their customary situation. On the same test occasions the severity of their psychopathology was rated by means of the CPRS. A significant improvement in CPRS rating was ascertained on the second test occasion. In contrast only small changes occurred in the subscales of the KSP. The score referring to 'psychic anxiety' and to 'somatic anxiety' decreased slightly but significantly (p less than 0.05). The scores referring to 'social desirability' also showed a significant (p less than 0.01) slight decrease. Of particular note is that no significant differences were found in the 6 KSP subscales concerned with aspects of aggression, or in the factors which can be obtained from these subscales. Our findings amongst this population of non-psychotic depressed patients do not support the assumption that changes in the direction of aggression occur during depression.


[Pathological lability of venous fasting blood sugar regulation in psychotic disease]. The lability of peripheral venous postabsorptive blood sugar regulation was investigated in 98 patients suffering from floridly psychotic diseases (45 somatically based psychoses, 27 endogenous/involutional depressions, and 26 schizophrenic psychoses). In total, 259 times, in 30-sec intervals, 10 fasting blood sugar values each were determined (so-called 'Anderson curves'). The maximal normal range of 36 mg% of spontaneous blood sugar oscillations in normal probands was exceeded in 17% of depressive, in 15% of schizophrenic, and in 12% of somatically based psychoses. The frequency and probability of appearance of pathological Anderson curves proved independently of any clinical-psychiatric diagnosis, and only significantly correlated with the criterion 'psychotically ill'. Discussed are primary central deviations from nominal gluco-sensitive regulatory 'tone' as postulated cause of pathological lability of venous blood sugar homeostasis resulting. Besides additional, pre-known glucose-metabolic derangements accompanying certain neuropsychiatric syndromes, pathological Anderson curves in psychotic illness are looked at as unspecific functional deviations involving bipolar-adrenergic dysbalances.


Recent advances in platelet structural physiology. Platelet structural physiology has contributed significantly to our understanding of basic mechanisms of platelet function in hemostasis and thrombosis. Current evidence indicates that platelets are a form of muscle cell with specialized capabilities for secretion and adhesion-aggregation. Activation of the discoid cell by any agent appears to involve a perturbation of the membrane resulting in movement of calcium from the cell wall to the interior. The calcium flux stimulates phospholipase A2 to cleave arachidonic acid from platelet phospholipids starting the cascade of prostaglandin synthesis. In addition, the movement of calcium to the cytoplasm initiates contraction leading to shape change. Products formed during prostaglandin synthesis, particularly thromboxane A2, act as ionophores to transport additional calcium from the dense tubular system to the cytoplasm amplifying the wave of contraction. Alterations in organelle membranes result in their fusion with channels of the open canalicular system. The contractile wave causes extrusion of secretory products which stimulate other platelets to become involved in formation of irreversible aggregates in vitro and hemostatic plugs in vivo. Mechanisms regulating platelet stimulation-contraction-secretion coupling are currently under investigation.


Current noise parameters derived from voltage noise and impedance in embryonic heart cell aggregates. We have recorded membrane impedance and voltage noise in the pacemaker range of potentials (-70 to -59 mV) from spheroidal aggregates of 7-d embryonic chick ventricle cells made quiescent by exposure to tetrodotoxin in medium containing 4.5 mM K+. The input capacitance is proportional to aggregate volume and therefore to total membrane area. The specific membrane capacitance is 1.24 microF/cm2. The input resistance at constant potential is inversely proportional to aggregate volume and therefore to total membrane area. The specific membrane resistance in 18 k omega . cm2 at -70 mV and increases to 81 k omega . cm2 at -59 mV. The RC time constant is 22 ms at -70 mV and increases to 146 ms at -59 mV. The aggregate transmembrane small-signal impedance can be represented by a parallel RC circuit itself in parallel with an inductive branch consisting of a resistor (rL) and an inductor (L) in series. The time constant of the inductive branch (L/rL) is 340 ms, and is only weakly dependent on potential. Correlation functions of aggregate voltage noise and the impedance data were modeled by a population of channels with simple open-close kinetics. The time constant of a channel (tau s) derived from the noise analysis is 300 ms. The low frequency limit of the pacemaker current noise (SI[0]), derived from the voltage noise and impedance, increases from 10(-20) A2/Hz . cm2 at -67 mV to 10(-19) A2/Hz . cm2 at -61 mV.


An analytic solution to the Förster energy transfer problem in two dimensions. An analytic solution of the Förster energy transfer problem in two dimensions is presented for the case in which the orientation factor is independent of the donor-acceptor distance, and both the donors and acceptors are randomly distributed in a plane. A general solution based on the method of Förster is possible since all distances are measured in units of R0. The analytic solution is extended to the cases of donors embedded in structures that exclude acceptors, and donors that bind acceptors. The validity of the analytic solutions is demonstrated by comparison with numerical simulation calculations. Numerical approximations to the exact solutions are given for ease of computation. Specific applications to the case of fluorescence quenching of a membrane-bound donor by membrane-bound acceptors are presented.


Contraction of glycerinated muscle fibers as a function of the ATP concentration. We have measured the force-velocity curves of glycerinated rabbit psoas fibers over a range of ATP concentration from 2.5 microM to 5 mM. As the ATP concentration is increased, the isometric tension increases to a maximum around 50 microM, then decreases to a plateau at 70% of the maximum by 1 mM ATP. At low ATP concentrations the maximum velocity of contraction is low and increases with increasing ATP, reaching a plateau at approximately 2 lengths per second by 1 mM ATP. Our studies suggest that the binding of ATP dissociates the myosin head from actin in the contracting muscle, a reaction similar to that seen in solution. We have constructed models of the actin-myosin-nucleotide interactions based on a kinetic scheme derived from solution studies. The fit of these models to the data shows that the rates of some reactions in the fiber must be considerably different from the rates of the analogous reactions in solution. The data is best fit by models in which head attachment occurs rapidly at the beginning of a power stroke, head detachment occurs rapidly at the end of the power stroke, and the force produced by a myosin head in a power stroke is independent of velocity.


Effect of the anesthetics benzyl alcohol and chloroform on bilayers made from monolayers. The neutral anesthetics chloroform and benzyl alcohol, at concentrations that block the nerve impulse, greatly modify the transport parameters of positive and negative ions in lipid bilayers made from monolayers. Both chloroform and benzyl alcohol increase the membrane permeability to these ions and increase the translocation rate for tetraphenylborate. It was found that both anesthetics increase the membrane permeability to positive ions more markedly than to negative ions. It was also found that the membrane capacitance increases lineary with the concentration of benzyl alcohol. At 51 mM benzyl alcohol, the increase in capacitance is approximately 6%. Chloroform also increases the membrane capacitance; the increase in capacitance was found to be 6% at 18 mM chloroform. An analysis of the changes in the transport parameters of the lipophilic ions, together with the changes in membrane capacitance, suggests that benzyl alcohol and chloroform modify the dipole potential and dielectric constant of the membrane. Benzyl alcohol may also increase the "fluidity" of the lipid bilayer membranes. At 36 mM benzyl alcohol, the membrane permeability to acetamide increases by 38%.


Fluorescence redistribution after photobleaching. A new multipoint analysis of membrane translational dynamics. A theoretical formulation and experimental methodology are presented for a new multipoint analysis of membrane translational dynamics. The redistribution of fluorescent probe after a localized photobleaching pulse is monitored at several locations by a focused laser beam sequentially scanned through the bleached area. The spatial information so obtained provides a unique sensitivity to possible systematic flow and a direct internal calibration of the characteristic transport distance. These capabilities are demonstrated with experimental data on a reconstituted multibilayer system.


Some preliminary studies of the effects of a static magnetic field on the life cycle of the Lebistes reticulatus (guppy). Lebistes reticulatus (guppy) was subjected to a continuous treatment of a 500-G homogeneous magnetic field within a specially designed horseshoe magnet encompassing a small aquarium. The experiment was carried through several generations with the following results: in the first generation, the brood size was normal but the gestation period was reduced by 30%; the second generation had an average reduction of spawn rate of 50% and a reduction of the gestation period of 30%; and in the third generation, reproduction was completely inhibited as long as the fish remained within the magnetic field.


Correlation among the rates of dimer excision, DNA repair replication, and recovery of human cells from potentially lethal damage induced by ultraviolet radiation. The kinetics of excision repair in confluent cultures of diploid human fibroblasts after ultraviolet irradiation at varying doses was measured by three different methods: (a) removal of thymine-containing dimers, (b) DNA excision repair synthesis, and (c) biological recovery of cells from the potentially lethal effects of the irradiation. Each method gave similar results and indicated that the excision rate was dependent upon the number of thymine-containing dimers induced (substrate concentration). For example, at a dose of 40 J/m2 (0.2% dimerization), the repair rate was 1.6 J/m2 per h as determined by a modified method to measure the number of thymine-containing dimers remaining in DNA and 1.65 J/m2 as measured by excision repair synthesis. At a dose of 7.5 J/m2, the repair rate was 0.5 J/m2 per h as measured by biological recovery, and at a dose of 7 J/m2, the repair rate was 0.46 J/m2 per h as measured by excision repair synthesis.


Nuclear magnetic resonance multiwindow analysis of proton local fields and magnetization distribution in natural and deuterated mouse muscle. The proton free-induction decays, spin-spin relaxation times, local fields in the rotating frame, and spin-lattice relaxation times in the laboratory and rotating frames, in natural and fully deuterated mouse muscle, are reported. Measurements were taken above and below freezing temperature and at two time windows on the free-induction decay. A comparative analysis show that the magnetization fractions deduced from the different experiments are in good agreement. The main conclusion is that the resolution of the (heterogeneous) muscle nuclear magnetic resonance (NMR) response is improved by the multiwindow analysis.


Internally perfused Myxicola giant axons showing long-term survival. An improved method for internally perfusing the Myxicola giant axon based on removing the axoplasm by dispersing it in KCl-KF salt solutions is described. Proteolytic enzymes are not introduced. With this improved method perfused preparations show long-term stability of their electrical properties and the ability to generate action potentials for many hours. Mean initial values for resting membrane potential, action potential amplitude, and peak inward current were -68 mV, 118 mV, and 3.62 mA/cm2, respectively. Mean resting membrane resistance was 75% of that in intact axons. In one series of voltage clamp experiments, perfused preparations remained excitable for a mean period of 5 1/2 h, but this period could exceed 10 h. 4 min are needed for exchange of internal solutions. At least 50 mM KF is required both in the axoplasm liquefying solution and in the standard perfusate to obtain stable preparations.


Fluctuations in interbeat interval in rhythmic heart-cell clusters. Role of membrane voltage noise. Small clusters of ventricular cells prepared from 7-d chick heart maintain spontaneous, stationary, rhythmic beating in culture for many hours. For clusters containing I-125 cells, mean interbeat interval (IBI) is 0.45 +/- 0.08 s and is independent of cell number (N), whereas, the coefficient of variation of IBI (C) is proportional to N-1/2. Because membrane voltage noise in such clusters would also be expected to vary as N-1/2, we propose a model relating fluctuation in IBI (sigma IBI) to voltage noise (sigma v). A simplified model consisting of random voltage fluctuations superimposed upon a linear pacemaker depolarization of slope a is used to analyze the N-dependent shape of the IBI histogram. Values of sigma v derived from the relation sigma IBI = sigma v/a, or calculated from the skewness of the measured IBI histograms, both agree well with those extrapolated from steady-state noise recorded from resting heart-cell aggregates.


Involvement of mitochondria in changes in fluorescein excitation and emission polarization spectra in living cells. The comparison of fluorescein polarization spectra in living cells and in isolated subcellular structures identified the mitochondria as the cytoplasmic domain in which on excitation at 470 nm the sharp fluorescein emission polarization peak at 510 nm is formed. Changes in the emission polarization peak during the cell cycle or those induced by growth stimulators and inhibitors reflect structural changes in the mitochondria on their transition from the resting, orthodox into the active, ATP-generating, condensed conformation and vice versa. Possible mechanisms for the formation of the sharp emission polarization peak are discussed.


Effect of boundaries on the response of a neural network. The effect an abrupt boundary has upon the dynamical response of a neural network is investigated. The retina of the Limulus eye is used as a model system for studying this effect. A theoretical technique is presented for the quantitative prediction of the manner in which this neural network responds in the vicinity of its boundary. Corresponding experimental measurements of the response to moving stimuli by single optic neurons located near retinal boundaries are presented. Theory and experiment show detailed quantitative agreement.


Absorption spectra for the complexes formed from vitamin-A and beta-lactoglobulin. The interactions between vitamin-A and beta-lactoglobulin have been investigated. We have found that two different complexes can be formed: one involving vitamin-A, and one involving a derivative of vitamin-A that most probably has a retro-beta-ionylidene structure. Room temperature absorption spectra for these complexes in phosphate buffer at pH 7.50 are reported and discussed.


Quasi-elastic light-scattering spectra of swimming spermatozoa. Rotational and translational effects. The electric field autocorrelation functions of light scattered from normal swimming bull spermatozoa are shown to be dependent on the mean head rotation frequency and not on the translational speed of the cells, as previously believed. This result was obtained from numerical generation of functions in which spermatozoa were modeled as Rayleigh-Gans-Debye ellipsoids having semiaxes a = 0.5 micrometer, b = 2.3 micrometer, and c = 9.0 micrometer. The magnitude of c required to achieve agreement with the experimental data is larger than the half-length of the head region of the cell. This implies that the midpiece, which also lies along c, contributes to the scattering power. Details regarding swimming trajectory and head orientation are included in the model. Analyses of the calculated functions and comparisons with experimentally determined ones suggest that at a scattering angle of 15 degrees the electric field autocorrelation function can be fit a simple Lorentzian whose half-width is inversely proportional to the scattering vector and the mean head rotational frequency.


An analysis by low-angle neutron scattering of the structure of the acetylcholine receptor from Torpedo californica in detergent solution. The acetylcholine receptor from the electric tissue of Torpedo californica is a large, integral membrane protein containing four different types of polypeptide chains. The structure of the purified receptor in detergent solution has previously been investigated by sedimentation analysis and gel filtration. Sedimentation analysis yielded a molecular weight of 250,000 for the protein moiety of the receptor monomer-detergent complex; hydrodynamic characteristics such as the Stokes radius, however, refer to the receptor-detergent complex. In this paper we report the results of our use of low-angle neutron scattering to investigate the shape of the receptor-detergent (Triton X-100 from Rohm & Haas Co., Philadelphia, Pa.) complex and separately of its protein and detergent moieties. By adjustment of the neutron-scattering density of the solvent with D2O to match that of one or the other of the moieties, its contribution to the scattering can be nearly, if not completely, eliminated. Neutron scattering from Triton X-100 micelles established that this detergent is contrast matched in approximately 18% D2O. Scattering measurements on the receptor-detergent complex in this solvent yielded a radius of gyration of the acetylcholine receptor monomer of 46 +/- 1A. The radius of gyration and molecular volume (305,000 A3) of the receptor are inconsistent with a compact spherical shape. These parameters are consistent with, for example, a prolate cylinder of dimensions (length x diameter) approximately 150 x approximately 50 A or an oblate cylinder, approximately 25 x approximately 130 A. More complex shapes are possible and in fact seem to be required to reconcile the present results with previous electron microscopic and x-ray analyses of receptor in membrane and with considerations of the function of the receptor in controlling ion permeability. The neutron-scattering data yield, in addition, an independent determination of the molecular weight of the receptor protein (240,000 +/- 40,000), the extent of Triton X-100 binding in the complex (approximately 0.4 g/g protein), and from the extended scattering curve, an approximation to the shape of the receptor-Triton X-100 complex, namely an oblate ellipsoid of axial ratio 1:4.


X-ray response of Chinese hamster ovary cells during the latter part of G2. The ability of Chinese hamster ovary (CHO) cells to repair x-radiation damage during the transit from the late G2 to early M cell cycle stages was investigated by conventional dose-fractionation techniques. Despite their relatively high radiation sensitivity, CHO cells positioned in late G2 exhibit increased survival when a given dose of ionizing radiation is administered as two fractions (separated by 40-50 min) instead of as a single fraction. This increased survival apparently represents repair since neither cell cycle progression nor changes in the number of "effective targets" can account for the observed dose-sparing effect.


Autocorrelation analysis of hydrophobic ion current noise in lipid bilayer membranes. The autocorrelation function of a given process is related to its spectral density by the Wiener-Khintchine theorem, and both expressions contain the same information. We report here a measurement of the current noise produced in a lipid bilayer membrane doped with hydrophobic anions of dipicrylamine. The results are in good agreement both with relaxation measurements on the same membrane and with an analysis of the spectral density of the current noise for this system which has been presented by other workers. Although measurement of the spectral density function is generally more complete for technical reasons, the autocorrelation function provides, for the case studied here, more physical insight into the underlying charge transport mechanism. We find that the measured autocorrelation function is negative at short, but nonzero, times. This is a consequence of the operative conductance mechanism in this case, which cannot carry current continuously in the same direction without compensatory reverse flow.


Clinical spectrum of "unstable angina".

Clinical spectrum of "unstable angina". In order to determine the natural evolution of different clinical types of "unstable angina", 167 patients were included in a prospective study. After angiography, 11 (6.5%) were excluded because they had no significant coronary lesions. The remaining 156 were sorted into different groups according to their clinical characteristics and were followed up for a period of 24 months at least. After that follow-up period, mortality and incidence of acute myocardial infarction (AMI) were as follows: angina of recent onset (Class III--IV NYHA): 8.5% (3/35) and 34.2% (12/35). Progressive angina: 7.4% (2/27) and 7.4% (2/27). Intermediate syndrome: 41.6% (10/24) and 37.5% (9/24). Prinzmetal's angina: 10% (1/10) and 10% (1/10). Post acute myocardial infarction angina: 35% (7/20) and 10% (2/20). Acute persistent ischemia: 2.5% (1/40) and 20% (8/40). Comparison of these figures pointed out significant differences (p less than 0.001 for mortality and p less than 0.03 for AMI incidence respectively). We conclude that it is clinically possible to identify different groups within the so-called unstable angina. Such a division not only allows for the creation of more homogeneous groups, but it contributes to a more rational therapeutic approach and also permits identification of high risk prodromes of greater complications, such as myocardial infarction or sudden death.


Exercise 201thallium myocardial scans in patients with disease limited to the secondary branches of the left coronary system. Coronary disease (greater than or equal to 50% narrowing) confined to only the diagonal branch of the left anterior descending artery or to the marginal branch of the left circumflex artery, or both, is uncommon. Only 19 patients with disease as defined above were identified in a group of 1000 consecutive patients with an angiographic diagnosis of coronary heart disease. All 19 patients were studied because of angina pectoris and all underwent stress myocardial perfusion scintigraphy with 201Tl (201thallium) during maximal treadmill exercise testing (exercise electrocardiogram: E/ECG). Ten patients (52%) had positive E/ECG's; seven patients (36%) had positive 201Tl and 13 patients (68%) had one or both tests positive. In 12 patients, the diseased branch was small, i.e. it supplied a comparatively small portion of myocardium, and in seven patients it was determined to be large. The 201Tl test results were positive in four out of seven patients (57%) with large diseased branches, as compared with three out of 12 (25%) with small diseased branches (p: NS). Also, three out of seven patients (42%) with large diseased branches had positive E/ECG's as compared with seven out of 12 patients (58%) with small diseased branches (p: NS). Patients with branch disease may present with typical angina pectoris, however, they are rare and thus not likely to account for the majority of false-negative 201Tl test results among symptomatic patients with CHD. Approximately one-third of the patients with branch disease have positive 201Tl test results, one-half have positive E/ECG's, and in two-thirds, one or both tests are positive.


Dimeditiapramine (Ro 11-1781), a new calcium antagonist, in the management of supraventricular tachyarrhythmias in patients with acute myocardial infarction. 18 patients with acute myocardial infarction and sustained arrhythmias were treated with a new Ca2+ antagonist, Ro 11-1781, at the dose of 1.0 mg/kg i.v. The drug was effective in reducing heart rate to less than 90 beats/min in 9/10 patients with atrial fibrillation, in 3/4 patients with atrial flutter and in 3/4 patients with supraventricular tachycardia. The peak effect was observed within 2--5 min after the intravenous administration of Ro 11-1781. In cases with recurring tachyarrhythmias, the drug was also effective in repetitive administration. Systolic blood pressure was reduced, but severe hypotension (less than 90 mm Hg) was not observed. The atrioventricular conduction in these patients remained unimpaired and asystole did not occur. The drug appears to be an effective and a well tolerated antiarrhythmic agent.


Beneficial effects of prolonged low dose dopamine in hospitalized patients with severe refractory heart failure. In 10 hospitalized patients with severe congestive heart failure refractory to standard medical therapy for three days, low dose intravenous dopamine (2-4 micrograms/kg/min) was infused for 48 h. Heart rate and systolic blood pressure were unchanged throughout the study. Mean pulmonary artery wedge pressure decreased significantly during the dopamine infusion from 27 +/- 6 (SD) to 18 +/- 6 mmHg (p less than 0.01) and cardiac output increased from 3.2 +/- 1.1 to 4.6 +/- 0.8 l/min (p less than 0.001). A diuresis was initiated in all patients and there was a significant weight loss during the study which averaged 5 lbs (p less than 0.01). All patients improved symptomatically from class IV (NYHA) to class III and were more responsive to conventional therapy after the study. No adverse reactions were noted in this dose range. We conclude that low dose intravenous dopamine is efficacious in improving hemodynamics and initiating a diuresis in patients with severe refractory congestive heart failure.


The superiority of mitral E point-ventricular septum separation to other echocardiographic indicators of left ventricular performance. M-mode echocardiography, angiocardiography, and coronary arteriography were done in 40 patients with coronary heart disease, 12 with congestive cardiomyopathy, and 14 with no detectable cardiac or coronary abnormality. We measured mitral E point-ventricular septum separation (EPSS) at the moment of the E peak; the previously described method measures EPSS as the vertical distance between the nadir of systolic septal motion and the subsequent mitral E peak. Angiocardiographic ejection fractions correlated better with EPSS (r = 0.83) than with left ventricular (LV) end-diastolic internal diameter (r = 0.62), LV internal diameter systolic shortening fraction (r = 0.64), LV echocardiographic ejection fraction (r = 0.70), and LV posterior wall systolic thickening (r = 0.58). Patients with angiocardiographic ejection fractions below 55% usually had EPSS values over 10 mm by our method. Six false negatives and one false positive occurred. Our observations in patients with impaired LV performance suggest that LV dilatation, and especially dilatation of the LV outflow tract, is relatively more important than reduction in the amplitude of diastolic anterior mitral excursion in the production of high EPSS values. Although the usual method for measuring EPSS and ours are equally satisfactory, ours has certain theoretical advantages.


Prenylamine. Autoradiographic and neuropathological studies on myocardial mechanisms of action. Myocardial localization of prenylamine (PNL), a well known antianginal drug, was studied by means of an autoradiographic technique to detect microscopical distribution of tritiated PNL (3H-PLN). Forty Wistar rats received 35 muCi/kg b. w. 3H-PNL i. p., the animals being killed 30 min after injection. Heart slices, 1 mm thick, were processed for both autoradiographic and conventional histological techniques.  3H-PNL was observed, mainly, as striae along sarcolemma; sarcolemmal/intramyocardial 3H-PNL distribution ratio was 6 : 1. Preferential membrane deposition of 3H-PNL is probably related to the calcium transport inhibiting action of the drug, previously described.


An unusual form of mitral insufficiency accompanying atrial septal defect. An unusual case of atrial septal defect secundum type, associated with intermittent severe mitral insufficiency due to billowing anterior mitral leaflet, in a 56-year old female is described. The degree of mitral insufficiency ranged from severe to none. This phenomenon manifested itself by an intermittent systolic apical thrill and intermittent mitral regurgitation on angiocardiography. Pulling the anterior mitral leaflet at operation through the atrial septal defect demonstrated that this leaflet could be caught in the left atrium, thus causing intermittent mitral insufficiency. Closure of the atrial septal defect and replacement of the mitral valve was performed.


Fetal cardiovascular system as influenced by maternal smoking. Primary prevention of atherosclerosis should be initiated early in life, preferably in childhood. Nevertheless, it tends to be forgotten that a child has existed for nine months before birth, and that the newborn child might already have been exposed to agents capable of causing vessel damage. Studies of the umbilical artery, umbilical vein, and vessels of the placental villi (2, 3, 4, 5, 6) revealed that, in this portion of the fetal cardiovascular system, severe damage to the vessel wall is associated with maternal tobacco smoking during pregnancy. These alterations within the fetal cardiovascular system were never found in the children of non-smoking mothers. If similar changes occur in the other vessels of the newborn child, which it seems reasonable to expect, they might give rise to sequelae later in life. It should therefore strongly be advocated that pregnant women abandon tobacco smoking.


Approaches to determination of left ventricular volume and ejection fraction by real-time two-dimensional echocardiography. Left ventricular volumes and ejection fraction were derived from real time two-dimensional echocardiographic images (2 DE) and single plane (RAO) left ventricular cineangiograms in a series of 50 patients. Prospective application of a series of 6 alternate algorithms showed that a modified Simpson's rule approach using mitral and papillary muscle cross sections and an apical four chamber view provided the best 2 DE - angiographic correlations: for end-diastolic volume r = 0.82, SEE = 39 ml; for end-systolic volume r = 0.90, SEE = 29 ml and for ejection fraction r = 0.80, SEE = 0.09. The large SEE for volume determination indicates that further refinements are necessary to predict left ventricular volumes adequately; however, ejection fraction can be derived with an accuracy which allows practical clinical decisions in patients with satisfactory 2 DE images.


Radionuclide assessment of cardiac performance and myocardial perfusion in congestive cardiomyopathies. To determine the reliability of radionuclide techniques in the diagnosis of congestive cardiomyopathy (COCM), the function of the right ventricle (RV) and left ventricle (LV) was evaluated in 32 patients with COCM and 21 normal subjects using radionuclide angiography (first pass and gated blood pool scan) combined with quantitative 201 thallium (Tl) myocardial perfusion imaging. In COCM parameters of RV and LV performance were significantly reduced (p less than 0.01); regional wall motion analysis revealed a reduced radial shortening ability (p less than 0.05). 201 Tl distribution within the myocardium was not different between COCM and N; however, segmental 201Tl-uptake was significantly reduced (p less than 0.01). RV free wall was visualized on 201Tl scan in 80% of patients with COCM. There was no correlation between RV free wall visualization and RV hemodynamics. Thus these scintigraphic aspects provide an atraumatic and sensitive technique for the evaluation of patients with COCM.


Comprehensive analysis of exertional ECG changes before and after oral propranolol. In 12 patients with symptomatic coronary heart disease and three normal persons, comprehensive analyses of the electrocardiographic changes associated with symptom-limited upright exercise are made by computer analysis of the electrocardiogram recorded using a Frank XYZ lead system. This analysis provided a display of the 12 lead ECG, vectorcardiogram, polarcardiogram, and spatial cardiogram and measurements of spatial magnitudes of heart vectors. The effect of 40 mg of oral propranolol was assessed by repeating the exercise protocol 60--90 min later. There is evidence that propranolol reduces the electrocardiographic features of myocardial ischemia. This reduction in myocardial ischemia correlates with reductions in pressure rate product and heart rate. The presence of infarct criteria with exercise is variable and not apparently influenced by propranolol.


Patient profile and follow-up in medically and surgically treated young adults with myocardial infarction. Twenty-four young patients with myocardial infarction (average age 32.1 years) undergoing coronary arteriography after infarction were followed for an average of 33 months after catheterization. Prior inferior infarction was a predictor of two and three vessel coronary occlusive disease. Prior anterior infarction patients had a 64% incidence of single vessel coronary occlusive disease. Improvement in anginal symptoms over the follow-up period from the time of catheterization for the entire group was 69%. Employment at follow-up was excellent in both medically and surgically treated patients (80%). Cardiac mortality from the time of catheterization was extremely low (4%).